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ADDICTIVE BEHAVIOR ENCYCLOPEDIA of DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR Editorial Board EDITOR IN CHIEF Rosalyn Carson-DeWitt, M.D. Durham, North Carolina

EDITORS Kathleen M. Carroll, Ph.D. Associate Professor of Psychiatry Yale University School of Medicine Jeffrey Fagan, Ph.D. Professor of Public Health Joseph L. Mailman School of Public Health, Columbia University Henry R. Kranzler, M.D. Professor of Psychiatry University of Connecticut School of Medicine Michael J. Kuhar, Ph.D. Georgia Research Alliance Eminent Scholar and Candler Professor Yerkes Regional Primate Center EDA&AB-ttlpgs/v1 10/27.qx4 10/27/00 3:49 PM Page 3

ADDICTIVE BEHAVIOR ENCYCLOPEDIA of DRUGS, ALCOHOL & ADDICTIVE BEHAVIOR

SECOND EDITION

VOLUME 1 A – D

ROSALYN CARSON-DEWITT, M.D. Editor in Chief Durham, North Carolina Copyright © 2001 by Macmillan Reference USA, an imprint of the Gale Group

All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the Publisher.

Macmillan Reference USA Macmillan Reference USA An imprint of the Gale Group An imprint of the Gale Group 1633 Broadway 27500 Drake Rd. New York, NY 10019 Farmington Hills, MI 48331-3535

Printed in the United States of America printing number 12345678910

Library of Congress Cataloging-in-Publication Data Encyclopedia of drugs, alcohol, and addictive behavior / Rosalyn Carson-DeWitt, editor-in-chief.–Rev. ed. p. cm. Rev. ed. of: Encyclopedia of drugs and alcohol. c1995. Includes bibliographical references and index. ISBN 0-02-865541-9 (set) ISBN 0-02-865542-7 (Vol. 1) ISBN 0-02-865543-5 (Vol. 2) ISBN 0-02-865544-3 (Vol. 3) ISBN 0-02-865545-1 (Vol. 4) 1. Drug abuse–Encyclopedias. 2. Substance abuse–Encyclopedias. 3. Alcoholism–Encyclopedias. 4. Drinking of alcoholic beverages–Encyclopedias. I. Carson-DeWitt, Rosalyn II. Encyclopedia of drugs and alcohol. HV5804 .E53 2000 362.29'03–dc21 00-046068 CIP

This paper meets the requirements of ANSI-NISO Z39.48-1992 (Permanence of Paper) ⅜oo™ Contents

Preface ix List of Articles xi List of Authors xxxvii Encyclopedia of Drugs, Alcohol, and Addictive Behavior 1 Appendix 1373 Index 1821

v EDITORIAL AND PRODUCTION STAFF

Project Editor AMANDA C. QUICK

Contributing Editors & Copy Editors MARY ALAMPI ERIN E. BRAUN PATTI BRECHT DEBBIE BUREK DONNA CRAFT SHEILA DOW ANDREW J. HOMBURG THAI ISHIZUKA-CAPP PETER JASKOWIAK MARK KLEIMAN SARAH KNOX JANE MALONIS REBECCA MARLOW-FERGUSON CHRYSTAL ROSZA

Indexer SYNAPSE, THE KNOWLEDGE LINK CORPORATION

Typesetter GGS INFORMATION SERVICES

Production Staff MARY BETH TRIMPER, Composition Manager EVI SEOUD, Assistant Production Manager WENDY BLURTON, Senior Buyer

Imaging Staff BARBARA J. YARROW, Manager, Imaging and Multimedia Content ROBYN V. Y OUNG, Project Manager, Imaging and Multimedia Content KELLY A. QUIN, Editor, Imaging and Multimedia Content RANDY BASSETT, Imaging Supervisor

Art Staff KENN J. ZORN, Product Design Manager PAMELA A.E. GALBREATH, Senior Art Director

ANNE DAVIDSON, Senior Editor LINDA S. HUBBARD, Director

ELLY DICKASON, Publisher Preface

Why a second edition of the Encyclopedia of Drugs and Alcohol? And why change the name to the Encyclopedia of Drugs, Alcohol, and Addictive Behavior? Consider a smattering of statistics: • In 1999, 10.3 million people (4.7% of the American population) ages 12 years or older were dependent on illicit drugs or alcohol (National Household Survey on Drug Abuse, 1999) • In 1998, it was estimated that approximately 19,000 alcohol-induced deaths occur annually in the United States (excluding those deaths due to motor vehicle accidents involving alcohol) (National Vital Statistics Reports, Murphy, 2000) • In 1993, it was reported that 13,984 people were killed in alcohol-related motor vehicle accidents; 3,765 of these individuals had not been drinking themselves (Heien, 1996) • In 1998, 16,926 deaths were attributed to drug-induced causes (National Vital Statistics Reports, Murphy, 2000) • In 1998, chronic liver disease and cirrhosis ranked as the tenth leading cause of death in the United States (National Vital Statistics Reports, Murphy, 2000) • Fetal alcohol syndrome affects one in every 600–750 births, and is currently the leading cause of mental retardation, beating out previous contenders such as Down syndrome and spina bifida (Abel, 1986) • Economic costs to society related to alcohol and drug abuse were projected at nearly $246 million in 1992; projections for 1995 suggested that economic costs related to alcohol and drug abuse would reach over $276 million (National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism) • Smokers ages 18–25 have a fourfold increased likelihood of illicit drug use compared to their nonsmoking peers; smokers ages 12–17 have a sevenfold increased likelihood of illicit drug use compared to their nonsmoking peers (1999 National Household Survey on Drug Abuse) • In 2000, the United States put together an emergency aid package to Colombia, totaling $1.3 billion, intended in part to address the issues of drug trafficking between Colombia and the United States (White House, Office of the Press Secretary, 2000) • In 1999, the annual cost for problem and pathological gambling reached $5 billion, with lifetime costs projected at $40 billion associated with decreased productivity, social service costs, and creditor losses (Gerstein et al., 1999) Drugs, alcohol, and addictive behaviors have enormous ramifications on a global scale, and include political, economic, legal, social, and public health issues, as well as family well-being and physical and psychological health. These ramifications can be studied as a macrocosm of the way in which the issues attendant to addictions affect every stratum of society, or collapsed down into the microcosm of misery visited on a single individual struggling to loosen the stranglehold of addiction. The first edition of Macmillan’s Encyclopedia of Drugs and Alcohol is an amazing compendium of

ix x PREFACE information on the effects of addictions at every level. Drs. Jaffe, Anthony, Johanson, Kuhar, Moore, and Sellers and their team of experts put together an intelligently organized, complete survey of drug and alcohol addictions. Our task, then, was to respectfully update these articles to reflect the impressive amount of research performed over the five years since the publication of the original edition. The newly renamed second edition, now called the Encyclopedia of Drugs, Alcohol, and Addictive Behavior, retains the first edition’s organizational format, but includes new and updated articles that address the exciting frontiers that have opened up in the field of addiction studies. New brain imaging techniques, an explosion of information about the human genome and its relevance to health, excellent efforts at data collection to define the scope and nature of the problem of addictions, and carefully designed studies aimed at uncovering the statistical relevance of various prevention, diagnosis, and treatment programs are all illuminating and igniting the process of understanding addictions. The encyclopedia’s name change reflects acknowledgment that behaviors not involving chemical substances (such as pathological gambling) are being seriously and thoughtfully studied, and appear to involve some physiological and psychological pathways in common with those addictions involving chemical substances. Far from being an esoteric consideration of theoretical concepts, research within the field of addiction studies quickly doubles back to benefit those individuals who are trapped in the mundane, nitty-gritty ugliness of an addiction. For this reason, and because issues within the field of addictions surely touch the lives of essentially every member of society, this second edition preserves the first edition’s mission of providing information that will be useful, interesting, and accessible to nonspecialists seeking an understanding of addiction topics. The second edition’s editorial board (Drs. Kathleen Carroll, Jeffrey Fagan, Henry Kranzler, and Michael Kuhar) has been impressively dedicated in their efforts to produce this encyclopedia. Their expertise and guidance have been invaluable, as have the expertise and knowledge of the various writers who have contributed to this work. All of us who have worked on this encyclopedia have appreciated the forbearance of publisher Elly Dickason, senior editor Anne Davidson, and editor Amanda Quick. I wish to thank my husband, Toby, and my daughters, Anna, Emma, and Isabelle, for their patience as “the encyclopedia project” took its place in our family life. Last, we wish to acknowledge with appreciation all of the researchers and academicians who continue to illuminate issues relevant to addiction, the professionals who work compassionately with those affected by addiction, and the many individuals who continue to reach for a life free of addiction’s grip.

ROSALYN CARSON-DEWITT, M.D. Editor in Chief October 2000

BIBLIOGRAPHY

ABEL, E. L. & SOKOL, R. J. (1986). Fetal alcohol syndrome is now leading cause of mental retardation. Lancet, 2, 1222. Gambling Impact and Behavior Study: Final Report to the National Gambling Impact Study Commission. (1999). Chicago: National Opinion Research Center, University of Chicago. HARWOOD, H., FOUNTAIN, D., & LIVERMORE, G. (1998). The Economic Costs of Alcohol and Drug Abuse in the United States, 1992. National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism: DHHS, NIH, NIH Publication no. 98-4327. Bethesda, MD. HEIEN, D. M. (1996). Are higher alcohol taxes justified? The Cato Journal, 15. MURPHY, S. L. (2000). Deaths: Final data for 1998. Center for Disease Control and Prevention’s National Vital Statistics Report, 48(11). U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, SUBSTANCE ABUSE AND MENTAL HEALTH SERVICES ADMINISTRATION. (2000). Summary of findings from the 1999 National Household Survey on Drug Abuse. THE WHITE HOUSE, OFFICE OF THE PRESS SECRETARY. (2000). Fact sheet: Presidential decision directive on the Colombia initiative: Increased U.S. assistance for Colombia.

x List of Articles

Abstinence Violation Effect Alan Marlatt (AVE) Molly Carney Revised by Patricia Ohlenroth Abuse Liability of Drugs: William Woolverton Testing in Animals Revised by James T. McDonough, Jr. Abuse Liability of Drugs: Testing in Humans Joseph V. Brady Accidents and Injuries from Alcohol Cheryl J. Cherpitel Accidents and Injuries from Drugs James E. Rivers Acetylcholine Floyd Bloom Addicted Babies Joyce F. Schneiderman Revised by Sheila Dow Addiction Griffith Edwards Addiction: Concepts and Definitions Harold Kalant Addiction Research Unit (ARU) (U.K.) Griffith Edwards Addiction Severity Index A.Thomas McLellan (ASI) Revised by Rebecca Marlow-Ferguson Addictive Personality William A. Frosch Addictive Personality and Psychological Tests William A. Frosch Adjunctive Drug Taking John L. Falk Administrative and Public Health Law Lorraine Green Mazerolle Adolescents and Drug Use Alison M. Trinkoff Carla L. Storr Revised by Mary Carvlin Adult Children of Alcoholics (ACOA) Marc A. Schuckit

xi xii LIST OF ARTICLES

Advertising and the Alcohol G. Borges Industry Charles M. Rongey Advertising and the Pharmaceutical Industry Charles M. Rongey Advertising and Tobacco Use Charles M. Rongey Aggression and Drugs, Research Issues Klaus A. Miczek Aging, Drugs, and Alcohol Madhu R. Korrapati Robert E. Vestal Revised by James T. McDonough, Jr. Agonist Nick E. Goeders Agonist-Antagonist (Mixed) Nick E. Goeders Al-Anon Harrison M. Trice Alateen Harrison M. Trice Alcohol: Chemistry and Scott E. Lukas Pharmacology Revised by Andrew J. Homburg Alcohol: Complications Ronald R. Watson Alcohol: History of Drinking Dwight B. Heath Revised by Andrew J. Homburg Alcohol: Psychological Herman H. Samson Consequences of Chronic Nancy L. Sutherland Abuse Revised by Andrew J. Homburg Alcohol and AIDS Ronald R. Watson Alcohol- and Drug-Free Friedner D. Wittman Housing Jim Baumohl Alcoholics Anonymous (AA) Harrison M. Trice Alcoholism: Abstinence versus Stanton Peele Controlled Drinking Revised by Kimberley A. McGrath Alcoholism: Origin of the Term Frederick B. Glaser Alkaloids Nick E. Goeders Allergies to Alcohol and Drugs Marlene Aldo-Benson Amantadine Thomas R. Kosten American Academy of Addiction Faith K. Jaffe Psychiatry (AAAP) Revised by Nancy Faerber American Society of Addiction Marc S. Galanter Medicine (ASAM) Jerome H. Jaffe Revised by Nancy Faerber Amobarbital Scott E. Lukas Revised by Rebecca J. Frey Amotivational Syndrome Chris-Ellyn Johanson Amphetamine Marian W. Fischman Amphetamine Epidemics Marissa Miller Nicholas Kozel Revised by Martin Leamon

xii LIST OF ARTICLES xiii

Amygdala Stephanie DallVecchia-Adams Anabolic Steroids Kirk J. Brower Analgesic Gavril W. Pasternak Anhedonia Anthony Phillips Anorectic Timothy H. Moran Anorexia Timothy H. Moran Anslinger, Harry J., and U.S. Rufus King Drug Policy Revised by James T. McDonough, Jr. Antagonist Nick E. Goeders Antidepressant George R. Uhl Valina Dawson Revised by Rebecca J. Frey Antidote Michael J. Kuhar Antipsychotic George R. Uhl Valina Dawson Antisocial Personality Kathleen K. Bucholz Anxiety Myroslava Romach Karen Parker Aphrodisiac Nick E. Goeders Argot David Vlahov Arrestee Drug Abuse Scott Decker Monitoring System (ADAM) Eric D. Wish Asia, Drug Use in Christian G. Schutz Revised by Frederick K. Grittner Assessment of Substance Abuse: DAST Harvey Skinner Assessment of Substance David Metzger Abuse: HIV Risk Behaviors George Woody Survey Helen Navaline Assessment of Substance Abuse: TACE Robert Sokol Asset Forfeiture Frederick K. Grittner Association for Medical Education and Research in Substance Abuse Marc S. Galanter (AMERSA) Revised by Donna Craft Attention Deficit Disorder Ralph E. Tarter Ada C. Mezzich Revised by Chris Lopez Ayahuasca Jerome H. Jaffe Barbiturates Scott E. Lukas Barbiturates: Complications Jat M. Khanna Beers and Brews Scott E. Lukas Revised by Nancy Faerber

xiii xiv LIST OF ARTICLES

Behavioral Economics Warren Bickel Louis A. Giordano Behavioral Tolerance Marc N. Branch Benzodiazepines Domenic A. Ciraulo Clifford Knapp Benzodiazepines: Complications Malcolm H. Lader Benzoylecognine Marian W. Fischman Betel Nut Marc A. Schuckit Jerome H. Jaffe Bhang Leo E. Hollister Blood Alcohol Concentration, Measures of A.W. Jones Blood Alcohol Content Myroslava Romach Karen Parker Bolivia, Drug Use in James A. Inciardi Revised by Frederick K. Grittner Border Management Richard L. Williams Revised by Frederick K. Grittner Brain Structures and Drugs James E. Smith Steven I. Dworkin Breathalyzer Myroslava Romach Karen Parker Revised by Frederick K. Grittner Britain, Drug Use in Virginia Berridge British System of Drug-Addiction Treatment John Stang Bulimia Nervosa Marion Olmsted David Goldbloom Myroslava Romach Karen Parker Revised by Rebecca Marlow-Ferguson Buprenorphine Gavril W. Pasternak Caffeine Kenneth Silverman Roland R. Griffiths Calcium Carbimide John E. Peachey Revised by Rebecca J. Frey California Civil Commitment Harry K. Wexler Program Revised by Terrence P. Murphy Canada, Drug and Alcohol Manuella Adrian Use in Revised by Reginald G. Smart Cancer, Drugs and Alcohol Manuella Adrian Revised by Rebecca J. Frey Cannabis sativa Leo E. Hollister

xiv LIST OF ARTICLES xv

Catecholamines Floyd Bloom Causes of Substance Abuse: Drug Effects and Biological Everett H. Ellinwood Responses George R. King Causes of Substance Abuse: George R. Uhl Genetic Factors Revised by Amy Loerch Strumolo Causes of Substance Abuse: Learning Steven J. Robbins Causes of Substance Abuse: Psychological (Psychoanalytic) Perspective Ed Khantzian Center on Addiction and Jerome H. Jaffe Substance Abuse (CASA) Revised by Herb Kleber Centre for Addiction and Mental Health Belinda Rowland Child Abuse and Drugs Karol L. Kumpfer Jan Bays Childhood Behavior and Later Judith S. Brook Drug Use Patricia Cohen Chinese Americans, Alcohol Richard F. Catalano and Drug Use among Tracy W. Harachi Chloral Hydrate Scott E. Lukas Chlordiazepoxide Scott E. Lukas Revised by Rebecca Marlow-Ferguson Chocolate Michael J. Kuhar Chromosome Michael J. Kuhar Chronic Pain Belinda Rowland Civil Commitment Harry K. Wexler Clinical Trials Network Alan I. Leshner Clone, cloning Michael J. Kuhar Clonidine Mark S. Gold Club Drugs Richard G. Hunter Cocaethylene Ronald R. Watson Cocaine Marian W. Fischman Coca Paste Marian W. Fischman Coca Plant Marian W. Fischman Codeine Gavril W. Pasternak Codependence Timmen L. Cermak Coerced Treatment for Marie Ragghianti Substance Offenders Revised by Carl G. Leukefeld Coffee Kenneth Silverman Roland R. Griffiths

xv xvi LIST OF ARTICLES

Cognitive-behavioral Therapy Kathleen Carroll Cola/Cola Drinks Michael J. Kuhar College on Problems of Drug Arthur E. Jacobson Dependence (CPDD), Inc. Revised by Nancy Faerber Colombia As Drug Source James Van Wert Revised by Frederick K. Grittner Commissions on Drugs Jennifer K. Lin Committees of Correspondence Otto Moulton Timothy Regan Complications: Cardiovascular Robert Saporito System (Alcohol and Cocaine) Revised by Andrew J. Homburg Complications: Cognition Peter Martin George Mathews Complications: Dermatological David E. Smith Richard B. Seymour Revised by Ralph Myerson Complications: Endocrine and Lawrence S. Brown, Jr. Reproductive Systems Complication: Immunologic Ronald R. Watson Complications: Liver (Alcohol) Charles S. Lieber Complications: Liver (Other Drugs) Paul Devenyi Revised by Ralph Myerson Complications: Medical and John T. Sullivan Behavioral Toxicity Overview Revised by Ralph Myerson Complications: Mental Disorders Brian L. Cook George Winokur Revised by Daniel Hayes Complications: Neurological Peter L. Carlen Mary Pat McAndrews Revised by Mary Carvlin Complications: Nutritional Daphne Roe Revised by Mary Carvlin Complications: Route of David E. Smith Administration Richard B. Seymour Compulsions Belinda Rowland Conditioned Tolerance Riley Hinson Conduct Disorder and Drug Use Ada C. Mezzich Ralph E. Tarter Revised by Mary Carvlin Conduct Disorder in Children Myroslava Romach Karen Parker

xvi LIST OF ARTICLES xvii

Contingencv Management Stephen T. Higgins Alan J. Budney Sarah Heil Controlled Substances Act of 1970 Richard J. Bonnie Controls: Scheduled Drugs/Drug Rolley E. Johnson Schedules, U.S. Anastasia E. Nasis Revised by Frederick K. Grittner Coping and Drug Use Ralph E. Tarter Crack Marian W. Fischman Craving Stephen T. Tiffany Creativity and Drugs Arnold M. Ludwig Crime and Alcohol James J. Collins Revised by Frederick K. Grittner Crime and Drugs David N. Nurco Timothy W. Kinlock Thomas E. Hanlon Revised by Frederick K. Grittner Crop-Control Policies (Drugs) James Van Wert Cults and Drug Use David Halperin Revised by James T. McDonough, Jr. Delirium Myroslava Romach Karen Parker Delirium Tremens (DTs) Myroslava Romach Karen Parker Depression Myroslava Romach Karen Parker Designer Drugs Nick E. Goeders Detoxification: As Aspect of Treatment John T. Sullivan Dextroamphetamine Marian W. Fischman Diagnosis of Drug Abuse: Thomas F. Babor Diagnostic Criteria Revised by Chris Lopez Diagnostic and Statistical Thomas F. Babor Manual (DSM) Revised by Amy Loerch Strumolo Diagnostic Interview Thomas F. Babor Schedule (DIS) Revised by Rebecca Marlow-Ferguson Dihydromorphine Gavril W. Pasternak Dimethyltryptamine (DMT) R.N. Pechnik Daniel X. Freedman Disease Concept of Jerome H. Jaffe Alcoholism and Drug Abuse Roger E. Meyer Distillation Scott E. Lukas Distilled Spirits Scott E. Lukas

xvii xviii LIST OF ARTICLES

Distilled Spirits Council Paul F. Gavaghan Revised by Frederick K. Grittner Disulfiram Richard K. Fuller Raye Z. Litten Revised by Rebecca J. Frey Dogs in Drug Detection Carl A. Newcombe Dom R.N. Pechnik Daniel X. Freedman Dopamine Floyd Bloom Revised by Michael J. Kuhar Dose-Response Relationship Nick E. Goeders Dover’s Powder Verner Stillner Dramshop Liability Laws Christopher B. Anthony Revised by Richard J. Bonnie Driving, Alcohol, and Drugs Herbert Moskowitz Driving Under the Influence Myroslava Romach (DUI) Karen Parker Revised by Frederick K. Grittner Dropouts and Substance Abuse Eric O. Johnson Drug Nick E. Goeders Drug Abuse Reporting Program (DARP) Dwayne Simpson Drug Abuse Treatment Outcome Robert Hubbard Study (DATOS) Revised by Dwayne Simpson Drug Abuse Warning Network Clare Mundell (DAWN) Revised by Patricia Ohlenroth Drug Courts John Goldkamp Drug Interaction and the Brain Nick E. Goeders Revised by Jill Lectka Drug Interactions and Alcohol Arthur I. Cederbaum Revised by Rebecca J. Frey Drug Interdiction Peter Reuter Revised by Frederick K. Grittner Drug Laws: Financial Analysis Clifford L. Karchmer in Enforcement Revised by Frederick K. Grittner Drug Laws: Prosecution of Stephen Goldsmith Drug Metabolism Ted Inaba Revised by Mary Carvlin Drug Policy Foundation Jerome H. Jaffe Revised by Frederick K. Grittner Drug Testing Methods and Clinical Interpretations of Test Results Bhushan K. Kapur Drug Types Nick E. Goeders

xviii LIST OF ARTICLES xix

Drunk Driving James B. Jacobs Dynorphin Stephanie DallVecchia-Adams Economic Costs of Alcohol Abuse Dorothy P. Rice and Alcohol Dependence Revised by Frederick K. Grittner ED50 Nick E. Goeders Education and Prevention John D. Swisher Eric Goplerud Revised by Matthew Miskelly Elimination of the Drug Addiction and Alcoholism Category in Jim Baumohl Social Security Disability Programs Sharon R. Hunt Employee Assistance Programs (EAPs) Steven W. Gust Endorphins Floyd Bloom Enkephalin Floyd Bloom Epidemics of Drug Abuse Carla Storr Marsha F. Rosenberg James C. Anthony Epidemiology of Drug Abuse Marsha F. Rosenberg James C. Anthony Ethchlorvynol Scott E. Lukas Ethinamate Scott E. Lukas Ethnic Issues and Cultural Relevance David E. Smith in Treatment Richard B. Seymour Revised by Sarah Knox Ethnicity and Drugs Marsha Lillie-Blanton Amelia Arria Ethnopharmacology Nick E. Goeders Exclusionary Rule Robert T. Angarola Alan Minsk Revised by Frederick K. Grittner Expectancies Alan Marlatt Molly Carney Revised by Mary Carvlin Families and Drug Use R.A. Lewis M.S. Irwanto Family Violence and Substance Abuse Barbara Lex Fermentation Scott E. Lukas Fetal Alcohol Syndrome (FAS) Robin A. LaDue Fetus: Effects of Drugs on the Loretta P. Finnegan Michael P. Finnegan George A. Kanuck Revised by Patricia Ohlenroth

xix xx LIST OF ARTICLES

Fly Agaric Robert Zaczek Foreign Policy and Drugs W. Kenneth Thompson Revised by Frederick K. Grittner Freebasing Marian W. Fischman Revised by Grace O’Leary Revised by Roger Weiss Freud and Cocaine Robert Byck Gambling As an Addiction Sheila B. Blume Gambling Addiction: Assessment Marvin Steinberg Gambling Addiction: Epidemiology Marvin Steinberg Gamma-Aminobutyric Acid (GABA) Floyd Bloom Gangs and Drugs Jeffrey Fagan Ganja Leo E. Hollister Gender and Complications of Substance Abuse Joyce F. Schneiderman Gene Michael J. Kuhar Gene Regulation: Drugs Michael J. Kuhar Genome Project Michael J. Kuhar Ginseng Michael J. Kuhar Glutamate Floyd Bloom Glutethimide Scott E. Lukas Golden Triangle As Drug Source James Van Wert Revised by Frederick K. Grittner Hair Analysis As a Test for Drug Edward J. Cone Use Revised by Amy Loerch Strumolo Halfway Houses Jim Baumohl Jerome H. Jaffe Hallucination Myroslava Romach Karen Parker Hallucinogenic Plants R.N. Pechnik Daniel X. Freedman Hallucinogens R.N. Pechnik Daniel X. Freedman Harrison Narcotics Act of 1914 Robert T. Angarola Alan Minsk Hashish Leo E. Hollister Hemp Leo E. Hollister Heroin Gavril W. Pasternak Heroin: The British System Bruce D. Johnson High School Senior Survey Patrick M. O’Malley Hispanics and Drug Use, in the United States Joan Moore

xx LIST OF ARTICLES xxi

Homelessness, Alcohol, and Other Drugs Margaret Murray Homelessness and Drugs, History of Jim Baumohl Hydromorphone Gavril W. Pastenak Iatrogenic Addiction Russell K. Portenoy Ibogaine Jerome H. Jaffe Imaging Techniques: June M. Stapleton Visualizing the Living Edythe D. London Brain Revised by Mary Carvlin Immunoassay Jeffrey A. Gere Impaired Physicians and Donald R. Wesson Medical Workers Walter Ling Revised by Andrew J. Homburg Industry and Workplace, Drug Use in Michael Walsh Inhalants Ronald W. Wood Inhalants: Extent of Use and Neil Swan Complications Revised by Donna Craft Injecting Drug Users and HIV Faye E. Reilly Carl G. Leukefeld Revised by Rebecca Marlow-Ferguson International Classification of Diseases (ICD) Thomas F. Babor International Drug Supply Systems James Van Wert Italy, Drug Use in Ustik Avico Jellinek Memorial Fund H. David Archibald Revised by Donna Craft Jews, Drug and Alcohol Use Among Sheila B. Blume Jimsonweed Robert Zaczek Revised by James T. McDonough, Jr. Kava Robert Zaczek Khat Peter Kalix L-Alpha-Acetylmethadol (LAAM) Gavril W. Pasternak Laudanum Gavril W. Pasternak LD50 Nick E. Goeders Legal Regulation of Drugs and Alcohol Richard J. Bonnie Le Patriarche David A. Deitch

xxi xxii LIST OF ARTICLES

Limbic System James E. Smith Steven I. Dworkin Lysergic Acid Diethylamide R.N. Pechnik (LSD) and Psychedelics Daniel X. Freedman Mandatory Sentencing Michael Tonry Revised by Frederick K. Grittner Marihuana Commission: Recommendations on Decriminalization Richard J. Bonnie Marijuana Leo E. Hollister Revised by James T. McDonough, Jr. MDMA R.N. Pechnik Daniel X. Freedman Memory and Drugs: State Dependent Learning Donald A. Overton Memory, Effects of Drugs on Ivan Izquierdo James L. McGaugh Meperidine Gavril W. Pasternak Meprobamate Scott E. Lukas Mescaline R.N. Pechnik Daniel X. Freedman Methadone Gavril W. Pasternak Methadone Maintenance Joan Ellen Zweben Programs J. Thomas Payte Methamphetamine Marian W. Fischman Methanol Scott E. Lukas Methaqualone Scott E. Lukas Methedrine Marian W. Fischman Methylphenidate Marian W. Fischman Mexico As Drug Source James Van Wert Revised by Frederick K. Grittner Michigan Alcoholism Screening Test (MAST) A. Thomas McLellan Military, Drug and Alcohol Abuse in the U.S. Robert M. Bray Minimum Drinking Age Laws Alexander C. Wagenaar Minnesota Multiphasic Personality Inventory (MMPI) Thomas F. Babor Money Laundering Clifford L. Karchmer Revised by Ronald Goldstock Monoamine Floyd Bloom Moonshine Scott E. Lukas

xxii LIST OF ARTICLES xxiii

Morning Glory Seeds R.N. Pechnik Daniel X. Freedman Morphine Gavril W. Pasternak Mothers Against Drunk Driving (MADD) Dianne Shuntich MPTP Gavril W. Pasternak Multidoctoring Myroslava Romach Karen Parker Myths About Drug Abuse and Treatment James T. McDonough, Jr. Naloxone Gavril W. Pasternak Naltrexone Gavril W. Pasternak Naltrexone in Treatment of Drug Dependence David A. Gorelick Narcotic Gavril W. Pasternak Narcotic Addict Rehabilitation Jerome H. Jaffe Act (NARA) James F. Maddux Narcotics Anonymous (NA) Harrison M. Trice National Association of State Alcohol and Drug Abuse Directors Belinda Rowland National Commission on Marihuana and Drug Abuse Richard J. Bonnie National Council on Alcoholism and Drug Dependence (NCADD) Sheila B. Blume National Household Survey on Joseph C. Gfroerer Drug Abuse (NHSDA) Revised by Patricia Ohlenroth Needle and Syringe Exchanges Don C. Des Jarlais and HIV/AIDS Denise Paone Revised by Kimberley A. McGrath Netherlands, Drug Use in the Charles Kaplan Revised by Frederick K. Grittner Neuroleptic George R. Uhl Valina Dawson Revised by Donna Craft Neuron Floyd Bloom Neurotransmission Floyd Bloom Neurotransmitters Floyd Bloom New York State Civil Harry K. Wexler Commitment Program Revised by Frederick K. Grittner Nicotine Neal L. Benowitz Alice B. Fredericks Nicotine Delivery Systems for Smoking Cessation Jed E. Rose

xxiii xxiv LIST OF ARTICLES

Norepinephrine Floyd Bloom Revised by Michael J. Kuhar Nucleus Accumbens James E. Smith Revised by Michael J. Kuhar Nutmeg R.N. Pechnik Daniel X. Freedman Obesity Timothy H. Moran Revised by Rebecca Marlow-Ferguson Operation Intercept Richard B. Craig Opiates/Opioids Gavril W. Pasternak Revised by Rebecca Marlow-Ferguson Opioid Complications and William R. Martin Withdrawal Revised by Rebecca J. Frey Revised by Rebecca Marlow-Ferguson Opioid Dependence: Course James F. Maddux of the Disorder Over Time David P. Desmond Opioids and Opioid Control: Caroline Jean Acker History Revised by Sheigla Murphy Opium Gavril W. Pasternak Overdose, Drug (OD) Myroslava Romach Karen Parker Overeating and Other Excessive Behaviors Jerome H. Jaffe Over-the-Counter (OTC) Myroslava Romach Medication Karen Parker Oxycodone Gavril W. Pasternak Oxymorphone Gavril W. Pasternak Pain: Behavioral Methods for Measuring Analgesic Effects of Drugs Linda Dykstra Pain: Drugs Used in Gavril W. Pasternak Treatment of Revised by Rebecca Marlow-Ferguson Papaver somniferum Gavril W. Pasternak Paraphernalia, Laws against Richard J. Bonnie Parasite Diseases and Alcohol Ronald R. Watson Paregoric Gavril W. Pasternak Parents Movement Sue Rusche Partnership for a Drug-Free America Thomas A. Hedrick, Jr. Pemoline Marian W. Fischman Personality As a Risk Factor William A. Frosch for Drug Abuse

xxiv LIST OF ARTICLES xxv

Personality Disorder Myroslava Romach Karen Parker Revised by Rebecca J. Frey Peyote R.N. Pechnik Daniel X. Freedman Pharmacodynamics Usoa E. Busto Pharmacokinetics: General Usoa E. Busto Pharmacokinetics: Implications in Abusable Symptoms David J. Greenblatt Pharmacokinetics of Alcohol A.W. Jones Pharmacology Nick E. Goeders Phencyclidine (PCP) Marilyn E. Carroll Sandra D. Comer Phencyclidine (PCP): Adverse Robert L. Balster Effects Revised by Rebecca J. Frey Revised by Rebecca Marlow-Ferguson Phenobarbital Scott E. Lukas Physical Dependence Harold Kalant Plants, Drugs from Nick E. Goeders Poison Michael J. Kuhar Policy Alternatives: Analysis of Drug Legalization Jonathan Caulkins Policy Alternatives: Prohibition Duane C. McBride of Drugs Pro and Con Revised by Jonathan Caulkins Policy Alternatives: Safe Use of Drugs Andrew T. Weil Polydrug Abuse Chris-Ellyn Johanson Poverty and Drug Use Nora Jacobson Margaret E. Ensminger Revised by Patricia Ohlenroth Pregnancy and Drug Dependence: Loretta P. Finnegan Opioids and Cocaine Michael P. Finnegan George A. Kanuck Prescription Drug Abuse Malcolm H. Lader Revised by Jill Lectka Prevention: The Citizens’ Drug Prevention Movement Sue Rusche Prevention: Community Drug Robert C. Davis Resistance Arthur J. Lurigio Revised by Jill Lectka Prevention: Prevention of Alcoholism, the Ledermann Model of Consumption Bryan M. Johnstone

xxv xxvi LIST OF ARTICLES

Prevention Programs Gilbert J. Botvin Brian R. Flay William B. Hansen Sewhan Kim Rebecca Marlow-Ferguson Armand L. Mauss Jonnie McLeoud Matthew Miskelly Sue Rusche Eric Schaps Carl Shantzis Dianne Shuntich Prisons and Jails Harry K. Wexler Revised by Frederick K. Grittner Prisons and Jails: Drug Harry K. Wexler Treatment in Revised by Richard Dembo Prisons and Jails: Drug Use Harry K. Wexler and AIDS in Revised by Ted Hammett Processes of Change Model James Prochaska Productivity: Effects of Alcohol on Dean R. Gerstein Productivity: Effects of Drugs on Dean R. Gerstein Professional Credentialing M. Marlyne Kilbey Amy L. Stirling Prohibition of Alcohol Jerome H. Jaffe Propoxyphene Jerome H. Jaffe Psilocybin R.N. Pechnik Daniel X. Freedman Psychoactive Nick E. Goeders Revised by Nicholas DeMartinis Psychoactive Drug Nick E. Goeders Revised by Nicholas DeMartinis Psychoanalysis William A. Frosch Psychomotor Effects of Alcohol Mauri J. Mattila and Drugs Esko Nuotto Psychomotor Stimulant Marian W. Fischman Psychopharmacology Nick E. Goeders Revised by Nicholas DeMartinis Psychotropic Substances Convention of 1971 Robert T. Angarola Public Intoxication Peter Barton Hutt Racial Profiling David Cole Rational Authority Harry K. Wexler

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Rational Recovery (RR) Marc Galanter Jerome H. Jaffe Rave Richard G. Hunter Receptor: Drug Nick E. Goeders Revised by Michael J. Kuhar Receptor: NMDA George R. Uhl Valina Dawson Reinforcement James E. Barrett Revised by Maxine Stitzer Relapse Myroslava Romach Karen Parker Religion and Drug Use Jerald G. Bachman John M. Wallace, Jr. Remove Intoxicated Drivers (RID-USA, Inc.) Faith K. Jaffe Research: Aims, Description, and Goals Christine R. Hartel Research: Clinical Research Belinda Rowland Research: Developing Medications to Treat Substance Abuse and Dependence Therese A. Kosten Research: Drugs As Discriminative Stimuli James E. Barrett Research: Measuring Effects of Drugs on Behavior Linda A. Dykstra Research: Measuring Effects of Drugs Kenzie L. Preston on Mood Sharon L. Walsh Research: Motivation Anthony G. Phillips Research, Animal Model: An Overview of Drug Abuse William Woolverton Research, Animal Model: Conditioned Place Preference William Woolverton Research, Animal Model: Conditioned Charles Schindler Withdrawal Steven Goldberg Research, Animal Model: Drug Discrimination Studies William Woolverton Research, Animal Model: Drug Self-Administration William Woolverton Research, Animal Model: Environmental Influences on Drug Effects James E. Barrett Research, Animal Model: Intracranial Self-Stimulation Heather Kimmel

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Research, Animal Model: Learning, Conditioning, and Drug Effects— An Overview James E. Barrett Research, Animal Model: Learning Modifies Drug Effects James E. Barrett Research, Animal Model: Operant Learning Is Affected by Drugs Linda A. Dykstra Reward Pathways and Drugs Conan Kornetsky Rockefeller Drug Laws Michael Tonry Revised by Frederick K. Grittner Rohypnol Richard G. Hunter Rolleston Report of 1926 (U.K.) Bruce D. Johnson Rubbing Alcohol Scott E. Lukas Rutgers Center of Alcohol Peter E. Nathan Studies Revised by Matthew Miskelly Schizophrenia Myroslava Romach Karen Parker Revised by Kimberley A. McGrath Scopolamine and Atropine Robert Zaczek Secobarbital Scott E. Lukas Secular Organizations for Sobriety (SOS) Jerome H. Jaffe Sedative Scott E. Lukas Sedative-Hypnotic Scott E. Lukas Revised by Nicholas DeMartinis Sedatives: Adverse Consequences Valerie Curran of Chronic Use Revised by Rebecca J. Frey Seizures of Drugs Peter Reuter Revised by Frederick K. Grittner Sensation and Perception and Linda Dykstra Effects of Drugs Revised by Rebecca Marlow-Ferguson Serotonin Floyd Bloom Serotonin-Uptake Inhibitors in Treatment of Substance Claudio A. Naranjo Abuse Karen E. Bremner Shanghai Opium Conference Robert T. Angarola of 1911 Alan Minsk Shock Incarceration and Boot Doris Layton MacKenzie Camp Prisons Revised by Frederick K. Grittner Single Convention on Narcotic Drugs Robert T. Angarola Slang and Jargon Richard Lingeman Revised by Mary Carvlin

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Sleep, Dreaming, and Drugs Timothy A. Roehrs Thomas Roth Revised by Ron Gasbarro Sleeping Pills Scott E. Lukas Sobriety John N. Chappel Revised by Rebecca J. Frey Social Costs of Alcohol and Philip J. Cook Drug Abuse Revised by Sarah Knox Source Countries for Illicit James Van Wert Drugs Revised by Frederick K. Grittner Still Scott E. Lukas Street Value Peter Reuter Revised by Mary Carvlin Stress Lorenzo Cohen Andrew Baum Structured Clinical Interview Thomas F. Babor for DSM-IV (SCID) Revised by Michael First Students Against Destructive Michael Klitzner Decisions (SADD) Revised by Patricia Ohlenroth Substance Abuse and AIDS Harry W. Haverkos D. Peter Drotman Revised by Rebecca J. Frey Suicide and Substance Abuse Michael J. Bohn Sweden, Drug Use in Jonas Hartelius A.W. Jones Revised by Sarah Knox Synapse, Brain Floyd Bloom Tax Laws and Alcohol Philip J. Cook Tea Roland R. Griffiths Kenneth Silverman Temperance Movement Phyllis A. Langton Terrorism and Drugs Mark S. Steinitz Revised by Frederick K. Grittner Terry & Pellens Study Eric O. Johnson Tetrahydrocannabinol (THC) Leo E. Hollister Revised by Rebecca J. Frey Theobromine Michael J. Kuhar Tobacco: Dependence Neal L. Benowitz Alice B. Fredericks Revised by Lirio S. Covey Tobacco: History of Neal L. Benowitz Alice B. Fredericks Revised by Andrew J. Homburg

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Tobacco: Industry John Slade Revised by Andrew J. Homburg Tobacco: Medical Complications Jerome H. Jaffe Donald R. Shopland Revised by Rebecca J. Frey Tobacco: Smokeless Elbert Glover Penny N. Glover Revised by Matthew Miskelly Tobacco: Smoking Cessation Scott J. Leischow and Weight Gain Revised by Beti Thompson Tolerance and Physical Howard D. Cappell Dependence Revised by Mary Carvlin Toughlove Gregory W. Brock Ellen Burke Transit Countries for Illicit James Van Wert Drugs Revised by Frederick K. Grittner Treatment Alternatives to Jerome H. Jaffe Street Crime (TASC) Faith K. Jaffe Treatment Funding and Service Delivery Salvatore Di Menza Treatment, History of, in the Jim Baumohl United States Jerome H. Jaffe Treatment in the Federal Prison System John J. Dilulio, Jr. Treatment Outcome Prospective Study (TOPS) Robert Hubbard Treatment Programs/Centers/ Alfonso Acampora Organizations: an Jerome F.X. Carroll Historical Perspective Shirley Coletti David A. Deitch Daniel S. Heit Faith K. Jaffe Jerome H. Jaffe Sarah Knox J. Clark Laundergan Arlene R. Lissner David J. Mactas Kevin McEneaney Ethan Nebelkopf John Newmeyer Richard B. Seymour Sidney Shankman David E. Smith Robin Solit Jane Velez Ronald R. Watson

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Treatment: Alcohol Abuse: 2000 and Beyond Enoch Gordis Treatment: Alcohol, An Overview Richard K. Fuller John P. Allen Raye Z. Litten Treatment: Alcohol, Behavioral William R. Miller Approaches Revised by Anne Davidson Treatment: Alcohol, Richard K. Fuller Pharmacotherapy Raye Z. Litten Revised by Rebecca J. Frey Treatment: Cocaine, An Charles P. O’Brien Overview Revised by Charles Dackis Treatment: Cocaine, Behavioral Stephen T. Higgins Approaches Revised by Patricia Ohlenroth Treatment: Cocaine, Thomas R. Kosten Pharmacotherapy Revised by Patricia Ohlenroth Treatment: Drug Abuse: 2000 and Beyond Alan I. Leshner Treatment: Heroin, Behavioral Maxine L. Stitzer Approaches Michael Kidorf Treatment: Heroin, Pharmacotherapy Marc Rosen Treatment: Marijuana Roger Roffman Robert S. Stephens Treatment: Polydrug Abuse, An Overview Garth Martin Treatment: Polydrug Abuse, Robert M. Swift Pharmacotherapy Revised by Rebecca J. Frey Treatment: Tobacco, An Lynn T. Kozlowski Overview Revised by Patricia Ohlenroth Treatment: Tobacco, Leslie M. Schuh Pharmacotherapy Jack E. Henningfield Treatment: Tobacco, Dorothy Hatsukami Psychological Approaches Joni Jensen Revised by Marc E. Mooney Treatment: Twelve Step Facilitation Joe Nowinski Treatment Types: An Overview Frances R. Levin Herbert D. Kleber Treatment Types: Acupuncture Joyce H. Lowinson Jerome H. Jaffe Treatment Types: Approaches Stephen T. Higgins Based on Behavior Principles Alan J. Budney Sarah Heil

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Treatment Types: Aversion Therapy Donald W. Goodwin Treatment Types: Cognitive Therapy Molly Carney Alan Marlatt Treatment Types: Contingency Stephen T. Higgins Management Sarah Heil Treatment Types: Group and Family Therapy Edward Kaufman Treatment Types: Hypnosis David Spiegel Treatment Types: Long-term versus Brief Jim McKay Treatment Types: Minnesota Model J. Clark Laundergan Treatment Types: Nonmedical Detoxification Tim Stockwell Treatment Types: Outpatient Arthur I. Alterman versus Inpatient Revised by Donna Coviello Treatment Types: Pharmacotherapy, Elizabeth Wallace An Overview Thomas R. Kosten Treatment Types: Psychological Sharon Hall Approaches Meryle Weinstein Treatment Types: Self-Help and Anonymous Groups Harrison M. Trice Treatment Types: Therapeutic George De Leon Communities Jerome H. Jaffe Treatment Types: Traditional Dynamic Psychotherapy William A. Frosch Treatment Types: Twelve Steps, The Harrison M. Trice Triplicate Prescription Myroslava Romach Karen Parker Revised by Andrew J. Homburg UKAT: U.K. Alcohol Treatment Trial Gillian Tober United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988 Jerome H. Jaffe U.S. Government: Agencies in Drug Law Enforcement and Supply Control Jerome H. Jaffe U.S. Government: Agencies Supporting Substance Abuse Prevention and Treatment Richard A. Millstein

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U.S. Government: Agencies Supporting Substance Abuse Research Christine Hartel U.S. Government: Drug Policy Offices in the Executive Office Richard L. Williams of the President Revised by Chris Lopez U.S. Government: The Organization of Richard L. Williams U.S. Drug Policy Revised by Rebecca Marlow-Ferguson U.S. Government Agencies: Bureau of Narcotics and Dangerous Drugs (BNDD) Richard L. Williams U.S. Government Agencies: Center for Substance Elaine Johnson Abuse Prevention (CSAP) Revised by Rebecca Marlow-Ferguson U.S. Government Agencies: Center for Substance Abuse Treatment (CSAT) Beny J. Primm U.S. Government Agencies: National Institute on Alcoholism and Alcohol Abuse (NIAAA) Enoch Gordis U.S. Government Agencies: National Institute on Drug Richard A. Millstein Abuse (NIDA) Revised by Alan I. Leshner U.S. Government Agencies: Office of Drug Abuse Law Enforcement (ODALE) Richard L. Williams U.S. Government Agencies: Office of Drug Abuse Policy (ODAP) Richard L. Williams U.S. Government Agencies: Richard L. Williams Office of National Drug Control Policy (ONDCP) Revised by Chris Lopez U.S. Government Agencies: Special Action Office for Drug Abuse Prevention Faith K. Jaffe (SAODAP) Jerome H. Jaffe U.S. Government Agencies: Substance Abuse and Mental Health Services Administration Elaine Johnson (SAMHSA) Revised by Teddi Fine U.S. Government Agencies: U.S. Customs Service Richard L. Williams

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U.S. Government Agencies: U.S. Public Health Service Hospitals James F. Maddux Values and Beliefs: Existential Models of Addiction Stanton Peele Ventral Tegmental Area Stephanie DallVecchia-Adams Vietnam: Drug Use in Lee N. Robins Vietnam: Follow-up Study Lee N. Robins Vitamins Michael J. Kuhar Vulnerability As Cause of Substance Abuse: An Roy W. Pickens Overview Dace S. Svikis Vulnerability As Cause of Margaret E. Ensminger Substance Abuse: Gender Jennean Everett Vulnerability As Cause of Dace S. Svikis Substance Abuse: Genetics Roy W. Pickens Vulnerability As Cause of Substance Abuse: Psychoanalytic Perspective William A. Frosch Vulnerability As Cause of Margaret E. Ensminger Substance Abuse: Race Sion Kim Jennean Everett Revised by Isidore S. Obot Vulnerability As Cause of Substance Abuse: Sensation Seeking Marvin Zuckerman Vulnerability As Cause of Substance Abuse: Sexual Margaret E. Ensminger and Physical Abuse Colleen J. Yoo Vulnerability As Cause of Lorenzo Cohen Substance Abuse: Stress Andrew Baum Revised by Rajita Sinha Welfare Policy and Substance Abuse in the United States Jim Baumohl Wikler’s Pharmacologic Theory of Drug Addiction Steven J. Robbins Withdrawal: Alcohol John T. Sullivan Withdrawal: Benzodiazepines Carl Salzman Withdrawal: Cocaine Sally L. Satel Thomas R. Kosten Withdrawal: Nicotine (Tobacco) Jack E. Henningfield Leslie M. Schuh Revised by Beti Thompson

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Withdrawal: Nonabused Drugs Darrell R. Abernethy Paolo DePetrillo Revised by Patricia Ohlenroth Women and Substance Abuse Cynthia Robbins Women’s Christian Temperance Union (WCTU) Gary Bennett Wood Alcohol (Methanol) Myroslava Romach Karen Parker World Health Organization Expert Committee on Drug Dependence Louis Harris Yippies Patrick H. Hughes Zero Tolerance Amy Windham Revised by Frederick K. Grittner

xxxv List of Authors

Darrell R. Abernethy PSYCHOTROPIC SUBSTANCES CONVENTION OF Division of Clinical Pharmacology 1971 Roger Williams General Hospital, Providence, RI SHANGHAI OPIUM CONFERENCE OF 1911 WITHDRAWAL: NONABUSED DRUGS SINGLE CONVENTION ON NARCOTIC DRUGS Alfonso Acampora Christopher B. Anthony Walden House, Inc., San Francisco, CA Sparks, MD TREATMENT DRAMSHOP LIABILITY LAWS PROGRAMS/CENTERS/ORGANIZATIONS: AN James C. Anthony HISTORICAL PERSPECTIVE Department of Mental Hygiene Caroline Jean Acker Johns Hopkins School of Hygiene and Mental Health Department of History Baltimore, MD Carnegie Mellon University, Pittsburgh, PA EPIDEMICS OF DRUG ABUSE OPIOIDS AND OPIOID CONTROL: HISTORY EPIDEMIOLOGY OF DRUG ABUSE COMORBIDITY AND VULNERABILITY Manuella Adrian Addiction Research Foundation, Toronto, Canada H. David Archibald CANADA, DRUG AND ALCOHOL USE IN Addiction Research Foundation, Toronto, Canada CANCER, DRUGS, AND ALCOHOL JELLINEK MEMORIAL FUND Marlene Aldo-Benson Amelia Arria Indiana University School of Medicine, Bloomington, Johns Hopkins University, Baltimore, MD IN ETHNICITY AND DRUGS ALLERGIES TO ALCOHOL AND DRUGS Ustik Avico John P. Allen Instituto Superiore di Sanita, Rome, Italy Naitonal Institute on Alcoholism and Alcohol Abuse, ITALY, DRUG USE IN Rockville MD Thomas F. Babor TREATMENT: ALCOHOL Alcohol Research Center Arthur I. Alterman Department of Psychiatry Department of Psychiatry, University of University of Connecticut Health Center, Pennsylvania Farmington, CT Veterans Administration Medical Center DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC Philadelphia, PA CRITERIA TREATMENT TYPES: OUTPATIENT VERSUS DIAGNOSTIC AND STATISTICAL MANUAL (DSM) INPATIENT DIAGNOSTIC INTERVIEW SCHEDULE (DIS) INTERNAL CLASSIFICATION OF DISEASES (ICD) Robert T. Angarola MINNESOTA MULTIPHASIC PERSONALITY Hyman, Phelps, and McNamara, Washington, DC INVENTORY (MMP) EXCLUSIONARY RULE STRUCTURED CLINICAL INTERVIEW FOR DSM-IV HARRISON NARCOTICS ACT OF 1914 (SCID)

xxxvii xxxviii LIST OF AUTHORS

Jerald G. Bachman Neal L. Benowitz Institute for Social Research Division of Clinical Pharmacology University of Michigan, Ann Arbor, MI San Francisco General Hospital, San Francisco, CA RELIGION AND DRUG USE NICOTINE TOBACCO: DEPENDENCE Robert L. Balster TOBACCO: HISTORY OF Departmemt of Pharmacology and Toxicology Medical College of Virginia, Virginia Commonwealth Virginia Berridge University, Richmond, VA AIDS Social History Program, Health Policy Unit PHENCYCLIDINE (PCP): ADVERSE EFFECTS London School of Medicine, London, England BRITAIN, DRUG USE IN James E. Barrett Warren Bickel American Cyanamid Co., Lederle Laboratory, Pearl Department of Psychiatry River, NY Ira Allen School, University of Vermont, Burlington, REINFORCEMENT VT RESEARCH DRUGS AS DISCRIMINATIVE STIMULI : BEHAVIORAL ECONOMICS RESEARCH, ANIMAL MODEL: ENVIRONMENTAL INFLUENCES ON DRUG EFFECTS Floyd Bloom RESEARCH, ANIMAL MODEL: LEARNING, Research Institute Scripps Clinic, La Jolla, CA CONDITIONING, AND DRUG EFFECTS—AN ACETYLCHOLINE OVERVIEW CATECHOLAMINES RESEARCH, ANIMAL MODEL: LEARNING DOPAMINE MODIFIES DRUG EFFECTS ENKEPHALIN ENDORPHINS Andrew Baum GAMMA-AMINOBUTYRIC ACID (GABA) Department of Psychiatry GLUTAMATE Uniformed Services University of Health Science, MONAMINE Bethesda, MD NEURON STRESS NEUROTRANSMISSION VULNERABILITY AS CAUSE OF SUBSTANCE NEUROTRANSMITTERS ABUSE: STRESS NOREPINEPHRINE SEROTONIN Jim Baumohl SYNAPSE, BRAIN Graduate School of Social Work and Social Research Bryn Mawr College, Bryn Mawr, PA Sheila B. Blume ALCOHOL- AND DRUG-FREE HOUSING South Oaks Hospital, Amityville, NY ELIMINATION OF THE DRUG ADDICTION AND GAMBLING AS AN ADDICTION ALCOHOLISM CATEGORIES IN SOCIAL JEWS, DRUG AND ALCOHOL USE AMONG NATIONAL COUNCIL ON ALCOHOLISM AND SECURITY DISABILITY PROGRAMS DRUG DEPENDENCE NCADD HALFWAY HOUSES ( ) HOMELESSNESS, ALCOHOL, AND OTHER DRUGS, Michael J. Bohn HISTORY OF Department of Psychiatry TREATMENT: HISTORY OF, IN THE UNITED University of Wisconsin Hospitals, Madison, WI STATES SUICIDE AND SUBSTANCE ABUSE WELFARE POLICY AND SUBSTANCE ABUSE IN THE UNITED STATES Richard J. Bonnie School of Law Jan Bays University of Virginia, Charlottesville, VA Emmanuel Hospital, Portland, OR CONTROLLED SUBSTANCES ACT OF 1970 CHILD ABUSE AND DRUGS DRAMSHOP LIABILITY LAWS LEGAL REGULATION OF DRUGS AND ALCOHOL Gary Bennett MARIHUANA COMMISSION: RECOMMENDATION Center for Prevention Research ON DECRIMINALIZATION University of Kentucky, Lexington, KY NATIONAL COMMISSION ON MARIHUANA AND WOMEN’S CHRISTIAN TEMPERANCE UNION DRUG ABUSE (WCTU) PARAPHERNALIA, LAWS AGAINST

xxxviii LIST OF AUTHORS xxxix

G. Borges Alan J. Budney Instituto de Psichiatra, Xochimilco, Mexico Department of Psychiatry PREVENTION PROGRAMS: LIFE SKILLS TRAINING University of Vermont, Burlington, VT CONTINGENCY CONTRACTS Gilbert J. Botvin TREATMENT: COCAINE, PSYCHOLOGICAL Cornell Medical Center, New York, NY APPROACHES PREVENTION PROGRAMS: LIFE SKILLS TRAINING TREATMENT TYPES: BEHAVIOR MODIFICATION Joseph V. Brady Ellen Burke Johns Hopkins University School of Medicine Department of Family Studies Baltimore, MD University of Kentucky, Lexington, KY ABUSE LIABILITY OF DRUGS: TESTING IN TOUGHLOVE HUMANS Usoa E. Busto Marc N. Branch Department of Pharmacy Department of Psychology Addiction Research Foundation, Toronto, Canada University of Florida, Gainesville, FL PHARMACODYNAMICS BEHAVIORAL TOLERANCE PHARMACOKINETICS: GENERAL

Robert M. Bray Howard D. Cappell Research Triangle Institute, Triangle Park, NC Addiction Research Foundation, Toronto, Canada MILITARY, DRUG AND ALCOHOL ABUSE IN THE TOLERANCE AND PHYSICAL DEPENDENCE UNITED STATES Peter L. Carlen Karen E. Bremner Playfair Neuroscience Unit, Division of Neurology Psychopharmacology Research Program The Toronto Hospital, University of Toronto, Canada Sunnybrook Health Science Centre, Toronto, Canada COMPLICATIONS: NEUROLOGICAL SEROTONIN-UPTAKE INHIBITORS IN Molly Carney TREATMENT OF SUBSTANCE ABUSE Department of Psychology University of Washington, Seattle, WA Gregory W. Brock ABSTINENCE VIOLATION EFFECT Department of Family Studies EXPECTANCIES University of Kentucky, Lexington, KY TREATMENT TYPES: COGNITIVE THERAPY TOUGHLOVE Jerome F. X. Carroll Judith S. Brook Project Return Foundation, Inc., New York, NY Psychiatry and Behavioral Sciences TREATMENT New York Medical College, Valhalla, NY PROGRAMS/CENTERS/ORGANIZATIONS: AN CHILDHOOD BEHAVIOR AND LATER DRUG USE HISTORICAL PERSPECTIVE Kirk J. Brower Kathleen Carroll Department of Michigan Alcohol Research Center Yale University School of Medicine, West Haven, CT Ann Arbor, MI COGNITIVE-BEHAVIORAL THERAPY ANABOLIC STEROIDS Marilyn E. Carroll Lawrence S. Brown, Jr. Department of Psychiatry Division of Medical Services Evaluation and Research University of Minnesota, Twin Cities Campus Addiction Research and Treatment Corporation Minneapolis, MN Brooklyn, NY PHENCYCLIDINE (PCP) COMPLICATIONS: ENDOCRINE AND REPRODUCTIVE SYSTEMS Mary Carvlin Blue Island, IL Kathleen K. Bucholz ADOLESCENTS AND DRUG USE Department of Psychiatry COMPLICATIONS: NUTRITIONAL Washington University School of Medicine St. Louis, COMPLICATIONS: NEUROLOGICAL MO CONDUCT DISORDER AND DRUG USE ANTISOCIAL PERSONALITY DRUG METABOLISM

xxxix xl LIST OF AUTHORS

EXPECTANCIES David Cole IMAGING TECHNIQUES: VISUALIZING THE Georgetown University Law School, Washington, DC LIVING BRAIN RACIAL PROFILING SLANG AND JARGON STREET VALUE Shirley D. Coletti TOLERANCE AND PHYSICAL DEPENDENCE Operation PAR, St. Petersburg, FL TREATMENT Richard Catalano PROGRAMS/CENTERS/ORGANIZATIONS: AN Social Development Research Group, Seattle, WA HISTORICAL PERSPECTIVE CHINESE AMERICANS, ALCOHOL AND DRUG USE AMONG James J. Collins Research Triangle Institute, Triangle Park, NC Jonathan Caulkins CRIME AND ALCOHOL Heinz School of Public Policy and Management Carnegie Mellon University, Pittsburgh, PA Sandra D. Comer RAND’s Drug Policy Research Center, Pittsburgh, PA Department of Psychiatry University of Minnesota, Minneapolis, MN POLICY ALTERNATIVES: ANALYSIS OF DRUG PHENCYCLIDINE PCP LEGALIZATION ( ) POLICY ALTERNATIVES: PROHIBITION OF DRUGS, Edward J. Cone PRO AND CON Addiction Research Center, National Institute on Arthur I. Cederbaum Drug Abuse, Baltimore, MD HAIR ANALYSIS AS A TEST FOR DRUG USE Department of Biochemistry Mt. Sinai School of Medicine, New York, NY Brian L. Cook DRUG INTERACTIONS AND ALCOHOL Psychiatry Service Veterans Medical Center, Iowa City, IA Timmen L. Cermak COMPLICATIONS: MENTAL DISORDERS San Francisco, CA CODEPENDENCE Philip J. Cook Duke University, Durham, NC John N. Chappel SOCIAL COSTS OF ALCOHOL AND DRUG ABUSE Department of Psychiatry TAX LAWS AND ALCOHOL University of Nevada School of Medicine Reno, NV SOBRIETY Lirio Covey Department of Psychiatry Cheryl J. Cherpitel Columbia University, New York, NY Alcohol Research Group, Berkeley, CA TOBACCO: DEPENDENCE ACCIDENTS AND INJURIES FROM ALCOHOL Donna Coviello Domenic Ciraulo University of Pennsylvania, Philadelphia, PA Psychiatry Service TREATMENT TYPES: OUTPATIENT VERSUS VA Outpatient Clinic, Boston, MA INPATIENT BENZODIAZEPINES Donna Craft Lorenzo Cohen Farmington Hills, MI Department of Medical Psychology ASSOCIATION FOR MEDICAL EDUCATION AND Uniformed Services University of Health Sciences RESEARCH IN SUBSTANCE ABUSE (AMERSA) Bethesda, MD INHALANTS: EXTENT OF USE AND STRESS COMPLICATIONS VULNERABILITY AS CAUSE OF SUBSTANCE JELLINEK MEMORIAL FUND ABUSE: STRESS NEUROLEPTIC

Patricia Cohen Richard B. Craig New York State Psychiatric Institute Department of Political Science Columbia University, New York, NY Kent State University, Kent, OH CHILDHOOD BEHAVIOR AND LATER DRUG USE OPERATION INTERCEPT

xl LIST OF AUTHORS xli

Valerie Curran Nicholas DeMartinis Institute of Psychiatry, London, England Department of Pyschiatry SEDATIVES: ADVERSE CONSEQUENCES OF University of Connecticut Health Center, CHRONIC USE Farmington, CT PSYCHOACTIVE Charles Dackis PSYCHOACTIVE DRUG University of Pennsylvania, Philadelphia, PA PSYCHOPHARMACOLOGY TREATMENT: COCAINE, AN OVERVIEW SEDATIVE-HYPNOTIC Stephanie DallVecchia-Adams Richard Dembo Neurosciences Division Department of Criminology Yerkes Research Center, Atlanta, GA University of South Florida, Tampa, FL AMYGDALA PRISONS AND JAILS: DRUG TREATMENT IN DYNORPHIN VENTRAL TEGMENTAL AREA Paolo DePetrillo Division of Clinical Pharmacology Michael Darcy Roger Williams General Hospital, Providence, RI Gateway Foundation, Chicago, IL WITHDRAWAL: NONABUSED DRUGS TREATMENT PROGRAMS/CENTERS/ORGANIZATIONS: AN Don C. Des Jarlais HISTORICAL PERSPECTIVE Chemical Dependency Unit Beth Israel Medical Center, New York, NY Anne C. Davidson NEEDLE AND SYRINGE EXCHANGES AND New York, NY HIV/AIDS TREATMENT: ALCOHOL, PSYCHOLOGICAL APPROACHES David P. Desmond Department of Psychiatry Robert C. Davis University of Texas Health Center, San Antonio, TX Victim Services, New York, NY OPIOID DEPENDENCE: COURSE OF THE PREVENTION: COMMUNITY DRUG RESISTANCE DISORDER OVER TIME Valina Dawson Paul Devenyi Molecular Neurobiology Laboratory, Addiction Don Mills, Ontario, Canada Research Center COMPLICATIONS: LIVER DAMAGE National Institute on Drug Abuse, Baltimore, MD ANTIDEPRESSANT John J. DiIulio, Jr. Woodrow Wilson School ANTIPSYCHOTIC Princeton University, Princeton, NJ NEUROLEPTIC TREATMENT IN THE FEDERAL PRISON SYSTEM RECEPTOR: NMDA George De Leon Salvatore Di Menza ADAMHA Center for Therapeutic Community Research New National Institute on Drug Abuse, Rockville, MD York, NY TREATMENT FUNDING AND SERVICE DELIVERY TREATMENT TYPES: THERAPEUTIC COMMUNITIES Sheila Dow Farmington Hills, MI Scott Decker ADDICTED BABIES University of Missouri, St. Louis, MO ARRESTEE DRUG ABUSE MONITORING PROGRAM Lewis Donohew (ADAM) Department of Communication University of Kentucky, Lexington, KY David A. Deitch PREVENTION: SHAPING MASS-MEDIA MESSAGES Department of Psychiatry, School of Medicine TO VULNERABLE GROUPS University of California, San Diego, CA LE PATRIARCHE Peter Drotman TREATMENT Division of Chemical Research PROGRAMS/CENTERS/ORGANIZATIONS: AN National Institute on Drug Abuse, Rockville. MD HISTORICAL PERSPECTIVE SUBSTANCE ABUSE AND AIDS

xli xlii LIST OF AUTHORS

D. Colin Drummond Nancy Faerber Department of Psychiatry Canton, MI The Bethlem Royal Hospital and Maudsley Hospital AMERICAN ACADEMY OF ADDICTION PSYCHIATRY University of London, England AMERICAN SOCIETY OF ADDICTION MEDICINE BRITISH SYSTEM OF DRUG-ADDICTION (ASAM) TREATMENT BEERS AND BREWS HEROIN: THE BRITISH SYSTEM COLLEGE ON PROBLEMS OF DRUG DEPENDENCE (CPDD), INC. Steven I. Dworkin Department of Psychology Jeffrey Fagan University of North Carolina at Wilmington Joseph L. Mailman School of Public Health Wilmington, NC Columbia University, New York, NY BRAIN STRUCTURES AND DRUGS GANGS AND DRUGS LIMBIC SYSTEM John L. Falk Linda Dykstra Department of Psychology Department of Psychology Rutgers University, New Brunswick, NJ University of North Carolina, Chapel Hill, NC ADJUNCTIVE DRUG TAKING PAIN: BEHAVIORAL METHODS FOR MEASURING ANALGESIC EFFECTS OF DRUGS Teddi Fine RESEARCH: MEASURING EFFECTS OF DRUGS ON Substance Abuse and Mental Health Services BEHAVIOR Administration RESEARCH, ANIMAL MODEL: OPERANT Rockville, MD LEARNING IS AFFECTED BY DRUGS U.S. GOVERNMENT AGENCIES: SUBSTANCE SENSATION AND PERCEPTION AND EFFECTS OF ABUSE AND MENTAL HEALTH SERVICES DRUGS ADMINISTRATION (SAMHSA) Griffith Edwards Michael P. Finnegan Addiction Research Unit (U.K.) Alcohol, Drug Abuse, and Mental Health Institute of Psychiatry, London, England Administration ADDICTION Division of State Assistant ADDICTION RESEARCH UNIT (ARU) (U.K.) Office of Treatment Improvement, Rockville, MD FETUS: EFFECTS OF DRUGS ON THE PREGNANCY Everett H. Ellinwood AND DRUG DEPENDENCE: OPIOIDS AND Department of Psychiatry COCAINE Duke University Medical Center, Durham, NC CAUSES OF SUBSTANCE ABUSE: DRUG EFFECTS Loretta P. Finnegan AND BIOLOGICAL RESPONSES Women’s Health Institute National Institute of Health, Bethesda, MD Margaret E. Ensminger FETUS: EFFECTS OF DRUGS ON THE PREGNANCY Department of Health Policy and Management AND DRUG DEPENDENCE OPIOIDS AND Johns Hopkins School of Public Health, Baltimore, COCAINE MD POVERTY AND DRUG USE Michael First VULNERABILITY AS CAUSE OF SUBSTANCE College of Physicians and Surgeons ABUSE: GENDER Columbia University, New York, NY VULNERABILITY AS CAUSE OF SUBSTANCE STRUCTURED CLINICAL INTERVIEW FOR DSM-IV ABUSE: RACE Marian W. Fischman VULNERABILITY AS CAUSE OF SUBSTANCE College of Physicians and Surgeons ABUSE: SEXUAL AND PHYSICAL ABUSE Columbia University, New York, NY Jennean Everett AMPHETAMINE Johns Hopkins University School of Medicine BENZOYLECOGNINE Baltimore, MD COCAINE VULNERABILITY AS CAUSE OF SUBSTANCE COCA PASTE ABUSE: GENDER COCA PLANT VULNERABILITY AS CAUSE OF SUBSTANCE CRACK ABUSE: RACE DEXTROAMPHETAMINE

xlii LIST OF AUTHORS xliii

FREEBASING William A. Frosch METHAMPHETAMINE Department of Psychiatry METHEDRINE Cornell University Medical School, New York, NY METHYLPHENIDATE ADDICTIVE PERSONALITY PEMOLINE ADDICTIVE PERSONALITY AND PSYCHOLOGICAL PSYCHOMOTOR TESTS PERSONALITY AS A RISK FACTOR FOR DRUG Brian R. Flay ABUSE School of Public Health, Prevention Research Center PSYCHOANALYSIS University of Illinois, Chicago, IL TREATMENT TYPES: TRADITIONAL DYNAMIC PREVENTION PROGRAMS: WATERLOO SMOKING PSYCHOTHERAPY PREVENTION PROJECT VULNERABILITY AS CAUSE OF SUBSTANCE Alice B. Fredericks ABUSE: PSYCHOANALYTIC PERSPECTIVE Division of Clinical Pharmocology Richard K. Fuller San Francisco General Hospital San Francisco, CA National Institute on Alcoholism and Alcohol Abuse NICOTINE Rockville, MD TOBACCO: DEPENDENCE DISULFIRAM TOBACCO: HISTORY OF TREATMENT: ALCOHOL, AN OVERVIEW Daniel X. Freedman TREATMENT: ALCOHOL, PHARMACOTHERAPY Department of Pharmacology Marc S. Galanter Louisiana State University Medical Center New Department of Psychiatry Orleans, LA New York University School of Medicine, New York, DIMETHYLTRYPTAMINE (DMT) NY DOM AMERICAN SOCIETY OF ADDICTION MEDICINE HALLUCINOGENS (ASAM) HALLUCINOGENIC PLANTS ASSOCIATION FOR MEDICAL EDUCATION AND LYSERGIC ACID DIETHYLAMIDE (LSD) AND RESEARCH IN SUBSTANCE ABUSE (AMERSA) PSYCHEDELICS MDM Ron Gasbarro MESCALINE New Milford, PA MORNING GLORY SEEDS SLEEP, DREAMING, AND DRUGS NUTMEG Paul F. Gavaghan PEYOTE Chevy Chase, MD PSILOCYBIN DISTILLED SPIRITS COUNCIL Betsy Frey Jeffrey A. Gere New Haven, CT Harman, MD AMOBARBITAL IMMUNOASSAY ANTIDEPRESSANT CALCIUM CARBIMIDE Dean R. Gerstein CANCER, DRUGS, AND ALCOHOL National Opinion Research Center Washington, DC DISULFIRAM PRODUCTIVITY: EFFECTS OF ALCOHOL ON DRUG INTERACTIONS AND ALCOHOL PRODUCTIVITY: EFFECTS OF DRUGS ON OPIOID COMPLICATIONS AND WITHDRAWAL Joseph C. Gfroerer PHENCYCLIDINE: ADVERSE EFFECTS Office of Applied Studies SEDATIVES: ADVERSE CONSEQUENCES ON Substance Abuse and Mental Health Services CHRONIC ABUSE Administration, Rockville, MD SOBRIETY NATIONAL HOUSEHOLD SURVEY ON DRUG SUBSTANCE ABUSE AND AIDS ABUSE (NHSDA) TETRAHYDROCANNABINOL TOBACCO: MEDICAL COMPLICATIONS Louis A. Giordano TREATMENT: ALCOHOL, PHARMACOTHERAPY Department of Psychiatry TREATMENT: POLYDRUG ABUSE, Ira Allen School, University of Vermont, Burlington, VT PHARMACOTHERAPY BEHAVIORAL ECONOMICS

xliii xliv LIST OF AUTHORS

Frederick B. Glaser John Goldkamp University of Michigan Medical Center Ann Arbor, Crime and Justice Research Institute MI Philadelphia, PA ALCOHOLISM: ORIGIN OF THE TERM DRUG COURTS Elbert Glover Stephen Goldsmith Department of Psychiatry Indianapolis, IN University of West Virginia Medical School DRUG LAWS, PROSECUTION OF Morgantown, WV Ronald Goldstock TOBACCO: SMOKELESS Kroll Associates, Larchmont, NY Penny N. Glover MONEY LAUNDERING Department of Psychiatry Donald W. Goodwin University of West Virginia Medical School Department of Psychology Morgantown, WV University of Kansas Medical Center TOBACCO: SMOKELESS School of Medicine, Kansas City, KS TREATMENT TYPES: AVERSION THERAPY Nick E. Goeders Department of Pharmacology Eric Goplerud Louisiana State University Medical Center Pennsylvania State University, State College, PA Shreveport, LA EDUCATION AND PREVENTION AGONIST-ANTAGONIST (MIXED) Enoch Gordis AGONIST National Institute on Alcoholism and Alcohol Abuse ALKALOIDS Rockville, MD APHRODISIAC TREATMENT: ALCOHOL ABUSE: 2000 AND ANTAGONIST BEYOND DESIGNER DRUGS U.S. GOVERNMENT AGENCIES: NATIONAL DOSE-RESPONSE RELATIONSHIP INSTITUTE ON ALCOHOLISM AND ALCOHOL DRUG ABUSE (NIAAA) DRUG TYPES ETHNOPHARMACOLOGY David A. Gorelick Addiction Research Center, National Institute on ED50 Drug Abuse, Baltimore, MD DRUG INTERACTION AND THE BRAIN NALTREXONE IN TREATMENT OF DRUG LD50 DEPENDENCE PHARMACOLOGY PSYCHOACTIVE David J. Greenblatt RECEPTOR: DRUG Department of Pharmacology and Experimental PSYCHOACTIVE DRUG Therapeutics PSYCHOPHARMACOLOGY Tufts University School of Medicine, Boston, MA PLANTS, DRUGS, FROM PHARMACOKINETICS: IMPLICATIONS IN ABUSABLE SYMPTOMS Mark S. Gold Department of Neuro-Science and Psychiatry Roland R. Griffiths Brain Institute, University of Florida, Gainesville, FL Department of Psychiatry and Behavioral Science CLONIDINE Johns Hopkins School of Medicine Baltimore, MD CAFFEINE Steven Goldberg COFFEE Addiction Research Center TEA National Institute on Drug Abuse, Baltimore, MD RESEARCH, ANIMAL MODEL: CONDITIONED Frederick K. Grittner WITHDRAWAL St. Paul, MN ASIA, DRUG USE IN David Goldbloom ASSET FORFEITURE Department of Psychiatry BOLIVIA, DRUG USE IN Toronto Hospital, Toronto, Canada BORDER MANAGEMENT BULIMIA NERVOSA BREATHALYZER

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COLOMBIA AS DRUG SOURCE Tracy W. Harachi CONTROLS: SCHEDULED DRUGS/DRUG Social Development Research Group, Seattle, WA SCHEDULES, U. S. CHINESE AMERICANS, ALCOHOL AND DRUG USE CRIME AND ALCOHOL AMONG CRIME AND DRUGS Louis Harris DISTILLED SPIRITS COUNCIL Department of Pharmacology and Toxicology DRIVING UNDER THE INFLUENCE (DUI) Medical College of Virginia, Richmond, VA DRUG INTERDICTION WORLD HEALTH ORGANIZATION EXPERT DRUG LAWS: PROSECUTION OF COMMITTEE ON DRUG DEPENDENCE DRUG POLICY FOUNDATION Christine Hartel ECONOMIC COSTS OF ALCOHOL ABUSE AND American Psychological Association, Washington, DC ALCOHOL DEPENDENCE RESEARCH: AIMS, DESCRIPTION, AND GOALS EXCLUSIONARY RULE U.S. GOVERNMENT: AGENCIES SUPPORTING FOREIGN POLICY AND DRUGS SUBSTANCE ABUSE RESEARCH GOLDEN TRIANGLE AS DRUG SOURCE MANDATORY SENTENCING Jonas Hartelius MEXICO AS DRUG SOURCE Department of Alcohol Toxicology NETHERLANDS, DRUG USE IN THE National Laboratory of Forensic Chemistry NEW YORK STATE CIVIL COMMITMENT PROGRAM University Hospital, Linkoping, Sweden PRISONS AND JAILS SWEDEN, DRUG USE IN ROCKEFELLER DRUG LAW Dorothy Hatsukami SEIZURES OF DRUGS Department of Psychiatry SHOCK INCARCERATION AND BOOT CAMP PRISONS University of Minnesota, Minneapolis, MN SOURCE COUNTRIES FOR ILLICIT DRUGS TREATMENT: TOBACCO, PSYCHOLOGICAL TERRORISM AND DRUGS APPROACHES TRANSIT COUNTRIES FOR ILLICIT DRUGS Harry Haverkos ZERO TOLERANCE Division of Chemical Research Steven Gust National Institute of Drug Abuse, Rockville, MD National Institute on Drug Abuse, Rockville, MD SUBSTANCE ABUSE AND AIDS EMPLOYEE ASSISTANCE PROGRAMS (EAPS) Daniel Hayes Sharon Hall West Linn, OR COMPLICATIONS: MENTAL DISORDERS Psychiatry Service Veterans Affairs Medical Center Dwight B. Heath San Francisco, CA Department of Anthropology TREATMENT TYPES: PSYCHOLOGICAL Brown University, Providence, RI APPROACHES ALCOHOL: HISTORY OF DRINKING David Halperin Thomas A. Hedrick, Jr. Department of Psychiatry Partnership for a Drug-Free America, New York, NY Mt. Sinai School of Medicine, New York, NY PARTNERSHIP FOR A DRUG-FREE AMERICA CULTS AND DRUG USE Sarah Heil Department of Psychiatry Ted Hammett University of Vermont, Burlington, VT Abt Associates, Inc., Cambridge, MA TREATMENT TYPES: APPROACHES BASED ON PRISONS AND JAILS: DRUG USE AND AIDS IN BEHAVIORAL PRINCIPLES Thomas E. Hanlon TREATMENT TYPES: CONTINGENCY Human Behavior Associates, Inc., Annapolis, MD MANAGEMENT CRIME AND DRUGS Daniel S. Heit William B. Hansen Abraxas Group, Philadelphia, PA Bowman Gray School of Medicine TREATMENT Wake Forest University, Winton-Salem, NC PROGRAMS/CENTERS/ORGANIZATIONS: AN PREVENTION PROGRAMS: PROJECT SMART HISTORICAL PERSPECTIVE

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Jack E. Henningfield Richard G. Hunter Addiction Research Center, Clinical Pharmacology Neurosciences Division Branch Yerkes Research Center, Atlanta, GA National Institute on Drug Abuse, Baltimore, MD CLUB DRUGS TREATMENT: TOBACCO, PHARMACOTHERAPY RAVE WITHDRAWAL: NICOTINE (TOBACCO) ROHYPNOL Stephen T. Higgins Peter Barton Hutt Department of Psychiatry Covington and Burling, Washington, DC University of Vermont, Burlington, VT PUBLIC INTOXICATION TREATMENT: COCAINE, PSYCHOLOGICAL APPROACHES Ted Inaba Department of Pharmacology TREATMENT TYPES: APPROACHES BASED ON BEHAVIORAL PRINCIPLES University of Toronto, Canada DRUG METABOLISM TREATMENT TYPES: CONTINGENCY MANAGEMENT James A. Inciardi Riley Hinson Department of Sociology Department of Psychology University of Delaware, Newark, DE University of Western Ontario, London, Canada BOLIVIA, DRUG USE IN CONDITIONED TOLERANCE M. S. Irwanto Leo E. Hollister Department of Child Development and Family Studies Harris County Psychiatric Center, Houston, TX Purdue University, West Lafayette, IN BHANG FAMILIES AND DRUG USE CANNABIS SATIVA Ivan Izquierdo HASHISH Center of Neurobiology of Learning HEMP University of California, Irvine, CA GANJA MEMORY, EFFECTS OF DRUGS ON MARIJUANA TETRAHYDROCANNABINOL (THC) James B. Jacobs New York University Law School. New York, NY Andrew J. Homburg DRUNK DRIVING Farmington Hills, MI ALCOHOL: CHEMISTRY AND PHARMACOLOGY Arthur E. Jacobson ALCOHOL: HISTORY OF DRINKING National Institute of Health, Bethesda, MD ALCOHOL: PSYCHOLOGICAL CONSEQUENCES OF COLLEGE OF PROBLEMS OF DRUG CHRONIC ABUSE DEPENDENCE (CPDD), INC. COMPLICATIONS: CARDIOVASCULAR SYSTEM Nora Jacobson (ALCOHOL AND COCAINE) School of Public Health IMPAIRED PHYSICIANS AND MEDICAL WORKERS Johns Hopkins University, Baltimore, MD TOBACCO: HISTORY OF POVERTY AND DRUG USE TOBACCO: INDUSTRY TRIPLICATE PRESCRIPTION Faith K. Jaffe Robert Hubbard Towson, MD Research Triangle Institute, Triangle Park, NC AMERICAN ACADEMY OF PSYCHIATRISTS IN ALCOHOLISM AND ADDICTIONS AAPAA DRUG ABUSE TREATMENT OUTCOME STUDY ( ) REMOVE INTOXICATED DRIVERS (RID-USA, INC.) (DATOS) TREATMENT ALTERNATIVES TO STREET CRIME TREATMENT OUTCOME PERSPECTIVE STUDY (TASC) (TOPS) TREATMENT John R. Hughes PROGRAMS/CENTERS/ORGANIZATIONS: AN Department of Psychiatry HISTORICAL PERSPECTIVE University of Vermont, Burlington, VT U.S. GOVERNMENT AGENCIES: SPECIAL ACTION TOBACCO: WITHDRAWAL (ABSTINENCE) OFFICE FOR DRUG ABUSE PREVENTION SYNDROME (SAODAP)

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Jerome H. Jaffe Elaine Johnson School of Medicine Substance Abuse and Mental Health Services University of Maryland, Baltimore, MD Administration, Rockville, MD AMERICAN SOCIETY OF ADDICTION MEDICINE U.S. GOVERNMENT AGENCIES: CENTER FOR (ASAM) SUBSTANCE ABUSE PREVENTION (CSAP) AYAHUASCA U.S. GOVERNMENT AGENCIES: SUBSTANCE BETEL NUT ABUSE AND MENTAL HEALTH SERVICES CENTER OF ADDICTION AND SUBSTANCE ABUSE ADMINISTRATION (SAMHSA) (CASA) DISEASE CONCEPT OF ADDICTION Eric O. Johnson DRUG POLICY FOUNDATION (DPF) Drug Dependence Epidemiology HALFWAY HOUSES National Institute on Drug Abuse, Rockville, MD IBOGAINE Johns Hopkins University, Baltimore, MD NARCOTIC ADDICT REHABILITATION ACT NARA ( ) DROPOUTS AND SUBSTANCE ABUSE OVEREATING AND OTHER EXCESSIVE BEHAVIORS TERRY AND PELLENS STUDY PROHIBITION OF ALCOHOL PROPOXYPHENE Rolley E. Johnson RATIONAL RECOVERY (RR) Behavioral Pharmacology Research Unit SECULAR ORGANIZATIONS FOR SOBRIETY (SOS) Francis Scott Key Medical Center, Baltimore, MD TOBACCO: MEDICAL COMPLICATIONS CONTROLS: SCHEDULED DRUGS/DRUG TREATMENT ALTERNATIVES TO STREET CRIME SCHEDULES, U.S. (TASC) TREATMENT, HISTORY OF, IN THE UNITED Bryan Johnstone STATES Department of Behavioral Science TREATMENT PROGRAMS/CENTERS/ University of Kentucky, Lexington, KY ORGANIZATIONS: AN HISTORICAL PREVENTION: PREVENTION OF ALCOHOLISM, PERSPECTIVE THE LEDERMANN MODEL OF CONSUMPTION TREATMENT TYPES: ART OF ACUPUNCTURE TREATMENT TYPES: THERAPEUTIC A.W. Jones COMMUNITIES Department of Alcohol Toxicology UNITED NATIONS CONVENTION AGAINST ILLICIT National Laboratory of Forensic Chemistry TRAFFIC IN NARCOTIC DRUG AND University Hospital, Linkoping, Sweden PSYCHOTROPIC SUBSTANCES, 1988 BLOOD ALCOHOL CONCENTRATION, MEASURES U S GOVERNMENT AGENCIES IN DRUG LAW . . : OF ENFORCEMENT AND SUPPLY CONTROL PHARMACOKINETICS OF ALCOHOL U.S. GOVERNMENT AGENCIES: SPECIAL ACTION SWEDEN, DRUG USE IN OFFICE FOR DRUG ABUSE PREVENTION (SAODAP) Harold Kalant Joni Jensen Department of Pharmacology Department of Psychiatry University of Toronto, Canada University of Minnesota, Minneapolis, MN ADDICTION: CONCEPTS AND DEFINITIONS TREATMENT: TOBACCO, PSYCHOLOGICAL PHYSICAL DEPENDENCE APPROACHES ADDICTION RESEARCH FOUNDATION OF ONTARIO, CANADA Chris-Ellyn Johanson Department of Psychiatry Peter Kalix Wayne State University School of Medicine, Detroit, Department of Pharmacology MI University of Geneva, Switzerland AMOTIVATIONAL SYNDROME KHAT POLYDRUG ABUSE George A. Kanuck Bruce Johnson Malvern Preparatory School, Malvern, PA Narcotic and Drug Research, Inc., New York, NY FETUS: EFFECTS OF DRUGS ON THE HEROIN: THE BRITISH SYSTEM PREGNANCY AND DRUG DEPENDENCE: OPIOIDS ROLLESTON REPORT OF 1926 (U.K.) AND COCAINE

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Charles Kaplan Heather Kimmel International Institute for Psychosocial and Neurosciences Division Socioecological Research Yerkes Research Center, Atlanta, GA Maastricht, The Netherlands RESEARCH, ANIMAL MODEL: INTRACRANIAL NETHERLANDS, DRUG USE IN THE SELF-STIMULATION Bhushan K. Kapur George King Department of Clinical Biochemistry Department of Psychiatry University of Toronto, Canada Duke University Medical Center, Durham, NC CRTI Addiction Research Foundation, Toronto, CAUSES OF SUBSTANCE ABUSE: DRUG EFFECTS Canada AND BIOLOGICAL RESPONSES DRUG TESTING METHODS AND CLINICAL Rufus King INTERPRETATIONS OF TEST RESULTS Berliner, Corcoran, and Rowe, Washington, DC Clifford L. Karchmer ANSLINGER, HARRY J., AND U.S. DRUG POLICY Police Executive Research Forum Washington, DC Timothy W. Kinlock DRUG LAWS: FINANCIAL ANALYSIS IN Human Behavior Associates, Inc., Annapolis, MD ENFORCEMENT CRIME AND DRUGS MONEY LAUNDERING Herbert D. Kleber Ed Kaufman Department of Psychiatry Capistrano by the Sea Hospital, Dana Point, CA College of Physicians and Surgeons Columbia TREATMENT TYPES: GROUP AND FAMILY THERAPY University, New York, NY Jat M. Khanna CENTER ON ADDICTION AND SUBSTANCE ABUSE TREATMENT TYPES: AN OVERVIEW Department of Pharmacology University of Toronto, Canada Michael Klitzner BARBITURTATES: COMPLICATIONS Litzner & Associates, Vienna VA SADD (STUDENTS AGAINST DESTRUCTIVE Ed Khantzian DECISIONS) Department of Psychiatry Cambridge Hospital, Cambridge, MA Clifford Knapp CAUSES OF SUBSTANCE ABUSE: PSYCHOLOGICAL Department of Pharmacology and Experimental (PSYCHOANALYTIC) Therapeutics Tufts University School Medicine, Boston, MA Michael Kidorf BENZODIAZEPINES Behavioral Pharmacology Research Unit Johns Hopkins Bayview Medical Center, Baltimore, Sarah Knox MD Farmington Hills, MI TREATMENT: HEROIN, PSYCHOLOGICAL ETHNIC ISSUES AND CULTURAL RELEVANCE IN APPROACHES TREATMENT SOCIAL COSTS OF ALCOHOL AND DRUG ABUSE M. Marlyne Kilbey SWEDEN, DRUG USE IN Department of Psychology TREATMENT PROGRAMS/CENTERS/ Wayne State University, Detroit, MI ORGANIZATIONS: AN HISTORICAL PROFESSIONAL CREDENTIALING PERSPECTIVE

Sewhan Kim Conan Kornetsky Drug Education Center, Charlotte, NC Department of Psychiatry and Pharmacology Boston University School of Medicine, Boston, MA PREVENTION PROGRAMS: OMBUDSMAN PROGRAM REWARD PATHWAYS AND DRUGS Sion Kim Madhu R. Korrapati Johns Hopkins University, Baltimore, MD Research Service VULNERABILITY AS CAUSE OF SUBSTANCE Veterans Administration Medical Center Boise, ID ABUSE: RACE AGING, DRUGS, AND ALCOHOL

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Therese A. Kosten THEOBROMINE Substance Abuse Treatment Unit VITAMINS Yale University School of Medicine New Haven, CT RESEARCH: DEVELOPING MEDICATIONS TO Karol L. Kumpfer TREAT SUBSTANCE ABUSE AND DEPENDENCE Department of Health Education University of Utah, State Lake City, UT Thomas R. Kosten CHILD ABUSE AND DRUGS Substance Abuse Treatment Unit Yale University School of Medicine, New Haven, CT Malcolm H. Lader AMANTADINE Institute of Psychiatry, London, England COCAINE, TREATMENT STRATEGIES BENZODIAZEPINES: COMPLICATIONS TREATMENT: COCAINE, PHARMACOTHERAPY PRESCRIPTION DRUG ABUSE TREATMENT TYPES: PHARMACOTHERAPY, AN Robin A. LaDue OVERVIEW Native American Center for Excellence WITHDRAWAL: COCAINE University of Washington, Seattle, WA Nicholas Kozel FETAL ALCOHOL SYNDROME (FAS) National Vaccine Program Office, Rockville, MD Phyllis A. Langton AMPHETAMINE EPIDEMICS Department of Sociology Lynn T. Kozlowski George Washington University, Washington, DC Department of Health and Human Development TEMPERANCE MOVEMENT Pennsylvania State University, University Park, PA J. Clark Laundergan TOBACCO: TREATMENT, AN OVERVIEW Center for Addiction Studies, Duluth, MN Henry Kranzler TREATMENT PROGRAMS/CENTERS/ORGANIZA- University of Connecticut School of Medicine, TIONS: AN HISTORICAL PERSPECTIVE Farmington, CT TREATMENT TYPES: MINNESOTA MODEL DEPRESSION Martin Leamon ETHCHLORVYNOL Department of Psychiatry ETHINAMATE University of California at Davis Medical Center LAUDANUM Sacramento, CA OVER-THE-COUNTER MEDICINE AMPHETAMINE EPIDEMICS PLANTS, DRUGS FROM WOOD ALCOHOL (METHANOL) Jill Lectka New York, NY Mark L. Kraus DRUG INTERACTION AND THE BRAIN Internal Medicine PRESCRIPTION DRUG ABUSE Westside Medical Group, Waterbury, CT PREVENTION: COMMUNITY DRUG RESISTANCE WITHDRAWAL: ALCOHOL, BETA BLOCKERS Scott J. Leischow Michael J. Kuhar Division of Community and Environmental Health Division of Neuroscience, Department of School of Health Related Professions, Tucson, AZ Pharmacology TOBACCO: SMOKING CESSATION AND WEIGHT Emory University, Atlanta, GA GAIN ANTIDOTE CHOCOLATE Alan I. Leshner CHROMOSOME National Institute on Drug Abuse, Bethesda, MD CLONE, CLONING CLINICAL TRIALS NETWORK COLA/COLA DRINKS TREATMENT: DRUG ABUSE: 2000 AND BEYOND DOPAMINE U.S. GOVERNMENT AGENCIES: NATIONAL GENE INSTITUTE ON DRUG ABUSE GENOME PROJECT GENE REGULATION: DRUGS Carl G. Leukefeld GINSENG Research Center on Drug and Alcohol Abuse NOREPINEPHRINE University of Kentucky, Lexington, KY NUCLEUS ACCUMBENS COERCED TREATMENT FOR SUBSTANCE POISON OFFENDERS RECEPTOR: DRUG INJECTING DRUG USERS AND HIV

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Frances R. Levin Chris Lopez Department of Psychiatry Farmington Hills, MI College of Physicians and Surgeons Columbia ATTENTION DEFICIT DISORDER University, New York, NY DIAGNOSIS OF DRUG ABUSE TREATMENT TYPES: AN OVERVIEW U.S. GOVERNMENT AGENCIES: OFFICE OF NATIONAL DRUG CONTROL POLICY (ONDCP) R. A. Lewis U.S. GOVERNMENT: DRUG POLICY OFFICES IN Department of Family Studies Purdue University, THE EXECUTIVE OFFICE OF THE PRESIDENT West Lafayette, IN FAMILIES AND DRUG USE Joyce H. Lowinson Division of Substance Abuse Barbara Lex Albert Einstein College of Medicine, Bronx, NY Harvard Medical School TREATMENT TYPES: ART OF ACUPUNCTURE McLean Hospital, Belmont, MA FAMILY VIOLENCE AND SUBSTANCE ABUSE Arnold Ludwig Department of Psychiatry Charles S. Lieber University of Kentucky College of Medicine Alcoholism Research and Treatment Center Lexington, KY Bronx Veterans Administration Medical Center CREATIVITY AND DRUGS Bronx, NY COMPLICATIONS: LIVER (ALCOHOL) Scott E. Lukas Harvard Medical School Marsha Lillie-Blanton McLean Hospital, Belmont, MA School of Hygiene and Public Health ALCOHOL: CHEMISTRY AND PHARMACOLOGY Johns Hopkins University, Baltimore, MD AMOBARBITAL ETHNICITY AND DRUGS BARBITURATES Jennifer K. Lin BEERS AND BREWS Drug Dependence Epidemiology CHLORAL HYDRATE National Institute on Drug Abuse, Rockville, MD CHLORDIAZEPOXIDE DISTILLATION COMMISSIONS ON DRUGS DISTILLED SPIRITS Walter Ling ETHCHLORVYNOL Beverly Hills, CA ETHINAMATE IMPAIRED PHYSICIANS AND MEDICAL WORKERS FERMENTATION GLUTETHIMIDE Richard Lingeman MEPROBAMATE New York, NY ETHANOL SLANG AND JARGON METHAQUALONE Arlene R. Lissner MOONSHINE Abraxas Group, Philadelphia, PA PHENOBARBITAL TREATMENT RUBBING ALCOHOL PROGRAMS/CENTERS/ORGANIZATIONS: AN SECOBARBITAL HISTORICAL PERSPECTIVE SEDATIVE SEDATIVE-HYPNOTIC Raye Z. Litten SLEEPING PILLS National Institute on Alcoholism and Alcohol Abuse STILL Rockville, MD DISULFIRAM Arthur J. Lurigio TREATMENT: ALCOHOL, AN OVERVIEW Victim Services, New York, NY TREATMENT ALCOHOL, PHARMACOTHERAPY PREVENTION: COMMUNITY DRUG RESISTANCE Edythe D. London Doris Layton MacKenzie Intramural Research Program Department of Criminal Justice National Institute on Drug Abuse, Rockville, MD University of Maryland, College Park, MD IMAGING TECHNIQUES: VISUALIZING THE SHOCK INCARCERATION AND BOOT CAMP LIVING BRAIN PRISONS

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David J. Mactus Peter Martin Center for Substance Abuse Treatment Rockville, MD Department of Psychiatry and Pharmacology TREATMENT Vanderbilt University School of Medicine, Nashville, PROGRAMS/CENTERS/ORGANIZATIONS: AN TN HISTORICAL PERSPECTIVE COMPLICATIONS: COGNITION

James F. Maddux William R. Martin Department of Psychiatry Department of Pharmacology University of Texas Health Center, San Antonio, TX University of Kentucky, Lexington, KY OPIOID DEPENDENCE: COURSE OF THE OPIOID COMPLICATIONS AND WITHDRAWAL DISORDER OVER TIME George Mathews NARCOTIC ADDICT REHABILITATION ACT (NARA) Department of Psychiatry and Pharmacology U.S. GOVERNMENT AGENCIES: U.S. PUBLIC Vanderbilt University School of Medicine, Nashville, HEALTH SERVICE HOSPITALS TN COMPLICATIONS: COGNITION Alan Marlatt Department of Psychology Mauri J. Mattila University of Washington, Seattle, WA Department of Psychiatry and Pharmacology ABSTINENCE VIOLATION EFFECT University of Helsinki, Finland EXPECTANCIES PSYCHOMOTOR EFFECTS OF ALCOHOL AND RELAPSE PREVENTION DRUGS TREATMENT TYPES: ASSERTIVENESS TRAINING Armand L. Mauss TREATMENT TYPES: COGNITIVE THERAPY Department of Sociology Rebecca Marlow-Ferguson Washington State University, Pullman, WA Farmington Hills, MI PREVENTION PROGRAMS: “HERE’S LOOKING AT YOU SERIES ADDICTION SEVERITY INDEX ” BULIMIA NERVOSA Lorraine Green Mazerolle CHLORDIAZEPOXIDE School of Criminology and Criminal Justice DIAGNOSTIC INTERVIEW SCHEDULE Griffith University, Brisbane, Queensland, Australia INJECTING DRUG USERS AND HIV/AIDS ADMINISTRATIVE AND PUBLIC HEALTH LAW NALTREXONE OBESITY Mary Pat McAndrews OPIATES/OPIOIDS Department Psychology PAIN: DRUGS USED FOR Playfair Neuroscience Unit PHENCYCLIDINE (PCP) The Toronto Hospital, University of Toronto, Canada SENSATION AND PERCEPTION AND EFFECTS OF COMPLICATIONS: NEUROLOGICAL DRUGS Duane C. McBride PREVENTION PROGRAMS Behavioral Sciences Department U.S. GOVERNMENT AGENCIES: CENTER FOR Andrews University, Berrien Springs, MI SUBSTANCE ABUSE PREVENTION (CSAP) POLICY ALTERNATIVES: PROHIBITION OF DRUGS: U.S. GOVERNMENT AGENCIES: CENTER FOR PRO AND CON SUBSTANCE ABUSE TREATMENT (CSAT) U.S. GOVERNMENT AGENCIES: U.S. CUSTOMS James T. McDonough, Jr. SERVICE Bala-Cynwyd, PA U.S. GOVERNMENT: THE ORGANIZATION OF U.S. ABUSE LIABILITY OF DRUGS: TESTING IN DRUG POLICY ANIMALS ANSLINGER, HARRY J., AND U.S. DRUG POLICY Garth Martin AGING, DRUGS, AND ALCOHOL Addiction Research Foundation CULTS AND DRUG USE Clinical Research and Treatment Institute, Toronto, JIMSONWEED Canada MARIJUANA TREATMENT: POLYDRUG ABUSE, AN OVERVIEW MYTHS ABOUT DRUG ABUSE AND TREATMENT

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Kevin McEneaney Marissa Miller Phoenix House, New York, NY National Vaccine Program Office, Rockville, MD TREATMENT AMPHETAMINE EPIDEMICS PROGRAMS/CENTERS/ORGANIZATIONS: AN William R. Miller HISTORICAL PERSPECTIVE Department of Psychology James L. McGaugh University of New Mexico, Albuquerque, NM Center for Neurobiology of Learning TREATMENT: ALCOHOL, PSYCHOLOGICAL University of California, Irvine, CA APPROACHES MEMORY, EFFECTS OF DRUGS ON Richard A. Millstein Kimberley A. McGrath National Institute on Drug Abuse, Rockville, MD U.S. GOVERNMENT: AGENCIES SUPPORTING Farmington Hills, MI SUBSTANCE ABUSE PREVENTION AND ALCOHOLISM: ABSTINENCE VERSUS TREATMENT CONTROLLED DRINKING U.S. GOVERNMENT AGENCIES: NATIONAL NEEDLE AND SYRINGE EXCHANGES AND INSTITUTE ON DRUG ABUSE (NIDA) HIV/AIDS SCHIZOPHRENIA Alan Minsk Hyman, Phelps, and McNamara, Washington, DC Jim McKay EXCLUSION RULE University of Pennsylvania, Philadelphia, PA HARRISON NARCOTICS ACT OF 1914 RELAPSE PSYCHOTROPIC DRUG CONVENTION OF 1971 TREATMENT TYPES: LONG-TERM VERSUS BRIEF SHANGHAI OPIUM CONFERENCE OF 1911 SINGLE DRUG CONVENTION OF 1961 A. Thomas McLellan Veterans Administration Medical Center Matthew Miskelly Philadelphia, PA Farmington Hills, MI ADDICTION SEVERITY INDEX (ASI) EDUCATION AND PREVENTION MICHIGAN ALCOHOLISM SCREENING TEST PREVENTION: NATIONAL FAMILIES IN ACTION (MAST) (NFIA) RUTGERS CENTER OF ALCOHOL STUDIES Jonnie McLeod TOBACCO: SMOKELESS University of North Carolina, Charlotte, NC PREVENTION PROGRAMS: OMBUDSMAN PROGRAM Marc E. Mooney Tobacco Use Research Center, Department of David Metzger Psychiatry University of Pennsylvania, Philadelphia, PA University of Minnesota, Minneapolis, MN ASSESSMENT OF SUBSTANCE ABUSE: HIV RISK TREATMENT: TOBACCO, PSYCHOLOGICAL BEHAVIORS SURVEY APPROACHES

Roger E. Meyer Joan Moore George Washington University, Washington, DC Department of Sociology DISEASE CONCEPT OF ALCOHOLISM AND DRUG University of Wisconsin, Milwaukee, WI HISPANICS AND DRUG USE, IN THE UNITED ABUSE STATES Ada C. Mezzich Timothy H. Moran Western Psychiatric Institute Department of Psychiatry University of Pittsburgh School of Medicine Johns Hopkins University, Baltimore, MD ATTENTION DEFICIT DISORDER ANORECTIC CONDUCT DISORDER AND DRUG USE ANOREXIA Klaus A. Miczek OBESITY Department of Psychology Herbert Moskowitz Tufts University, Medford, MA Encino, CA AGGRESSION AND DRUGS, RESEARCH ISSUES DRIVING, ALCOHOL, AND DRUGS

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Otto Moulton Carl A. Newcombe Committees of Correspondence, Danvers, MA U.S. Customs Service COMMITTEES OF CORRESPONDENCE Canine Enforcement Training Center Front Royal, VA DOGS IN DRUG DETECTION Rod Mullen Amity, Inc., Tucson, AZ John Newmeyer TREATMENT Haight-Ashbury Free Clinics Inc. San Francisco, CA PROGRAMS/CENTERS/ORGANIZATIONS: AN TREATMENT HISTORICAL PERSPECTIVE PROGRAMS/CENTERS/ORGANIZATIONS: AN HISTORICAL PERSPECTIVE Clare Mundell Department Joe Nowinski DRUG ABUSE WARNING NETWORK (DAWN) Yale University, West Haven, CT COGNITIVE-BEHAVIORAL THERAPY Terrence Murphy TREATMENT: TWELVE STEP FACILITATION Institute for Scientific Analysis, San Francisco, CA CALIFORNIA CIVIL COMMITMENT PROGRAM Esko Nuotto National Medicines Control Lab, Helsinki, Finland Sheigla Murphy PSYCHOMOTOR EFFECTS OF ALCOHOL AND Institute for Scientific Analysis, San Francisco, CA DRUGS OPIOIDS AND OPIOID CONTROL: HISTORY David Nurco Margaret Murray Human Behavior Associates, Inc., Annapolis, MD National Institute on Alcoholism and Alcohol Abuse CRIME AND DRUGS Rockville, MD Charles P. O’Brien HOMELESSNESS, ALCOHOL, AND OTHER DRUGS Treatment Research Center Ralph Myerson University of Pennsylvania, Philadelphia, PA Merion Station, PA TREATMENT: COCAINE, AN OVERVIEW COMPLICATIONS: DERMATOLOGICAL Grace O’Leary COMPLICATIONS: LIVER (OTHER DRUGS) Department of Psychiatry COMPLICATIONS: MEDICAL AND BEHAVIORAL McLean Hospital, Belmont, MA TOXICITY OVERVIEW FREEBASING Claudio A. Naranjo Patrick M. O’Malley Psychopharmacology Research Program Institute for Social Research Sunnybrook Health Science Centre, Toronto, Canada University of Michigan, Ann Arbor, MI SEROTONIN-UPTAKE INHIBITORS IN TREATMENT HIGH SCHOOL SENIOR SURVEY OF SUBSTANCE ABUSE Isidore S. Obot Anastasia E. Nasis Department of Mental Hygiene, School of Public Behavioral Pharmacology Research Unit Health Francis Scott Key Medical Center, Baltimore, MD Johns Hopkins University, Baltimore, MD CONTROLS SCHEDULED DRUGS DRUG : / VULNERABILITY AS CAUSE OF SUBSTANCE SCHEDULES, U.S. ABUSE: RACE Peter E. Nathan Patricia Ohlenroth University of Iowa City, IA Seattle, WA RUTGERS CENTER OF ALCOHOL STUDIES ABSTINENCE VIOLATION EFFECT (AVE) Helen Navaline DRUG ABUSE WARNING NETWORK (DAWN) University of Pennsylvania, Philadelphia, PA FETUS, EFFECTS OF DRUGS ON THE BEHAVIORAL ECONOMICS NATIONAL HOUSEHOLD SURVEY ON DRUG ABUSE (NHSDA) Ethan Nebelkopf POVERTY AND DRUG USE Walden House, Inc., San Francisco, CA STUDENTS AGAINST DESTRUCTIVE DECISIONS TREATMENT (SADD) PROGRAMS/CENTERS/ORGANIZATIONS: AN TREATMENT: COCAINE, BEHAVIORAL HISTORICAL PERSPECTIVE APPROACHES

liii liv LIST OF AUTHORS

TREATMENT: COCAINE, PHARMACOTHERAPY CODEINE TREATMENT: TOBACCO, AN OVERVIEW DIHYDROMORPHINE WITHDRAWAL: NONABUSED DRUGS HEROIN HYDROMORPHONE Marion Olmsted L-ALPHA-ACETYLMETHADOL (LAAM) Toronto Hospital Eating Disorder Day Centre, LAUDANUM Toronto, Canada MEPERIDINE BULIMIA NERVOSA METHADONE S. Victoria Otton MORPHINE Addiction Research Foundation, Toronto, Canada MPTP NALOXONE PHARMACOGENETICS (GENETIC FACTORS AND NALTREXONE DRUG METABOLISM) NARCOTIC Donald A. Overton OPIATES/OPIOIDS Department of Psychology OPIUM Temple University, Philadelphia, PA OXYCODONE MEMORY AND DRUGS: STATE DEPENDENT OXYMORPHONE LEARNING PAIN: DRUGS USED IN TREATMENT OF PAPAVER SOMNIFERUM Denise Paone PAREGORIC Chemical Dependency Unit Beth Israel Medical Center, New York, NY J. Thomas Payte NEEDLE AND SYRINGE EXCHANGES AND School of Medicine HIV/AIDS University of California at San Francisco San Francisco, CA Karen Parker METHODONE MAINTENANCE PROGRAMS Addiction Research Foundation, Toronto, Canada ANXIETY John E. Peachey BLOOD ALCOHOL CONTENT Addiction Services BREATHALYZER Royal Ottawa Hospital, Ontario Canada BULIMIA CALCIUM CARBIMIDE DELIRIUM Robert N. Pechnick DELIRIUM TREMENS (DTS) Department of Pharmacology CONDUCT DISORDER IN CHILDREN Louisiana State University Medical Center New DEPRESSION Orleans, LA DRIVING UNDER THE INFLUENCE (DUI) DIMETHYLTRYPTAMINE (DMT) HALLUCINATION DOM NICOTINE GUM HALLUCINOGENS MULTIDOCTORING HALLUCINOGENIC PLANTS OVERDOSE, DRUG (OD) LYSERGIC ACID DIETHYLAMIDE (LSD) AND OVER-THE-COUNTER (OTC) MEDICATION PSYCHEDELICS PERSONALITY DISORDER MDMA RECIDIVISM MESCALINE RELAPSE MORNING GLORY SEEDS SCHIZOPHRENIA NUTMEG SUICIDE ATTEMPT PEYOTE SUICIDE GESTURE PSILOCYBIN TRIPLICATE PRESCRIPTION WOOD ALCOHOL (METHANOL) Stanton Peele Lindesmith Center, New York, NY Gavril W. Pasternak ALCOHOLISM: ABSTINENCE VERSUS Department of Neurology CONTROLLED DRINKING Memorial Sloan Kettering Cancer Center New York, ALCOHOLISM: CONTROLLED DRINKING VERSUS NY ABSTINENCE ANALGESIC VALUES AND BELIEFS: EXISTENTIAL MODELS OF BUPRENORPHINE ADDICTION

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Anthony G. Phillips Dorothy P. Rice Department of Psychology School of Nursing University of British Columbia, Vancouver, Canada University of California, San Francisco, CA ANHEDONIA ECONOMIC COSTS OF ALCOHOL ABUSE AND RESEARCH: MOTIVATION ALCOHOL DEPENDENCE Roy Pickens James E. Rivers National Institute of Drug Abuse, Rockville, MD Comprehensive Drugs Research Center VULNERABILITY AS CAUSE OF SUBSTANCE University of Miami, Miami, FL ABUSE: AN OVERVIEW ACCIDENTS AND INJURIES FROM DRUGS VULNERABILITY AS CAUSE OF SUBSTANCE Cynthia A. Robbins ABUSE: GENETICS Department of Sociology Russell K. Portenoy University of Delaware, Newark, DE Memorial Sloan Kettering Cancer Center New York, ELDERLY AND DRUG USE NY WOMEN AND SUBSTANCE ABUSE IATROGENIC ADDICTION Steven J. Robbins Kenzie L. Preston Department of Psychology Haverford College, Haverford, PA Johns Hopkins Bayview Medical Center, Baltimore, CAUSES OF SUBSTANCE ABUSE: LEARNING MD WIKLER’S PHARMACOLOGIC THEORY OF DRUG RESEARCH: MEASURING EFFECTS OF DRUGS ON ADDICTION MOOD Lee N. Robins Beny J. Primm Department of Psychiatry Addiction Research and Treatment Corporation Washington University School of Medicine St. Louis, Brooklyn, NY MO U.S. GOVERNMENT AGENCIES: CENTER FOR VIETNAM: DRUG USE IN SUBSTANCE ABUSE TREATMENT (CSAT) VIETNAM: FOLLOW-UP STUDY James Prochaska Daphne Roe Cancer Prevention Research Center Department of Nutritional Sciences University of Rhode Island, Kingston, RI Cornell University, Ithaca, NY PROCESSES OF CHANGE MODEL COMPLICATIONS: NUTRITIONAL Marie Ragghianti Thomas A. Roehrs Center for Substance Abuse Research Sleep Disorders Center, Detroit, MI The University of Maryland, College Park, MD SLEEP, DREAMING, AND DRUGS COERCED TREATMENT FOR SUBSTANCE OFFENDERS Roger Roffman School of Social Work Timothy J. Regan University of Washington, Seattle, WA Division of Cardiovascular Disease TREATMENT: MARIJUANA New Jersey Medical School, Newark, NJ Myroslava Romach COMPLICATIONS: CARDIOVASCULAR SYSTEM Addiction Research Foundation, Toronto, Canada (ALCOHOL AND COCAINE) ANXIETY Faye E. Reilly BLOOD ALCOHOL CONTENT Department of Behavioral Science BREATHALYZER University of Kentucky, Lexington, KY BULIMIA INJECTING DRUG USERS AND HIV CONDUCT DISORDER IN CHILDREN DELIRIUM Peter Reuter DELIRIUM TREMENS (DTS) Rand Corporation, Washington, DC DEPRESSION DRUG INTERDICTION DRIVING UNDER THE INFLUENCE (DUI) SEIZURES OF DRUGS HALLUCINATION STREET VALUE MULTIDOCTORING

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NICOTINE GUM PREVENTION PROGRAMS: PRIDE (NATIONAL OVERDOSE, DRUG (OD) PARENTS RESOURCE INSTITUTE FOR DRUG OVER-THE-COUNTER (OTC) MEDICATION EDUCATION) PERSONALITY DISORDER RECIDIVISM Carl Salzman RELAPSE Massachusetts Mental Health Center SCHIZOPHRENIA Harvard Medical School, Boston, MA SUICIDE ATTEMPT WITHDRAWAL: BENZODIAZEPINES SUICIDE GESTURE Herman H. Samson TRIPLICATE PRESCRIPTION Department of Physiology and Pharmacology WOOD ALCOHOL (METHANOL) School of Medicine Charles M. Rongey Wake Forest University, Winston-Salem, NC Orlando, FL ALCOHOL: PSYCHOLOGICAL CONSEQUENCES OF ADVERTISING AND THE ALCOHOL INDUSTRY CHRONIC ABUSE ADVERTISING AND THE PHARMACEUTICAL INDUSTRY Robert Saporito ADVERTISING AND TOBACCO USE Division of Cardiovascular Disease UMDNJ, New Jersey Medical School, Newark, NJ Jed E. Rose COMPLICATIONS: CARDIOVASCULAR SYSTEM Nicotine Research Laboratory (ALCOHOL AND COCAINE) Veterans Administration Medical Center Durham, NC NICOTINE DELIVERY SYSTEMS FOR SMOKING Sally L. Satel CESSATION Substance Abuse Treatment Unit Yale University School of Medicine, New Haven, CT Marc Rosen WITHDRAWAL: COCAINE Department of Psychiatry Yale University School of Medicine New Haven, CT Eric Schaps TREATMENT: HEROIN, PHARMACOTHERAPY Development Studies Center, Oakland, CA PREVENTION PROGRAMS: NAPA PROJECT, Marsha Rosenberg REVISITED Department of Mental Hygiene Johns Hopkins School of Hygiene and Mental Health Charles Schindler Baltimore, MD Addiction Research Center Thomas Roth National Institute on Drug Abuse, Baltimore, MD Sleep Disorders Center, Detroit, MI RESEARCH, ANIMAL MODEL: CONDITIONED SLEEP, DREAMING, AND DRUGS WITHDRAWAL Belinda M. Rowland Joyce F. Schneiderman Voorheesville, NY Addiction Research Foundation, Toronto, Canada CENTRE FOR ADDICTION AND MENTAL HEALTH ADDICTED BABIES CHRONIC PAIN GENDER AND COMPLICATIONS OF SUBSTANCE COMPULSIONS ABUSE NATIONAL ASSOCIATION OF STATE ALCOHOL Marc Alan Schuckit AND DRUG ABUSE DIRECTORS Department of Psychiatry RESEARCH: CLINICAL RESEARCH Veterans of Administration Medical Center San Sue Rusche Diego, CA National Families in Action, Atlanta, GA ADULT CHILDREN OF ALCOHOLICS (ACOA) PARENTS MOVEMENT BETEL NUT PREVENTION: NATIONAL FAMILIES IN ACTION (NFIA) Leslie M. Schuh PREVENTION: NATIONAL FEDERATION OF National Institute on Drug Abuse PARENTS FOR DRUG-FREE YOUTH/NATIONAL Addiction Research Center, Baltimore, MD FAMILY PARTNERSHIP (NFP) TREATMENT: TOBACCO, PHARMACOTHERAPY PREVENTION MOVEMENT WITHDRAWAL: NICOTINE (TOBACCO)

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Christian G. Schutz John Slade Department of Psychiatry University of Medicine and Dentistry of New Jersey, Ludwig Maximilians University, Munich, Germany New Brunswick, NJ ASIA, DRUG USE IN TOBACCO: INDUSTRY Richard B. Seymour Reginald G. Smart Haight-Ashbury Free Clinics Inc. San Francisco, CA Addiction Research Foundation, Toronto, Canada COMPLICATIONS: DERMATOLOGICAL CANADA, DRUG AND ALCOHOL USE IN COMPLICATIONS: ROUTE OF ADMINISTRATION David E. Smith ETHNIC ISSUES AND CULTURAL RELEVANCE Haight-Ashbury Free Clinics Inc., San Francisco, CA TREATMENT COMPLICATIONS: DERMATOLOGICAL TREATMENT COMPLICATIONS: ROUTE OF ADMINISTRATION PROGRAMS/CENTERS/ORGANIZATIONS: AN ETHNIC ISSUES AND CULTURAL RELEVANCE IN HISTORICAL PERSPECTIVE TREATMENT TREATMENT PROGRAMS/CENTERS/ORGANIZA- Sidney Shankman TIONS: AN HISTORICAL PERSPECTIVE Second Genesis, Bethesda, MD TREATMENT PROGRAMS/CENTERS/ James E. Smith ORGANIZATIONS: AN HISTORICAL Department of Physiology and Pharmacology PERSPECTIVE Bowman Gray Medical School Wake Forest University, Winston-Salem, NC Carl Shantzis BRAIN STRUCTURES AND DRUGS LIMBIC SYSTEM Drug Education Center, Charlotte, NC NUCLEUS ACCUMBENS PREVENTION PROGRAMS: OMBUDSMAN PROGRAM Robin Solit Dianne Shuntich Department of Psychology Department of Mental Health University of California, San Diego, CA Cabinet for Human Resources, Frankfort, KY TREATMENT MOTHERS AGAINST DRUNK DRIVING (MADD) PROGRAMS/CENTERS/ORGANIZATIONS: AN PREVENTION PROGRAMS: TALKING WITH YOUR HISTORICAL PERSPECTIVE STUDENT ABOUT ALCOHOL (TWYSAA) Bob Sokol Kenneth Silverman Wayne State University School of Medicine Department of Psychiatry and Behavioral Science Detroit, MI Johns Hopkins School of Medicine Baltimore, MD ASSESSMENT OF SUBSTANCE ABUSE: T-ACE CAFFEINE David Spiegel COFFEE Department of Psychiatry and Behavioral Science TEA Stanford University School of Medicine, Stanford, CA Dwayne Simpson TREATMENT TYPES: HYPNOSIS Institute of Behavioral Research John Stang Texas Christian University, Fort Worth, TX National Addiction Centre, London, England DRUG ABUSE REPORTING PROGRAM (DARP) BRITISH SYSTEM OF DRUG-ADDICTION DRUG ABUSE TREATMENT OUTCOME STUDIES TREATMENT (DATOS) June M. Stapleton Rajita Sinha Addiction Research Center Department of Psychiatry National Institute on Drug Abuse, Baltimore, MD Yale University School of Medicine IMAGING, TECHNIQUES: VISUALIZING THE VULNERABILITY AS CAUSE OF SUBSTANCE LIVING BRAIN ABUSE: STRESS Marvin Steinberg Harvey Skinner Connecticut Council on Problem Gambling, Guilford, Department of Public Health Sciences CT University of Toronto, Ontario, Canada GAMBLING ADDICTION: ASSESSMENT ASSESSMENT OF SUBSTANCE ABUSE: DAST GAMBLING ADDICTION: EPIDEMIOLOGY

lvii lviii LIST OF AUTHORS

Mark S. Steinitz Dace Svikis Department of State National Institute on Drug Abuse, Rockville, MD Bureau of Intelligence and Research Washington, DC VULNERABILITY AS CAUSE OF SUBSTANCE TERRORISM AND DRUGS ABUSE: AN OVERVIEW VULNERABILITY AS CAUSE OF SUBSTANCE Robert S. Stephens ABUSE: GENETICS Department of Psychology Virginia Polytechnic Institute, Blacksburg, VA Neil Swan ROW Sciences, Rockville, MD Verner Stillner INHALANTS: EXTENT OF USE AND Department of Psychiatry COMPLICATIONS University of Kentucky, Lexington, KY DOVER’S POWER Robert M. Swift Department of Psychiatry Amy L. Stirling Roger Williams Hospital, Providence, RI Department of Psychology TREATMENT: POLYDRUG ABUSE, Wayne State University, Detroit, MI PHARMACOTHERAPY PROFESSIONAL CREDENTIALING John D. Swisher Maxine Stitzer Pennsylvania State University, State College, PA Behavioral Pharmacology Research Unit EDUCATION AND PREVENTION Francis Scott Key Medical Center, Baltimore, MD REINFORCEMENT Ralph E. Tarter TREATMENT: HEROIN, BEHAVIORAL APPROACHES Western Psychiatric Institute University of Pittsburgh School of Medicine Tim Stockwell Pittsburgh, PA National Centre for Research into the Prevention of ATTENTION DEFICIT DISORDER Drug Abuse CONDUCT DISORDER AND DRUG USE Curtin University, Perth, Australia COPING AND DRUG USE TREATMENT TYPES: NONMEDICAL DETOXIFICATION Beti Thompson Fred Hutchinson Cancer Research Center, Seattle, WA Carla L. Storr TOBACCO: SMOKING CESSATION AND WEIGHT Center for Substance Abuse Research GAIN The University of Maryland, College Park, MD WITHDRAWAL: NICOTINE (TOBACCO) ADOLESCENTS AND DRUG USE EPIDEMICS OF DRUG ABUSE W. Kenneth Thompson Bureau of International Narcotics Matters Chevy Amy Loerch Strumolo Chase, MD Farmington Hills, MI FOREIGN POLICY AND DRUGS CAUSES OF SUBSTANCE ABUSE: GENETIC FACTORS Stephen T. Tiffany Department of Psychological Sciences DIAGNOSTIC AND STATISTICAL MANUAL (DSM) HAIR ANALYSIS AS A TEST FOR DRUG USE Purdue University, West Lafayette, IN CRAVING John T. Sullivan Center for Chemical Dependence Gillian Tober Francis Scott Key Medical Center, Baltimore, MD Leeds Addiction Unit, Leeds, England UKAT: U.K. ALCOHOL TREATMENT TRIAL DETOXIFICATION: AS ASPECT OF TREATMENT COMPLICATIONS: MEDICAL AND BEHAVIORAL Michael Tonry TOXICITY OVERVIEW University of Minnesota Law School Minneapolis, MN WITHDRAWAL: ALCOHOL MANDATORY SENTENCING ROCKEFELLER DRUG LAW Nancy L. Sutherland Alcohol and Drug Abuse Institute Harrison M. Trice University of Washington, Seattle, WA New York School of Industry and Labor Relations ALCOHOL: PSYCHOLOGICAL CONSEQUENCES OF Cornell University, Ithaca, NY CHRONIC ABUSE AL-ANON

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ALATEEN Elizabeth Wallace ALCOHOLICS ANONYMOUS (AA) Substance Abuse Treatment Unit COCAINE ANONYMOUS (CA) Yale University School of Medicine New Haven, CT NARCOTICS ANONYMOUS (NA) TREATMENT TYPES: PHARMACOTHERAPY, AN TREATMENT TYPES: SELF-HELP AND OVERVIEW ANONYMOUS GROUPS John M. Wallace, Jr. TREATMENT TYPES: TWELVE STEPS, THE Institute for Social Research Alison M. Trinkoff University of Michigan, Ann Arbor, MI RELIGION AND DRUG USE School of Nursing University of Maryland, Baltimore, MD Michael Walsh ADOLESCENTS AND DRUG USE Drug Advisory Council Executive Office of the President, Washington, DC George R. Uhl INDUSTRY AND WORKPLACE, DRUG USE IN Molecular Neurobiology Laboratory, Addiction Research Center Sharon L. Walsh National Institute on Drug Abuse, Baltimore, MD Francis Scott Key Medical Center, Baltimore, MD RESEARCH MEASURING EFFECTS OF DRUGS ON ANTIDEPRESSANT : MOOD ANTIPSYCHOTIC NEUROLEPTIC Ronald R. Watson RECEPTOR: NMDA College of Public Health and School of Medicine SUBSTANCE ABUSE, GENETIC FACTORS AND University of Arizona, Tucson, AZ VULNERABILITY ALCOHOL AND AIDS ALCOHOL: COMPLICATIONS James Van Wert COCAETHYLENE Small Business Administration, Silver Springs, MD COMPLICATIONS: IMMUNOLOGIC COLOMBIA AS DRUG SOURCE PARASITE DISEASES AND ALCOHOL CROP-CONTROL POLICIES (DRUGS) TREATMENT PROGRAMS/CENTERS/ORGANIZA- GOLDEN TRIANGLE AS DRUG SOURCE TIONS: AN HISTORICAL PERSPECTIVE INTERNATIONAL DRUG SUPPLY SYSTEMS Andrew T. Weil MEXICO AS DRUG SOURCE Tucson, AZ SOURCE COUNTRIES FOR ILLICIT DRUGS POLICY ALTERNATIVES: SAFE USE OF DRUGS TRANSIT COUNTRIES FOR ILLICIT DRUGS Meryle Weinstein Jane Velez Psychiatry Service Project Return Foundation, Inc., New York, NY Veterans Affairs Medical Center San Francisco, CA TREATMENT PROGRAMS/CENTERS/ TREATMENT TYPES: PSYCHOLOGICAL APPROACHES ORGANIZATIONS: AN HISTORICAL Roger Weiss PERSPECTIVE Department of Psychiatry Robert E. Vestal McLean Hospital, Belmont, MA Clinical Pharmacology and Gerontology Research FREEBASING Unit Donald R. Wesson Veterans Administration Medical Center Boise, ID Beverly Hills, CA AGING. DRUGS, AND ALCOHOL IMPAIRED PHYSICIANS AND MEDICAL WORKERS David Vlahov Harry R. Wexler School of Hygiene and Mental Health The Psychology Center, Laguna Beach, CA Johns Hopkins University, Baltimore, MD CALIFORNIA CIVIL COMMITMENT PROGRAM ARGOT CIVIL COMMITMENT NEW YORK STATE CIVIL COMMITMENT PROGRAM Alexander C. Wagenaar PRISONS AND JAILS School of Public Health, Division of Epidemiology PRISONS AND JAILS: DRUG TREATMENT IN University of Minnesota, Minneapolis, MN PRISONS AND JAILS: DRUG USE AND AIDS IN ALCOHOL: MINIUM DRINKING AGE LAWS RATIONAL AUTHORITY

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Richard L. Williams William Woolverton Alexandria, VA Department of Pharmacological Sciences BORDER MANAGEMENT Prizker School of Medicine, Chicago, IL U.S. GOVERNMENT: DRUG POLICY OFFICES IN ABUSE LIABILITY OF DRUGS: TESTING IN THE EXECUTIVE OFFICE OF THE PRESIDENT ANIMALS U.S. GOVERNMENT THE ORGANIZATION OF U.S. RESEARCH, ANIMAL MODEL: AN OVERVIEW OF DRUG POLICY DRUG ABUSE U.S. GOVERNMENT AGENCIES: BUREAU OF RESEARCH, ANIMAL MODEL: CONDITIONED NARCOTICS AND DANGEROUS DRUGS (BNDD) PLACE PREFERENCE U.S. GOVERNMENT AGENCIES: OFFICE OF DRUG RESEARCH, ANIMAL MODEL: DRUG ABUSE LAW ENFORCEMENT (ODALE) DISCRIMINATION STUDIES U.S. GOVERNMENT AGENCIES: OFFICE OF DRUG RESEARCH, ANIMAL MODEL: DRUG SELF- ABUSE POLICY (ODAP) ADMINISTRATION U.S. GOVERNMENT AGENCIES: OFFICE OF NATIONAL DRUG CONTROL POLICY (ONDCP) Colleen J. Yoo U.S. GOVERNMENT AGENCIES: U.S. CUSTOMS Department of Health Policy and Management SERVICE Johns Hopkins School of Public Health, Baltimore, Amy Windham MD VULNERABILITY AS CAUSE OF SUBSTANCE Department of Mental Hygiene ABUSE: SEXUAL AND PHYSICAL ABUSE Johns Hopkins School of Hygiene and Mental Health Baltimore, MD ZERO TOLERANCE Robert Zaczek Du Pont Merck Pharmaceuticals Wilmington, DE George Winokur FLY AGARIC Department of Psychiatry JIMSONWEED University of Iowa College of Medicine, Iowa City, IA KAVA COMPLICATIONS: MENTAL DISORDERS SCOPOLAMINE AND ATROPINE Eric D. Wish Center for Substance Abuse Research Marvin Zuckerman Department of Psychology University of Maryland, College Park, MD University of Delaware, Newark, DE DRUG USE FORECASTING PROGRAM (DUF) VULNERABILITY AS CAUSE OF SUBSTANCE Friedner D. Wittman ABUSE: SENSATION SEEKING KLEW Associates, Berkeley, CA ALCOHOL- AND DRUG-FREE HOUSING Joan Ellen Zweben School of Medicine Ronald W. Wood University of California at San Francisco San New York University Medical Center Tuxedo Park, NY Francisco, CA INHALANTS Clinic and Medical Group and East Bay Community George Woody Recovery Project, Oakland, CA University of Pennsylvania, Philadelphia, PA METHADONE MAINTENANCE PROGRAMS BEHAVIORAL ECONOMICS

lx A

AA See Alcoholics Anonymous; Treatment: the person can quickly return to the goal of absti- Twelve Step Facilitation nence andnot ‘‘lose control’’ of the behavior. Spe- cific intervention strategies include helping the per- son identify and cope with high-risk situations, ABRAXAS See Treatment Programs/Cen- eliminating myths regarding a drug’s effects, man- ters/Organizations: An Historical Perspective aging lapses, and addressing misperceptions about the relapse process. Other more general strategies include helping the person develop positive addic- ABSTINENCE See Addiction: Concepts and tions andemploying stimulus-control andurge- Definitions; Alcoholism; Sobriety; Withdrawal management techniques. Researchers continue to evaluate the AVE andthe efficacy of relapse pre- vention strategies. ABSTINENCE VIOLATION EFFECT (AVE) The abstinence violation effect (AVE) oc- (SEE ALSO: Treatment) curs when an individual, having made a personal commitment to abstain from using a substance or BIBLIOGRAPHY to cease engaging in some other unwantedbehav- CRONCE,JESSICA M. Interview with author. Addictive Be- ior, has an initial lapse whereby the substance or behavior is engaged in at least once. Some individ- haviors Research Center, University of Washington, uals may then proceedto uncontrolleduse. The 2000. AVE occurs when the person attributes the cause of CURRY, S. J., MARLATT, G. A., & GORDON, J. R. (1987). the initial lapse (the first violation of abstinence) to Abstinence violation effect: Validation of an attribu- internal, stable, andglobal factors within (e.g., lack tional construct with smoking cessation. Journal of of willpower or the underlying addiction or Consulting and Clinical Psychology, 55, 145–149. disease). LARIMER,MARY E.; PALMER,REBEKKA S.; MARLATT,G. In RELAPSE PREVENTION, the aim is to teach ALAN. ‘‘Relapse prevention: An overview of Marlatt’s people how to minimize the size of the relapse (i.e., cognitive-behavioral model.’’ Alcohol Research & to counter the AVE) by directing attention to the Health 23 (1999): 151–160. more controllable external or situational factors LAWS, D. R. ‘‘Relapse prevention—The state of the art.’’ that triggeredthe lapse (e.g., high-risk situations, Journal of Interpersonal Violence 14 (1999): 285– coping skills, andoutcome expectancies), so that 302.

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MARLATT, G. A., & GORDON, J. R. (1985). Relapse pre- way a human would, alternate methods are em- vention: Maintenance strategies in the treatment of ployed. Animals may be taught to push levers or do addictive behaviors. New York: GuilfordPress. similar actions in order to get a dose of a drug. The SHIFFMAN,SAUL;HICKCOX,MARY;PATY,JEAN A.; GNYS, results of these drug self-administration studies in MARYANN;KASSEL,JON D.; RICHARDS,THOMAS J. ‘‘The animals play a critical role in the prediction of the abstinence violation effect following smoking lapses likelihoodof abuse of new drugsin human beings. andtemptations.’’ Cognitive Therapy & Research The liability that a drug will be abused is often 21(5) (1997): 497–523. evaluatedby what has been termeda ‘‘substitution SHIFFMAN,SAUL;HICKCOX,MARY;PATY,JEAN A.; GNYS, procedure.’’ Such research begins with the admin- MARYANN; ET AL. ‘‘Progression from a smoking lapse istration of a known drug, which is then substituted to relapse: Prediction from abstinence violation ef- with a new drug under investigation. The first fects, nicotine dependence, and lapse characteristics.’’ phase in the substitution procedure is designed to Journal of Consulting & Clinical Psychology 64(5) establish a baseline of how much effort an animal is (1996): 993–1002. willing to make to obtain a drug dose in general. ALAN MARLATT Each day an animal is allowed to give itself a drug MOLLY CARNEY of known potential for abuse. The researcher notes REVISED BY PATRICIA OHLENROTH how frequently the animal takes a dose and how much effort it is willing to make to get a dose of the drug. The researcher can make a lever harder to ABUSE See Addiction: Concepts and Defini- push, make the animal push it repeatedly, or make tions the animal follow a complicatedset of actions to get a dose. This provides a baseline against which to compare the effects of the new drug which will be studied. ABUSE LIABILITY OF THERAPEUTIC For example, a monkey may give itself COCAINE DRUGS: TESTING IN ANIMALS Deter- or CODEINE via intravenous injections during ses- mining the probability that a new drug will be sions that last several hours. When session-to- abusedis an important step in reducingthe overall session intake of the known drug is stable (that is, abuse of therapeutic drugs. Since the likelihood stays about the same, thus showing the dosage that a drug will be abused by a patient must be carefully weighedagainst the benefit providedby which is sufficient to satisfy the animal andreduce the drug, it is important that research outline any its drive to obtain more), the liquid in which it was andall reinforcing effects a drugmay have which dissolved is substituted for the baseline drug for couldleadto subsequent abuse. Predictionof the several consecutive sessions. Since this liquidis likelihoodof abuse has historically been based usually neutral, with no positive or negative effects, upon human experiments andobservation. This the animal gives itself fewer andfewer injections method, however, is increasingly being replaced until it hardly bothers pushing the lever at all. The with experimentation on animals. animal is briefly returnedto baseline conditions, Research conducted since the early 1960s has followedby a substitution periodduringwhich a shown that animals such as monkeys andrats will, dose of the test drug is made available. This contin- with very few exceptions, repeatedly self-adminis- ues for at least as many sessions as were required ter the same drugs that human beings are likely to for the animal to stop bothering with pushing the abuse. Moreover, test animals do not self-adminis- lever for the neutral liquid. This process is repeated ter drugs that human beings do not abuse. with different concentrations of the new drug until Research basedon animal testing is conducted the experimenter has testeda range of possible in a slightly different manner and often requires doses of the new medicine. laboratory procedures not needed for research The rates at which the animal gives itself the test basedon human test subjects. Provisions must be drug, neutral liquid, and known addictive drug are made to allow the animal a means by which to self- then compared. A new drug that the animal prefers administer the drug. Since animals frequently are to the neutral liquidis consideredtobe a substance not physically able to administer a drug in the same that reinforces the desire for itself (a ‘‘positive rein- ABUSE LIABILITY OF THERAPEUTIC DRUGS: TESTING IN ANIMALS 3 forcer’’) andwouldthus be predictedtohave abuse may be usedto predictpotential subjective effects liability. in human beings. Since subjective effects play a Such substitution procedures provide informa- major role in drug abuse, such experiments are an tion which indicates whether or not a drug is liable important tool usedin the evaluation of the likeli- to be abused, but do not allow a comparative esti- hood of abuse in new drugs. A new drug with mate as to whether or not a new drug is more subjective effects similar to those of a known, ad- addictive or less addictive than other known drugs. dictive, and often abused drug is likely to be abused These procedures measure how frequently the ani- itself. Additionally, drug-discrimination experi- mal gives itself a dose, a measure that reflects both the direct effects of the drug and the effects of the ments not only identify the potential for abuse but drug’s reinforcement of the desire for itself. An- also provide important information which allows other methodmust be usedto measure the reinforc- researchers to classify new drugs based on their ing effect of a drug separately from its other effects. predicted subjective effects, something that drug To compare drugs, it is useful to know how big the self-administration experiments cannot do. Thus, maximum reinforcing effect is—termedits rein- drug discrimination provides additional informa- forcing efficacy. Several procedures have been de- tion relevant to the comparison between the new velopedto measure reinforcing efficacy. Most either drug and drugs that we already know are addictive allow an animal to choose between the new drug andfrequently abused.For example, a monkey and another drug or non-drug reinforcer(choice shows a similar discrimination pattern using a new procedures), or they measure how hard an animal drug as it has shown previously using a known drug will work to obtain an injection (progressive-ratio such as cocaine. This new drug is likely to be procedures). In choice procedures, the measure of reinforcing abusedandto have subjective effects similar to efficacy is how often the new drug is chosen in those produced by cocaine. preference to the other drug (or non-drug). In pro- gressive-ratio procedures, the number of times the CONCLUSION animal must push the lever in order to get a drug injection is increaseduntil the animal no longer Researchers have improved methods for predict- bothers to push the lever. At some point the animal ing the likelihood that a new drug will be abused. determines that it is not worth the extra effort to get Using animals in substitution, choice, andprogres- another dose. This point is called the break point sive-ratio procedures has greatly enhanced re- andis a measure of the reinforcing efficacy of the searchers’ understanding of factors involved in de- drug. termining the liability that a new drug or chemical The fact that animals given a choice between compoundwill be abused.Current research tech- different strengths of the same drug show a propen- niques allow the evaluation of likely preference and sity to choose the higher dose most often is evidence that these procedures provide a valid measure of the reinforcing efficacy of a new compoundbased reinforcing efficacy. In addition, break points are on experiments with animals such as monkeys and higher in progressive-ratio experiments involving rats. This information is then usedto reliably pre- higher stable doses and lower for experiments in- dict whether a drug is likely to be abused and to volving lower doses. Results of both the choice and which known drugs it is likely to be similar, both in the progressive-ratio procedures in animal research terms of how addictive it is and what its subjective are consistent with what is known about abuse of effects will be. Such information is clearly valuable drugs in human beings—that is, drugs such as CO- in deciding how much to restrict a new drug and is CAINE, a highly preferred drug in choice studies, a critical tool in the effort to reduce the abuse of maintain higher break points in progressive-ratio therapeutic drugs. studies than other drugs, and are frequently abused. These experiments show how animals discrimi- (SEE ALSO: Abuse Liability of Drugs: Testing in nate among drugs, and the extent to which they Humans; Controlled Substances Act of 1970; Rein- prefer certain drugs over other drugs. The results forcement; Research: Animal Model ) 4 ABUSE LIABILITY OF DRUGS: TESTING IN HUMANS

BIBLIOGRAPHY HUMAN VOLUNTEER SELECTION

BRADY,J.V.,&S.E.LUKAS (1984). Testing drugs for One of the most important factors in drug- physical dependence potential and abuse liability. abuse-liability testing with humans is the way the NIDA Research Monograph no. 52. Washington, volunteer subjects are chosen to participate in the D.C.: U.S. Government Printing Office. assessment procedures. In most studies, the human THOMPSON, T., & K. R. UNRA (Eds.) (1977). Predicting volunteer subjects are experienceddrugusers, but dependence liability of stimulant and depressant wide variations exist in the nature and extent of drugs, Baltimore: University Park Press. their drug use and abuse. Some studies, for exam- WILLIAM WOOLVERTON ple, use students and other volunteers whose mis- REVISED BY JAMES T. MCDONOUGH,JR. use andabuse of drugshas been mostly ‘‘recrea- tional’’; other studies involve people with histories of more intensive drug use and abuse over extended ABUSE LIABILITY OF DRUGS: TEST- periods. Also, the settings in which the tests are ING IN HUMANS There is probably no drug conducted vary widely, from residential laboratory usedto treat illness that doesnot also pose certain environments, where the subjects live for several risks. One such risk, generally limitedto drugsthat days or weeks at a time, to laboratories, where the have actions on the central nervous system, is that subjects do not remain in residence but continue the drug will be misused or abused because of these their daily routine after drug ingestion. Variations effects. Drugs such as these are saidto have abuse also occur in the age of the subjects testedandthe potential or abuse liability. If the drugs have im- time of day that the drug is administered. Often portant therapeutic use, they may still be made subjects have been selectedfor certain human available, but they will be subject to certain legal drug-abuse-liability tests on the basis of some spe- controls under various federal and state laws (see cial features (e.g., anxiety levels, level of alcohol CONTROLLED SUBSTANCES ACT). Over the past fifty consumption) to determine the extent to which years, a number of methods have been developed to such factors influence the outcome of the tests. test new drugs to determine their abuse liability, so Convincing evidence now exists that many of that both the public andthe medicalprofession can these factors—particularly the prior experience of be warnedabout the needfor appropriate caution the subject with respect to drug and alcohol use and when using certain drugs. These methods involve misuse—play an important role in the assessment both testing in animals (preclinical) andtesting in of abuse liability. The obvious value in using such humans (clinical). subjects lies in the fact that these individuals are Several important reasons exist for why testing similar to those most likely to abuse drugs with with humans is useful andnecessary in the devel- abuse liability—for example, drug abusers who opment of safer andmore effective pharmacologi- help determine whether a new drug has a greater or cal agents. The research on laboratory animals lesser chance for abuse than the one they already demonstrating greater or lesser degrees of the abuse know. It is also important to carry out abuse- liability of drugs must be validated with humans; liability testing with people who, for example, do this reduces the likelihood of error in assessing po- not usually abuse drugs but are light social drink- tential risks. Moreover, certain self-reported ers—to assess the likelihoodof abuse of certain changes associatedwith the subjective effects of generally available medications, such as sleeping medicinal drugs can be more readily evaluated in pills or appetite suppressants. the humans for whom they were developed. Human clinical studies are also important in determining DRUG COMBINATIONS appropriate dose levels and dosage forms to ensure safety andefficacy while minimizing unwantedside The prediction of a drug’s abuse liability, based effects. Finally, comprehensive andeffective test- on a wide variety of testing procedures with hu- ing with humans helps to reduce the availability of mans, is further complicatedby the fact that drugs abusable drugs to those who are likely to misuse of abuse are often usedin combination andsimul- them and to provide for the legitimate medical and taneously with other pharmacological agents. This scientific needs for such pharmacological agents. creates some very difficult problems for the testing ABUSE LIABILITY OF DRUGS: TESTING IN HUMANS 5 of abuse liability, because of the large number of DEVELOPMENT OF ABUSE-LIABILITY possible drug combinations that need to be tested TESTING PROCEDURES andtheir unknown, potentially toxic, effects. While The origins of assessing drug-abuse liability it has long been known that drugs such as COCAINE with humans can be foundin some of the earliest andH EROIN or MARIJUANA andA LCOHOL are used writings of civilization, describing the subjective simultaneously by drug abusers, few testing proce- effects of naturally occurring substances, such as dures have been developed for assessing their inter- wine. Since the mid-nineteenth century, literary actions. Even more puzzling is that some drugs accounts of the use andmisuse of opium, mari- with opposite effects (e.g., stimulants like the AM- juana, andcocaine, among other substances, have PHETAMINES anddepressantslike the B ARBITU- emphasizedtheir mood-alteringeffects andtheir RATES) are known to be usedsimultaneously by potential for abuse. Only in recent years, however, POLYDRUG ABUSERS, suggesting that unique sub- have systematic methods for measuring such sub- jective-effect changes may be important factors in jective effects been refinedthrough the use of stan- such abuse patterns. dardized questionnaires. Volunteers who are expe- rienceddrugusers complete the questionnaires PRINCIPLES OF ABUSE-LIABILITY after they have taken a drug; their answers to the TESTING subjective-effects questions—how they feel, their likes and dislikes—readily distinguish between the Basedon extensive research undertakenover the various drugs and doses, as well as between drug past several decades, some important general prin- presence or absence (i.e., placebo). ciples governing abuse-liability testing with hu- This basic subjective-effects methodology has mans have been established. In the first instance, been further refinedin recent years by using a for example, a meaningful assessment requires that training procedure to ensure that the human volun- the test drug be compared with a drug of known teer can differentiate a given drug (e.g., morphine) abuse liability to provide a standard for evaluation. from a placebo (i.e., nondrug). Then new drugs are Second, the assessment procedure must involve the testedto evaluate their similarity to the trained indicated comparison over a range of doses of both reference drug of abuse. This behavioral drug dis- the test drug and the standard drug of abuse. This crimination methodpermits the volunteer to com- permits both a quantitative anda qualitative com- pare a wide range of subjective and objective effects parison of the drugs, while guarding against the of abused drugs with those of new drugs. These possibility of overlooking some unique high- or highly reliable procedures have proven very useful low-dose effects. Third, the testing procedures in identifying drugs that may have abuse liability. should include measures of drug effects in addition Among the most important factors in assessing to those like drug taking in the lab, which directly abuse liability is the determination of whether hu- predict the likelihood of abuse. With these addi- mans will take the drug when it is offered to them tional measures, it is often possible to obtain reli- andwhether such drugtaking is injurious to the able estimates of abuse liability by comparing test individual or society. These cardinal signs of drug drugs with a drug of abuse across a range of effects abuse have provided an important focus for labora- as a standard for evaluation. Fourth, confidence in tory animal self-injection experiments, but system- conclusions regarding the abuse liability of a drug atic studies in which humans self-administer drugs compoundcan be enhancedby utilizing a multi- of abuse have been less common. Methods have plicity of measures andexperimental procedures. been developed with humans, however, for com- This is the case because our present level of knowl- paring the behavioral andphysiological changes edge in this area does not permit a firm determina- produced by self-administration of a known drug tion of the best or most validpredictorof the likeli- of abuse with the changes produced by other self- hoodof abuse. Finally, a population of test subjects administered drugs. with histories of drug use appears to be the most The measure that has proven most useful in this appropriate selection for predicting the likelihood approach to human drug-abuse-liability assess- of abuse of a new test drug, since this is the popula- ment is the ability of a drug to reinforce and tion who might use such a drug in that way. maintain self-administration behaviors much like 6 ABUSE LIABILITY OF DRUGS: TESTING IN HUMANS the behaviors usedto obtain foodandwater. Such tests (e.g., speedof movement) are measuredafter reinforcing effects of drugs are an important deter- different drugs are administered to volunteers, the minant influencing the likelihoodthat a particular results can be comparedto determinewhether the drug will be abused. Laboratory studies with volun- behavioral changes produced by a test drug are teers who are experienceddrugusers, for example, the same as or different from those of a known drug have shown that they will perform bicycle-riding of abuse. When a number of different performance exercises to obtain doses of abused drugs (e.g., tests (e.g., arithmetic calculations, memory for pentobarbital). There is a systematic relationship numbers andletters, speedof reaction) are given between the amount of exercise performedandthe following such drug administration, it is possible to amount of drug available (i.e., higher doses and construct a behavioral profile showing the perform- shorter intervals between doses produce more exer- ance effects of different drugs. Comparisons be- cise behavior than lower doses and longer interdose tween different drugs and test drugs with regard to intervals). When a placebo or a drug that is not the similarity of such profiles across their respective abused(e.g., Thorazine) is madeavailable for bicy- dose ranges increase confidence in assessments cle riding, on the other hand, the rate of self- made of the abuse liability of unknown drugs. administration declines to near zero. Differences between drugs in abuse liability can EFFECTIVENESS OF ABUSE- also be assessedby determiningwhether humans LIABILITY TESTING prefer one drug of abuse to another. During a train- ing period, for example, experienced drug users Because of the availability of procedures for sample coded capsules containing different drugs abuse-liability testing in humans, it seems reason- or different doses of a drug. Then, during subse- able to ask how well they work. That is, has it been quent test sessions, they are presentedwith the possible to predict from the results of these tests coded capsules and allowed to choose the one con- whether a new drug will be abused when it becomes taining the drug or drug dose they prefer. This generally available? The two major sources avail- ‘‘blind’’ procedure (i.e., the volunteers are not told able for checking the effectiveness of human abuse- what drugs the capsules contain) prevents biases liability testing procedures are case reports by clini- that might be introduced by using the drug names. cians of patient drug abuse, and EPIDEMIOLOGICAL When neither the volunteer subject nor the person surveys of large numbers of individuals as well as conducting the test knows what drug the capsules of specific target sites (e.g., hospital emergency contain, the procedure is referred to as ‘‘double rooms). Both of these approaches have many short- blind.’’ comings, since they lack the precision andfocus Not surprisingly, it has also been shown that the that human laboratory testing can provide. But preference for one drug over another or one drug despite the draw-backs, they can detect abuse- dose over another agrees well with ratings of ‘‘drug liability problems in both specific groups of indi- liking’’ made independently of the choice tests just viduals and the population at large, in a manner described. In self-administration studies in which that has generally validated the results of human volunteers show a preference for one drug of abuse laboratory-testing procedures. over another, subjective ratings of ‘‘liking’’ and positive moodchanges were clearly more frequent ETHICAL CONSIDERATIONS for the preferred drug than for the drug chosen less often. Such self-reports have inherent limitations, A number of codes and regulations agreed on by however, because of variations in individual verbal scientists andthe lay public providenorms for the skills, which make it necessary to confirm such conduct of research and testing with human volun- findings with other measures. teers. In general, they require a clear statement, In addition to the self-administration and sub- understandable to the volunteer, of the risks and jective-effects measures of obvious value in testing benefits of the testing procedure, as well as an the abuse liability of drugs in humans, other quan- explicit consent document in written form. After it titative drug-effect measurements have proven use- is clear that the participant thoroughly appreciates ful. When, for example, observer ratings (e.g., all that is involvedandthe potential consequences nurses watching the patients) andperformance of participation, the volunteer signs the consent ACCIDENTS AND INJURIES FROM ALCOHOL 7 form in the presence of a witness who is not associ- atedwith the research. These requiredprocedures ensure both the autonomy andthe protection of volunteers for drug-abuse-liability testing.

(SEE ALSO: Abuse Liability of Drugs: Testing in Animals; Research: Animal Model )

BIBLIOGRAPHY

BRADY,J.V.,&LUKAS, S. E. (1984). Testing drugs for physical dependence potential and abuse liability. NIDA Research Monograph 52. Washington, DC: U.S. Government Printing Office. FISCHMAN, M. W., & MELLO, N. K. (1989). Testing for abuse liability of drugs in humans. NIDA Research Monograph, 92, No. 89-1613. Washington, DC: U. S. Government Printing Office. JOSEPH V. BRADY

ACCIDENTS AND INJURIES FROM AL- COHOL Trauma (bodily injury) is a major social and medical problem in both developed and devel- oping countries. Injuries are among the leading cause of death and disability in the world, and affect all populations, regardless of age, sex, in- Roslyn Cappiello, president of the Omaha, come, or geographic region. In 1998 about 5.8 mil- Nebraska, chapter of Mothers Against Drunk lion people died of injuries worldwide, and injuries Driving, was paralyzed from the neck down in caused 16 percent of the global burden of disease an accident caused by a drunk driver. (AP Photo/ (Krug, et al, 2000). In developed countries injuries Nati Harnik) are the leading cause of death between the ages of one andforty, andin the U.S. population it is the ies indicate that a large proportion of victims of fourth leading cause of death (exceeded only by both fatal andnonfatal injuries test positive for heart disease, stroke, and cancer). Of all deaths bloodalcohol—this proportion is greater than one from injury in the UnitedStates, about 65 percent wouldexpect to findin the general population on are classifiedas unintentional (which excludes any given day. The consumption of alcohol (etha- deaths from suicide, homicide, and other criminal nol) has been highly associatedwith fatalities and offenses); of these, about half result from motor serious injuries, but this may be the result of other vehicle accidents. Trauma also accounts for high high-risk behaviors on the part of the drinking rates of morbidity (number of sick to well). In the accident victim, such as not using seat belts or UnitedStates, the rate of serious injury is estimated motorcycle helmets. Studies of alcohol, injury, and to be at least three hundred times the death rate. risk-taking dispositions in the general population The first documentation of alcohol’s involve- have foundrisk-taking, impulsivity, andsensation- ment in injury dates to 1500 B.C.E., with an Egyp- seeking to be associatedwith both injury occur- tian papyrus warning that excessive drinking leads rence andalcohol consumption. Those who scored to falls andbroken bones. The scientific studyof high on risk-taking andsensation-seeking were alcohol andinjuries has been the subject of much twice as likely to report an injury for which treat- investigation throughout the twentieth century. ment was obtainedduringthe last year, andwere Data from both coroner andemergency room stud- also more likely to report heavier drinking 8 ACCIDENTS AND INJURIES FROM ALCOHOL

(Cherpitel, 1999). Although alcohol cannot be said so the independent effect of alcohol on both fatal to actually cause the accident in most cases, alcohol andnonfatal accidentsis not possible to ascertain. consumption is thought to contribute to both fatal andnonfatal injury occurrence, primarily because TRAUMA RELATED TO it is known to diminish motor coordination and MOTOR VEHICLES balance andto impair attention, perception, and judgment with regard to behavior, placing the Motor vehicle crashes are the leading cause of drinker at a higher risk of accidental injury than death from injury—and the greatest single cause of the nondrinker. The residual or hangover effects of all deaths for those between the ages of one and alcohol consumption may also contribute to injury thirty-four in the UnitedStates. It has been esti- occurrence. matedthat 7 percent of all crashes and44 percent of fatal crashes involve alcohol use, andalcohol’s involvement is greater for drivers in single-vehicle ESTIMATES OF nighttime fatal crashes (U.S. Department of Health ALCOHOL’S INVOLVEMENT andHuman Services, 1997). The risk of a fatal In emergency room (ER) studies, such as those crash is estimatedto be from three to fifteen times conducted by Cherpitel (1988), patients testing higher for a drunk driver (one with a BAL of at positive for alcohol have hadlevels that ranged least .10 to 100 milligrams of alcohol for each 100 from 6 to 32 percent—establishedeither directlyor milliliters of blood—the legal limit in most U.S. from a breath sample taken at the time of admis- states) than for a nondrinking driver, according to sion to the ER. In a review of ER studies, Cherpitel Roizen (1982). Alcohol is more frequently present (1993a) determined that this variation in blood in fatal than in nonfatal crashes. It is estimatedthat alcohol level (BAL) or BLOOD ALCOHOL about 25 to 35 percent of those drivers requiring CONCENTRATION (BAC) is due to differences in the ER care for injuries resulting from such crashes time that passedbetween the injury andarrival in have a BAL of .10 or greater. The number of alco- the ER, to individual characteristics of the particu- hol-relatedcrashes has declinedinrecent years, lar ER populations studied (such as age, sex, and particularly among younger and older drivers, but socioeconomic status—all known to be associated has increasedamong women. with alcohol consumption in the general popula- Motorcyclists are at a greater risk of death than tion) andto the mix of various types of injury in the automobile occupants, andit has been estimated ER caseload. For example, alcohol has been found that up to 50 percent of fatally injuredmotor- to have a higher prevalence in injuries resulting cyclists have a BAL of at least .10. Pedestrians from violence than from any other cause. In studies killedor injuredby motor vehicles have also been that have been restrictedto weekendevenings, foundmore likely to have been drinkingthan those when one wouldexpect a large proportion of the not involvedin such accidents.Estimates of 31 to population to be consuming alcohol, the proportion 44 percent of fatally injuredpedestrianswere of those testing positive for alcohol at the time of drinking at the time of the accident. According to ER admission has been found to be close to 50 Giesbrecht et al. (1989), 14 percent of fatal pedes- percent. In coroner studies, such as those con- trian accidents involved an intoxicated driver, but ducted by Haberman and Baden (1978), alcohol- 24 percent involvedan intoxicatedpedestrian. relatedfatalities were estimatedto account for about 43 percent of all unintentional injuries. HOME ACCIDENTS (However, the distinction between intentional and unintentional injury is not always readily apparent Among all nonfatal injuries occurring in the among victims of fatal injuries.) Studies that have home, an estimated22 to 30 percent involve alco- comparedestimatedBAC between fatal and hol, with 10 percent of those injuredhaving a BAL nonfatal injuries in the same geographic locality at the legally intoxicatedlevel at the time of the have foundhigher rates of positive BACs among accident. Coroner data suggest that alcohol con- fatal injuries (57%) comparedto nonfatal injuries sumption immediately before a fatal accident oc- (15%) (Cherpitel, 1996). It is well known that curs more often in deaths from falls and fires than many who drink also consume psychoactive drugs in motor vehicle deaths. ACCIDENTS AND INJURIES FROM ALCOHOL 9

Falls. Falls are the most common cause of non- in the UnitedStates, since drinkingon the job is not fatal injuries in the United States (accounting for a widespread or regular activity. Among work-re- over 60%) and the second leading cause of fatal latedfatalities, an estimated15 percent has been accidents, according to Baker, et al (1992). Alco- foundpositive for bloodalcohol, anda range of 1 to hol’s involvement in fatal falls has been found to 16 percent has been estimatedfor nonfatal injuries, range from 21 to 48 percent (with an average of according to Giesbrecht et al. (1989). 33%) according to Roizen; for nonfatal falls, alco- hol’s involvement has been estimatedfrom 17 to 53 VIOLENCE-RELATED TRAUMA percent (with an average of 30%). Alcohol may increase the likelihoodof a fall as much as sixty Both fatal andnonfatal injuries commonly result times in those well over the legal limit for intoxica- from violence, andthese injuries are more likely to tion, comparedwith those having no alcohol expo- be alcohol-relatedthan injuries from any other sure. cause, for men andfor women, regardlessof age. Fires and Burns. Fires andburns are the Such injuries are considered intentional and in- fourth leading cause of accidental death in the clude those nonfatal injuries resulting from assaults UnitedStates, accordingto Baker andco-workers. andfights, as well as fatal injuries from homicides Alcohol involvement has been estimatedin 12 to 83 andsuicides.Alcohol is more likely to be involved percent of these fatalities (with a median value of in fatal injuries from violence than in nonfatal inju- 46%), andbetween 0 and50 percent among ries treatedin an ER in the same geographic local- nonfatal burn injuries (with a median value of ity, anda positive BAC in nonfatal injuries among 17%). In a review of studies of burn victims, ER patients has been foundto range from 17 to 70 Hingson andHowland(1993) estimatedthat about percent (Cherpitel, 1993b). These figures refer to 50 percent of burn fatalities were intoxicatedand alcohol involvement among the victims of violence- that alcohol exposure is most frequent among vic- relatedevents, andlittle is known about the alcohol tims of fires causedby cigarettes. involvement of the perpetrator of such events, but the correlation is thought to also be high. ER pa- tients with violence-relatedinjuries are also more RECREATIONAL ACCIDENTS likely to be heavier drinkers and to report alcohol- Drownings. Drownings rank as the thirdlead- relatedproblems than those with injuries from ing cause of accidental death in the United States. other causes. Haberman andBaden(1978) reportedthat 68 per- cent of drowning victims had been drinking, but ALCOHOLISM VERSUS other estimates have rangedfrom 30 to 54 percent UNWISE DRINKING (with an average of 38%) (Hingson andHowland, 1993). Alcohol is consumedin relatively large The available literature on the role of alcoholism quantities by many of those involvedin water-rec- as opposedto unwise drinkingin injury occurrence reation (especially boating) activities, andstudies suggests that problem drinkers and those diag- suggest that those involvedin aquatic accidentsare nosedas alcoholics are at a greater risk of both fatal more likely to be intoxicatedthan those not in- andnonfatal injuries than those in the general pop- volvedin such accidents.In a review of the litera- ulation who may drink prior to an accident. Alco- ture on those who came close to drowning, Roizen holics andproblem drinkersare significantly more (1982) foundthat about 35 percent hadbeen likely to be drinking and to be drinking heavily drinking at the time. prior to an accident than others. Haberman and Baden (1978) found among fatalities from all causes that alcoholics andheavy drinkerswere WORK-RELATED ACCIDENTS more than twice as likely as nonproblem drinkers Alcohol’s involvement in work-relatedaccidents to have a BAL at the legal limit. Alcoholics have varies greatly by type of industry, but the propor- also been foundto experience higher rates of both tion of those testing positive for bloodalcohol fol- fatal andnonfatal accidents,even when sober. lowing a work-related accident is considerably Analysis of national mortality data found that those lower than for other kinds of injuries, particularly who died of injury drank more frequently and more 10 ACCIDENTS AND INJURIES FROM DRUGS

heavily than those who died of disease, and that CHERPITEL, C. J., ET AL. (1995). Alcohol andnon-fatal daily drinking, binge drinking (consuming 5 or injury in the U.S. general population: A risk function more drinks per occasion), and heavier drinking analysis. Accident Analysis and Prevention, 27, 651- (14 or more drinks per week) increased the likeli- 661. hood of injury as the underlying cause of death (Li CHERPITEL, C. J. (1993a). Alcohol andinjuries: A review et al., 1994). of international emergency room studies. Addiction, Data from the general U.S. population foundthe 88, 923-937. risk of injury increasedwith an average of one CHERPITEL, C. J. (1993b). What emergency room studies drink a day for both men and women, regardless of reveal about alcohol involvement in violence-related age. The risk of injury also increasedwith the fre- injuries. Alcohol Health and Research World, 17, quency of consuming five or more drinks a day 162-166. more often than twice a year (Cherpitel et al., CHERPITEL, C. J. (1988). Alcohol consumption andca- 1995). This suggests that the risk for injury may be sualties: A comparison of emergency room popula- increasedat relatively low levels of consumption, in tions. British Journal of Addiction, 83, 1299-1307. which case preventive efforts aimedat more mod- GIESBRECHT, N., ET AL. (Eds.) (1989). Drinking and ca- erate drinkers, who are greater in number, may sualties: Accidents, poisonings and violence in an in- have a larger impact on the reduction of alcohol- ternational perspective. London: Croom Helm. relatedaccidentsthan efforts focusedon heavier HABERMAN, P. W., & BADEN, M. M.(1978). Alcohol, other drinkers, who are fewer in number. drugs, and violent death. New York: OxfordUniver- Chronic alcohol abuse has long-term physiologic sity Press. andneurological effects that may increase the risk HINGSON, R., & HOWLAND, J.(1993). Alcohol andnon- of accidents. Chronic drinking also impairs liver traffic unintended injuries. Addiction, 88, 877-883. function, which plays an important part in injury KRUG, E. G., SHARMA,G.K.,&LOZANO, R.(2000). The recovery. A damaged liver compromises the im- global burden of injuries. American Journal of Public mune system, predisposing the alcoholic to bacte- Health, 90, 523-526. rial infections following injury. The risk of acciden- LI, G., SMITH, G. S., & BAKER, S. P. (1994). Drinking tal death has been estimated to be from three to behavior in relation to cause of death among US sixteen times greater for alcoholics than for nonal- adults. American Journal of Public Health, 84, 1402- coholics, with the highest risk being death from 1406. fires andburns. Haberman andBaden(1978) ROIZEN, J. (1982). Estimating alcohol involvement in se- rious events. In Alcohol consumption and related foundthat among all fatalities from fires, 34 per- problems. DHHS Publication no. ADM 8201190. cent were alcoholics. Washington, DC: U.S. Government Printing Office. U.S. DEPARTMENT OF HEALTH AND HUMAN SER- (SEE ALSO: Alcohol; Driving, Alcohol, and Drugs; VICES(1997). Ninth Special Report to the U.S. Con- Driving under the Influence; Industry and gress on Alcohol and Health. NIH Publication No. Workplace, Drug Use in; Social Costs of Alcohol 97-4017. and Drug Abuse) CHERYL J. CHERPITEL

BIBLIOGRAPHY

BAKER, S. P., O’NEILL,B.&KARPF, R. (1992). The injury ACCIDENTS AND INJURIES FROM fact book. Lexington, MA: Lexington Books. DRUGS Throughout history, humans have CHERPITEL, C. J. (1999). Substance use, injury, andrisk- taken substances other than foodinto their bodies taking dispositions in the general population. Alcohol- in ways that usually were socially accepted. The ism: Clinical and Experimental Research, 23, 121- most common form has been as medicine, in at- 126. tempts to change some feeling of ill-being or dis- CHERPITEL, C. J. (1996). Alcohol in fatal andnonfatal ease, such as PAIN, fatigue, or tension. Some cul- injuries: A comparison of coroner andemergency tures distinguish between socially approved and room data from the same county. Alcoholism: Clinical disapproved uses of substances by labeling those and Experimental Research, 20, 338-342. approved as ‘‘medicine’’ and those disapproved as ACCIDENTS AND INJURIES FROM DRUGS 11

‘‘drugs.’’ Although the word medicine derives from a Latin wordmeaning ‘‘of a physician,’’ through- out much of recorded history and even today, ‘‘folk’’ medicine and ‘‘home remedies’’ are widely practiced. Early medicines were taken exclusively from nature, andP LANTS are still an important source of medicinal products (e.g., foxglove for heart problems, breadmoldfor penicillin). Organic HALLUCINOGENIC substances (plants with perception-altering properties, such as peyote andmescaline, andfungi, such as psilocybin mush- rooms) have been usedin various cultures in the context of religious rituals, with the dramatic visual andaural hallucinations inducedbeing interpreted in spiritual terms. Intoxicating beverages (with al- cohol and/or other drugs) also have a long history of use, usually recreationally (i.e., for their relaxing anddisinhibitingeffects in social situations), but sometimes also for supposedmedicinalpurposes, as in elixirs andtonics that were marketedas patent medicines in the United States in the late 1800s and early 1900s. With the development of modern chemistry and scientific growing methods, there has been an in- crease in the number, types, andstrength of both organically derived (principally MARIJUANA) and chemically synthesized(laboratory-created)sub- stances, which has promptedthe implementation of measures to regulate their processing or manufac- An ambulance crew unloads a patient at the ture, distribution, and dispensing (by pharmacists emergency room entrance at Beth Israel andphysicians). In the UnitedStates, this regula- Hospital, New York City. In 1995, there were tory scheme is calledthe FederalC ONTROLLED SUB- 531,800 drug-related visits to U.S. hospital STANCES ACT (Public Law 91-513, H.R. 18583, emergency rooms; more than half were due to October 27, 1970). This act, which is regularly drug overdoses. ( EdEckstein/CORBIS) updated, classifies substances into five categories according to the potential for abuse, accepted med- There have been increases since the mid-1960s ical effectiveness anduse, andpotential for creating in both substance abuse andpublic awareness of it. physiological or psychological dependence. The Here the emphasis will be on an aspect of substance ControlledSubstances Act is the basis for federal and state drug laws that specify the conditions abuse—the unintended, negative consequences— making specific substances illicit (illegal) drugs and that is relatively well known to researchers but less define differential criminal penalties for their man- familiar to the general public andtheir representa- ufacture, distribution, sale, and possession. Sub- tives in government. stance abuse, for the purposes of this discussion, is defined as the use of illicit drugs, the misuse of UNINTENDED AND medicines (particularly those which must be pre- NEGATIVE CONSEQUENCES scribedby physicians but also those which are available OVER THE COUNTER). Accidents and inju- Data do not exist to document in a comprehen- ries from the excessive or prohibited(e.g., sive or detailed manner the extent to which the underage) use of other legal drugs, such as alco- negative consequences of substance abuse exist holic beverages, are not included here. worldwide, for specific nations (including the 12 ACCIDENTS AND INJURIES FROM DRUGS

UnitedStates), or for given states or cities. Conse- cesses) where medications and/or drugs are the quently, I have chosen to present mainly summary means chosen. information that is basedon the best evidence Chronic Drug-Caused Problems. available rather than partial statistical data of Intravenous drug users can suffer from chronic questionable accuracy, which wouldsoon be out cardiovascular problems that may be primarily at- of date. tributable to infections anddamagefrom The following discussion is divided into four cat- ‘‘fillers’’—talcum powder, cornstarch, or baking egories of drug problems; acute, chronic, drug- soda added to drugs to increase volume, unit sales, caused, and drug-related. Acute problems are de- andprofits—that have been injected.Some fined as those which usually occur suddenly and drugs—especially the DESIGNER DRUGS, where an often can be remedied in a relatively short time. easily added molecule can produce a deadly variant Chronic problems typically have a relatively grad- of the intended substance—are neurotropic/neuro- ual onset andtendto persist, sometimes indefi- pathic (have an affinity for and do damage to nerve nitely. Drug-causedproblems, for the purposes of endings and tissue). Researchers and clinicians are this discussion, are defined as those which have an studying and treating individuals who are afflicted obvious and/or demonstrated direct causal connec- with Parkinson’s disease caused by such ‘‘party’’ tion between the use of a substance anda negative drugs. effect. In drug-related problems, negative out- One chronic drug-caused problem is particularly comes result from drug-diminished capacities and tragic because the individuals most damaged are their effects on user behaviors. totally innocent anddefenselessagainst the sub- Acute Drug-Caused Problems. The National stances that can cause them permanent disabilities or even death. I refer here to teratogenic drug use Institute on Drug Abuse’s DRUG ABUSE WARNING (use by pregnant women that causes abnormal fetal NETWORK (DAWN) estimates that alcohol-in-com- development). bination (alcohol usedwith another drug,the crite- When the use of CRACK-cocaine exploded in the rion for reporting this substance to DAWN) repre- mid-1980s, fetal developmental damage resem- sents the most frequently reportedcategory in bling FETAL ALCOHOL SYNDROME began to be noted drug-related hospital emergency department visits. among infants born to women who hadusedthis ‘‘Other drugs’’ (illicit drugs, accidentally mis- drug during the pregnancy. Although accurate used, and intentionally abused legal medications) counts are difficult to obtain, estimates cited in a collectively represent an acute drug-caused prob- 1990 government report—which are not basedon lem that may equal or surpass ALCOHOL in this representative national samples—range from category. The DAWN system is the best source of 100,000 infants annually exposedto cocaine alone documentation of these problems, capturing data to as many as 375,000 annually exposedto drugsin on substance abusers who come or are brought to general; more recent research, however, produced hospital emergency departments, particularly for much lower estimates. negative and/or unexpected reactions. These cases Acute Drug-Related Problems. Acute drug- are usually thought of as overdoses, attributable to relatedproblems are typifiedby physical trauma; (a) tolerance effects (the needto use increasingly because of inebriation- or intoxication-impaired larger doses to achieve the same PSYCHOACTIVE judgment or motor control/coordination, sub- effects). (b) inexperiencedusers with panic reac- stance-abusing individuals can and do accidentally tions, or (c) the use of a substance of greater injure themselves. strength than intended or expected. There also is Common examples in this category are acciden- increasing evidence that users of some drugs, such tal weapon dischargesandmotor vehicle andboat- as COCAINE, can experience medical emergencies ing accidents; drownings, falls, and electrocutions and deaths from seizure disorders and allergic reac- are less common but not rare. tions. This is true not only for first-time users but Even more unfortunate are instances where also experiencedusers at their regular (andsome- others—clean andsober—are injuredor killedby times low) dosage levels. Other frequently noted the impairedsubstance abuser. (These cases often hospital emergency department (and medical ex- go unnoted; for example, DAWN records only cases aminer) cases involve SUICIDE ATTEMPTS (andsuc- where the injured or deceased had drugs ‘‘on ACCIDENTS AND INJURIES FROM DRUGS 13 board.’’) In addition to the types of accidental inju- well include legal substances that are abused by ries noted immediately above, there are anecdotal inhalation, such as gasoline, airplane glue, andvar- (verbally reported but not documented) accounts ious solvents, which are mundane but widely which suggest that spouses, children, other rela- used—especially in economically depressed areas tives, and friends often are the victims of drug- of the UnitedStates andin developingnations. impaired individuals. With diminished emotional These are very harmful to lungs andbrain cells, control, inhibitions, andjudgment, substance and are often deadly. abusers often inflict physical trauma (e.g., gunshot, Marijuana. The smoking of marijuana, prob- blunt force, or penetrating injuries) in chance en- ably the most widely used illicit drug, may well counters with strangers (other drivers, business- have more serious acute andchronic consequences people), in disputes with coworkers or friends, in than once thought. Recent andcontinuing research domestic disputes, or in physical abuse of their is casting new light on the chronic health risks children. Moreover, analysis by Brookoff and his posedby marijuana smoking, contradictingthe colleagues (1993) conclude that DAWN reporting conventional wisdom that it is less harmful than procedures seriously underreport drug-involved either drinking alcoholic beverages or smoking to- emergency department cases, especially those with bacco. For example, it is reportedthat three times serious trauma. the tar is delivered (and four times more is depos- Chronic Drug-Related Problems. Some of ited) to the mouth and lungs per puff from a mari- the most common chronic drug-related problems juana joint than from a filter-tippedcigarette. are similar to those resulting from in utero exposure Smoking marijuana also produces up to five times of fetuses to cocaine andother development-im- more carbon monoxide in the user’s blood than pairing substances, in that severe illness anddeath does tobacco. Knowledge is also being accumulated are frequently involvedandindividualsother than regarding the specific health-damaging mecha- the users themselves are victims. This class of drug- nisms from the 426 known chemicals containedin relatedproblems is most closely associatedwith Cannabis sativa (which are transformedinto over injecting drug use because the category is defined 2,000 when ignited). by infectious diseases that can be transmitted via Among the pertinent facts already established is sharing of unsanitized hypodermic needles. The that 70 of these chemicals are fat-soluble andaccu- most deadly infectious agent spread in this manner mulate in fatty body tissue, notably the brain, is the HUMAN IMMUNODEFICIENCY VIRUS (HIV), lungs, liver, andreproductiveorgans. This repre- which causes ACQUIRED IMMUNODEFICIENCY SYN- sents a persistence-of-residue effect in which por- DROME (AIDS). Another potentially deadly infec- tions of THC (delta-9-TETRAHYDROCANNABINOL), tion spreadin this manner is the liver diseasehepa- the most potent psychoactive chemical in mari- titis B. Various sexually transmitteddiseases juana, not only remain in the body (and are thus (including AIDS, syphilis, and gonorrhea), as well detectable) for several weeks following use, but also as tuberculosis, are among the other debilitating accumulate with repeateduse. This THC buildupis andoften fatal diseasesthat are chronic problems particularly noteworthy when one considers that relatedto substance abuse. the potency (THC content) of marijuana has in- creaseddramaticallysince the 1960s, when the average potency was about 0.2 percent. DRUG-SPECIFIC NEGATIVE Regular marijuana smoking can contribute to CONSEQUENCES emotional andother behaviorally definedmental- Discussion in this section is limitedto the specific health problems through degraded interpersonal negative consequences of a few of the most preva- relationships andarresteddevelopment.The mech- lent illicit drugs: marijuana, cocaine, and heroin. anism for this seems to be a drug-induced percep- Other illicit substances that couldhave been dis- tion of well-being andproblem abatement that may cussedhere includeL YSERGIC ACID DIETHYLAMIDE not reflect reality andcontributes to avoidance (LSD), PHENCYCLIDINE (PCP), andother ‘‘alpha- rather than coping with life situations. bet’’ or ‘‘designer’’ drugs (‘‘ecstacy,’’ etc.), Research findings from the 1980s and 1990s AMPHETAMINE, andM ETHAMPHETAMINE (andits highlight a marijuana health risk that is largely smokable form, ‘‘ice’’). This discussion also could unmeasuredbut may be much greater than gener- 14 ACCIDENTS AND INJURIES FROM DRUGS ally considered. Researchers examined blood sam- exhausted. In the study of reckless drivers noted ples from over 1,000 individuals brought to a hos- earlier, 25 percent testedpositive for cocaine. pital trauma unit with severe injuries. Two-thirds The risk of infection with HIV andother sexu- of these individuals had accidental injuries associ- ally transmitteddiseasesis high among compulsive atedwith the operation of motor vehicles (drivers, cocaine users, particularly female crack users. Of- passengers, andpedestriansinjuredby cars, trucks, ten forsaking socially acceptable means of earning or motorcycles). Using a bloodtest that normally income, they live an existence that revolves around ceases to detect THC around 4 hours after use, the crack use. Many maintain their crack supply by researchers foundabout 34 percent of these acci- repeatedly selling or trading their sexual services, dent victims had psychoactive levels of THC in with each unprotectedsexual contact increasing the their bloodwhen they arrivedat the hospital. A chance that they will have an HIV-infectedpartner. more recent study found that 45 percent stopped Other manifestations of negative effects of co- for reckless driving tested positive for marijuana. caine abuse include hyperstimulation; digestive Given that there currently are no simple, legally disorders, nausea, loss of appetite and weight; tooth recognizedtests to detectmarijuana use, the extent erosion; nasal mucous membrane erosion, includ- of marijuana-relatedvehicular injuries anddeaths ing perforations of the nasal septum (holes in the is an unknown but potentially sizable statistic. membrane separating the nostrils); cardiac irregu- Cocaine. Many readers undoubtedly have larities; stroke (from vascular constriction); con- heardthat SigmundF REUD, the famous Viennese vulsions (especially among individuals prone to sei- psychoanalyst, was an aviduser andproponent of zure disorders); and paranoid psychoses and cocaine. The initial account of his observations of delusions of persecution. Cocaine is a notoriously the drug’s effects for himself and some of his pa- fickle drug—some experts say it behaves as though tients indeed was glowing. It was translated from it belongs in other pharmacological categories be- German andreprintedin an American medical sides stimulant. A highly publicized case was the journal in the mid-1880s, thus popularizing the 1986 cocaine-induced death of the athlete Len drug in the United States and prompting its incor- Bias, who reportedly was a first-time user of a small poration into products from patent medicines to amount. In addition, research indicates that the soft drinks. Less well reported is the fact that Freud concurrent use of cocaine andalcohol (a common andhis colleagues haddiscoveredthe significant practice) produces a new, liver-and brain-accumu- negative effects of cocaine by the endof that same lating and -damaging drug (COCA-ETHYLENE) decade and had withdrawn their support for its within the user’s body. It is implicated in puzzling applications in medical therapy. low-dosage ‘‘excited delirium’’ fatalities and in- Cocaine has hadseveral periodsof popularity in creased mortality risks for individuals with existing the UnitedStates as a drugof abuse, with the most heart problems. recent beginning in the early 1980s. Toutedas a Some of the fetal damage from maternal cocaine safe, nonaddicting, recreational drug, cocaine hy- use occurs because cocaine is a vasoconstrictor, a drochloride (in powder form) was ‘‘snorted’’ (in- useful characteristic for topical application in deli- haled) by millions who liked the absence of hypo- cate medical procedures, such as eye surgery, but a dermic needles, the lack of lung-cancer risk, and decided negative as it concerns the placenta of a the rapidhigh, with its feelings of alertness, wit- pregnant woman. The restriction of bloodflow tiness, andsexual prowess. through the placenta limits nutrients andoxygen to Unfortunately, cocaine users often progress from the fetus, leading to retarded growth and develop- casual to compulsive patterns of use. The grandiose ment of vital organs. Heavy cocaine use during perceptions of heightenedmental andphysical pregnancy also can cause spontaneous abortion, abilities inevitably wane (typically within 20 min- andanecdotalreports of cocaine being usedinten- utes following use), andthe resulting dysphoria tionally for this purpose are not uncommon. Pre- (opposite of euphoria) is so markedin contrast that mature separation of the placenta from the uterus, it resembles depression. Trying to relieve the de- another common medical complication among co- pression andregain the euphoria, cocaine abusers caine-using pregnant women, results in either a repeat this cycle over long periods (called binges) premature birth or a stillbirth. Surviving infants until their supplies, resources, and/or stamina are usually have low (sometimes very low) birth- ACCIDENTS AND INJURIES FROM DRUGS 15 weights, andlow birthweight itself increases risk Gerstein andHarwood(1990) produceda set of for a variety of problems. Cocaine-exposedunder- estimatedsocietal E CONOMIC COSTS of the illicit weight newborns have been documented to be at drug problem in the United States totaling 71.9 greater risk for stroke andrespiratory ailments, billion dollars. This total is broken down into cate- and at much greater risk for sudden infant death gories; almost half ($33.3 billion) of the total esti- syndrome (SIDS or crib death). Research studies matedcosts was attributedto productivitylosses are being conducted to confirm anecdotal and pre- resulting from substance-abuse-impairedworkers. liminary studies that indicate higher rates of re- More than half of the total estimatedcost was at- tarded emotional, motor, and cognitive develop- tributedto the criminal aspects of drugabuse ($5.5 ment, including ATTENTION DEFICIT DISORDERS, billion to tangible losses to crime victims; $12.8 among such children entering school. billion to law enforcement; $17.6 billion to lost Heroin. Paradoxically, the negative direct economic productivity because of time spent in physiological consequences to the user that are at- crime or in prison). A minor portion of the esti- tributable to heroin itself are less than from the use matedcosts was assignedto drugprevention and of tobacco, alcohol, cocaine, or many prescription treatment ($1.7 billion) anddrug-relatedAIDS drugs. This does not mean that heroin is a drug ($1.0). whose use is without negative consequences, how- The Gerstein andHarwoodestimate is an up- ever. Heroin is highly addictive, and once its cen- date incorporating ‘‘a number of statistical updates tral nervous system depressive effects wear off, andrevisions’’ of a similar estimate for 1980 (typically in 4 to 6 hours), users tendcompulsively (Harwoodet al., 1984), which totaled$46.9 billion to seek sources andmeans for another ‘‘hit.’’ This dollars. often leads to socially unproductive, self-neglectful Rice et al. (1990) produced what is probably the lifestyles, not uncommonly involvedwith income- most authoritative work currently available on this producing crime committed to maintain the addic- topic: The Economic Costs of Alcohol and Drug tion. Fetuses exposedto heroin from their mothers’ Abuse and Mental Illness: 1985. Among the multi- use during pregnancy suffer many of the same neg- ple objectives of the study were the following: to ative effects as those exposedto cocaine. estimate as precisely as possible the economic costs In addition, heroin users frequently experience to society of alcohol abuse, drug abuse, and mental negative reactions andoverdoses because of illness (ADM) for 1985, the most recent year for TOLERANCE effects, since the drug purity and type which reliable data were available; to update previ- of filler may vary widely among dealers. Often, they ous cost estimates, using new data sources and a are unknown with certainty by the user. However, revised methodology; and to develop an improved the greatest threat to current heroin users’ health approach to deal with the issues of COMORBIDITY and lives undoubtedly stems from the risks of hepa- (the tendency for cases to overlap, that is, for indi- titis andHIV infection from sharing contaminated viduals to have problems in more than one ADM hypodermic syringes and needles. Their risks of category). Briefly, Rice et al. produced ADM cost infection with HIV andother diseasesthrough sex- estimates for 1980, 1985, and1988. Estimated ual activity are elevatedin ways similar to those costs for illicit drug problems (in billions of dollars) described for cocaine users. The risks of fetal HIV were 1980, 46.9; 1985, 44.1; 1988, 58.3. infection among pregnant heroin-using women is Their cost estimates are considered to be the best also increasedbecause of their own needleuse and available, but even the analysts who produced the likelihoodthat they have hadat least one intra- them will readily agree that they are probably not venous-drug-using sexual partner. very precise. It is probable, in my opinion, that the health andsocial care costs for AIDS-infecteddrug abusers is underestimated even for the years ad- ECONOMIC COSTS OF dressed, and are undoubtedly significantly higher SUBSTANCE ABUSE in the new millenium. Similarly, health andsocial Numerous studies designed to estimate the cost service costs for infants andchildrenwho have or burden of drug abuse were conducted in recent suffered prenatal exposure to drugs undoubtedly years. This presentation will focus on two of the have mushroomedsince 1985, the approximate be- most recent andauthoritative reports. ginning of the crack-cocaine epidemic (these costs 16 ACETALDEHYDE couldbecome astronomical if the worst fears re- choline was shown to be the general neurotransmit- garding permanent learning disabilities are con- ter for the neuromuscular junctions. In all verte- firmed). brate species, it is the major neurotransmitter for all autonomic ganglia andthe neurotransmitter be- (SEE ALSO: Accidents and Injuries from Alcohol; tween parasympathetic ganglia andtheir target Alcohol: History of Drinking; Dover’s Powder; Driv- cells. Acetylcholine neurotransmission occurs ing, Alcohol, and Drugs; Fetus: Effects of Drugs on; widely within the central nervous system. Collec- Social Costs of Alcohol and Drug Abuse) tions of NEURONS arising within the brain—the medulla, the pons, or the anterior diencephalon— BIBLIOGRAPHY innervate a wide set of cortical and subcortical targets; some of these circuits are destroyed in Alz- BROOKOFF, D., CAMPBELL, E. A., & SHAW, L. M. (1993). heimer’s disease. The underreporting of cocaine-related trauma: Drug Abuse Warning Network reports vs. hospital toxicol- (SEE ALSO: Scopolomine and Atropine) ogy tests. American Journal of Public Health, 83 (March), 369. BIBLIOGRAPHY BROOKOFF, D., COOK, C. S., WILLIAMS, C., & MANN,C.S. (1994). Testing reckless drivers for cocaine and mari- COOPER, J. R., BLOOM, F. E., & ROTH, R. H. (1996). The juana. New England Journal of Medicine, 331 (Au- biochemical basis of neuropharmacology, 7th ed. gust), 518. New York: OxfordUniversity Press. GERSTEIN, D. R., & HARWOOD,H.J.(EDS.). (1990). FLOYD BLOOM Treating drug problems, vol. 1. Washington, DC: Na- tional Academy Press. HARWOOD, H. J., NAPOLITANO, D. M., KRISTIANSEN, P., & ACETYLMETHADOL See L-Alpha- COLLINS, J. J. (1984). Economic costs to society of al- Acetylmethadol (LAAM) cohol and drug abuse and mental illness: 1980. Re- search Triangle Park, NC: Research Triangle Insti- tute. RICE, D. P., KELMAN, S., MILLER, L. S., & DUNMEYER,S. ACID See Lysergic AcidDiethylamide(LSD) (EDS.). (1990). The economic costs of alcohol and andPsychedelics;Slang andJargon drug abuse and mental illness: 1985. San Francisco: Institute for Health andAging. JAMES E. RIVERS ACUPUNCTURE See Treatment Types: Acupuncture

ACETALDEHYDE See Complications: Liver (Alcohol), Disulfuram ADAMHA See Treatment, History of

ACETAMINOPHEN See Analgesic; Drug ADDICT See Addiction; Concepts and Defi- Metabolism; Pain, Drugs Usedfor nitions

ACETYLCHOLINE Acetylcholine (ACh) is ADDICTED BABIES Technically, the term a major NEUROTRANSMITTER in the central andpe- addicted babies shouldrefer to infants who are ripheral nervous systems. It is the ester of acetate born passively physically dependent on drugs. In andcholine, formedby the enzyme choline acetyl- practice, it is usedto refer to all babies extensively transferase, from choline andacetyl-CoA. This was exposed to drugs before birth. According to a recent the first substance (ca. 1906) to meet the criteria of federal government report estimated that in the identification for a neurotransmitter. Later, acetyl- UnitedStates each year some 320,000 babies are ADDICTED BABIES 17 born exposedto alcohol andillicit drugswhile in MANAGEMENT the uterus; a far larger number have been exposed, A thorough alcohol anddrughistory shouldbe in utero to sedatives and nicotine. The increased obtainedfrom the expectant mother—andthis recognition of such drug-exposed babies parallels shouldbe corroboratedby testing the urine of both the dramatic increase in drug use, both licit and mother andnewborn for alcohol andother drugs. illicit, by women since the beginning of the 1970s. Newborns shouldbe closely monitoredfor signs of Drug-addicted women often use multiple sub- withdrawal for a minimum of forty-eight to sev- stances—including ALCOHOL,NICOTINE,MARI- enty-two hours, andlonger when the mother has JUANA,TRANQUILIZERS,COCAINE, andO PIOIDS been on METHADONE-maintenance treatment. (e.g., HEROIN andM ETHADONE). The drugs are car- Since symptoms of withdrawal are nonspecific and riedacross the placenta from mother to fetus. The may be confusedwith a variety of infections or clinical presentation of the newborn (neonate) de- metabolic disturbances, a search for concurrent ill- pends on the substance, the amount and frequency ness to explain any symptoms is mandatory. usedduringpregnancy, andthe time since last use. Most hospital nurseries use a standardized neo- Withdrawal will occur in 55 to 94 percent of infants natal abstinence-syndrome scoring system. After exposedto heroin andother opioids.Infants of the infant is born the hospital will monitor their regular heavy users usually have a low birth sleep habits, temperature, andweight. The earliest weight, because of intrauterine growth retardation withdrawal symptoms are treated by intravenous andfrequent premature births. fluids, swaddling, holding, rocking, a low-stimula- If the mother has used a large dose of depressant tion environment, andsmall feedingsof hyper- drug (alcohol, any number of sedative-hypnotics, caloric formula—for weight gain. If symptoms con- or heroin) immediately before delivery, the neonate tinue or increase, medication may be initiated. may have respiratory depression and may require Common medications include PAREGORIC (cam- resuscitation. If the mother has usedone of these phoratedtincture of opium), or Phenobarbital for drugs regularly during pregnancy, there may be a opioidwithdrawal;P HENOBARBITAL or DIAZEPAM neonatal abstinence or withdrawal syndrome, for alcohol withdrawal. Diazepam is also used to which has as key features irritability, tremor, and help with cocaine hyper excitability. increasedmuscle tone. Other symptoms include Interviewing the mother is essential in reviewing poor nervous system irritability, gastrointestinal the anticipatedhome environment. Unfortunately, disorders that lead to poor feeding, vomiting, and addicted babies are often at high risk for either diarrhea; high-pitched cry; difficulty in sleeping; abuse or neglect or both. Normal maternal-infant andsneezing, sweating, yawning, nasal stuffiness, bonding is difficult in the case of an irritable poorly rapidbreathing, andseizures. Withdrawalfrom responding neonate and a mother dealing with the heroin generally occurs within forty-eight hours of guilt, low self-esteem, poverty, inadequate housing, birth, but it can be somewhat delayed with the andan abusive or absent partner or parent, which longer-acting methadone. Alcohol-exposed infants often accompany her own drug addiction. A refer- may develop a very similar withdrawal syndrome, ral to childprotection services may therefore be except with the more frequent occurrence of sei- indicated. zures. Cocaine, a stimulant, constricts bloodvessels, OUTCOME thereby decreasing oxygen delivery to the fetus. Consequently, neonatal stroke has occurred. Al- Some studies have indicated that addicted though cocaine withdrawal symptoms have been babies have an increasedrisk for breathing abnor- reportedin neonates, they probably reflect acute malities and sudden infant death syndrome (SIDS). cocaine intoxication when the mother’s last use was Many studies of opioid-exposed children up to close to the time of birth. Such infants often appear school age show few differences from nonexposed less alert andless responsive to external stimuli children of a similarly disadvantaged environment. than noncocaine-affectednewborns, which may According to a study conducted by the Society for represent true withdrawal—comparable to the Maternal-Feral Medicine, children who were ex- so-calledcrash seen in adults. posedto cocaine in utero are 2.4 times more likely 18 ADDICTION to have language problems than children not ex- Society for the Study and Cure of Inebriety. The posedto cocaine. The outcome for babies with pre- boundvolumes providea unique perspective on the natal alcohol exposure depends on the extent of the historical development of clinical practice, policy damage to the fetus born with FETAL ALCOHOL debates, and the emergence of a scientific tradition. SYNDROME (FAS). Addiction is today among the most international of The drug-addicted mother’s lifestyle is often journals focusing on addiction. In addition to pub- characterizedby inadequateor no prenatal care, lishing refereedresearch reports, editorialpolicy poor nutrition, andprostitution, any or all of which has been directed at establishing it as a leading may result in a high risk for medical and obstetrical forum for informeddebate—specially commis- complications. Needle use may result in infection sioned‘‘commentary’’ series contribute to this pur- with hepatitis B andHIV. Methadone-maintenance pose. The prestigious Addiction Book Prize is programs for heroin-addicted mothers generally awarded annually. In furtherance of its role as an offer medical and social services to help mitigate international medium of scientific exchange, the these negative influences andcontribute to the im- journal, which has its headoffice in Britain, in 1993 provedoutcome seen in their babies, despitea con- establishedregional offices in the UnitedStates and tinuation of opioid drug addiction on their part. Australia. Drug WITHDRAWAL, in the absence of other GRIFFITH EDWARDS problems, is now readily managed in hospitals. The outcome for addicted babies depends on any per- manent medical sequelae as well as the quality of ADDICTION RESEARCH UNIT (ARU) the postnatal environment. These babies often re- (U.K.) The Addiction Research Unit of the Insti- quire ongoing medical, school, and social services tute of Psychiatry, University of London, was set to ensure that they reach their maximal potential. up in 1967 on the Joint Maudsley Hospital/Insti- tute of Psychiatry campus in Camberwell, South (SEE ALSO: Fetus, Effects of Drugs on; Pregnancy East London, England. Its funding has come from and Drug Dependence) many different sources (principally the Medical Re- search Council), but its fundamental identity has always been that of a university center, which has BIBLIOGRAPHY close ties andvaluedlinks with a postgraduatepsy- CHASNOFF, I. J. (Ed.). (1988). Drugs, alcohol, pregnancy chiatric medical school (the Institute) and a teach- and parenting. Boston: Kluwer Academic Publishers. ing hospital (the Maudsley). Its present scientific COOK,P.SHANNON,PETERSEN, R. C., & MOORE,D.T. staff number thirty, with the mix of psychiatrists, (1990). Alcohol, tobacco, and other drugs may harm psychologists, statisticians, andsocial scientists re- the unborn. DHHS Publication no. (ADM)90-1711. flecting the ARU’s interdisciplinary commitment. Rockville, MD: U.S. Department of Health andHu- The ARU’s fieldof studyembraces T OBACCO as well man Services. as ALCOHOL andother drugs. JOHNSON,KATE. (2000). Prenatal Cigarette, Cocaine Ex- The ready access to hospital facilities has, over posure Tiedto Language Problems. OB GYN News, the years, greatly aided the ARU’s ability to con- 35, 13. duct clinical research. One line of investigation LESTER,BARRY. (2000). Drug-addicted Mothers Need continuously developed from this base has, for ex- Treatment, Not Punishment. Alcoholism & Drug ample, concentrated on definition, description, Abuse Weekly, 12,5. measurement, and validation of the dependence- syndrome concept—in relation to both alcohol and JOYCE F. SCHNEIDERMAN opiates. The Smoking Section has done much to REVISED BY SHEILA DOW demonstrate that the cigarette habit is indeed nic- otine dependence. A sustained effort has also been directed at the development of methods for assess- ADDICTION (formerly the British Journal of ing treatment efficacy through controlledtrials. As Addictions) is the oldest specialist journal in its regards both alcohol dependence and smoking, re- field, originating in 1884 as the Proceedings for the sults have generally tended to support research in ADDICTION SEVERITY INDEX (ASI) 19 fairly simple, minimalist interventions, often de- lar area (200 questions on 7 subscales). Developed liveredin the primary-care setting. Another line of by McLellan andcoworkers in 1981, the ASI has research has focusedon long-term follow-up stud- been translatedinto seventeen languages— ies andthe determinantsof ‘‘natural history and Japanese, French, Spanish, German, Dutch, and career.’’ Russian among them—and was designed to be ad- If the above paragraph identifies some of the ministeredby a technician or counselor. Consistent ARU’s core activities, much else has also gone on. guidelines for each question on the ASI have been For example, the ARU, for a number of years, compiled in training materials including two videos employeda professional historian, who didmuch to andthree instructional manuals. Self-training can open up an understanding of the history of opiate be accomplishedby using the videoalong with the use in Britain. Epidemiological research has at administration manual, although a one-day formal times been undertaken. As of the 1990s, the ARU training seminar is recommended. (Since the in- has been developing a computerized method for strument is in the public domain, there is no charge handling interview texts. In the psychophysiologi- for it; only a minor fee is chargedfor copies of the cal laboratories, studies of cue responsiveness are administration materials and the computer scoring being conducted with patients and normal subjects. disk.) A new line of research is focusing on the relation- The interview is based on the idea that addiction ship between the two axes of problems anddepen- to drugs or alcohol is best considered in terms of the dence. The Smoking Section has contributed to life events that preceded, occurred at the same time studies on the impact of passive smoking. as, or resultedfrom the substance-abuse problem. Besides the research, a great deal of clinical and The ASI focuses on seven functional areas, or research training is being undertaken, and the ARU subscales, that have been widely shown to be affec- runs a full-time one-year course leading to a Master tedby the substance abuse: medicalstatus, em- of Science (MSc) in clinical andpublic health as- ployment andsupport, druguse, alcohol use, legal pects of addiction. The ARU enjoys the benefits of status, family andsocial status, andpsychiatric sta- an extensive national andinternational network of tus. Each of these areas is examined individually by friendships and professional contacts through its collecting information regarding the frequency, du- many former staff and students who today hold ration, andseverity of symptoms of problems both influential positions. There are particularly strong historically over the course of the patient’s lifetime links with the developing world, and support has and more recently during the thirty days prior to often been given by the ARU to the WorldHealth the interview. Within each of the problem areas, Organization. the ASI provides both a 10-point, interviewer-de- In April 1991, the ARU movedto a purpose- terminedseverity rating of lifetime problems as built office andlaboratory accommodationon the well as a multi-item composite score (computer- same campus, andit became associatedwith the calculated) that indicates the severity of the prob- newly established National Addiction Centre. The lems in the past thirty days. ARU’s Smoking Section has also been strengthened The ASI is widely used clinically for assessing by involvement with the recently established substance-abuse patients at the time of their ad- Health Behaviour Research Unit, funded by the mission for treatment. It takes about an hour to Imperial Cancer Research Fund. gather the basic information that forms the first GRIFFITH EDWARDS step in the development of a patient profile for subsequent use by the staff in planning treatment. Researchers have foundthe ASI useful because the ADDICTION SEVERITY INDEX (ASI) composite scores and the individual variables can This is a semistructuredinterview designedto pro- be comparedwithin groups over time as a measure vide important information about aspects of the life of improvement, or between groups of patients at a of patients that may contribute to their substance- posttreatment follow-up point as a measure of out- abuse problems. The Addiction Severity Index come of treatment. The ASI has shown excellent (ASI) provides a general overview of substance- reliability andvalidityacross a range of types of abuse problems rather than a focus on one particu- patients andtreatment settings in this country and 20 ADDICTION SEVERITY INDEX (ASI)

abroad, although reliability in patients with severe BALL, J. C., ET AL. (1986). Medical services provided to mental illness varies considerably. 2,394 patients at methadone programs in three states. The ASI is particularly useful in the diagnosis Journal of Substance Abuse Treatment, 3, 203–209. andtreatment of alcohol problems. It providesin- CAREY,K.B,ET AL. Reliability and validity of the addi- formation on the frequency, duration, and intensity tion severity index among outpatients with severe of alcohol anddruguse. The ASI also examines mental illness. Psychological Assessment, December psychosocial functioning (medical, legal, employ- 1997, 422. ment, psychological, andsocial/family), which is HALL, G. W., ET AL. Pathological Gambling Among Co- crucial to understanding alcohol dependency. The caine-Dependent Outpatients. American Journal of ASI is also a cost-effective alternative for the as[- Psychiatry, 157, July 2000, 1127. fj]sessment of alcohol problems—when compared HENDRICKS, V. M. (1989). The Addiction Severity Index: to the StructuredClinical Interview for DSM-III-R Reliability and validity in a Dutch addict population. (SCID), a more formal andmore expensive Journal of Substance Abuse Treatment. approach. KOSTEN, T. R., ROUNSAVILLE, B., & KLEBER,H.D. The ASI has been used in many studies, includ- (1983). Concurrent validity of the Addiction Severity ing one in the late 1990s, involving cocaine-depen- Index. Journal of Nervous & Mental Disease, 171, dent pathological gamblers. This particular study 606–610. usedthe ASI to determinesocioeconomic charac- LAPORTE, D., ET AL. (1981). Treatment response in psy- teristics of the subjects. Another late-1990s study chiatrically impaireddrugabusers. Comprehensive (involving methadone patients) used results of the Psychiatry, 22(4), 411–419. ASI in comparison with criminal history andper- MCLELLAN, A. T., ET AL. (1992). The fifth edition of the sonality traits to support the idea that antisocial Addiction Severity Index: Cautions, additions and behavior is more than just a personality disorder. In normative data. Journal of Substance Abuse Treat- 2000, the outcome of a study on cocaine depen- ment, 9(5), 461–480. dents illustrated, by comparing Spielberger State- MCLELLAN, A. T., ET AL. L. Harris (Ed.) (1991). Using Trait Anxiety Inventory andthe Alcohol Composite the ASI to compare cocaine, alcohol, opiate andmixed Index of the ASI, that high anxiety scores decrease substance abusers. Problems of drug dependence with time, regardless of clinical management. 1990 (NIDA Research Monograph). Washington, DC: To further increase the usefulness of the ASI, U.S. Government Printing Office. clinicians and researchers have added questions to MCLELLAN, A. T., ET AL. (1985). New data from the supplement the ‘‘old’’ version, including questions Addiction Severity Index: Reliability and validity in about leisure time activities, childhood religion, three centers. Journal of Nervous and Mental Disease, childhood illnesses, age of first drug/alcohol use, 172, 84–91. sexual orientation, and military service. The addi- MCLELLAN, A. T., ET AL. (1983). Increasedeffectiveness tion of these questions is thought to supplement the of substance abuse treatment: A prospective study of already-sought information, since much of the im- patient-treatment ‘‘matching.’’ Journal of Nervous petus for these questions is from those who admin- and Mental Disease, 171(10), 597–605. istrate the ASI and deal directly with the tested MCLELLAN, A. T., ET AL. (1983). Predicting response to individuals. Also, a T-ASI (Teen-Addiction Sever- alcohol anddrugabuse treatments: Role of psychiat- ity Index) has been developed to help adolescents. ric severity. Archives of General Psychiatry, 40, 620– It is an age-appropriate modification of the original 625. ASI with 133 questions in 7 domains: Psychoactive MCLELLAN, A. T., ET AL. (1981). Are the addiction-re- Substance Use, Family Function, Peer-Social Rela- latedproblems of substance abusers really related? tionships, School-Employment Status, Legal Sta- Journal of Nervous and Mental Disease, 169(4), 232– tus, andPsychiatric Status. 239. MCLELLAN, A. T., ET AL. (1981). Psychological severity BIBLIOGRAPHY andresponse to alcoholism rehabilitation. Drug and ALTERMAN, A., ET AL. A typology of antisociality in meth- Alcohol Dependence, 8(1), 23–35. adone patients. Journal of Abnormal Psychology, 107, MCLELLAN, A. T., ET AL. (1980). An improveddiagnostic August 1998, 412. instrument for substance abuse patients: The Addic- ADDICTION: CONCEPTS AND DEFINITIONS 21

tion Severity Index. Journal of Nervous and Mental purposes, or in unnecessarily large quantities. With Disease, 168, 26–33. reference to licit but non-therapeutic substances NIAAA. (1901). Alcohol alert: Assessing alcoholism. AD- such as ALCOHOL, it is understood to mean a level AMHA Press, no. 12, PH 294, April. Washington, DC: of use that is hazardous or damaging, either to the U.S. Government Printing Office. user or to others. When appliedto illicit substances O’LEARY, Tracy A., ET AL. The Relationship Between that have no recognizedmedicalapplications, such Anxiety Levels andOutcome of Cocaine Abuse Treat- as PHENCYCLIDINE (PCP) or MESCALINE, any use is ment. American Journal of Drug and Alcohol Abuse, generally regarded as abuse. The term misuse refers 26, May 2000, 179. more narrowly to the use of a therapeutic drug in ROGALSKI, C. J. (1987). Factor structure of the Addiction any way other than what is regarded as good medi- Severity Index in an inpatient detoxification sample. cal practice. International Journal of Addiction, 22(10). 981–992. Substance abuse means essentially the same as ROUNSAVILLE, B. J., ET AL. (1987). Psychopathology as a drug abuse, except that the term ‘‘substance’’ predictor of treatment outcome in alcoholism. Ar- (shortenedform of psychoactive substance) avoids chives of General Psychiatry. any misunderstanding about the meaning of SAXE, L., ET AL. (1983). The effectiveness and costs of ‘‘drug’’. Many people regard as drugs only those alcoholism treatment (Health Technology Case Study compounds that are, or could be, used for the treat- 22). Washington, DC: Office of Technology Assess- ment of disease, whereas ‘‘substances’’ would also ment. include materials such as organic solvents, MORN- STOFFELMAYR, B., HARWELL, M., & MAVIS, B. (1991). ING GLORY SEEDS or toadvenoms, that have no Interrater reliability and validity of the Addiction Se- medical applications at present but are ‘‘abused’’ in verity Index. Journal of Educational Measurement. one or more of the senses defined above. SVIKIS, Dace S., ET AL. Detecting alcohol problems in The best general definition of drug abuse is the drug-dependent women of childbearing age. Ameri- use of any drug in a manner that deviates from the can Journal of Drug and Alcohol Abuse, November approvedmedicalor social patterns within a given 1996, 563. culture at a given time. This is probably the concept underlying the official acceptance of the term abuse A. THOMAS MCLELLAN in such instances as the names of the National Insti- REVISED BY REBECCA MARLOW-FERGUSON tute on Drug Abuse (USA) andthe CanadianCen- tre on Substance Abuse. Such official acceptance, however, does not prevent the occurrence of ADDICTION: CONCEPTS AND DEFINI- ambiguities such as those mentionedin the next TIONS This article deals with a number of con- section. cepts related to the basic nature of addiction, that are widely used but often misused, and that have RECREATIONAL OR CASUAL undergone significant changes since the term ad- DRUG USE diction first came into the common vocabulary. In the following discussion, the terms are grouped These two terms are generally understood to according to themes, rather than being arranged in refer to drug use that is small in amount, infre- alphabetic order. quent, andwithout adverseconsequences, but these characteristics are not in fact necessary parts ABUSE AND MISUSE of the definitions. In the terminology recommended by the WorldHealth Organization (WHO), the two In everyday English, abuse carries the connota- terms are synonymous. However, recreational use tions of improper, perverse, or corrupt use or prac- really refers only to the motive for use, which is to tice, as in childabuse, or abuse of power. As ap- obtain effects that the user regards as pleasurable plied to drugs, however, the term is difficult to or rewarding in some way, even if that use also define and carries different meanings in different carries some potential risks. Casual use refers to contexts. In relation to therapeutic agents such as occasional as opposedto regular use, andtherefore BENZONDIAZEPINES or MORPHINE, the term drug implies that the user is not dependent or addicted abuse is appliedto their use for other than medical (see below), but it carries no necessary implications 22 ADDICTION: CONCEPTS AND DEFINITIONS with respect to motive for use or the amount used HABIT AND HABITUATION on any occasion. Thus, a casual user might become In everyday English, a habit is a customary be- intoxicated(see below) or suffer an acute adverse havior, especially one that has become largely auto- effect on occasions, even if these are infrequent. matic or unconscious as a result of frequent repeti- Occasional use may also be circumstantial or utilitarian, if employedto achieve some specific tion of the same act. In itself, the wordis simply short-term benefit under special circumstances. descriptive, carrying no fixed connotation of good or bad. As applied to drug use, however, it is some- The use of AMPHETAMINES to increase endurance and postpone fatigue by students studying for ex- what more judgmental. It refers to regular persis- aminations, truck drivers on long hauls, athletes tent use of a drug, in amounts that may create some competing in endurance events, or military person- risk for the user, andover which the user doesnot nel on long missions, are all instances of such utili- have complete voluntary control. Indeed, an alco- tarian use. Most observers also consider the first hol habit has been defined in terms very similar to three of these to be abuse or misuse, but many those used to define dependence (see below). In wouldnot regardthe fourth example as abuse be- older writings, habit strength was usedto charac- cause it is or was prescribedby military authorities terize the degree of an individual’s habitual drug under unusual circumstances, for necessary com- use, in terms of the average amount of the drug bat goals. Nevertheless, in all four instances the taken daily. Reference to a drug habit implies that same drug effect is sought for the same purpose the drug use is the object of some concern on the (i.e., to increase endurance). This illustrates the part of the user or of the observer, but that it may complexities andambiguities of definitionsin the not yet be sufficiently strongly establishedto make fieldof druguse. treatment clearly necessary. Habituation refers either to the process of ac- quiring a drug habit, or to the state of the habitual INTOXICATION user. Since habitual users frequently show in- creasedtolerance (decreasedsensitivityto the ef- This is the state of functional impairment result- fects of the drug; see below), habituation is also ing from the actions of a drug. It may be acute, i.e., usedin the earlier literature to mean an acquired caused by consumption of a high dose of drug on increase in tolerance. In its early reports, the one occasion; it may be chronic, i.e., causedby WORLD HEALTH ORGANIZATION EXPERT COMMIT- repeateduse of large enough dosesto maintain an TEE ON DRUG DEPENDENCE (as it is now known, excessive drug concentration in the body over a after several changes of name) usedthe term habit- long periodof time. The characteristic pattern of uation to refer to a state arising from repeateddrug intoxication varies from one drug to another, de- pending upon the mechanisms of action of the use, that was less serious than addiction in the sense different substances. For example, intoxication that it included only psychological and not physical by alcohol or barbiturates typically includes dependence, and that harm, if it occurred, was only disturbances of neuromuscular coordination, to the user andnot to others. Drugs were classified speech, sensory functions, memory, reaction time, according to whether they caused habituation or reflexes, judgment of speeds and distances, and ap- addiction. These distinctions were later recognized propriate control of emotional expression andbe- to be basedon misconception, because havior. In contrast, intoxication by amphetamine (1) psychological (or psychic) dependence is even or cocaine usually includes raised blood pressure more important than physical dependence with re- andheart rate, elevation of bodytemperature, in- spect to the genesis of addiction; (2) any drug that tense hyperactivity, mental disturbances such as can damage the user is also capable of causing hallucinations andparanoiddelusions,andsome- harm to others andto society at large; and(3) the times convulsions. The term may be considered same drug could cause effects that might be classed equivalent to overdosage, in that the signs of intoxi- as ‘‘habituation’’ in one user and ‘‘addiction’’ in cation usually arise at higher doses than the plea- another. The WHO Expert Committee later recom- surable subjective effects for which the drug is mended that both terms be dropped from use, and usually taken. that dependence be usedinstead. ADDICTION: CONCEPTS AND DEFINITIONS 23

PROBLEM DRINKING sumption of a drug (natural or synthetic). Its char- acteristics include (1) an overpowering need (com- In an effort to avoidsemantic arguments and pulsion) to continue taking the drug and to obtain value judgments about abuse or addiction, clinical it by any means; (2) a tendency to increase the dose andepidemiologicalresearchers have increasingly [later saidto reflect tolerance]; (3) a psychic (psy- made use of objective operational definitions and chological) and generally a physical dependence on measures. Problem drinking is alcohol consump- the effects of the drug; and (4) detrimental effect tion at an average daily level that causes problems, on the individual and on society’’. Physical depen- regardless of whether these are of medical, legal, dence is an alteredphysiological state arising from interpersonal, economic, or other nature, to the the regular heavy use of a drug, such that the body drinker or to others. The actual level, in milliliters cannot function normally unless the drug is pres- of absolute alcohol per day, will obviously vary ent. This state is recognizable only by the physical with the individual, the type of problem, and the and mental disturbances that occur when drug use circumstances. The advantage of this term is that a is abruptly discontinued or ‘‘withdrawn’’, and the drinker who may not meet the criteria of depen- constellation of these disturbances is known as a dence or who is reluctant to accept a diagnostic withdrawal syndrome. The specific pattern of the label of alcoholism or addiction can often be led to withdrawal syndrome varies according to the type acknowledge that a problem exists and requires of drug that has been used, and usually consists of intervention. changes opposite in direction to those originally produced by the action of the drug. For example, if ADDICTION AND DEPENDENCE opiate drugs cause constipation, their withdrawal typically produces diarrhea; if cocaine causes pro- The term addiction was usedin everydayand longedwakefulness andeuphoria, the withdrawal legal English long before its application to drug syndrome will include profound sleepiness and de- problems. In the sixteenth century it was usedto pression; if alcohol decreases the reactivity of nerve designate the state of being legally bound or given cells, the withdrawal syndrome will include signs of over (e.g., bondage of a servant to a master) or, over-reactivity, such as exaggeratedreflexes or con- figuratively, of being habitually given over to some vulsions. In all cases, however, the withdrawal syn- practice or habit; in both senses, it implieda loss of drome is quickly abolished by resumption of ad- liberty of action. At the beginning of the twentieth ministration of the drug or of a substitute drug with century it came to be usedmore specifically for the a very similar pattern of actions. state of being given over to the habitual excessive It is now well recognizedthat a person can be- use of a drug, and the person who was ‘‘given over’’ come physically dependent on a drug given in high to such drug use was described as an addict.By doses for medical reasons (e.g., morphine given extension from the original meanings of addiction, repeatedly for relief of chronic pain) and yet not drug addiction meant a practice of drug use that show any subsequent tendency to seek and use the the user couldnot voluntarily cease, andloss of drug for non-medical purposes. The WHO Expert control over drinking was considered an essential Committee therefore revisedits definitionsand feature of alcohol addiction. The emphasis was concepts in 1973, substituting the single term de- placed upon the degree to which the drug use domi- pendence for the two terms addiction and habitua- natedthe person’s life, in such forms as constant tion. Unfortunately, this change has not ledto uni- preoccupation with obtaining andusing the drug, form terminology or concepts. andinability to discontinueits use even when In essence, dependence is a state in which the harmful effects made it necessary or strongly advis- individual can not function normally—physically, able to do so. mentally or socially—in the absence of the drug. A During the first half of the twentieth century, simple definition given in the fourth edition of the however, the pharmacological andsocial conse- Diagnostic and Statistical Manual of Mental Disor- quences of such use came increasingly to be the ders publishedby the American Psychiatric Associ- defining criteria. In 1957, the WHO Expert Com- ation (DSM-IV) includes only one fundamental ele- mittee defined addiction as ‘‘a state of periodic or ment: compulsive use of the drug despite the chronic intoxication produced by the repeated con- occurrence of adverse consequences. However, a 24 ADDICTION: CONCEPTS AND DEFINITIONS more detailed description of the dependence syn- an effect that alters the user’s perceptions, thoughts drome includes both physical components (in- andemotions in a manner that is usually (but not creasedtolerance to the drug;repeatedexperience always) experiencedas pleasurable or rewarding. of withdrawal symptoms; use of the drug to prevent The various drugs that are potentially abused or or relieve withdrawal symptoms) and behavioral addictive are all thought to act in different ways to signs of loss of control over drug use (e.g., increas- stimulate a common nerve-cell pathway originat- ing prominence of drug-seeking behavior, even at ing in the midbrain and running to the base of the the cost of disruption of other important parts of forebrain, where it releases the transmitter chemi- the user’s daily life; use of larger amounts than cal dopamine. This pathway is often referredto in intended; inability to cut down the amount used, scientific shorthandas the reward system, though despite persistent desire to do so; and awareness by this is probably a misnomer. Activation of this the user of frequent craving. pathway leads to an increased probability that the Psychic dependence or psychological depen- behavior that causedthe activation (in this case, dence refers to those components of the dependence the drug-taking) will be repeated or reinforced, and syndrome other than tolerance and withdrawal the drug is called a reinforcer. A drug must have a symptoms, in particular the urgency of drug-seek- reinforcing effect if it is to become addictive, but it ing behavior, craving, inability to function in daily is important to recognize that reinforcement is not life without repeateduse of the drug,andthe in- the same as addiction. Reinforcement is an essen- ability to maintain prolongedabstinence. It has tial mechanism for survival, learning andadapta- been attributedto a distressor tension, especially tion. The satisfaction of thirst by drinking water, during periods of abstinence from the drug, that and of hunger by eating food, as well as the avoid- the user seeks to relieve by taking the drug again. ance of harm by escape, are all examples of types of This is, however, really a description, rather than reinforcement by natural andnecessary behaviors. an explanation. Addictive drugs are regarded as ‘‘usurpers’’ of the Because of these differences in definition of de- reward system that produce reinforcement by di- pendence by different authorities, the term has rect drug action on it without serving any necessary proven to be less clear than intended, and has not biological function. displaced the term addiction from common use. Nevertheless, drug-induced reinforcement, like The latter carries a clearer emphasis on the behav- reinforcement by food, water, sexual activity, or ior of the individual, rather than the consequences escape from harm, simply means that the behavior of that behavior, as in the concept of nicotine ad- that causedit has an increasedlikelihoodof being diction. A committee report of the Academy of repeated. Some other process or processes must Sciences of the Royal Society of Canada concluded enter into play if that behavior is to become so that the only elements common to all definitions of strongly entrenchedthat it comes to dominatethe addiction are a strongly established pattern of re- individual’s thinking and activities. Various hy- peated self-administration of a drug in doses that potheses have been put forwardconcerning the reliably produce reinforcing psychoactive effects, nature of such additional processes. One suggestion andgreat difficultyin achieving voluntary long- is that activation of the rewardsystem is controlled term cessation of such use, even when the user is by something analogous to a thermostat, regulating strongly motivatedto stop. the ‘‘set-point’’ of the system, andthat frequent repetition of drug-taking leads to a change in set- point so that reinforcement grows progressively REINFORCEMENT AND ITS RELATION stronger over time. Another, perhaps related, hy- TO DEPENDENCE pothesis is that the degree of reinforcement by a No drug can give rise to dependence unless (1) it given drug is regulated by genetic factors, and produces some effect that causes the user to make therefore vulnerability to addiction is greater in efforts to obtain anduse the drugagain or (2) it is those who inherit either an abnormally high sensi- taken frequently enough to establish a strong pat- tivity to the rewardsystem or a low sensitivity to tern of drug-related behavior that is resistant to the aversive (punishing, disagreeable) effects of the eradication. The effect that leads to repetition of drug. Another view holds that the essential feature drug-taking is a psychoactive effect, that is to say, leading to addiction is not reward (i.e., pleasure or ADDICTION: CONCEPTS AND DEFINITIONS 25 liking for the drug) but drug-induced sensitization money (whether by legal or illegal means), contact- of the process of incentive saliency (i.e., the sub- ing the sources of supply, purchasing the drug, and ject’s awareness of, and‘‘wanting’’ for, drug-re- preparing it for use, are included under the term latedstimuli becomes progressively greater, so that drug-seeking behavior. The more intense the they have a steadily increased probability of con- craving, the more urgent, desperate, or irrational trolling behavior). Yet another, andclosely related, this behavior tends to become. hypothesis is that drug-taking generally occurs within certain specific environmental or social TOLERANCE AND SENSITIZATION contexts, andcues arising from these contexts can become linkedto the drugeffects as conditional The term tolerance, which has long helda prom- stimuli, which then become able to elicit drug-tak- inent place in the literature on drug dependence, ing behavior andfurther reinforcement. This is has a number of different meanings. All of them analogous to the role of the bell in Pavlov’s experi- relate to the degree of sensitivity or susceptibility of ments in which salivation, at first elicitedby the an individual to the effects of a drug. Initial toler- feeding of meat to a dog, could eventually be elic- ance refers to the degree of sensitivity or resistance itedby the bell alone if the bell was always sounded displayed on the first exposure to the drug; it is just before the presentation of the meat. In this expressedin terms of the degreeof effect (as mea- view, when the drug-taking comes under the con- suredon some specifiedtest) producedby a given trol of such extraneous stimuli andis no longer a dose of the drug, or by the concentration of drug in purely voluntary act, the transition to addiction has the body tissues or fluids resulting from that dose: occurred. These various hypotheses, and possibly the smaller the effect produced by that dose or others, require much further research before the concentration, the greater is the tolerance. Initial relation of reinforcement to addiction can be fully tolerance can vary markedly from one individual to explained. Moreover, all such hypotheses must rec- another, or from one species to another, as a result ognize that the degree of risk that any given indi- of genetic differences, constitutional factors, or en- vidual will become addicted to a particular drug, vironmental circumstances. even a strongly reinforcing one such as cocaine, is The more frequent meaning of tolerance, how- strongly influencedby environmental, social, eco- ever, is acquired tolerance (or acquired increase in nomic andother factors. tolerance)—increasedresistance or decreasedsen- sitivity to the drug as a result of adaptive changes CRAVING AND RELATED CONCEPTS produced in the body by previous exposure to that drug. This is expressed in terms of the degree of Craving refers to an intense desire for the drug, reduction in the magnitude of effect produced by expressedas constant, obsessive thinking about the drug and its desired effects, a sense of acute depri- the same dose or concentration, or (preferably) the vation that can be relievedonly by taking the drug, increase in dose or concentration required to pro- andan urgent needto obtain it. This state is proba- duce the same magnitude of effect. Acquired toler- bly induced by exposure to bodily sensations and ance can be due to two quite different processes. external stimuli that have in the past been linkedto Metabolic tolerance (also known as pharmacoki- circumstances andsituations in which druguse has netic tolerance or dispositional tolerance) is pro- been necessary, such as self-treatment of early duced by an adaptive increase in the rate at which withdrawal symptoms by taking more drug. Drug the drug is inactivated by metabolism in the liver hunger is essentially synonymous with craving, and andother tissues. This results in lower concentra- urge represents the same phenomenon but of lesser tions of drug in the body after the same dose, so intensity. that the effect is less intense andof shorter dura- The behavioral consequence of an urge or tion. Functional tolerance (also known as phar- craving is usually a redirecting of the person’s macodynamic tolerance or tissue tolerance) is pro- thoughts andactivities towardsobtaining andus- duced by a decrease in the sensitivity of the tissues ing a new supply of drug. All the behaviors directed on which the drug acts, primarily the central ner- toward this end, such as searching drawers and vous system, so that the same concentration of drug cupboards for possible remnants of drug, getting produces less effect than it did originally. 26 ADDICTION: CONCEPTS AND DEFINITIONS

Acquiredfunctional tolerance can occur in three does not apply to all effects of the drug, however; different time frames. Acute tolerance is that which tolerance can occur towards some effects (such as is displayed during the course of a single drug expo- the inhibition of appetite) at the same time that sure, even the first time it is taken. As soon as the sensitization develops to others. The reason for this brain is exposedto the drug,compensatory changes difference is not yet known. begin to develop and become more marked as time passes. As a result, the degree of effect produced by CROSS-TOLERANCE AND the same concentration of drug is greater at the CROSS-DEPENDENCE beginning of the exposure than it is in the later part; this phenomenon is sometimes calledthe Mellanby The term acquired tolerance is appliedto toler- effect. A secondtime pattern of tolerance develop- ance developing to the actions of the same drug that ment is known in the experimental literature as has been administered repeatedly. However, if a rapid tolerance. This refers to an increasedtoler- seconddrughas actions similar to those of the first, ance seen on the secondexposure to the drug,if this an individual who becomes tolerant to the first drug occurs not more than one or two days after the first is usually also tolerant to the seconddrug,even on exposure. Chronic tolerance is that form of ac- the first occasion when the latter is used. This quiredtolerance that developsprogressively over phenomenon is called cross-tolerance, andit may an extended period of time in which repeated expo- be partial or complete—it may extendto all the sure to the drug takes place. There is suggestive effects of the seconddrug,or only to some of them. evidence that these three forms may involve the The adaptive changes in the nervous system that same or very similar mechanisms. All experimental give rise to acquiredtolerance are believedby most interventions so far testedhave producedvirtually researchers (though not all) to be responsible also identical effects on rapid and chronic tolerance, for the development of physical dependence. Thus, andchronic tolerance is accompaniedby an in- an adaptive change in cell function, opposite in crease in the rate of development of acute tolerance. direction to the effect of the drug, will offset the Although acquiredtolerance involves important latter when the drug is present (tolerance), but will physiological changes in the nervous system, it is give rise to a withdrawal sign or symptom when the also markedly influenced by learning. Tolerance drug is removed. The term neuroadaptive state has develops much more rapidly if the individual is been proposedto designateall the physiological requiredto perform tasks underthe influence of the changes underlying the development of tolerance drug, than if the same dose of the same drug is and physical dependence. If the second drug, to experiencedwithout any performance requirement. which cross-tolerance is present, is given during Similarly, environmental stimuli that regularly ac- withdrawal from the first, it can prevent or sup- company drug administration can come to serve as press the withdrawal effect; this is known as cross- Pavlovian conditional stimuli that elicit tolerance dependence. A relatedconcept is that of transfer of as a conditional response, so that tolerance is dem- dependence, from a first drug on which a person onstratedmuch more rapidlyin the presence of has become dependent to a second drug with simi- these stimuli than in their absence. lar effects, that has been given therapeutically to Sensitization refers to a change opposite to toler- relieve the withdrawal signs produced by the first. ance, that occurs with respect to certain effects of a few drugs (most notably, central stimulant drugs BIBLIOGRAPHY such as cocaine andamphetamine, or low dosesof alcohol that produce behavioral stimulation rather AHMED,S.H.AND KOOB, G. F. (1998). Transition from than sedation) when these are given repeatedly. moderate to excessive drug intake: change in hedonic The degree of effect produced by the same dose or set point. Science, 282, 298-300. concentration grows larger rather than smaller. For AMERICAN PSYCHIATRIC ASSOCIATION (1994). Substance- example, after repeatedadministrationof amphet- RelatedDisorders. Diagnostic and Statistical Manual amine a dose that initially produced only a slight of Mental Disorders, 4th edition (pp. 175-272). increase in physical activity can come to elicit very Washington, DC:APA. markedhyperactivity, anda convulsion can be pro- BEGLEITER,H.AND KISSIN, B., EDS. (1995). The Genetics duced by a dose that did not initially do so. This of Alcoholism. New York: OxfordUniversity Press. ADDICTIVE PERSONALITY 27

BOCK,G.R.AND WHELAN, J., EDS. (1992). Cocaine: WORLD HEALTH ORGANIZATION (1952, 1957, 1973 and Scientific and Social Dimensions. Ciba Foundation others). Reports of the Expert Committee on Prob- Symposium 166. Chichester: John Wiley & Sons. lems of Drug Dependence (various). Technical Report CHAUDRON,C.D.AND WILKINSON, D. A., EDS. (1988). Series of the World Health Organization. Geneva: Theories on Alcoholism. Toronto: Addiction Research WHO. Foundation. HAROLD KALANT EDWARDS,G.AND GROSS, M. M. (1976). Alcohol depen- dence: provisional description of a clinical syndrome. British Medical Journal 1, 1058-1061. GLASS, I. B. (1991). The International Handbook of Ad- ADDICTION RESEARCH FOUNDATION diction Behaviour. London: Routledge. See Centre for Addiction and Mental Health GOLDSTEIN, A. (1994). Addiction: From Biology to Drug Policy). San Francisco: Freeman. GOUDIE,A.J.AND EMMETT-OGLESBY, M. (1989). Psycho- ADDICTIVE PERSONALITY The term active Drugs—Tolerance and Sensitization. Clifton, addictive personality has been usedin various NJ: Humana Press. ways, most commonly to refer to a recurrent pat- KALANT, H. (1989). The nature of addiction: an analysis tern observedin many alcoholics andother sub- of the problem. In A. Goldstein (Ed.), Molecular and stance abusers: impulsivity, immaturity (depen- Cellular Aspects of the Drug Addictions (pp. 1-28). dency and neediness), poor frustration tolerance, New York: Springer-Verlag. anxiety, anddepression.Many of these features KALANT, H. (1996). Current state of knowledge about disappear during extended periods of abstinence, the mechanisms of alcohol tolerance. Addiction Bio- however, suggesting that they may be either related logy 1, 133-141. directly to the drug use, to the life it imposes, or to KALANT, O. J. (1973). The Amphetamines: Toxicity and social response, rather than to personality. Addic- Addiction, 2ndEd.Toronto: University of Toronto tive personality—more accurately preaddictive Press. personality—has also been usedto refer to person- KALANT, O. J. (1987). Maier’s COCAINE ADDICTION ality characteristics presumed to predate drug use (Der Kokainismus). Toronto: Addiction Research andas such are predictiveof such use. These Foundation. aspects of personality are likely to include early KELLER,M.AND MCCORMICK, M. (1968). A Dictionary of Words about Alcohol. New Brunswick, NJ: Rutgers difficulties in impulse control and submission Center of Alcohol Studies. to authority—andsensitivity to anxiety and POULOS, C. X., HINSON,R.E.AND SIEGEL, S. (1981). The depresssion. role of Pavlovian processes in drug tolerance and de- pendence: implications for treatment. Addictive Be- (SEE ALSO: Addictive Personality and Psychologi- haviors 6, 205-211. cal Tests; Causes of Substance Abuse; Childhood RIGTER,H.AND CRABBE, J. C., JR., EDS. (1980). Alcohol Behavior and Later Drug Use; Coping and Drug Tolerance and Dependence. Amsterdam: Elsevier/ Use) North-HollandBiomedical. ROBINSON,T.E.AND BERRIDGE, K. C. (1993). The neural BIBLIOGRAPHY basis of drug craving: an incentive-sensitization the- ory of addiction. Brain Research Reviews, 18, 247- KANDEL, D. B. (1978). Convergences in prospective lon- 291. gitudinal surveys of drug use in normal populations. ROYAL SOCIETY OF CANADA (1989) Tobacco, Nicotine, In D. B. Kandel (Ed.), Longitudinal research on drug and Addiction. Ottawa: Royal Society of Canada. abuse: Empirical findings and methodological issues, U.S. SURGEON GENERAL (1988). The Health Conse- (pp. 3–38). Washington, DC: Hemisphere Publish- quences of Smoking. Nicotine Addiction. Rockville, ing. MD: USPHS/DHHS. SMITH, G. M., & FOGG, C. P. (1978). Psychological pre- WIKLER, A. (1977). The search for the psyche in drug dictors of early youth, late youth, and nonuse of mari- dependence—A 35-year retrospective survey. Journal huana among teenage students. In D. B. Kandel (Ed.), of Nervous and Mental Disease, 165, 29-40. Longitudinal research on drug abuse: Empirical find- 28 ADDICTIVE PERSONALITY AND PSYCHOLOGICAL TESTS

ings and methodological issues (pp. 101–113). these ‘‘illnesses’’ after they have been alcohol-free Washington, DC: Hemisphere Publishing. for some time. VAILLANT, G. E. (1983). The natural history of alcohol- A review of studies of personality in alcoholics ism. Cambridge; Harvard University Press. concluded that there appeared to be six constella- WILLIAM A. FROSCH tions: (1) those who drink to escape the pain of frustration; (2) those for whom drink gratifies child- ish dependency; (3) those who drink to reduce guilt andanxiety; (4) those who escape disappointment ADDICTIVE PERSONALITY AND PSY- into fantasy; (5) social isolates for whom alcohol CHOLOGICAL TESTS Psychological tests supplies a pseudo-life; (6) social context-driven al- andmeasurements (psychometrics) are structured coholics. Other studies have defined additional ways of evaluating an individual’s inner mental life groups, such as unsocial aggressive, psychopathic, andexternal behaviors. They present subjects with and inhibited-conflicted. Similar findings and clas- more or less standard stimuli to which the subjects sifications have been described in users of other respond. Depending on the test, these responses tell drugs. The overlapping, but not identical, or at us something about their intelligence, abilities and times contradictory descriptions can be accounted skills, educational and vocational interests and for at least partly. Each study has differed from the achievements, andpersonality. Often, the tests are others in obvious ways: different measures of per- especially helpful in diagnosing organic brain dis- sonality (e.g., the MINNESOTA MULTIPHASIC ease—its presence, presumedlocation, andthe PERSONALITY INVENTORY or the Rorschach Inkblot particular resulting functional deficits. The tests test); different subject populations (e.g., ALCOHOL- themselves range from structuredquestionnaires or ICS ANONYMOUS members or hospitalizedpatients); interviews, to pen-and-pencil tasks, to obtaining different comparison groups; or different statistical responses to purposely ill-defined stimuli such as analyses of the data. Future research in the under- ink blots (Rorschach test). They have been used standing of addictive personality(ies) needs to de- (1) to evaluate the probability of the presence of a fine in advance each of these parameters and build substance-abuse problem, (2) to examine the im- in true replications. pact of substance use on behavior andbrain func- While psychometric studies of personality have tion both acutely andchronically, and(3) to assess so far led to contradictory or confusing findings, personality features—profiling which ones are pre- they have proven useful in other ways: A variety of disposed to use and abuse or which are the result of structuredquestionnaires are goodscreening de- such use. vices andhelp the clinician towardfurther inquiry Historically, we have movedfrom the search for concerning alcohol or other drug use; tests of or- a single trait as cause to looking for a cluster of ganic brain function have identified both acute and traits (the addictive personality), to the recognition lasting effects of a wide variety of drugs; and the that a number of different pathways lead to addic- tests have helpedus identifysome of the common tive behavior(s); we now understand that different accompanying psychopathologies, such as antiso- types of people may use drugs for different reasons. cial personality disorder and depressive illness. Some underlying trait or combination of traits, however, may predispose individuals to problems (SEE ALSO: Causes of Substance Abuse; Conduct with drugs. In addition, the ‘‘addictive life’’ may so Disorder and Drug Use) structure behavior that it imposes similarities in attitudes, responses, and the like; it may present us BIBLIOGRAPHY with a state-relatedpersonality—that is, a pattern of typical response andbehavior that is present BARR, H. L. (1977). In Summary report of technical re- while living in the drugged state but that disap- view on the psychiatric aspects of opiate dependence. pears, in part or in whole, after a periodof absti- Arlington: National Institute on Drug Abuse. nence. For example, Vaillant’s long-term popula- NEURINGER, C. (1982). Alcoholic addiction: Psychologi- tion studies (1983) have shown that people cal tests andmeasurements. In E. M. Pattison & E. diagnosed with personality disorders or other psy- Kaufman (Eds.), Encyclopedia handbook of alcohol- chopathologies while drinking often appear to lose ism (pp. 517–528). New York: Gardner Press. ADJUNCTIVE DRUG TAKING 29

VAILLANT, G. E. (1983). The natural history of alcohol- the overdrinking occurred day after day during ism. Cambridge: Harvard University Press. each daily session. It seemed compulsive, for the WILLIAM A. FROSCH animals did not lose interest in drinking water heavily after a few days. The exaggerated drinking that occurred under this feeding condition did not disappear as long as the intermittent schedule of Drug ADJUNCTIVE DRUG TAKING feeding remained in force. abuse is usually viewedas a behavior that occurs It was easy to prove that the excessive drinking because of what the drugs do in the body. Most was not a physiological effect of reducing the daily people assume that drug abuse is mainly driven by intake of food: If, instead of being given pellets the immediate, attractive effects and sensations spreadacross the session, rats were given the same produced by the drugs—their physiological and 180 pellets all at once as a single ration, then they psychological effects. But there is another, less di- drank about 10 milliliters of water over the next 3 rect way drugs can become of overwhelming im- hours, rather than almost 100 milliliters. So, the portance to a person anddominatelife. Excessive rats did not really need the excessive amount of drug use can develop as a side effect of other water they drink under the schedule of intermittent strongly desired behavior that, for various reasons, pellet delivery. Something about doling out bits of cannot be engagedin or completed. foodto them over time drovethe exaggerated For example, for any one of a number of reasons drinking behavior. They got what they needed of a person may not be able to do something they are something of crucial value (in this case, food), but motivated to do: They may not be permitted to do the individual portions were rather small, and there it, the goals of the behavior may not be available to was a time delay between these portions. them, or the person may not have the skills or The details of how the size of the portions, the knowledge required to perform the behavior suc- amount of time between them, as well as the state cessfully. When blockedin any of these ways from of food deprivation, affects the degree of excessive performing a desired behavior, a person may turn drinking have been worked out in many experi- aside to some sort of easy, satisfying alternative— ments. The details of these relations will not be an adjunctive behavior. The following is a descrip- considered here, but a few additional facts indicate tion of the first kindof adjunctive behavior that was the widespread nature of this excessive-behavior produced in an experimental laboratory. It does not phenomenon. As described, this overdrinking of involve drug taking, but it has many of the exagger- plain water is referredto as schedule-induced poly- atedandcompulsive characteristics usually dipsia. The term polydipsia means the foodsched- thought to be a result of drug use. ule can induce excessive drinking of many sorts of Normal, adult laboratory rats were first reduced fluids. But in general, behaviors that become exag- in body weight; then it was arranged for them to gerated under these sorts of conditions are known receive much of their daily food ration in individual as adjunctive behaviors. chambers. The foodwas given as 45 milligram The phenomenon of adjunctive behavior is not pellets, andeach pellet was available only about limitedto the rat species andit can be inducedin once per minute over a 3-hour periodeach day. ways other than food-schedule intermittency. And Although water was always freely available back in adjunctive behaviors other than drinking can oc- each animal’s home cage, this schedule of intermit- cur. Adjunctive behavior can be induced in many tent foodavailability, in which the eating of small animal species, for example, mice, monkeys, pi- foodportions was spreadout over a 3-hour period, geons andchimpanzees, as well as in humans. The produced a strange result. When an animal re- behavior can be induced by a generator schedule ceiveda foodpellet, it quickly ate it andthen took a that is not based on doling out food; other kinds of large drink of water. Since an animal received a incentives also are effective in inducing excessive total of about 180 pellets during each daily, 3-hour behavior. For example, humans reinforcedinter- session, anddrinkingoccurredafter almost every mittently with money, by the opportunity to gam- pellet, by the endof the 3 hours an animal had ble, or even by maze solving, showedadjunctive drunk an amount of water equal to about one-half increases in fluidintake, general activity, eating or its body weight. That is an excessive amount, and smoking. In animal experiments, excessive aggres- 30 ADJUNCTIVE DRUG TAKING sion, overactivity, andeating are a few of the be- like an intense hobby. But it also can result in haviors that occurredadjunctivelyowing to the aggression or drug taking, depending upon per- intermittent availability of some important com- sonal history, the skills one possesses, andcurrently modity or activity. available opportunities. The adjunctive behavior of greatest interest with The pharmacological consequences of drug tak- respect to the problem of drug abuse is, of course, ing are only one factor sustaining drug abuse. The the excessive seeking andtaking of drugs.A few environmental generating conditions and the con- examples will be given. But first, as indicated text of alternative opportunities are of crucial im- above, it is important to understand that adjunctive portance. Drug abuse occurs out of conditions al- drug taking is only one kind of excessive behavior ready generating behavioral excesses. Although that can be driven by a generator schedule. Thus, drug abuse often is described as if it is a direct drug abuse is just one sort of adjunctive behavior; it consequence of exposure to a drug with abuse po- is not a special problem driven exclusively by the tential, the great majority of people experimenting pharmacological actions of drugs of abuse. with such drugs do not become abusers—they sim- Once research hadestablishedthe conditionsin- ply lose interest andturn to other pursuits. (This is ducing adjunctive drinking, it was of interest to not to approve of such hazardous experimenta- determine if fluids other than water would be tion.) Those self-administering such drugs for med- drunk to excess, especially drug solutions. Briefly, if ical reasons (opioids are prescribed on a long-term the drug concentration of a drinking solution is not basis for controlling chronic pain) almost never too high (a high concentration is usually too bitter), become drug dependent or motivated to abuse a much greater unforced(voluntary) oral drugin- these agents. take can be induced by a generator schedule than Adjunctive behavior studies teach us that drug wouldoccur otherwise. Several classes of drugs abuse stems more from environmental generating have been investigated, and excessive intakes of conditions, together with a lack of, or poor utiliza- alcohol, opioids (e.g., morphine), sedatives (e.g., tion of, other opportunities, than from any over- barbiturates), anxiolytics (e.g., benzodiazepines), whelming intrinsic attractiveness of agents with stimulants (e.g., cocaine), andother agents (e.g., abuse liability. A few drug-abuse situations can be nicotine) have been sustainedfor many months described briefly to clarify how drugs come to be so under these inducing conditions. For some of these attractive to some individuals, and what causes this agents, physical dependence results from the exces- behavior to persist in the face of the trouble it sive amounts ingestedby animals. However, if the causes for them. generator schedule is discontinued, drug intakes An example frequently given is that of a poorly decrease immediately to much lower levels. Thus, educated youth, living in an urban ghetto, with without the generator schedule, the high drug in- minimal job prospects, who deals in drugs for eco- takes do not continue. Similar generator schedules nomic reasons, andcomes to use them owing to the (intermittent food delivery) also can induce exces- sparse schedule of conventional opportunities and sive intravenous drug self-administration. satisfactions available in that environment. Al- These andrelatedstudiesclarify the nature of though that may be true, drug abuse is a problem what sustains excessive intake of drugs (drug that occurs not just for disadvantaged persons. The abuse). It is important to note that, by this analysis, conditions of life for the affluent rich do not strike drug abuse arises from a background of excessive us as being extreme conditions that can lead to drug behavior that is induced by a generator schedule. It abuse. But consider the overprivileged young per- is produced by the limited and intermittent avail- son, sent to a superior boarding school by parents ability of crucially important environmental with great expectations (i.e., demands), but with events. Such schedules are similar to conditions in little time to provide their children with direct so- natural andsocial environments that providecom- cial reinforcement. They may be too engagedwith modities we need, and activities we desire, but only their own lives, management responsibilities, and in little bits at a time, andwith delayintervals in range of personal advantages, to afford their chil- between the bits. The adjunctive behavior gener- dren much of their valuable time. The lean sched- atedmay be largely noninjurious, like water drink- ule of social reinforcement for the children, the ing. Or the adjunctive behavior may be creative, often competitive nature of social interactions in ADMINISTRATIVE AND PUBLIC HEALTH LAW 31

private schools, the young person’s migrant status ioral Pharmacology (pp. 301–328). Amsterdam: El- in a new or isolating school, together with a high sevier. disposable income, can lead to engaging in drug FALK, J. L. (1996) Environmental factors in the instiga- abuse, particularly if this activity gains one local tion andmaintenance of drugabuse. In W. K. Bickel power andsocial status, while the threat of endur- & R. J. DeGrandpre (Eds.), Drug Policy and Human ing legal consequences is negligible. Andthe per- Nature: Psychological Perspectives on the Prevention, son, although perhaps expectedto take over the Management and Treatment of Illicit Drug Abuse (pp. family business, together with its social obligations, 3–29). New York: Plenum. is not yet empoweredto doso, or to have their FALK, J. L. (1994) Schedule-induced behavior occurs in opinions taken seriously, so that their current social humans: a reply to Overskeid. The Psychological Rec- status is weak even if they appear privileged. ord, 44, 45–62. Consider a sales representative who travels for a FALK, J. L. (1998) Drug abuse as an adjunctive behavior. corporation, making intermittent sales agreements Drug and Alcohol Dependence, 52, 91–98. (which may be subject to cancellation), with little FALK,J.L.AND TANG, M. (1988) What schedule-induced effective influence on company policies or politics, polydipsia can tell us about alcoholism. Alcoholism: with little to do in brief stop-overs in strange towns. Clinical and Experimental Research, 12, 576–585. Given the demand characteristics of the job, the JOHN L. FALK uncertainty andintermittency of reinforcement, andthe sparse opportunities for creative efforts when ‘‘on the road,’’ a person so exposed may be ADMINISTRATIVE AND PUBLIC vulnerable to drinking too much in the easy HEALTH LAW Civil remedies are defined as ambiance of hotel bars. procedures and sanctions, specified by civil statutes Studies on the schedule-induced production and andregulations, usedto prevent or reducecriminal chronic maintenance of excessive intake for a vari- problems andincivilities (Mazerolle & Roehl, ety of drugs indicate that drug abuse is a problem 1998). Drug control is a primary application of that has its roots in the behavioral effects induced many civil remedy programs. Police departments, by environmental conditions, as well as in the phar- city prosecutors, andcommunity members use civil macological consequences of these elevatedin- remedies in an effort to disrupt illegal activities at takes. The exaggeratedandproblematic behavior drug-selling locations. This approach to drug con- designated as drug abuse is not behavior that is trol typically targets nonoffending third parties specific to, or the outcome of, a person’s interaction (e.g., landlords, property owners) and utilizes nui- with drugs. It is one possible adjunctive outcome of sance anddrugabatement statutes. These types of a set of conditions that comprise economically and/ abatement statutes include repair requirements, fi- or socially restrictedschedulesof reinforcement nes, padlocks/closing, and property forfeiture and that generate andsustain a host of possible exag- seek to make owners and landlords maintain drug- geratedandpersistent behaviors. andnuisance-free properties. Police often work with teams of city agency representatives to inspect BIBLIOGRAPHY drug nuisance properties, coerce landowners to FALK, J. L. (1971) The nature and determinants of ad- clean up blightedproperties, post ‘‘no trespassing’’ junctive behavior. Physiology and Behavior, 6, 577– signs, enforce civil law codes and municipal regula- 588. tory rules, andinitiate court proceedingsagainst FALK, J. L. (1977) The origin andfunctions of adjunctive property owners who fail to comply with civil law behavior. Animal Learning and Behavior, 5, 325– citations. 535. Growth in the use of civil remedies as a crime FALK, J. L. (1981) The environmental generation of ex- control or crime prevention tactic is attributable to cessive behavior. In S. J. Mule´ (Ed.), Behavior in Ex- several factors. First, the accessibility of civil rem- cess: An Examination of the Volitional Disorders (pp. edy tools provides frustrated and disadvantaged 313–337). New York: Free Press. communities with alternative avenues to reverse FALK, J. L. (1993) Schedule-induced drug self-adminis- the spiral of decline. Second, the increasing use of tration. In F. van Haaren (Ed.), Methods in Behav- civil remedies comes at a time when communities 32 ADMINISTRATIVE AND PUBLIC HEALTH LAW andlaw enforcement officials recognize that many as an official notice of drug activity. Fines and other criminal remedies are neither effective nor desir- civil penalties may occur if violations are not cor- able for a wide range of problems. Third, growth in rected, and there are fees for reinspections to cover civil remedy approaches to crime control coincides city costs. If owners do not correct the problem, with increasing societal emphasis on prevention. there are penalties that include fines, closure of the Many civil remedy actions seek to reduce signs of property for up to one year, andsale of the property physical (e.g., broken windows, graffiti, trash) and to satisfy city costs. The city attorney’s office can social (e.g., public drinking, loitering, public urina- file suit against owners who do not take responsibil- tion) incivilities in the hope that cleaned-up places ity for their property. will break the cycle of neighborhooddeclineand Civil remedies offer an attractive alternative to subsequently decrease victimization, fear of crime, criminal remedies since they are relatively inexpen- and alienation. Code enforcement, drug nuisance sive andeasy to implement. Citizens can make a abatement, neighborhoodcleanup andbeautifica- difference by documenting problems, pressuring tion, andCrime Prevention Through Environmen- police andprosecutors to take appropriate civil ac- tal Design (CPTED) interventions comprise civil tion, or spearheading drives to establish useful local remedy actions that are typically used to control ordinances. A group of neighbors can pursue a drug problems. Youth curfews, gang injunctions, nuisance abatement action in small claims court ordinances controlling public behavior, and re- without the assistance of police or public prosecu- straining orders are other examples of civil reme- tors (Roehl, Wong & Andrews, 1997). Moreover, dies that seek to alter criminal opportunities and civil laws require a lower burden of proof than prevent drug-selling problems from escalating. criminal actions anddonot involve the require- Pressures on property owners andmanagers of- ments of due process, making them easier to apply ten result in corrections of health andsafety viola- yet open to concerns about fairness andequity tions, enforcedcleanup andupkeep efforts, evic- (Cheh, 1991). tions of problem tenants, andimprovedproperty The use of civil remedies to solve crime and management. Bans on drug paraphernalia, alco- disorder problems continues to grow in popularity. hol-relatedbillboardadvertising,spray paint, and Police regularly use civil laws, local city regula- cigarette machines in high crime areas are usedin tions, and ordinances to control drug, disorder, and an attempt to disrupt the illegal activities at drug- other crime problems. Community groups often selling locations. Injunctions against gangs, youth work with policy makers to instigate civil remedy curfews, and domestic violence restraining orders action to solve intractable neighborhoodproblems. are usedto prevent anddeterpotential perpetrators The civil remedy approach appears to be an effec- from engaging in criminal behavior. When useful tive andrelatively cost-effective approach to con- civil statutes are absent, community groups, legis- trol drug problems (Mazerolle, Price & Roehl, lators, andpolicy makers often work together to 2000). enact new legislation. Unlike traditional criminal sanctions, civil reme- BIBLIOGRAPHY dies attempt to resolve underlying problems: the motel’s poor management, the absentee owner’s CHEH, M. M. (1991). Constitutional limits on using civil neglect. The use of civil remedies tends to be proac- remedies to achieve criminal law objectives: Under- tive andorientedtowardprevention, whereas, at standing and transcending the criminal-civil law dis- the same time, civil remedies aim to enhance the tinction. The Hastings Law Journal, 42:1325–1413. quality of life andeliminate opportunities for prob- MAZEROLLE,L.GREEN,J.F.PRICE, AND J. ROEHL (2000). lems to occur or reappear. Civil remedies and drug control: A randomized field Police use existing public health andcontrolled trial in Oakland, CA. Evaluation Review, 24, (2) 211– substances acts to sendwarning letters to property 239. owners informing them that complaints of problem MAZEROLLE,L.GREEN &J.ROEHL (1998). Civil remedies activities (e.g., drug dealing) have been reported on andcrime prevention: An introduction.In: L. Green their property, advise them of steps to take in pre- Mazerolle & J. Roehl (Eds.), Civil Remedies and Crime venting or minimizing the problems, andoffer as- Prevention: Crime Prevention Studies. Vol 9. Monsey, sistance in resolving the problem. The letters serve NY: Criminal Justice Press. 1–20. ADOLESCENTS AND DRUG USE 33

ROEHL, J., H. WONG, & C. ANDREWS (1997). The use of civil remedies by community organizations for neigh- borhood crime and drug abatement. Pacific Grove, CA: Institute for Social Analysis. LORRAINE GREEN MAZEROLLE

ADOLESCENTS AND DRUG USE As individuals pass through adolescence, they undergo many physical, cognitive, social, andemotional changes. Most learn to adapt to these changes in healthy ways. For others, turmoil, conflict, andde- viant behavior leadto upheaval anddisorganiza- Teenagers share a joint during an annual tion as they attempt to cope. Drug use as a behavior marijuana legalization rally in New York City’s may serve many functions in this attempt to cope, Washington Square Park, May 4, 1996. andit can have many consequences. A single epi- (AP Photo/Bebeto Matthews) sode of drug use does not necessarily lead to further use—but several episodes may lead to ever increas- of drugs may also occur because of unpleasant ing use, with abuse and dependence the result. symptoms—withdrawal—that may appear as the Use of a drug, age of first use, and reasons for use drug (e.g., heroin, nicotine, caffeine) begins to wear are all factors relatedto continueddruguse. Early off. To avoidthese withdrawalsymptoms, a user adolescents who try one type of drug may venture may feel compelledto establish a regular pattern of on to sample a diverse number of substances. This use, possibly resulting in physical dependence. can lead to regular use of certain drugs (e.g., daily The way a drug is used is also a factor in devel- cigarette or MARIJUANA smoking); it may become oping tolerance and physical dependence. For ex- part of a pattern of multiple drug use (e.g., week- ample, an adolescent who sniffs COCAINE may find end drinking and smoking or daily uppers and that the amount he or she has to inhale to get the downers) that by late adolescence becomes depen- desired effects becomes enormous. Because of this, dence or abuse. Factors related to initiation and the user may switch to injecting the cocaine instead progression into other drug phases—regular drug of inhaling it. This new route of administration use, abuse, and dependency—or into the use of exposes the user to a more potent form of the drug multiple drugs are important to understand in or- as well as to increasedmedicalcomplications. der to develop appropriate PREVENTION programs Other reasons that adolescents continue using a aimed at reducing all drug use—whether legal or particular drug may be socially and environmen- illicit. tally driven. Teenagers looking for peer acceptance or wanting to appear ‘‘cool’’ or mature might de- REASONS FOR DRUG USE cide to use drugs. For example, although the use of TOBACCO andA LCOHOL is illegal for adolescents, it For both pharmacological andpsychological is both legal andsocially acceptable for adults.A D- reasons, an adolescent who tries a particular type of VERTISING, the media, and role models portray drug is more likely to use that substance again if he drinking and smoking as desirable. Associating and or she enjoys the drug’s effects. However, if un- socializing with peers who are using drugs provides pleasant experiences are associatedwith the use, an opportunity for access to drugs that can encour- trying it again is less likely. age experimentation andongoing use. Because the body becomes accustomed to the Researchers have investigatedthe influence of effect of a drug, often the drug amount will need to parents andthe family environment on children’s be increasedin orderto obtain an effect. This alcohol and drug use, dysfunctional patterns of phenomenon is known as tolerance, andonce toler- coping, and delinquent activity. In one study, a ance to a drug develops, the level of drug use may large group of New Jersey adolescents was inter- escalate into larger andlarger doses.Continueduse viewedby phone at two differenttimes, three years 34 ADOLESCENTS AND DRUG USE apart. Between 1979 and1981, 1,380 subjects DRUG-USE SEQUENCE aged12, 15, and18 were interviewed.Three years The use of one drug is often related to the subse- later, 95 percent of them (1,308 subjects) were quent use of another. Typically, drug use begins interviewedagain. The interviews includedtopics with alcohol andcigarettes, which are followedby of family harmony andcohesion, parenting styles, marijuana andother illicit drugs.This typical se- andthe attitudesandbehaviors of parents. The quence of drug use was established in the 1970s results showedthat the alcohol consumption of the (Kandel & Faust, 1975) and was found to continue younger children was influenced by the alcohol use into the 1990s, in different populations and in dif- and attitudes of the parent of the same gender as ferent ethnic andcultural groups. Problem drink- the child. Older adolescents, though, were most ing typically fits into the pattern between ongoing strongly affectedby the father’s alcohol use. Paren- marijuana use andthe use of other illicit drugs tal hostility andlack of warmth towardthe children (Donovan & Jessor 1983). was associatedwith use of drugsandalcohol Cocaine use tends to follow marijuana use, with among adolescents (Johnson & Pandina, 1996). crack-cocaine use occurring after cocaine use A national householdsample of 4,023 adoles- (Kandel & Yamaguchi, 1993). For example, it is cents aged12 to 17 years was interviewedby tele- likely that someone who smokes CRACK has already phone about substance use, victimization experi- triedtobacco, alcohol, marijuana, andcocaine. ences, familial substance use, andposttraumatic Many adolescents who use drugs in one category, reactions to identify risk factors for substance however, do not necessarily progress to drug use in abuse or dependence. A major finding was that a ‘‘higher’’ category; many stop before becoming adolescents who had been physically assaulted or involvedin further use or habitual use. sexually assaulted, who had witnessed violence, or An important factor in the progression through who hadfamily members with alcohol or druguse the sequence of drug use is age of onset or initia- problems hadincreasedrisk for current substance tion. The use of alcohol andcigarettes typically— abuse or dependence (Kilpatrick et al., 2000). but not always—begins at an earlier age than does Data from the Centers for Disease Control and the use of illicit drugs. Adolescents who progress to Prevention Youth Risk Behavior Survey (YRBS) using illicit drugs such as crack generally begin was usedfrom 4,800 subjects to examine the rela- smoking and drinking earlier than those who do tionship between adolescents’ employment and not. Early drug use (before age fifteen) is highly substance abuse behaviors. The study concluded correlated with the development of drug and alco- that among public high school students with extra- hol abuse in adulthood (Robins & Przybeck, 1985). curricular jobs, those who workedabove 15 hours Studies of adult populations provide additional per week appearedto have an increasedrisk for support for a connection between regular adoles- substance abuse (Valois, 2000). cent drug use and later, further drug use. For ex- A study that examined the effects of family ample, illicit drug use during adolescence and early structure andfamily environments on the initiation adulthood has been found to occur more often in of illicit drug use among a sample of Hispanic, adults who have used psychotherapeutic medicines African American, andwhite adolescentboys found (e.g., tranquilizers, sedatives) (Trinkoff, Anthony, large differences in family structure among the & Mun˜ oz, 1990). Studies of people going to drug- three groups. African American adolescents re- treatment centers often demonstrate that these peo- ported the lowest incidence of illicit drug use initia- ple are not only entering treatment for use of sub- tion, andthe weakest effects of family structure and stances such as cocaine or heroin but that they are environment on substance use. Deteriorating also addicted to caffeine, tobacco, and/or alcohol, changes in family environments were stronger pre- the very substances they first startedusing. dictors of the initiation of drug use among Hispanic immigrants than nonimmigrants, andfamily socio- MULTIPLE-DRUG USE economic status was a predictor for immigrant His- panics only. For all groups, the accumulation of The use of one type of drug may lead to experi- family risk factors was a stronger predictor of illicit menting with other drugs as users add to or find drug initiation than family structure (Gil, 1998). substitutes for their original drug of choice. Some ADOLESCENTS AND DRUG USE 35 of this progression may be an effect of matura- hurdle in studying drug use is obtaining accurate tion—that is, of drug-using adolescents moving on information. Reports are assumedto be honest to other drugs as they grow older—or it may be andcorrect, basedon the respondents’memory. attributable to the cost andavailability of different Researchers try to promote honesty andaccuracy types of drugs, introduction to new substances by by providing memory aids (e.g., pictures of drugs) drug-using peers, or drug-seeking behavior in as well as by assurances of anonymity andconfi- which individuals continue trying different drugs dentiality. until they achieve the desired effect. Polydrug Another concern of researchers is that reports of (multiple-drug) use can also occur when people try drug use will be affected by the way the population to counteract the effect of one drug by the use of is sampledor by those participating. For example, another—for example, by taking tranquilizers a survey conducted in an inner-city public school (which relieve symptoms of anxiety) in order to may not reflect all adolescents. High school drop- counteract the anxiety-producing effects of co- outs who are not in class when the data are col- caine. lectedandstudentsenrolledin private schools may have levels of drug use that are different from those RESEARCH METHODS of students attending public schools. Much of the most useful data for studies of PREVENTION IMPLICATIONS adolescent drug use are collected either by self- administered questionnaires or during interviews. Adolescent drug use must be considered in rela- Often the questionnaires are given out in class- tion to the normal developmental challenges of ad- rooms for students to complete anonymously. This olescence. Because individuals use drugs in differ- type of study, which obtains data from all respon- ent ways for many reasons, no single prevention dents at the same time, is known as a cross-sec- program will be effective with all groups at all ages. tional survey, andit providesimportant clues about Understanding the factors that determine the link how the use of different substances relates to such between the usage of one drug to the usage of factors as age, gender, and ethnicity. In the drug- another has important policy implications for de- sequencing studies, researchers collect information veloping prevention andeducationalprograms. as to whether a substance was usedandthe age of The sequential nature of drug use, as it is now the person at the time of first use. Then, using a understood, would indicate that prevention efforts statistical technique calledGuttman scaling, they targeted toward reducing or delaying adolescents’ combine each drug category and the ages of first initiation into use of alcohol andcigarettes would use for the entire sample to establish a predominant reduce these adolescents’ use of marijuana and sequence of use, by age, for the different sub- other drugs. Similarly, efforts targeted toward re- stances. ducing adolescents’ marijuana use might reduce Longitudinal cohort study is the term usedfor the rates of these adolescents’ progression to the study design whereby researchers test the pro- ‘‘higher’’ stages of drug involvement. Prior drug gression of drug users to stronger substances. In use is a risk factor for progression; that is, the use of these studies, people are interviewed or given a one drug may increase the likelihood of use of questionnaire to fill out repeatedly over time. For another drug, but it is not in itself a cause of further example, the same youths may be contactedannu- progression. ally to provide information on their drug use during Data from the National Longitudinal Study on the year. Although this methodmay help establish Adolescent Health reveal that there are many fac- the correct timing and order of drug-use initiation tors that determine whether teenagers will be pre- for any given individual, it is a very difficult ap- disposed to engage in harmful behaviors. The sur- proach because of the cost andtime involvedin vey of 12,118 teenagers foundthat teenagers who tracking people for many years. felt close to their parents andsiblings, teachers, and Since illegal drug use has an antisocial connota- classmates were less likely to engage in risky be- tion, people may underreport their use, although haviors. (Resnick, 1997) some teenagers may exaggerate reports of their Educating young people on the dangers of drugs drug use to create an impression. The biggest has hadsome measurable success. A school-based 36 ADULT CHILDREN OF ALCOHOLICS (ACDA)

series of classes on the dangers of anabolic steroid GOLDBERG, Linn, ET AL. (1996). Effects of a multidimen- use appearedto help reducesteroiduse among sional anabolic steroidprevention intervention: The teenage athletes. Researchers evaluatedseven Adolescents Training and Learning to Avoid Steroids weekly, 50-minute classes that gave 702 teenage (ATLAS) Program. JAMA, The Journal of the Ameri- football players comprehensive education in the can Medical Association, 276, 1555. dangers of steroids and alternatives to their use. JOHNSON,V.,&PANDINA, R. J. (1991). Effects of the This intervention improvedthe athletes’ ability to family environment on adolescent substance use, de- drop steroid use when compared to a group of 804 linquency, andcoping styles. American Journal of athletes who just receiveda pamphlet about ste- Drug and Alcohol Abuse, 17, 71. roids. Athletes often use steroids to boost their KANDEL, D. B., & FAUST, R. (1975). Sequences and performance, but the drugs can have dangerous stages in patterns of adolescent drug use. Archives of side effects. (Goldberg, et al., 1996) General Psychiatry, 32, 923–932. KANDEL, D. B., & YAMAGUCHI, K. (1993). From beer to TRENDS crack: Developmental patterns of drug involvement. American Journal of Public Health, 83, 851–855. The annual survey of nearly 50,000 students KILPATRICK, D. G.; ET AL. (2000). Risk factors for adoles- aroundthe country, ‘‘Monitoring the Future,’’ con- cent substance abuse and dependence: Data from a ducted at the Institute for Social Research at the national sample. Journal of Consulting and Clinical University of Michigan, reportedin 1999 that, after Psychology, 68, 19. declining in recent years, drug use among Ameri- RESNICK, M. D., ET AL. (1997). Protecting adolescents can teens generally heldsteady.However, there from harm: Findings from the National Longitudinal were slight increases in adolescents’ use of anabolic Study on Adolescent Health. JAMA, The Journal of the steroids and the drug ecstasy. The report also noted American Medical Association, 278, 823. that teen tobacco smoking dropped slightly but was ROBINS,L.N.,&PRZYBECK, T. R. (1985). Age of onset of still well above rates of the early 1990s. Drugs that drug use as a factor in drug and other disorders. In N. showedlittle change in use includedmarijuana, Kozel & E. Adams (Eds.), Cocaine technical review. amphetamines, hallucinogens, tranquilizers, and Rockville, MD: National Institute on Drug Abuse. heroin. The only significant decline was in the use TRINKOFF, A. M., ANTHONY, J. C., & MUN˜ OZ, A. (1990). of crack cocaine among eighth andtenth graders, Predictors of the initiation of psychotherapeutic med- after several years of gradually increasing use. The icine use. American Journal of Public Health, 80,61– Michigan study had been tracking high school se- 65. niors for 25 years andfollowing eighth andtenth VALOIS, R. F. (2000). Association between employment graders for the previous nine years. The survey andsubstance abuse behaviors among public high included 45,000 students from 433 schools across school adolescents. JAMA, The Journal of the Ameri- the country. Researchers pointedout that druguse can Medical Association, 283, 180. rates were down from the peak levels in overall VISE, D. A., & ADAMS, L. (1999). Study indicates teen illicit drug use by American teenagers that were drug use may be leveling off; Researchers see resur- reachedin 1996 and1997. gence of ‘ecstasy’ among older youths in annual sur- vey. The Washington Post, A, 2:1. (SEE ALSO: Conduct Disorder and Drug Use; ALISON M. TRINKOFF Coping and Drug Use; High School Senior Survey) CARLA L. STORR REVISED BY MARY CARVLIN BIBLIOGRAPHY

DONOVAN, J. E., & JESSOR, R. (1983). Problem drinking and the dimension at involvement with drugs. Ameri- ADULT CHILDREN OF ALCOHOLICS can Journal of Public Health, 73, 543–552. (ACDA) Taken literally, this term indicates peo- GIL, A. G., ET AL. (1998). Temporal influences of family ple over the age of eighteen, who have at least one structure andfamily risk factors on druguse initiation biological parent with severe andrepetitive life in a multiethnic sample of adolescent boys. Journal of problems with alcohol. Because of their genetic and Youth and Adolescence, 27, 373. familial relationship to an alcoholic, these people ADULT CHILDREN OF ALCOHOLICS (ACDA) 37 carry an increasedrisk of severe alcohol problems attempting to draw conclusions. For example, it is themselves (a probability of two to four times that well establishedthat childrenof alcoholics are of children of nonalcoholics). Probabilities also in- much more likely to develop alcoholism them- dicate that they are not more vulnerable to severe selves, with the possibility that many of the charac- psychiatric disorders (such as schizophrenia or teristics being described relate to the consequences manic depressive disease) and that they do not of their own alcohol problems as they developed. A carry a heightenedrisk for severe problems with secondproblem is the variety of backgroundsthat some drugs of abuse (such as heroin). Nevertheless, can contribute to an alcoholism risk, with the possi- it is possible that when children of alcoholics reach bility that severe impulse-control disorders or the adolescence or adulthood, they might be slightly presence of an ANTISOCIAL PERSONALITY disorder more likely to have problems with marijuana-type drugs or with stimulants (such as cocaine or am- in the parents couldhave been associatedwith phetamines). It has also been observedthat if their passing on several biological characteristics to childhood home has been disrupted by alcohol- some, but certainly not all, children of alcoholics. In relatedproblems in either or both parents, the chil- this instance, the characteristics described would dren may have greater difficulties with a variety of relate to the associated disorder, such as the antiso- areas of life adjustment as they mature or go off on cial personality disorder, rather than the childhood their own. experiences. In considering these factors, it is also The label Adult Children of Alcoholics has been important to remember that a substantial propor- given to a self-help group, often abbreviatedas tion, perhaps a majority, of children of alcoholics ACOA. Within the group, people with at least one never develop alcoholism, are not likely to join alcoholic parent can meet with others for discus- ACOA groups, andappear to demonstratemany sion, the sharing of oldandcurrent experiences, personality andbehavioral characteristics that re- andthe chance to findinterpersonal support— semble those of individuals who do not have alco- which helps place their own individual experiences holic parents. into perspective. People who join this voluntary In summary, the term adult children of alcohol- organization are likely to be those who both feel ics has a variety of meanings. First, biological chil- impairedandseek help towardcoping with their dren of alcoholic parents carry a two-to-four-fold past and/or present problems. The term ACOA has also been thought to de- increasedrisk for alcoholism themselves. Thus, this scribe a group of characteristics of individuals who designation is an important risk factor for the fu- grew up with alcoholic parents in the home. There ture development of alcoholism. Second, the abbre- are research projects that do indicate that such men viation ACOA relates to a self-help group where a andwomen have a greater than chance likelihood minority of children of alcoholics, especially those of having problems expressing their feelings, feel- who expressedlevels of discomfort,have joined ing comfortable with intimacy, or in maintaining together to share experiences andoffer support. long-term relationships including marriages. There The third and least meaningful definition of adult are less data to support conclusions regarding a children of alcoholics relates to a variety of inade- possible association between an ACOA status and quately studied personality characteristics that problems with developing trust, impairment in might relate to the childhood environment in which feelings of well-being andachievement, enhanced an individual was raised, might be a result of addi- feelings of a needto rescue other people when they tional psychiatric conditions among the parents, are in emotional or psychological distress, excessive might reflect general factors associatedwith a dis- feelings of a needto control a situation, anda more ordered childhood home but have nothing specifi- global dissatisfaction with life and current situa- cally to do with alcoholism, or might relate to tions than wouldbe expectedfrom chance alone. While common sense woulddictatethat being specific alcohol-relatedexperiences in the child- raised in the home of an alcoholic individual might hoodhome. contribute to problems with intimacy andcause levels of psychological discomfort, most of the ex- (SEE ALSO: Al-Anon; Codependence; Conduct Dis- isting studies do not control for important factors in order and Drug Use) 38 ADVERTISING AND THE ALCOHOL INDUSTRY

BIBLIOGRAPHY usually find a vending machine or ask an older friendto buy for them. BURK,J.P.&SHER, K. J. (1990). Labeling the childof an alcoholic: Negative stereotyping by mental health professionals andpeers. Journal of the Study of Alco- hol, 51, 156–163. ALCOHOL USE BY AMERICANS DAWSON, D. A. (1992). The effect of parental alcohol In a survey conducted in 1996, 109 million dependence on perceived children’s behavior. Journal Americans age 12 and older hadusedalcohol in the of Substance Abuse, 4, 329–340. previous month (51% of the population). About 32 FISHER, G. L., ET AL. (1992). Characteristics of adult million people (15.5%) engagedin binge drinking, children of alcoholics. Journal of Substance Abuse, 4, defined as five or more drinks on the same occasion. 27–34. Of these, about 11 million Americans (5.4%) were FULTON,A,I.&YATES, W. R. Adult children of alcohol- heavy drinkers, defined as five or more drinks on ics. Journal of Nervous and Mental Disorders, 178, the same occasion on at least five different days in 505–509. the past month. GREENFIELD, S. F., ET AL. (1993). Long-term psychologi- The percentage of college freshmen who say they cal effects of childhood exposure to parental problem drink beer frequently or occasionally was 51.8 per- drinking. American Journal of Psychiatry; 150, 608– cent in 1998. Among all college students, the over- 613. all binge-drinking rate has stayed constant between SCHUCKIT, M. (1994). Low level of response to alcohol as 1993 and1999 at 44 percent, but frequent binge a predictor of future alcoholism. American Journal of drinkers rose from 20 percent in 1993 to 23 percent Psychiatry, 151, 184–189. in 1999. WERNER, E. E. (1986). Resilient offspring of alcoholics: The percentage of high school seniors who re- A longitudinal study from birth to age 18. Journal of portedhaving five or more drinksin a row in the the Study of Alcohol, 47, 34–40. last 2 weeks was 30.8 percent in 1999, up from MARC A. SCHUCKIT 27.5 percent in 1993. The Bureau of Alcohol, Tobacco andFirearms (ATF), in 2000, estimatedthat 14 million U.S. residents suffer from alcohol abuse and depen- ADVERTISING AND THE ALCOHOL dence, and 76 million are affected by the alcohol- INDUSTRY The beverage alcohol industry in- ism of a family member. cludes companies that market beers and brews The illegal use of alcoholic beverages by teen- (malt liquors), wines andsparkling wines (fer- agers has generateda high level of concern on the mented), and distilled spirits—whiskey, vodka, part of health-care professionals, police, parents, scotch, gin, rum, andflavoredliquors. Sales of andactivist groups such as Mothers Against Drunk these products, usually through distributors, are Driving (MAAD) andthe Center for Science in the limitedto those businesses that have obtainedspe- Public Interest (CSPI). cial licenses to sell one or more of the above catego- Another cause for concern is that the level of ries of products. For example, if a restaurant has alcohol use in 1996 was strongly associatedwith only a license to serve beer andwine, it cannot serve illicit drug use. Thirty-one percent of the heavy other types of alcoholic beverages. drinkers were current illicit drug users; 16 percent In the UnitedStates, alcoholic beverages and of the binge (but not heavy drinkers) were illicit tobacco products are the only consumer goods that drug users; 5.3 percent of the other drinkers, but are legally restrictedfor sale only to those who are only 1.9 percent of the nondrinkers, were illicit not minors—at least 21 years of age in the case of drug users. alcohol or 18 (19 in three states) in the case of tobacco. Sales to anyone under those ages, respec- tively, are illegal, yet every day thousands of mi- THE ADVERTISING PROBLEM nors buy beer, wine coolers, cigarettes, andsnuff with no questions askedby store clerks or owners. The high level of alcohol use by those under the Even if a store refuses to sell to minors, they can age of 21 creates an advertising problem for the ADVERTISING AND THE ALCOHOL INDUSTRY 39 companies that market alcoholic beverages. How liquors average 4.1 percent, wine 12 percent to 20 do you advertise to the 21-and-over group and also percent anddistilledspiritsfrom 40 percent (80 appear not to be appealing to the under-21 group? proof) to 50 percent (100 proof). Beer is usually Since teenagers have a very strong desire to grow soldin 12-ounce containers, whereas malt liquors up fast, or at least participate in activities they view are usually soldin 40-ounce bottles. as adult, they are very vulnerable to anything they The Federal Trade Commission (FTC) also re- believe would help them achieve adulthood. views advertising, with emphasis on instances of Critics accuse the alcoholic-beverage companies false or misleading ads. Neither the ATF nor FTC of making their advertising and promotional pro- has been very aggressive in challenging ads that grams inviting to teenagers, who are already very seem to be targetedto young drinkersor encourage receptive to the ideas of engaging in adult activities, heavy drinking. being successful, being more confident, and being The FoodandDrug Administration(FDA) in more attractive to the opposite sex. The alcoholic the Department of Health andHuman Services has beverage companies respondthat they follow the no jurisdiction over alcohol advertising, with the industry voluntary advertising guidelines and do exception of wines with less than 7 percent alcohol. not target teenagers. They also point to programs Unlike pharmaceuticals, there is no mandate that like the public service initiatives sponsoredby labels or advertising materials for alcoholic prod- America’s beer industry, which encourages drink- ucts provide a listing of the risks/consequences, as ers to ‘‘know when to say when,’’ ‘‘drink smart or well as the benefits. Americans regularly see ads, don’t start,’’ ‘‘think when you drink,’’ or ‘‘drink company logos, andbillboardsthat encourage peo- safely.’’ ple to drink, but such advertising fails to provide information about the down side of drinking, espe- cially excessive drinking. WHO MINDS THE STORE? The U.S. Bureau of Alcohol, Tobacco, andFire- arms (ATF) in the Department of the Treasury is WHAT IS ADVERTISING the federal agency with responsibility for over- Merriam-Webster’s Collegiate Dictionary de- seeing the alcohol industry. Its rules discourage ad- fines the verb advertise: ‘‘to call public attention to vertising claims that are obscene or misleading, as especially by emphasizing desirable qualities so as well as those that associate athletic ability with to arouse a desire to buy or patronize,’’ The noun drinking. Also, the ATF takes the position that advertising includes ‘‘by paid announcements.’’ ‘‘unqualifiedhealth claims on productsthat pose The broad umbrella of advertising—in addition to increasedhealth risks are deceptive.’’ television, radio, and print media—uses billboards, Alcoholic beverages soldin the UnitedStates point-of-purchase signs anddisplays,andincreas- have to carry a warning on the container that ingly, sponsorship of special events such as music states: ‘‘GOVERNMENT WARNING: (1) According to the Surgeon General, women festivals; auto, bicycle, andboat racing; andother should not drink alcoholic beverages during preg- sports. nancy because of the risk of birth defects. (2) Consumption of alcoholic beverages impairs your ability to drive a car or operate machinery, ROLE OF ADVERTISING andmay cause health problems.’’ Advertising is used as a major tool in marketing. Until the 1990s, the alcohol content of beer When a company first introduces a new product, couldnot be includedon the labeling of the con- the goals generally are: tainer or in any associatedadvertising.As a result of a suit by Adolph Coors Co., a federal court 1. To inform potential purchasers that a particular decision overturned this restriction on labeling, and product is available and why they might like to so companies are permittedto label their beers and try this new product. malt liquors with the alcohol content. Beer averages 2. To persuade people that they should go out and 5 percent alcohol, ales average 6 percent, malt buy the product. 40 ADVERTISING AND THE ALCOHOL INDUSTRY

3. To let people know where the product can be CORRELATION OF ADVERTISING purchased. TO CONSUMPTION 4. To reassure people who buy the product that In August 1993, the NATIONAL INSTITUTE ON they have made a wise choice in doing so. ALCOHOL ABUSE AND ALCOHOLISM (NIAAA) hadthis Where more than one company sells products in a to say about alcohol, media, and advertising: The given category, the goals generally become the fol- effects of mass communications in either promoting lowing: or preventing alcohol consumption andthe prob- lems associatedwith it are equivocal. Alcohol ad- 1. To increase market share by taking business vertisements and broadcast media programming away from a competitive product. This can be have been foundto encourage a favorable view of done by offering a better product or a better alcohol use. Yet studies provide only modest sup- value and/or by increasing the level of advertis- port for the hypothesis that favorable presentations ing andpromotion to out-shout the competition. lead to positive attitudes and distorted perceptions, 2. To increase the size of the market by inducing andconsequently to increasedconsumption, par- more people to start using the product. In the ticularly among youthful viewers. The effects of case of alcoholic beverages, this can be done by advertising bans and linkages between advertising aggressively promoting features that will appeal expenditures and per capita consumption also ap- to the potential purchaser, that is, makes you more confident, more outgoing, more appealing pear to be weak andinconsistent. to the opposite sex, and, in the case of minors, There is, however, a general feeling that adver- leads to participation in adult-type activities. tising, including all of the other promotions associ- 3. To increase the size of the market by inducing atedwith it, plays a significant role in creating an people to increase their usage of your prod- image of desirability as far as the use of alcohol is uct(s). This can be done by tying the product to concerned. Recent reviews in the literature (Atkin occasions such as spring break andby promot- 1995; Lastovicka, 1995; Grube, 1995) show a ing the product heavily to the target audiences. large body of research indicating that exposure to 4. To keep reassuring heavy drinkers that they are or awareness of advertising contributes to an in- in goodcompany by drinkingthe particular crease in drinking. For example, Atkin et al. (1983) brand of beer or liquor being advertised. Since foundthat greater exposure to advertisingstimu- the ten percent of those who drink most heavily lates drinking, excessive drinking, and drinking account for about 50 percent of all alcohol con- and driving (or riding with a driver who has been sumedin the UnitedStates, this is a very impor- drinking). tant reason to advertise. Although the majority of research supports an association between advertising and consumption, researchers do not agree on the magnitude of ad- ADVERTISING EXPENDITURES vertising’s contribution to heavy drinking. G. The alcoholic-beverage companies spendbe- Frank andG. Wilcox (1988) reported:Analysis of tween $1 and$2 billion each year in the print and the results reveals no significant relationship be- broadcast media to advertise their products. In tween total advertising expenditures and consump- 1998, Anheuser-Busch Co., spent $630 million, tion of beer. Significant relationships were found, Adolph Coors Co. spent $351 million, and Seagram however, between consumption of wine anddis- Co. spent $461 million. An estimated$1 billion tilledspirits andtheir advertising.It is emphasized more was spent on other alcohol-relatedadvertis- that the relationships are correlational, not neces- ing andpromotional programs. sarily causal. Brewers andbeer distributorsspent many mil- lions of dollars sponsoring sporting events, rock BEVERAGE ALCOHOL PER concerts, spring break promotions, andother activ- CAPITA CONSUMPTION ities heavily orientedto studentson college cam- puses. They were also heavy advertisers and sup- In the UnitedStates, per capita consumption of porters of baseball, football, racing events, and all alcoholic beverages combinedreachedits peak concerts or other cultural events. in 1980 to 1981; that of wine did not reach its peak ADVERTISING AND THE ALCOHOL INDUSTRY 41 until 1986. From 1980 to 1989, there was a 12 ● These guidelines apply to all brewer advertis- percent decrease in per capita ethanol (drinking ing andmarketing materials, includinginter- alcohol) consumption—the only sustainedde- net andother cyberspace media. crease since Prohibition—down to 2.43 gallons per ● Beer advertising and marketing materials are person. The greatest decrease was seen in the con- intended for adults of legal purchase age who sumption of distilled spirits. The U.S. Department choose to drink and beer consumption is in- of Health andHuman Services has an objective for tended as a complement to leisure or social the year 2000: To reduce the per capita alcohol activity. consumption to no more than two gallons of etha- ● Beer advertising and marketing materials nol (drinking alcohol) per person annually. shouldnot contain any lewdor indecentlan- guage or images, nor shouldit portray sexual BEVERAGE ALCOHOL SALES passion, promiscuity or any other amorous activities as a result of consuming beer. Beer ranks fourth (behindsoft drinks,milk, and ● Beer advertising and marketing activities on coffee) in per capita consumption of any kindof college anduniversity campuses, or in college beverage, a position it has heldfor many years. media, should not portray consumption of Beer sales, at retail in 1999, were reportedby Bev- beer as being important to education. erage World to be $54.2 billion, comparedto $54.3 billion for soft drinks. This represents 5.99 billion Anheuser-Busch has a College Marketing Guide. gallons of beer or approximately 500 million bot- In its Event Sponsorship andPromotion statement tles/cans of beer. it lists the following: For 1999, Beverage World reportedthat ● Anheuser-Busch Co. hadincreasedits share of the Events on Campus: Anheuser-Busch will market from 46.6 to 49.9 percent. Miller Brewing limit its event sponsorship andpromotion on Co. (part of Phillip Morris) had21.3 percent of the campus to licensedretail establishments and market, and Adolph Coors 11.0 percent. According those activities open to the general public, to Anheuser-Busch, in 1998, Budweiser commer- where most of the audience is reasonably ex- cials featuring Louis the Lizardandhis catch- pectedto be above the legal purchase age. phrase ‘‘We couldhave been huge’’ were rated ● Spring Break: At spring break destination lo- America’s most popular campaign ever. In the Jan- cations, Anheuser-Busch will not conduct beer uary 2000 Super Bowl ads, Budweiser’s ‘‘Rex the advertising, event sponsorships or promotions Dog’’ adratedvery high andthe catchphrase on beaches or at other outdoor locations or ‘‘Whassup’’ received an advertising award. non-licensedpremises where most of the audi- The alcoholic spirits market in 1999 tallied ence is reasonably expectedto be below the $34.05 billion in retail sales andtotaled330 mil- legal purchase age. lion gallons. Wine came in thirdin 1999 with retail sales of $17.38 billion, but secondin gallonage at LIMITATIONS OF VOLUNTARY BEER 530 million gallons. The combinedretail sales of all INDUSTRY ADVERTISING CODES three totaled$105.63 billion. The beer industry’s voluntary advertising codes are written so as to restrict advertising practices as BEER INSTITUTE’S ADVERTISING little as possible. Qualifications like ‘‘advertising AND MARKETING CODE shouldnot be usedwhere most of the audienceis The Beer Institute’s Advertising and Marketing reasonably expectedto be below the legal purchase Code is cited when the industry tries to deflect some age’’ or ‘‘will not conduct any event sponsorships or of its critics’ charges. A copy of the entire Advertis- promotions on beaches . . . where most of the audi- ing andMarketing Codemay be obtainedfrom the ence is reasonably expectedto be below the legal Beer Institute or the Internet. Some of the guide- purchase age’’ allows beer manufacturers a lot of lines are: leeway. 42 ADVERTISING AND THE PHARMACEUTICAL INDUSTRY

THE COSTS OF ALCOHOLISM WILLIAMS, G. D., ET AL., (1992). National Institute on Alcohol Abuse andAlcoholism. Surveillance Report, In the UnitedStates alcoholism is the most wide- No. 23. spreadform of drugabuse, affecting at least five million persons. CHARLES M. RONGEY G. BORGES In 1995, according to the Substance Abuse and Mental Health Services Administration, alcohol abuse andalcoholism cost an estimated$166.5 bil- lion, while drug abuse dependence cost $109.8 bil- ADVERTISING AND THE PHARMA- lion. More than 100,000 deaths each year are re- CEUTICAL INDUSTRY The pharmaceutical latedto alcohol abuse. industry, which researches, develops, produces, andmarkets prescription drugsin the United States, is the most heavily regulatedof all indus- (SEE ALSO: Advertising and the Pharmaceutical In- tries when it comes to the advertising and promo- dustry; Advertising and Tobacco Use; Social Costs tion of its products. Through its Drug Marketing, of Alcohol and Drug Abuse) Advertising, and Communications Divisions, the FoodandDrug Administration(FDA) regulates all BIBLIOGRAPHY advertising and promotional activities for prescrip- tion drugs, including statements made to physi- ADVERTISING AGE-AD AGE DATAPLACE 100 LEADING NA- cians andpharmacists by pharmaceutical sales rep- TIONAL ADVERTISERS(1998). The American Freshman resentatives. Advertising of over-the-counter Survey: U.C.L.A. andThe American Council of Edu- (OTC) drugs, which is not regulated by the FDA, is cation. Beverage World (2000) under the jurisdiction of the Federal Trade Com- ATKIN, C. K. (1990). Journal of Adolescent Health Care. mission (FTC). 11(1). 10-24. Before a new prescription drug is approved for ATKIN,C.E.ET. AL. (1983) Journal of Drug Education marketing, the FDA andthe pharmaceutical com- 13:313-325. pany must agree on the ‘‘full prescribing informa- BEER INSTITUTE. (1992) Advertising and Marketing tion’’ that will accompany the product and that Code. must be included in all ads, brochures, promotional BUREAU OF ALCOHOL,TOBACCO AND FIREARMS, (ATF), pieces, andsamples. This full prescribing informa- (2000) Department of the Treasury tion must include, in the correct order, the follow- CENTER FOR SCIENCE IN THE PUBLIC INTEREST. Washing- ing information about the drug: its trade name, its ton, D.C. assignedname, the strength of its dosageform, a COALITION FOR THE PREVENTION OF ALCOHOL PROBLEMS. caution statement (stating that a prescription is Washington, D.C. required), a description of its active ingredient, the clinical pharmacology of the drug, indications for DISTILLED SPIRITS COUNCIL OF THE UNITED STATES. (2000) its usage, contraindications for usage, precautions, adverse reactions, instructions on what to do in FRANK, G., AND WILCOX, G. (1988). Journal of Advertis- case of overdosage, dosage and administration, and ing, 16(3), 22-30. how the drug is supplied. GRUBE, J. W. (1995). National Institute on Alcohol Abuse Typically, this information is very detailed, and andAlcoholism. Research Monograph, 28. even when it is given in six-point type, it can run to HARVARD SCHOOL OF PUBLIC HEALTH (1999). Survey. two printedpages. The majority of pharmaceutical LASTOVICKA, J. L. (1995). National Institute on Alcohol companies pay to have this information published Abuse andAlcoholism. Research Monograph, 28. in the Physician’s Desk Reference, which is sent to LIEBERMAN,L.R.AND ORLANDI, M. A. (1987). Alcohol physicians free of charge. The book is also soldin Health and Research World, 12(1), 30-33. bookstores or is available on library reference NATIONAL INSTITUTE ON DRUG ABUSE (1998). University shelves for use by consumers who want to know of Michigan Monitoring the Future Survey. more about specific drugs. SMART, R. G. (1988). Journal of Studies on Alcohol, All promotional pieces andadsto be usedwhen 49(4), 214-223. a new drug is marketed must first be approved by ADVERTISING AND THE PHARMACEUTICAL INDUSTRY 43 the FDA before marketing begins—to ensure that to the general public. Merrell Dow was next, using the statements being made are consistent with DTC ads to inform the public that physicians had a those in the official labeling. After the introduction new treatment to help smokers who wantedto stop of a new drug has been completed, copies of all smoking. When the company’s new, nonsedating subsequent ads and promotional pieces must be antihistamine became available, it usedDTC adsto sent to the FDA at the time of their first use, too, but tell allergy sufferers that physicians now hada new they do not have to be preapproved. The FDA re- treatment for allergies. The ads did not mention the views ads, brochures, direct-mail pieces, and sales name of the products; rather, they asked patients aids to ensure that a ‘‘fair balance’’ has been main- with specific problems or symptoms to see their tainedin presenting both the benefits andrisks of a physician. medication. In the 1990s, the FDA directed its The next phase of DTC advertising led to ads in attention to ‘‘scientific symposia’’ andother medi- cal meetings at which information about new magazines andnewspapers that mentionedthe drugs, or new indications for drugs, are presented. name of the product and its indication for use. The This ensures that they are not just promotional advertising of prescription drugs on television or programs for a single drug. In no other industry are radio remained greatly restricted at this time since advertising and promotion required to meet such it was not possible to include the necessary brief strict standards. summary of prescribing information on the air. Be- cause of this limitation, the ads on television or THE CHANGING ROLE OF radio had to focus on either the name of the product PHARMACEUTICAL ADVERTISING or the indication for the product. To promote Nicorette, a NICOTINE-containing Traditionally, the advertising and promotion of gum designed to help smokers stop smoking, Mer- pharmaceutical products were directed primarily rell Dow advertised it on television with the mes- to physicians, with some limitedadvertisingand sage that Nicorette was now available at phamacies promotion being directed to pharmacists. With the expiration of patents on some major drugs in the but only by prescription and under a doctor’s su- 1980s and1990s, generic versions of the drugs pervision. became available from competing manufacturers. According to FDA rules at that time, Merrell The generic drugs were priced lower than the Dow couldnot say that Nicorette was useful in brand-name products, so pharmacists got laws helping smokers who wantedto stop smoking since passedallowing them to substitute generic products it had included the name of the product in the for the brand-name products. This gave pharma- commercial. When a company has the only—or the cists more control over which generic company’s major—product in the market, this approach can products to purchase and dispense. Advertising and be very effective because it increases awareness promotion to pharmacists increased. When com- among patients that a new treatment is available mittees, usually composedof pharmacists, became andinfluences them to see their doctors. very important in deciding which drugs could, or In 1997 the FDA changedthe regulations re- could not, be prescribed or reimbursed under third- garding DTC advertising of prescription products party payment programs (medicaid, HMOs, and on television andradio.It now allows both the other insurance programs), advertising and promo- name of the product and indications for it to be tion were also directed to the decision makers in advertised, as long as the main precautions or those organizations. More recently, advertising is warnings are given in the commercial. This has led also being directed to the consumer. to many prescription products being advertised on television, such as Rogaine, Claritin, Allegra, DIRECT-TO-CONSUMER Viagra, Pravachol, Prilosec, andothers. Nicorette ADVERTISING by this time hadbeen clearedby the FDA to be sold In the mid-1980s, two pharmaceutical compa- over-the-counter and, since it no longer required a nies began direct-to-consumer advertising (DTC). prescription, the product was no longer governed Pfizer ledthe way with its health-care series of ads by FDA rules but rather by FTC regulations. 44 ADVERTISING AND THE PHARMACEUTICAL INDUSTRY

PROMOTIONAL EXPENDITURES CODE OF PHARMACEUTICAL MARKETING PRACTICES The use of DTC ads on television and radio for prescription drugs has doubled since 1997 and The member companies of the Pharmaceutical reached$1.9 billion in 1999. By 2000, there were Research & Manufacturers of America (PhRMA) ninety-seven different prescription products that have workedtogether to create guidelinesfor the had been advertised on television or in print ads. In ethical promotion of prescription pharmaceutical products. addition to this advertising, a separate budget was The pharmaceutical industry undertakes: formulatedfor advertisingandpromotion to physi- cians, seminars, andsymposia, andthe large force ● that all products it makes available for pre- of medical service representatives who call on doc- scription purposes to the public are backedby tors, pharmacists, andother health-care profes- the fullest technological service andhave full sionals. These representatives inform them about regardfor the needsof public health: to pro- their companies’ products; that is, how to use them, duce pharmaceutical products under adequate procedures and strict quality assurance; the side effects to anticipate, and the different dos- ● To have the claims for substances andformu- age forms available for each product. They also lations on valid scientific evidence, thus deter- provide starter doses (samples) to physicians, mining the therapeutic indications and condi- which may be usedto initiate treatment for a pa- tions of use; tient or, in some cases, to provide medication for a ● To provide scientific information with objec- patient who cannot affordto buy it. The total for all tivity andgoodtaste, with scrupulous regard advertising and promotion, including the medical for truth, andwith clear statements with re- service representatives, can run as high as 25 per- spect to indications, contraindications, toler- cent of sales. ance, andtoxicity; Some members of Congress feel that pharma- ● To use complete candor in dealing with public ceutical companies are spending too much on ad- health officials, health-care professionals, and vertising andpromotion, andsome wouldeven like the public, andto comply with the regulations to limit these expenditures. Such restrictions are andpolicies issuedby the FoodandDrug Ad- ministration. already in effect in Great Britain. Proponents of ● Information on pharmaceutical products spending limits feel that they would result in lower shouldbe accurate, fair, andobjective, and prices for prescription drugs; these same individu- presentedin such a way as to conform not only als do not believe that the dissemination of infor- to legal requirements but also to ethical stan- mation about new drugs and new treatment proce- dards and to standards of good taste. dures would suffer as a result. However, many in ● Information shouldbe basedon an up-to-date the health industry think that if physicians had to evaluation of all the available scientific evi- depend on their medical journals for information dence and should reflect this evidence clearly. about new drugs, they might not know about them ● No public communication shouldbe made for several years. Meanwhile, their patients in need with the intent of promoting a pharmaceutical of the new drugs would be deprived of the latest product as safe and effective for any use before advances in medical care. In the United States, only the requiredapproval of the pharmaceutical 8.8 percent of health-care dollars was spent on product for marketing for such product is ob- tained. drugs. By comparison, in Canada 12.5 percent of ● Particular care shouldbe taken that essential the total health-care dollars were spent on drugs. information as to pharmaceutical products’ The advertising and promotion of prescription safety, contraindications, and side effects or drugs, including the cost for medical service repre- toxic hazards is appropriately and consistently sentatives who call on the nation’s physicians and communicatedsubject to the legal, regulatory, other health-care professionals, make up about 2 andmedicalpractices of the UnitedStates. percent of the total health-care expenditures in the ● Medical representatives should be adequately UnitedStates. trainedandpossess sufficient medicaland ADVERTISING AND THE PHARMACEUTICAL INDUSTRY 45

technical knowledge to present information on keting Practices, the following guidelines on gifts their company’s products in an accurate and given to physicians from industry as set forth in the responsible manner. Opinion of the Council on Ethics andJudicialAf- ● Symposia, congresses, andthe like are indis- fairs. pensable for the dissemination of knowledge Any gifts accepted by physicians individually andexperience. Scientific objectives shouldbe shouldprimarily entail a benefit to pa- the principal focus in arranging such meet- tients andshouldnot be of substantial ings, andentertainment andother hospitality value. Accordingly, textbooks, modest shouldnot be inconsistent with such objec- meals, andother gifts are appropriate if tives. they serve a genuine educational func- ● Scientific andtechnical information should tion. Cash payments shouldnot be ac- fully disclose properties of the pharmaceutical cepted. product as approved in the United States Individual gifts of minimal value are permissi- basedon current scientific knowledgeand ble as long as the gifts are relatedto the FDA regulations. physician’s work. (e.g., pens and ● Samples may be suppliedto the medicaland notepads). alliedprofessions to familiarize them with the Subsidies to underwrite the costs of continuing products or to enable them to gain experience medical education conferences or profes- with the product in their practice. The re- sional meetings can contribute to the im- quirements of the Prescription Drug Market- provement of patient care andtherefore ing Act of 1987 shouldbe observed. are permissible. Since the giving of a sub- The PhRMA Boardalso includesthese four posi- sidy directly to a physician by a com- tion statements as an adjunct to the PhRMA Code pany’s sales representative may create a of Pharmaceutical Marketing Practices. relationship which couldinfluence the use of the company’s products, any subsidy Gifts, hospitality or subsidies offered to physi- shouldbe acceptedby the conference cians by the pharmaceutical industry sponsor, who in turn can use the money to ought not to be acceptedif acceptance reduce the conference’s registration fee. might influence or appear to others to Payments to defray the costs of a confer- influence the objectivity of clinical judg- ence shouldnot be accepteddirectlyfrom ment. A useful criterion in determining the company by the physicians attending acceptable activities andrelationships is: the conference. Wouldyou be willing to have these ar- Subsidies from industry should not be ac- rangements generally known? ceptedto pay for the costs of travel, lodg- Independent institutional and organizational ing, or other personal expenses of physi- continuing medical education providers cians attending conferences or meetings, that accept industry-supported programs nor shouldsubsidiesbe acceptedto com- shoulddevelopandenforce explicit poli- pensate for the physicians’ time. Subsi- cies to maintain complete control of pro- dies for hospitality should not be accepted gram content. outside of modest meals or social events Professional societies shoulddevelopandpro- heldas a part of a conference or meeting. mulgate guidelines that discourage exces- It is appropriate for faculty at conferences sive industry-sponsored gifts, amenities, or meetings to accept reasonable hon- andhospitality to physicians at meetings. oraria andto accept reimbursement for Physicians who participate in practice-based reasonable travel, lodging, and meal ex- trials of pharmaceuticals shouldconduct penses. It is also appropriate for consul- their activities in accordwith basic pre- tants who provide genuine services to re- cepts of acceptedscientific methodology. ceive reasonable compensation andto The PhRMA Board of Directors also adopted, as accept reimbursement for reasonable part of the PhRMA Code of Pharmaceutical Mar- travel, lodging, and meal expenses. Token 46 ADVERTISING AND TOBACCO USE

consulting or advisory arrangements can- lations. The basic restrictions have been that com- not be usedto justify compensating physi- panies cannot use paidadvertisingon television or cians for their time or their travel. radio, they cannot claim what they cannot prove Scholarship or other special funds to permit (e.g., that low-tar cigarettes are less hazardous to medical students, residents, and fellows health), andthey must includeone of four warn- to attendcarefully selectededucational ings on cigarette packages andads.The fact that conferences may be permissible as long as warning labels are printedon a pack of cigarettes the selection of students, residents, or fel- has been successfully usedby the tobacco compa- lows who will receive the funds is made by nies as a defense against tobacco victims’ lawsuits. the academic or training institution. The whole picture changedwhen Florida,Min- No gifts shouldbe acceptedif there are strings nesota, Mississippi, andTexas were able to reach attached. For example, physicians should an agreement in 1997 andearly 1998 with the not accept gifts if they are given in rela- major tobacco companies andwon compensation tion to the physician’s prescribing prac- for the effects of smoking on their health-care ex- tices. In addition, when companies under- penses. Minnesota was able to obtain copies of write medical conferences or lectures long-secret memos, reports, letters, andother docu- other then their own, responsibility for ments that were made public as part of the $6.6 andcontrol over the selection of content, billion settlement reachedin their lawsuit against faculty, educational methods, and mate- cigarette makers. rials shouldbelong to the organizers of On November 23, 1998, the major tobacco com- the conferences or lectures. panies enteredinto an agreement with the other forty-six states. This agreement, which is known as (SEE ALSO: Advertising and the Alcohol Industry; the Master Settlement Agreement (MSA), settled Advertising and Tobacco Use) litigation brought by the states andother entities that were seeking the reimbursement of expendi- CHARLES M. RONGEY tures relatedto smoking andhealth. Underthis agreement, the states andtobacco companies jointly agreedto concrete provisions to reduce ADVERTISING AND TOBACCO USE youth smoking, new public health initiatives, and Tobacco companies spendmore than $5 billion an- important new rules for governing a tobacco com- nually to advertise and promote cigarettes and pany’s way of doing business. other tobacco products. Tobacco companies claim The cigarette companies agreedto pay $368.5 that the purpose anddesiredeffect of marketing billion over 25 years. Of this, $246 billion goes to are merely to provide information and to influence the states, andthey have startedto receive pay- brandselection among current smokers, although ments under this agreement. The state of Florida only about 10 percent of smokers switch brands in receives $450 million each year under this agree- any one year. Since more than one million adult ment, Iowa $54.9 million, andthe other states dif- smokers stop smoking every year andalmost half a fering amounts. Iowa, Kansas, andWashington million other adult smokers die from smoking-re- have agreedto set asidethis money entirely for lateddiseases,the tobacco companies must recruit health care. Iowa has passeda law that their money an average of 3,300 new young smokers every day shall go to three areas: access to health care, public to replace those who die or otherwise stop smoking. health andsmoking prevention, andsubstance- Tobacco companies contendthat smoking is an abuse treatment andprevention. In other states, ‘‘adult habit’’ and that adult smokers ‘‘choose’’ to this new-foundmoney has createdhot political bat- smoke. However, many medical researchers assert tles over how much of their tobacco settlement to that cigarette smoking is primarily a childhood spendon tobacco prevention programs. addiction or disease and that most of the adults A two-year education effort and ad campaign who smoke startedas childrenandcouldnot quit. has loweredthe number of teen smokers in Florida. Unlike the pharmaceutical companies, which The campaign reduced middle-school smoking by are tightly regulatedas to their advertisingand more than half andloweredsmoking among high- promotion, the tobacco industry has had few regu- school students by 24 percent. This multimillion- ADVERTISING AND TOBACCO USE 47

longer market, distribute, offer or sell, or li- cense any apparel or merchandise bearing a tobacco brandname. ● Free product sampling is banned anywhere, except for a facility or enclosedspace where an operator may ensure that no minors are pres- ent. ● Manufacturers may not sell or distribute ciga- rette packs containing less than twenty ciga- rettes until the year 2001. ● There shall be no payment for the use of to- bacco products in movies, TV programs, live performances, videos, or video games. (Does not apply to media viewed in an adult-only facility or to media not intended for distribu- The Marlboro man, a controversial tobacco icon, tion to or display to the public.) on a billboard in downtown Denver, June 20, ● There shall be no licensing of thirdparties to 1997. (Archive Photos, Inc.) use or advertise any brand name in a way that wouldconstitute a violation of the MSA if done dollar campaign was financed by Florida’s $11.3 by the participants. billion tobacco settlement, of which Florida has ● No nonbranded item may be given in ex- already received $2 billion. change for the purchase of tobacco products or The MSA has changedthe way cigarette compa- redemption of coupons or proof of purchase nies can market, advertise, and promote their ciga- without proof of age. rettes. The agreement specifically includes the fol- ● No use of a tobacco brandname as part of the lowing: name of a stadium shall be allowed. ● Tobacco sponsorships are limitedto one per ● No participating manufacturer may take any year, after a three-year grace period(from action, directly or indirectly, to target youth in November 1998). Such brand-name sponsor- the advertising, promotion, or marketing of ship may not include concerts, events in which tobacco products. It also prohibits any action any paidparticipant or contestants are youth, the primary purpose of which is to initiate, or any athletic event between opposing teams maintain, or increase the incidence of youth in any football, basketball, baseball, soccer, or smoking. hockey league. ● Effective April 23, 1999, billboards, stadium signs, andtransit signs advertisingtobacco are The previous voluntary cigarette advertising and banned. However, this does not apply to retail promotion code rules are also still in effect: establishments selling tobacco. They may ● Cigarette smoking is an adult custom. Chil- have signs up to 14 square feet inside or out- dren should not smoke. Laws prohibiting the side their stores. sale of cigarettes to minors shouldbe strictly ● Effective May 22, 1999, the use of cartoon enforced. The cigarette manufacturers adver- characters in advertising, promoting, packag- tise and promote their products only to adults ing, or labeling of tobacco products is banned. smokers. They support the enactment anden- (This applies only to ‘‘exaggerateddepictions, forcement of state laws prohibiting the sale of or depictions of entities with superhuman cigarettes to persons under 18 years of age. powers’’. It does not cover the standard camel Advertising. logo or simple drawings of a camel. It does not prohibit the continueduse of the Marlboro 1. Cigarette advertising shall not appear in publi- man or other human characters.) cations directed primarily to those under 21 ● Beginning July 1, 1999 participating manu- years of age, including school, college, or uni- facturers andothers licensedby them may no versity media (such as athletic, theatrical, or 48 ADVERTISING AND TOBACCO USE

other programs). Comic books or comic supple- time an attorney general has taken a cigarette com- ments are included. pany to court to enforce the terms of the MSA. 2. No one depicted in cigarette advertising shall be Reynolds said it was part of a program of ‘‘con- or appear to be under 25 years of age. sumer testing’’ andwas therefore allowable under 3. Cigarette advertising shall not suggest that the agreement. The attorney general alleges Reyn- smoking is essential to social prominence, dis- olds mailed the free cigarettes ‘‘under the guise of tinction, success, or sexual attraction, nor shall consumer testing or evaluation in order to market it picture a person smoking in an exaggerated and advertise its products.’’ According to the suit, manner. Reynolds sent more than 900,000 multipack ciga- 4. Cigarette advertising may picture attractive, rette mailings to more than 115,000 California res- healthy-looking persons provided there is no idents during 1999, some receiving as many as ten suggestion that their attractiveness andgood packs at a time. health are due to cigarette smoking. In his memoirs, former Surgeon General C. Ev- 5. Cigarette advertising shall not depict as a erett Koop saidthis about the tobacco industry, smoker anyone who is or has been well known as ‘‘After studying in depth the health hazards of an athlete, nor shall it show any smoker partici- smoking, I was dumbfounded—and furious. How pating in, or obviously just having participated could the tobacco industry trivialize extraordinar- in, a physical activity requiring stamina or ath- ily important public-health information: the con- letic conditioning beyond that of normal recre- nection between smoking andheart disease,lung ation. and other cancers, and a dozen or more debilitating 6. No sports or celebrity testimonials shall be used andexpensive diseases?The answer was—it just or those of others who wouldhave special appeal did. The tobacco industry is accountable to no to persons under 21 years of age. one.’’ All the agreed-on advertising and promotional restrictions spelledout in the MSA shouldbe very UNDERSTANDING THE helpful in curbing underage smoking, but the to- SMOKING HABIT bacco companies have always foundways to bypass Almost all smokers startedbefore the age of the bans andadvertisein other venues. Billboard 21—most before the age of 18—many before the advertising is now banned but tobacco companies age of 14. Young people who learn to inhale ciga- have increasedtheir level of advertisingin maga- rette smoke andexperience the mood-alteringef- zines, many of which are readby teenagers. Sev- fects from the inhalednicotine quickly become de- enty-three percent of teens (aged12 to 17) reported pendent on cigarettes to help them cope with the seeing tobacco advertising in the previous 2 weeks, complexities of everyday life. Having developed a compared to only 33 percent of adults surveyed. nicotine dependence, they find they must continue Since billboards were banned, 61 percent of teens smoking to avoid the downside of nicotine with- who recalledtobacco advertisingsaw it in maga- drawal. The earlier they start to smoke, the more zines, comparedto 50 percent the year before. dependent they seem to become—and the sooner A survey also revealedthat 77 percent of teens they start to experience smoking-relatedhealth say it is easy for people under the age of 18 to buy problems. Six years of research at the National cigarettes and other tobacco products. Many dis- Center on Addiction and Substance Abuse at Co- plays of cigarettes in convenience stores are at waist lumbia University reveals that a childwho reaches level, making them plainly available to children. age 21 without smoking, using illegal drugs, or The campaign to restrict access by youths under abusing alcohol is virtually certain never to do so. the age of 18 to cigarettes has not been too success- A survey conducted by the U.S. Department of ful. Health andHuman Services among high school A California suit against R.J. Reynolds Tobacco, students who smoked half a pack of cigarettes a day filedon May 11, 2000, charges that the company foundthat 53 percent hadtriedto quit but could has violatedthe legal settlement with state govern- not. When askedwhether they wouldbe smoking 5 ments by improperly distributing large quantities years later, only 5 percent saidthey wouldbe—but of free cigarettes by mail. This case marks the first 8 years later, 75 percent were still smoking. ADVERTISING AND TOBACCO USE 49

PURPOSE OF 4. To associate cigarette smoking with becoming CIGARETTE ADVERTISING an adult. Realizing that teenagers desire to be considered adults, to be free to make their own The tobacco companies are very adept at using decisions, and to be free from restrictions on advertising and different kinds of promotional pro- what they can andcannot do,the tobacco com- grams to help them accomplish several major ob- panies go to great lengths to stress that smoking jectives: is an ‘‘adult habit’’—that only adults have the 1. To reassure current smokers. To offset the effect right to choose whether or not to smoke. Since of thousands of studies showing the adverse teenagers are in a hurry to grow up andbe free, health effects of smoking andof the requested the simple act of smoking cigarettes can become warning labels on cigarette packages, the to- their way of showing to the worldthat they are bacco industry has continued to claim that no indeed adults. one has yet ‘‘proven’’ that smoking ‘‘causes’’ 5. To associate cigarette smoking with attractive- health problems—that these are just ‘‘statistical ness to the opposite sex. Many ads for cigarettes associations.’’ But, recently in Florida, a six- imply that if you smoke, you will also be attrac- person jury decided, on April 7, 2000, that to- tive to members of the opposite sex. In fact, bacco companies’ cigarettes were a deadly, ad- surveys of young people andadultsshow that dictive, and defective product and caused can- most people prefer to date nonsmokers. 6. To associate smoking with women’s liberation. cer for three smokers who suedthe industryin a ‘‘You’ve come a long way baby’’ was the theme class-action lawsuit. The companies must pay of the early ads for Virginia Slims cigarettes. $12.7 million to the plaintiffs. The jury has yet What these ads did not say is that women who to decide the punitive damages, which could be smoke like men will die like men who smoke. massive. The state of Florida, in order to protect The slogan ‘‘Torches of Freedom’’ coupled with its tobacco payments in the future, passeda law an image of women smoking cigarettes while capping the amount of bondthe companies marching down Fifth Avenue in the Easter Pa- wouldhave to post in orderto appeal such rade was a cigarette company’s public relations punitive damages at $100 million or 10 percent ploy years ago to influence women to start of the company’s net worth, whichever is less. smoking. In the 1990s, lung cancer became the 2. To associate smoking with pleasurable activi- number one cancer foundin women, exceeding ties. In their ads, tobacco companies show the incidence of breast cancer. healthy young people enjoying parties, dancing, 7. To show that smoking is an integral part of our attending sporting events, having a picnic at the society. The sheer number of cigarette ads— beach, sailing, andso on. The implication is that those on billboards, on articles of clothing, on if you smoke, you too will experience the kindof signs at sporting events—leave the impression goodtimes enjoyedby the smokers in the ads. that smoking is socially acceptedby the major- 3. To associate smoking with other risk-taking ac- ity of people. This image is supportedby movies tivities. Since as indicated by the warning labels that include scenes of cigarette smoking. Many on every package of cigarettes, smoking involves events sponsoredby tobacco companies include risk to one’s health, the tobacco companies at- the name of a major brandof cigarettes or tempt to counter this by showing in their ads smokeless tobacco, such as the Kool Jazz Festi- such risk-taking activities as ballooning, moun- val, the Benson & Hedges Blues Festival, the tain climbing, sky diving, and motorcycle rid- Magna Custom Auto Show, the Winston Cup ing. This is the industry’s not so subtle way of (stock car racing), the Marlboro Cup (soccer), saying: Go aheadandtake a risk by smoking. the Marlboro Stakes (horse racing), andthe You are capable of deciding the level of risk you Virginia Slims Tennis Tournament, just to name want to assume. The tobacco companies are a few. Although tobacco advertising is legally betting on the fact that most young people con- prohibitedon television, the ban has been ig- sider themselves to be immortal and do not be- noredby the strategic placement of tobacco- lieve any of smokings badeffects will ever hap- product ads in baseball and football stadiums, pen to them. basketball arenas, andhockey rinks, around 50 ADVERTISING AND TOBACCO USE

auto racetracks, andat tractor pulls andother pack offers were an additional $552 million, fol- sporting events. lowedby specialty item distribution,$512 million; 8. To discourage articles in magazines about the point of sale advertising, $305 million; outdoor ad- health risks of smoking. So important to maga- vertising, $295 million; magazines, $236 million; zines are the ads they carry for cigarettes, beer, public entertainment, $195 million; and$130 mil- food, and other products, which are marketed lion for all other forms of advertising. by the major cigarette companies or their parent There were no restrictions on cigarette advertis- companies, that many publishers are very reluc- ing in the UnitedStates until the first Report of the tant to antagonize cigarette producers by run- Surgeon General was releasedon January 11, ning articles on the health risks of smoking. This 1961. Because of the health hazards described is especially true with women’s magazines. therein, the report ledto the FederalCigarette La- 9. To gain legitimacy. Tobacco companies seek beling and Advertising Act of 1965 and, beginning public acceptance andrecognition by support- in 1966, Congress mandated that a health warning ing worthwhile groups andprograms. Many appear on all cigarette packages, although not in groups receive significant amounts of funding advertisements. On June 2, 1967, the Federal Com- from the tobacco companies to support their munications Commission (FCC) ruledthat the programs. One especially large grant, from RJR Fairness Doctrine in advertising applied to ciga- Nabisco, was a contribution of $30 million for rette ads on television and radio and required ‘‘innovative education programs’’ to schools broadcasters who aired cigarette commercials to across the country. In1989, Philip Morris made provide ‘‘a significant amount of time’’ to citizens arrangements to sponsor the Philip Morris Bill who wishedto point out that smoking ‘‘may be of Rights Exhibit, which touredthe United hazardous to the smoker’s health.’’ This rule went States in celebration of the 200th anniversary of into effect on July 1, 1967. The FCC requiredthat the Bill of Rights. In this way, Philip Morris tried there be one free public-service announcement to associate its company—including its tobacco (PSA) for every three paidcigarette commercials. subsidiary—with the Bill of Rights, and to reap During the three-year periodof 1968 to 1970, in positive press coverage as the exhibit went on which the PSAs were mandated by the Fairness display in each city. Doctrine, per capita cigarette sales decreased by 6.9 percent. In January 1970, the cigarette industry offered HISTORY OF TOBACCO ADVERTISING voluntarily to endall cigarette advertisingon tele- AND PROMOTION vision andradioby September 1970—a move that Tobacco companies’ advertising, before restric- wouldalso eliminate any PSAs, which were hurting tions were implemented, was focused on television, sales. Ultimately, Congress approvedthe Public radio, newspapers, and magazines. The advertising Health Cigarette Act of 1969, which prohibited was representedby adssuch as ‘‘I’dwalk a mile for cigarette advertising in the broadcast media as of a camel’’ or the ‘‘Call for Phillip Morris’’ or ‘‘More January 1, 1971. doctors smoke Camels’’ or ‘‘Not a cough in a In September 1973, the Little Cigar Act of 1973 carload.’’ This evolved into the ‘‘Joe Camel’’ ads, banned broadcast advertising of little cigars (ciga- the ‘‘Kool Penguin’’ ads, and the ‘‘Newport Men- rette-sizedcigars). During the three-year periodof thol’’ cigarette ads. 1971 to 1973, following the endof the PSAs re- Tobacco advertising and promotional expenses quiredby the Fairness Doctrine andthe beginning have steadily increased. In 1997, the tobacco com- of the broadcast advertising ban, cigarette sales panies spent $5.66 billion to promote their prod- increasedby 4.1 percent. ucts, up from $5.11 billion in 1996. The largest More than a decade later, smokeless-tobacco category of spending was for promotional allow- advertising in the broadcast media was banned by ances to wholesalers andretailers, $2.4 billion, the Comprehensive Smokeless Tobacco Health Ed- more than double their spending in 1990. Next ucation Act of 1986. This ban took effect on August were expenditures for retail value added. At $970 27, 1986. The Federal Trade Commission (FTC) million, this category includes non-cigarette items Bureau of Consumer Protection ruledin 1991 that given away with cigarettes. Coupons andmultiple the Pinkerton Tobacco Company violatedthe 1986 AGGRESSION AND DRUGS: RESEARCH ISSUES 51 statute banning the advertising of smokeless to- representing one of the means by which an expen- bacco andprohibitedit from ‘‘displayingits brand sive cocaine or heroin habit is financed. Systematic name, logo, color or design during televised experimental studies in animals represent the pri- (sports) events’’ of its RedMan Chewing Tobacco mary means to investigate the proximal anddistal andsnuff. This was the first action of its kindby the causes of aggressive behavior, whereas studies in FTC. humans most often attempt to infer causative rela- STAT (Stop Teenage Addiction to Tobacco), at tionships mainly from correlating the incidence of their 1991 STAT-91 Conference, addressed the violent andaggressive behavior with past alcohol problem of tobacco companies’ efforts to encourage intake or abuse of other drugs. The ethical dilemma tobacco addiction in young people. It was learned of research on aggression in animals andhumans is that the RJR Nabisco cartoon camel was at the the demand for reducing harm and risk to the center of the most extensive advertising campaign research subject, on the one hand, and on the other, ever createdto influence the values andbehavior of to validly capture the essential features of human young people. Camel’s share of the teenage market violence that is by definition injurious and harmful. rose from almost nothing to almost 35 percent in Methodologically, aggression research stems just three years by ‘‘this sleazy dromedary.’’ from several scientific roots, the experimental- psychological, ethological, andneurological tradi- (SEE ALSO: Advertising and the Alcohol Industry; tions being the most important. The use of aversive Tobacco: Dependence; Tobacco: Industry) environmental manipulations in order to produce CHARLES M. RONGEY defensive and aggressive behavior has been the focus of the experimental-psychological approach. During the 1960s, ‘‘models’’ of aggression were AFRICAN AMERICANS See Ethnic Issues developed that rely upon prolonged isolated hous- andCultural Referance in Treatment; Ethnicity ing or crowding; exposure to noxious, painful elec- andDrugs; Vulnerability as Cause of Substance trical shock pulses; omission of scheduled rewards; Abuse: Race or restrictedaccess to limitedfoodsupplies as the major aversive environmental manipulations. The behavioral endpoints in these models are defensive AGGRESSION AND DRUGS: RE- postures and bites in otherwise placid, domesti- catedlaboratory animals. The validityof such ex- SEARCH ISSUES ALCOHOL,narcotics, perimental preparations in terms of the ethology of HALLUCINOGENS, andP SYCHOMOTOR STIMULANTS differ markedly one from the other in terms of the animal, i.e. how animals normally react outside pharmacology andneurobiological mechanisms, of the laboratory, andin their relation to human dependence liability, legal and social restraints, aggressive andviolent behavior remains to be de- expectations andcultural traditions.No general termined. Aggression research using human sub- andunifying principle applies to all these sub- jects studied under controlled laboratory condi- stances, andit wouldbe misleadingto extrapolate tions has employedaversive environmental from the conditions that promote violence in indi- manipulations, such as the administration of elec- viduals under the influence of alcohol to those with tric shocks, noxious noise, or loss of prize money to other drugs. Different types of drugs interact with a fictitious opponent. This type of experimental aggressive andviolent behavior in several direct aggression research highlights the dilemma of at- and indirect ways from (1) direct activation of tempting to model essential features of valid vio- brain mechanisms that control aggression, mainly lence under controlled laboratory conditions with- in individuals who have already been aggressive in out risking the harm andinjury that are the past; (2) drug states, such as alcohol or halluci- characteristic of such phenomena. While it is un- nogen intoxication, serving as license for violent ethical to demand experimental studies that involve andaggressive behavior; (3) drugssuch as heroin ‘‘realistic’’ violent behavior, the relation between or cocaine serving as commodities in an illegal competitive behavior in laboratory situations to distribution system, drug trafficking, that relies on violence outside the laboratory remains to be violent enforcement tactics; to (4) violent behavior validated. 52 AGGRESSION AND DRUGS: RESEARCH ISSUES

In addition to environmental manipulations, sion and violence? Epidemiological and criminal histopathological findings of brain tumors in vio- statistics link alcohol to aggressive andviolent be- lent patients promptedthe developmentof experi- havior in a human pattern large in magnitude, mental procedures that ablate and destroy tissue in consistent over the years, widespread in types of areas of the brain such as the septal forebrain, aggressive andviolent acts, massive in cost to indi- medial hypothalamus, or certain midbrain regions vidual,family, andsociety, andserious in suffering of laboratory rats andother animals. Such experi- andharm. Systematic experimental studieshave mental manipulations most often result in ragelike identified the early phase after a low acute (short- defensive postures and biting, often called rage, term) alcohol dose as a condition that increases the hyperreactivity, hyperdefensiveness. Alternatively, probability of many types of social interactions, electrical stimulation of specific brain regions can including aggressive and competitive behaviors, evoke predatory attack, aggressive and defensive and high-dose alcohol intoxication as the condition responses in certain animal species. When animals most likely to be linked to many different kinds of are given very high, near-toxic amphetamine doses violent activities. Yet, most alcohol drinking is as- andsimilar drugs,bizarre, rage-like responses may sociatedwith acceptable social behavior. This is emerge. Similarly, aggressive anddefensivebehav- because individuals differ markedly in their pro- ioral elements are induced by exposure to very high pensity to become intoxicatedwith alcoholic bever- doses of hallucinogens and during withdrawal from ages andto subsequently engage in violent and opiates. The inappropriate context, the unusually aggressive behavior, rendering population averages fragmentedbehavioral response patterns, andthe poor representations of how alcohol causes individ- limitation to domesticated laboratory rodents make uals to behave violently. The sources for the indi- aggressive and defensive reactions that are induced vidual differences may be genetic, developmental, by lesions, electrical brain stimulation, drugs and social, andenvironmental. Genetic association be- toxins difficult to interpret or generalize to the hu- tween antisocial personality, possibly diagnosed man situation. with the aidof certain electrophysiological mea- In contrast to the emphasis on aversive environ- sures, andalcoholism remains to be firmly estab- mental determinants or on neuropathologies, the lished. In the early 1990s, the neurobiological ethological approach to the study of animal aggres- mechanisms of alcohol action for a range of physio- sion has focusedon adaptiveforms of aggressive logical andbehavioral functions began to be identi- behavior. Defense of a territory, rival fighting fied; it appears that the actions of alcohol on brain among mature males during the formation and serotonin andthe benzodiazepine/GABA A receptor maintenance of a group, defense of the young by a complex are particularly relevant to alcohol’s ef- female, and anti-predator defense are examples of fects on aggressive andviolent behavior. For exam- these types of aggressive, defensive, and submissive ple, studies in rodents and primates indicate that behavior patterns, often referredto as agonistic benzodiazepine-receptor antagonists prevent the behavior. Sociobiological analysis portrays these aggression-heightening effects of alcohol. Simi- behavior patterns as having evolvedas part of larly, the actions of alcohol on neuroendocrine reproductive strategies ultimately serving the events that control testosterone andadrenalhor- transmission of genetic information to the next mones appear important in the mechanisms of al- generation. The focus on aggressive behavior as it cohol’s aggression-heightening effects. Among the serves an adaptive function in the reproductive environmental determinants of alcohol’s effects on strategies, however, complicates the extrapolation violence that are of paramount significance are so- to violent behavior as it is defined at the human cial expectations andcultural habits as well as the level. How the range of human violent acts relate to early history of the individual in situations of social the various types of animal aggression andhow conflict. Impairedappraisal of the consequences, they may share common biological roots remains to inappropriate sending and receiving of socially sig- be specified. nificant signals, disrupted patterns of social inter- How have these ethological, neurological, and actions are characteristic of alcohol intoxication experimental-psychological research traditions that contribute to the violence-promoting effects. A contributed to our understanding of the link be- particularly consistent observation is the high prev- tween drugs of abuse and alcohol to human aggres- alence of alcohol in victims andtargets of aggres- AGGRESSION AND DRUGS: RESEARCH ISSUES 53 sion andviolence. In contrast to heroin andco- associatedwith the supplying, dealing,andsecur- caine, since alcohol is not an illicit drug, its link to ing of crack-cocaine, as documented in epidemio- violence is not a characteristic of the economic logical studies. distribution network for this substance. Most experimental studies with animals and hu- Violence in the context of drug addiction is due mans, as well as most data from chronic users, largely to securing the resources to maintain the emphasize that Cannabis preparations (e.g., mari- drug habit as well as to establishing and conducting juana, hashish) or the active agent tetrahydrocan- the business of drug dealing. Neither animal nor nabinol (THC) decrease aggressive and violent be- human data suggest a direct, pharmacological as- havior. Owing to the relatively widespread access, sociation between violence andacute or chronic lower cost, andcharacteristic pattern of use, socio- administration of opiates. Although measures of economic causes of violence in Cannabis dealing hostility and anger are increased in addicts seeking andprocuring are less significant than they are methadone treatment, these feelings usually do not with cocaine or heroin. leadto aggressive or violent acts. Rather, the ten- LSD was not of significance in the early 1990s, dency to commit violent crimes correlates with pre- but older data suggest that certain psycho- addiction rates of criminal activity. However, ex- pathological individuals who begin using LSD may perimental studies in animals point to the phase of engage in violent acts; however, this phenomenon is withdrawal from chronic opiates as the most vul- rare. nerable periodto be provokedto heightenedlevels Phencyclidine (PCP) cannot be causally linked of aggressive behavior. Nevertheless, although hu- to violent or assaultive behavior in the population mans undergoing opiate withdrawal may experi- as a whole. Generally, personality traits anda his- ence increasedfeelings of anger, there is no evi- tory of violent behavior appear to determine dence suggesting that they are more likely to whether or not PCP intoxication leads to violence. become violent as a result. PCP violence is a relatively rare phenomenon, al- The most serious link of amphetamine to vio- lence is in individuals who, after taking intravenous though when it occurs, it stands out by its highly amphetamine—most often chronically—develop a unusual form and intensity. It depends on the indi- paranoidpsychotic state duringwhich they commit vidual’s social and personal background. violent acts. Most psychiatric reports andpolice The impact of genetic predispositions to be sus- records do not support a psychiatric opinion of the ceptible to becoming involved with dependence- early 1970s that ‘‘amphetamines, more than any producing drugs—such as alcohol, heroin, or co- other group of drugs, may be related specifically to caine—andto act violently has, as of yet, not been aggressive behavior.’’ The prevalence of violence delineated in terms of specific neural mechanisms. by individuals who experience amphetamine para- Similarly, the modulating influences of learning, noidpsychosis may be less than 10 percent in gen- social modeling, or parental physical abuse on the eral population samples andas high as 67 percent neural substrate for drug action and for aggressive among individuals who showed evidence of psycho- behavior have not been specified. Since these criti- pathology prior to amphetamine use. Low acute cal connections remain poorly understood, it is not amphetamine doses can increase various positive possible at present to support specific modes of andnegative social behaviors; higher dosesoften intervention on the basis of neurobiological data. leadto disorganizingeffects on social interactions andto severe social withdrawal.At present, the (SEE ALSO: Alcohol: Psychological Consequences of neurobiological mechanisms for the range of am- Chronic Abuse; Crime and Alcohol; Crime and phetamine effects on aggressive andsocial behavior Drugs) remain unknown. There are surprisingly few pharmacological and BIBLIOGRAPHY psychiatric studies on cocaine’s effects on aggres- sion andviolence; the available evidencepoints to EVANS, C. M. (1986). Alcohol andviolence: Problems psychopathological individuals who may develop relating to methodology, statistics and causation. In the propensity to engage in violent acts. However, P. F. Brain (Ed.), Alcohol and aggression. London: the far more significant problem is the violence Croom Helm. 54 AGING, DRUGS, AND ALCOHOL

MICZEK, K. A. (1987). The psychopharmacology of ag- Monane, S; & Semla, 1997; Stein, 1994). Although gression. In L. L. Iversen, S. D. Iversen, & S. H. they comprisedonly 12 percent of the U.S. popula- Snyder (Eds.), New directions in behavioral pharma- tion in 1988, the aging accountedfor 35 percent of cology (Handbook of psychopharmacology, vol. 19). prescription-drug expenditures (Health Care Fi- New York: Plenum. nancing Administration, 1990). Furthermore, the MICZEK, K. A., ET AL. (1994). Alcohol, drugs of abuse, elderly—like the rest of the population—may also aggression andviolence. In A. Reis & J. Roth (Eds.), take over-the-counter drugs such as aspirin or al- Understanding and preventing violence, vol. 3. Wash- lergy tablets, smoke tobacco, drink caffeine-laden ington, DC: National Academy of Sciences Press. andalcoholic beverages, andeven use illicit drugs. KLAUS A. MICZEK Because of certain changes in their bodies, their responses to all medicines and to the interactions of one drug to another drug, and of medicines to alco- hol, may differ from those in younger people AGING, DRUGS, AND ALCOHOL One of (Montamat, Cusack, & Vestal, 1989). the most important developments of the twentieth The use andabuse of ALCOHOL is a public-health century has been the enormous rise in worldwide problem. Among people sixty-five years of age and population in general, andespecially the survival of older, 33 percent report using some alcohol (Na- an estimatedsix hundredmillionpeople agedsixty tional HouseholdSurvey on Drug Abuse, 1999). or older (Ikels, 1991). The increase in the percent- About 6 percent of the elderly are considered heavy age of elderly in the total population results from drinkers (more than two drinks per day), but about medical, economic, and social factors plus a decline 5 to 12 percent of men and1 to 2 percent of women in the birthrate. According to 1989 U.S. Bureau of in their sixties are problem drinkers (Atkinson, the Census figures, persons over sixty-five repre- 1984). Alcoholism andprescription-drugabuse sented12 percent of the U.S. population, andit is may result in physical, psychological, andsocial projectedthat this proportion will almost doubleby illnesses and premature death among the elderly the year 2030—since the baby-boom generation, from either severe withdrawal symptoms, medical born after 1945, will start reaching 65 in 2010. complications, or suicide. Medicines intended to af- This fastest-growing segment—the elderly— fect the mind (including ones intended to combat uses pharmacological andhealth services more of- psychosis, depression, anxiety, and sleep problems) ten than any other part of the population (Brock, are commonly prescribedfor the elderly Guralnik, & Brody, 1990). Aging people are more (Rummans, Evans, Krahn, & Fleming, 1995). susceptible to infectious disease. Many suffer from Studies suggest that the BENZODIAZEPINES or other multiple chronic diseases and often from conditions SEDATIVE-HYPNOTICS are the most commonly pre- that have grown slowly worse throughout their scribedclasses of these medicines.The effects of lifetimes. Some conditions are the result of acci- these medicines add to and interact with those of dents and some are from degenerative diseases. The alcohol (Scott, 1989). All these factors taken to- latter include many kinds of cancer; diseases of the gether—alcohol, oldage, multiple diseases,and immune system such as lupus; diseases of the heart multiple medications—can lead to poisonous, even andbloodvessels such as stroke andhardeningof fatal, interactions of two or more medicines. The the arteries; diseases of the glands such as diabetes; complexities of alcohol, age, anddruginteractions bone andjoint diseasessuch as arthritis andosteo- are discussed in the sections that follow. porosis; anddiseasesof the lungs such as emphy- sema. Like the rest of the population, the elderly NORMAL AGING AND also suffer from psychiatric disorders, some of BODILY CHANGES which may respondto medication.Hence physi- cians (sometimes multiple physicians) often pre- Today, there is great interest in gerontology, the scribe multiple medicines for treatment. If each study of aging, because there are now more older physician does not know all the medications pre- persons in society than ever before, andtheir num- scribedby all the other physicians treating the pa- ber is expectedto rise dramatically.The present tient, two or more of these medications may inter- goal of gerontology is not necessarily to increase the act, sometimes even causing death (Monane, M; life span but rather to increase the health span— AGING, DRUGS, AND ALCOHOL 55 that is, the number of years that a person will enjoy health of diet and exercise. For example, diseases goodhealth. Aging comprises multiple ongoing involving hardening of the arteries are less preva- processes; disease and disability are disruptions. lent in populations that eat no meat andlittle fat. Several factors once thought part of normal hu- For large populations, increasedage is associ- man aging have now been shown to be diseases. atedwith increasedvariability in most dimensions With aging, the immune system no longer performs of health. Thus it is difficult to discriminate be- as it once did. For example, the thymus gland, one tween normal andabnormal states. Moreover, even of the central pacemakers of the immune system, those aging changes considered usual or normal gradually decreases in size, and eventually most of within a defined population do not necessarily hap- it is replacedby fat andconnective tissue. The risk pen in a particular aging person. of cancer andautoimmune diseasesincreases among the elderly. An older person exhibiting a weaker response to bacteria andmay produceauto- AGING AND ALTERED antibodies (antibodies which work against his or DRUG RESPONSE her own tissues), instead of defending against for- eign parasites andaggressors (Weksler, 1990). Some drugs act differently in old persons than This problem, if it occurs, shows that the immune they do in the young or middle-aged. The differ- system is no longer functioning normally. These ence stems from age-relatedchanges in immune changes may be responsible for the in- PHARMACOKINETICS, the bodily processes that ab- creasedrisk among the elderlyof sickness and sorb, distribute within the body, make use of, and death from infectious diseases. A decline in the excrete medicines (Vestal & Cusack, 1990). All hormonal system may affect many different organs these factors can affect the levels of medicines in of the body. For example, diabetes is a common bloodandtissues. For example, with aging, the development in older persons. The pancreas makes percent of water andlean tissue (mainly muscle) in insulin, but cells in the body cannot utilize it as the body decreases, while the percent of fat tissue effectively as they used to do. Both thyroid-stimu- increases. These changes can affect the distribution lating hormone produced in the pituitary gland and of a drug to different parts of the body, the length of thyroidhormone secretedby the thyroidglandit- time that it stays in the body, as well as the amount self show a decline with advancing age. This pro- that is absorbedby bodytissues. One reason that cess is functionally reflectedin a decreasein the drinking the same amount of alcohol has a greater basal metabolism of as much as 20 percent from effect on the elderly is that there is a smaller volume age thirty to age seventy. Thus, aging may result in of total body fluids, resulting in higher blood-alco- part from the loss of hormonal activities anda hol levels than in the young (Vestal et al., 1977). decline in the functions they control. Most medicines are eliminated from the body by With advancing age, persons tend to have slower metabolism in the liver followedby excretion by the reactions to stimuli, wider variations in function, kidney. (To a limited extent, metabolism occurs in andslower return to resting states. This declinein other organs as well, including the stomach and stability within the body (or homeostasis) is found intestines, the kidneys, and the lungs.) Although in a number of body systems. For example, the enzymes continue in general to metabolize at the sensitivity of the baroreceptors, which help main- same rate in the oldas in the young, both the total tain a normal bloodpressure by changing the heart weight of the liver as a percentage of total body rate andthe tension in bloodvessels, declineswith weight andthe total blood-flowthrough the liver age. Likewise, the elderly are prone to being too hot decrease with aging (Loi & Vestal, 1988). As a (hyperthermia) or cold(hypothermia) because of a result, the overall capacity of the liver to convert weakenedability to regulate bodytemperature. A some medicines to their inactive break-down prod- large proportion of age-relatedproblems in the ucts declines with age. For example, some studies stomach andintestines, such as constipation, are show that medicines such as diazepam (Valium), causedandmadeworse by long-term abuse of lax- alprazolam (Xanex), chlordiazepoxide (Librium), atives, poor eating habits, not drinking enough propranolol, valproic acid, lidocaine, and theo- fluids, and lack of exercise. Some elderly persons phylline are metabolizedat a slower rate in old are not aware of the importance to their general persons than in young ones. This decline is highly 56 AGING, DRUGS, AND ALCOHOL variable, however, andnot all drugsmetabolized AGING AND ADVERSE by the liver show an age-relatedslowing in the rate DRUG REACTIONS of metabolism. In fact, the metabolism of alcohol In general, because of multiple andchronic dis- by the liver does not decline with age (Vestal et al., eases, older patients often take multiple prescrip- 1977). tion andover-the-counter drugs.Persons over The most consistent physiological change with sixty-five may take seven or more prescription aging is a decline in kidney function. Both the drugs in addition to some over-the-counter drugs rate at which tiny bloodvessels in the kidneyfil- (Stewart & Cooper, 1994). However, such multi- ter the bloodandthe total flow of bloodthrough ple-drug therapy predisposes the elderly to an in- the kidneys decline with age. As a result, medi- creased risk of unintended, adverse drug reactions cines that are in general excretedby the kidneys (ADRs). The overall incidence of ADRs in this age regularly are excretedmore slowly in the urine of group is two to three times that foundin young the elderly and hence build up more quickly in adults. Although the results of studies vary, about their bloodstream. This fact is particularly impor- 20 percent of all adverse drug reactions occur in the tant for medicines with a narrow therapeutic win- elderly (Korrapati, Loi, & Vestal, 1992); they may dow (a small difference between the amount of result from drug overuse, from drug misuse, from the medicine which is enough to do any good and sloweddrugmetabolism, or from slow elimination the amount of the medicine which is poisonous) of the drug in the urine. These bad side-effects may such as digoxin, aminoglycoside antibiotics, lith- be causedor increasedby age-relatedchronic dis- eases, by intake of alcohol, and/or by incompatibil- ium, andchlorpropamide(Greenblatt, Sellars, & ities between the foods and the medicines which the Shader, 1982). elderly person takes. Furthermore, ADRs are more Another mechanism of age-relatedchanges in severe than among young adults. At increased risk the response to some medicines is an apparent are women, persons living alone, persons suffering change in how sensitive the nerve cells are to the from multiple diseases, persons taking multiple presence of the drug and how well they take the drugs (especially prescribed by multiple physicians drug inside the nerve cell through tiny pipe-like who do not each know what the other physicians structures calledreceptors which are foundin the have prescribed), persons with poor nutritional cell wall. In general, drugs acting on the central habits, andpersons with less sharp sense percep- nervous system produce a stronger effect in older tions or mental clarity. Some of the age-related patients. Any drug that affects alertness, coordina- physiological causes for increasedlevels of medi- tion, andbalance will likely cause more falls and cines remaining in the bloodstream and examples other accidents in elderly persons than in younger of increasedsensitivity of nerve cells to drugshave ones. Thus, hangover effects of sedative-hypnotic already been discussed. The elderly who drink reg- drugs and other mind-altering medicines such as ularly, even if they are not alcoholic, place them- ANTIPSYCHOTICS, ANTIDEPRESSANTS,and selves at increasedrisk for badinteractions be- anxiolytics) are common andoften more serious in tween alcohol andtheir medicines.This risk would the elderly. The dangerous consequences of the be greater still if an elderly person combined alco- hangover effects, such as falls which cause broken hol, prescription medicines, and illegal drugs. hips, suggest, in part, that the receptors in the nerve Thus, since both the kidneys and the liver are often slower at eliminating substances from the body in cells in the elderly are more sensitive, even super- oldage, medicinesshouldgenerally be taken at sensitive, to the presence of these medicines. In lower initial doses by older patients. contrast to mind-altering medications, the response of the heart to stimulation by adrenalin and other AGING AND ALCOHOLISM such substances is diminished in the elderly. For example, a larger dose of isoproterenol is needed to Alcohol is an addictive drug for many individu- achieve the same increase in heart rate in the el- als. Although its victims often do not recognize derly as in the young (Vestal, Wood, & Shand, their alcoholism as a disease, it does meet the medi- 1979). cal criteria for a disease: it has definite symptoms; it AGING, DRUGS, AND ALCOHOL 57 is chronic; andit often progresses until it causes government-supportedhealth programs. In gen- death—but it is treatable. It destroys its victims not eral, the medical complications of alcohol abuse only physically but also mentally, emotionally, and observed in older individuals are the same as those spiritually. Many people with this disease die from foundin younger alcoholics. They includealcoholic physical complications, from accidents, even from liver disease, acute and chronic inflammation of the suicide. In Western society, smoking cigarettes and pancreas, gastrointestinal (affecting the stomach excessive drinking of alcohol are two of the most and intestines) bleeding and other GI-tract dis- insidious forms of drug abuse. Yet they are often eases, an increasedrisk of infections, anddistur- considered socially acceptable. In the United bances in metabolism. The elderly tolerate GI States, two-thirds of all adults use alcohol occa- bleeding and infection less well than do younger sionally. It is estimatedthat between 2 and10 per- persons. They are particularly prone to vitamin de- cent of persons over the age of sixty suffer from ficiencies, malnutrition (that is to getting too few heavy drinking that interferes with their health and calories overall andconsuming too little protein on well-being. These persons by definition suffer from a daily basis), anemia, loss of bone mass (lighter, alcoholism (Jinks & Raschko, 1990). If cigarette weaker bones are more apt to break), diseases of smoking is excluded, alcoholism is by far the most the central andperipheral nervous systems, heart serious drug problem in the United States and in conditions, and cancer. Finally, alcohol-induced most other countries. Alcohol anddrugabuse degeneration of the brain and the rest of the ner- causes thousands of premature deaths, and the cost vous system will add to the effects of the normal of complications contributes billions of dollars to loss of nerve cells that occurs with age. any large nation’s health expenditure. A number of studies have shown that alcohol in Men in their sixties continue to drink at a rate moderate amounts is actually a good medicine for that is almost equal to that of their twenties, but the elderly (even the Prohibition Amendment per- fortunately problem drinking decreases in the mid- mittedthe sale of alcohol for medicinalpurposes) seventies. The prevalence of alcoholism andprob- andthat it improves social interaction, mental lem drinking is lower in women than in men. A alertness, andseveral signs of physical health. Al- large majority of male alcoholics have strong family cohol is primarily a drug which depresses or histories of alcoholism, begin problem drinking deadens the central nervous system (CNS). Para- early in life, andbecome alcoholics not slowly and doxically, in moderate amounts it may seem to act gradually but suddenly and severely. These are the as a stimulant with mood-elevating effects that early-onset or problem drinkers, called type II alco- account for its popularity. What it is actually doing holics (Rigler, 2000; Atkinson, 1984). It is suspec- in these cases is to depress or deaden inhibitions. tedthat alcoholism in this group is largely genetic. The lack of inhibitions contributes to feelings of The other main group consists of later-onset alco- relaxation, confidence, and euphoria. However, al- holics. They may drink from grief, loneliness, or a cohol abuse can result in serious damage to the needto numb pain andto try to escape from other brain andto the rest of the nervous system. It can consequences of poor health. The many losses and cause brain tissue to shrink or waste away, un- stresses of later life make the elderly especially vul- steadiness and lack of coordination in movement, nerable to alcoholism andsuicide(Schonfeld& and damage to nerves throughout the body. Large Dupree, 1991). Depression puts the elderly at par- doses of alcohol cause inflammation of the stom- ticular risk for suicide, especially when it is height- ach, pancreas, andintestine that can hurt the di- enedby alcohol anddrugabuse. gestion of foodandthe absorption of nutrients into the bloodstream. The adult population appears less knowledgeable about the many adverse effects of ALCOHOL AND ITS COMPLICATIONS alcohol on health than about the effects of smoking. IN THE ELDERLY For example, although many people recognize that Health-care costs for a family with an alcoholic heavy alcohol drinking often leads to cirrhosis of member are typically twice those for other families, the liver, only about one-thirdare aware of the andup to half of all emergency-room admissions association between alcohol use andcancers of the are alcohol-related. Alcohol abuse contributes to mouth andthroat. Alcohol use can lessen the effec- the high health-care costs of elderly beneficiaries of tiveness of routine drug therapy or can create new 58 AGING, DRUGS, AND ALCOHOL medical problems requiring additional therapy. some drugs by the liver. In contrast, alcohol con- Excessive alcohol use together with medications in sumedon a regular basis brings on the manufac- the elderly can severely compromise and compli- ture of enzymes in the body, leading in turn to cate a well-plannedtherapeutic program. Thus, acceleratedmetabolism andincreasedclearance of even casual use of alcohol may be a problem for the some drugs, including blood-thinners, oral diabetic elderly, particularly if they are taking medications medicine, and medicine prescribed against convul- that interact badly with alcohol. Difficulties can sions. Thus, these therapeutic drugs can become also arise from the interaction of alcohol andover- less effective, so the patient needs closer monitor- the-counter (OTC) medications. The combination ing. Alcohol-drug interactions do not generally re- of alcohol andprescribedor OTC sleeping pills, for sult directly in death. However, there is evidence example, coulddecreaseintellectual function by for a contributory role of alcohol in drug-related producing an organic brain syndrome; frequent re- fatalities, for example, in car accidents. Anyone sults include confusion, falls, wild swings in emo- who drinks even moderately should ask a physician tions, andother adversedrugreactions or pharmacist about possible alcohol-drug interac- (Adams,1995). tions. It is very difficult to determine the actual inci- PRECAUTIONS WHILE dence of combined drug and alcohol use by the USING ALCOHOL elderly, but it is likely to be reasonably high for the following reasons: the average adult over sixty-five Patients with liver disease and GI ulcers should takes two to seven prescription medicines daily in not use alcohol. Alcohol shouldbe avoidedby pa- addition to over-the-counter medications; most el- tients with damage, caused by previous drinking, to derly persons do not view alcohol as a drug and the heart muscle or other muscles. Clearly, it therefore falsely assume that modest amounts of shouldbe taken only in strict moderationor not at alcoholic beverages can do little harm to an already all. For older individuals who have no medical aged body; and few elderly persons hold to the reasons to the contrary andwho take no drugs traditional notion that mixing alcohol and medica- (prescription or over-the-counter or illegal) that in- tions will have badconsequences. Certainly not teract with alcohol, one drink a day is a prudent every medication reacts dangerously with alcohol; level of alcohol consumption. In general, the use of however, a variety of drugs interact consistently. alcohol in the presence of any particular disease or The most dangerous of these reactions occurs when medication is a matter that the physician and pa- alcohol is combinedwith another CNS depressant. tient must decide. Since alcohol itself is a potent CNS depressant, its use with antihistamines, barbiturates, sedative- ALCOHOL AND DRUG ABUSE IN hypnotics, or other mind-altering drugs adds to THE ELDERLY andreinforces synergistic CNS-depressanteffects, effects that in turn may inhibit one’s mental alert- Alcohol, itself a drug, mixes unfavorably with ness andeven consciousness as well as one’s control many other drugs, including those purchased over of movement (Gerbino, 1982). In one study, the counter. In addition, use of certain prescription diazepam, codeine, meprobamate (Equanil), and drugs may intensify the older person’s reaction to fluorazepam (Dalmane) were the top four agents alcohol, leading to more rapid intoxication. Alco- responsible for drug-alcohol interactions (Jinks & hol, when combinedsubstantially andquickly with Raschko, 1990). Antihistamines, including certain groups of drugs, can dangerously slow diphenhydramine (Benadryl), dimenhydrinate down performance skills such as driving, running (Dramamine), andmost coldmedicationsandanti- machinery, andeven walking. It lessens judgment, cholinergics such as scopolamine, which are found and reduces alertness when taken with drugs such in over-the-counter medications, can also cause as those prescribedagainst psychosis, those meant confusion in the elderly. An important consider- to lessen anxiety, sedative-hypnotics, pain-killers ation in the elderly is the confused and altered derived from opium, antihistamines, and certain behavior that so regularly follows excessive con- blood-pressure medicines (Table 1). Large sumption of alcohol. Many times, elderly alcoholics amounts drunk quickly reduce the clearance of show symptoms of falls, confusion, andself-ne- AGING, DRUGS, AND ALCOHOL 59

TABLE I Drug-Alcohol Interactions and Adverse Effects Drug Adverse effects with alcohol

Acetaminophen Severe hepatotoxicity with therapeutic doses of acetaminophen in chronic alcoholics Anticoagulants, oral Decreased anticoagulant effect with chronic alcohol abuse Antidepressants, Combined CNS depression decreases the psychomotor tricyclic performance, especially in the first week of treatment Aspirin and other Increased the possibility of gastritis and GI hemorrhage nonsteroidal antiinflammatory drugs Barbiturates Increased CNS depression (additive effects) Benzodiazepines Increased CNS depression {additive effects) Beta-adrenergic Masked signs of delirium tremens blockers Bromocriptine Combined use increases the GI side effects Caffeine Possible further decreased reaction time Cephalosporins Antabuse-like reaction with some cephalosporins Chloral hydrate Prolonged hypnotic effect and adverse cardiovascular effects Cimetidine Increased CNS depressant effect of alcohol Cycloserine Increased alcohol effect or convulsions Digoxin Decreased digitalis effect Disulfiram (Antabuse) Abdominal cramps, flushing, vomiting, hypotension, confusion, blurred vision, and psychosis Glutethimide Additive CNS depressant effect Guanadrel Increased sedative effect and orthostatic hypotension Heparin Increased bleeding Hypoglycemics, Acute ingestion-increased hypoglycemic effect of sulfonylurea sulfonylurea drugs Chronic ingestion-decreased hypoglycemic effect of these drugs Antabuse-like reaction lsoniazid Increased liver toxicity Ketoconazole Antabuse-like reaction Lithium Increased lithium toxicity Meprobamate Synergistic CNS depression Methotrexate Increased hepatic damage in chronic alcoholics Metronidazole Antabuse-like reaction Nitroglycerin Possible hypotension Phenformin Lactic acidosis (synergism) Phenothiazines Additive CNS depressant activity Phenytoin Acutely ingested, alcohol can increase the toxicity of phenytoin Chronically ingested, alcohol can decrease the anticonvulsant effect of phenytoin Quinacrine Antabuse-like reaction Tetracyclines Decreased effect of doxycycline

Adapted from M.A. Rizack & C.D.M. Hillman (1987), Adverse interactions of drugs. In The Medical Letter handbook of adverse drug interactions. New York: Medical Letter. 60 AGING, DRUGS, AND ALCOHOL glect. Such changes may lessen the elderly patient’s cine that depresses the CNS (Hartford & ability to adhere to a prescribed treatment, and Samorajski, 1982). Therefore, as a general rule, increase the risk of mistakes or mishaps in dosage elderly patients should be instructed to stay away (Gerbino, 1982). Some of the well-described inter- from alcohol while taking such medicines, includ- actions are discussed in the following sections. ing benzodiazepines, barbiturates, muscle relaxants, andantihistamines (both by prescription ALCOHOL AND ANALGESICS andas over-the-counter coldremediesor sleeping aids). Alcohol increases the clinical effects of these Aspirin is the active ingredient in many over- drugs, which already are hazardous in a segment of the-counter arthritis pain formulas andin numer- the population with decreased agility and greater ous nonprescription combination headache-and- danger of serious complications from falls and minor-pain products. The ability of aspirin to cause other accidents. inflammation of the stomach, erosion of the GI tract, and GI bleeding is well recognized. Alcohol ALCOHOL AND not only produces inflammation of the stomach but MIND-ALTERING DRUGS also increases the risk of GI bleeding caused by aspirin andother nonsteroidalanti-inflammatory When alcohol is combinedwith mind-altering drugs (Bush, Sholtzhauer, and Imai, 1991). Elderly (psychotropic) drugs such as those prescribed to people at high risk for bleeding should avoid regu- fight psychosis anddepression,the combinedef- lar use either of alcohol or of aspirin. Chronic alco- fects of alcohol and the medicine are less predict- hol abuse can cause poisoning of the liver in a able than with other drugs. Antipsychotic drugs patient taking acetaminophen (Tylenol), probably inhibit the metabolism of alcohol andmay thus because it leads to the production of enzymes which markedly increase its effects on the CNS in the in turn leadto the formation of poisonous interme- elderly. Antidepressants increase the response to diary breakdown products of the Tylenol. alcohol andharm one’s control over one’s mo-

ALCOHOL AND CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANT MEDICINES Alcohol and medicines that by themselves de- press the CNS, when combinedwith each other, may depress the system more than either does by itself. Much controversy exists as to whether the combined effect is merely additive (what one would expect by adding the two effects together) or whether it is synergistic (greater than the sum of its two parts), whether each somehow reinforces the action of the other as well as adding its own action. When combinedwith CNS depressants,alcohol— even in small quantities—produces undesirable andsometimes dangerouseffects. The interaction of alcohol with benzodiazepine drugs, however, may be much greater in the elderly than in the other age groups. This is especially true for diazepam (Valium) and chlordiazepoxide (Li- brium). Commonly observed side-effects include high bloodpressure, sleepiness, confusion, andde- pression of the CNS that may leadto slowing down of breathing, or even to stopping it. Two drinks can bring about a drug-alcohol interaction with a medi- AGING, DRUGS, AND ALCOHOL 61 tions—a significant hazardin the elderlyfor whom codeine in combination with antihistamines. When falls often leadto broken bones. Depression of the taken together with alcohol, these drugs are haz- CNS may range from drowsiness to coma and ardous and can cause altered alertness, even loss of therefore death, because acute alcohol consump- consciousness, andmay slow downone’s breathing tion may increase the CNS effects of antidepres- or even stop it. Despite the fact that heart disorders sants. Alcohol may also increase the risk of danger- are very common in older individuals, few of those ously lowering body temperature in the elderly who suffer from these problems modify their drink- taking tricyclic antidepressants. Hence the avoid- ing patterns. This tendency may be dangerous, ance of alcohol in elderly patients taking any of since as little as one cocktail can severely reduce the these drugs is a prudent recommendation (Scott & efficiency of the heart in the presence of heart Mitchell, 1988). disease. For example, alcohol consumption in a person suffering from angina (pain felt in the heart ALCOHOL AND OTHER DRUGS during physical activity) can mask the pain that Many elderly patients with adult-onset (Type II) might otherwise serve as a warning signal of a heart diabetes take antidiabetic pills instead of insulin. attack (Horowitz, 1975). When alcohol is taken along with pills such as sulfonylureas, it may cause dangerously low levels ALCOHOL AND ILLICIT DRUGS of bloodsugar, especially in patients whose diet Abuse of hallucinogens, illicit psychomotor calls for decreasing the eating of carbohydrates. Another problem associatedwith this combination stimulants andsedatives,andmarijuana is uncom- is an Antabuse-like reaction (fortunately quite rare mon in old age; use of these drugs by the elderly is and usually mild), causing nausea, vomiting, head- almost exclusively by longstanding users of opium- ache, blurredvision, andflushing. However, symp- like substances andby aging criminals. The low toms of severe Antabuse-like reactions include incidence of this type of substance abuse in old age speeding up of the heart to more than one hundred may result from the fact that users of illegal drugs beats a minute, abdominal distress, sweating, epi- die young, and even from the fact that the use of sodes of low blood pressure, death of heart muscle, such drugs by the elderly is often underreported. andtearing of the esophagus brought about by However, problem drinkers may abuse drugs such vomiting; psychosis may also occur, andfatal reac- as sedatives, opioids, marijuana, and amphet- tions have been reported. Use of alcohol at the same amines. Sometimes these drugs are used in combi- time with a variety of other drugs (Table 2) can nation with alcohol; at other times, such drugs are also leadto an Antabuse-like reaction. Cough med- taken in preference to alcohol, andalcohol is used icines may contain a narcotic pain-killer such as only when the drug of choice is not available. 62 AGING, DRUGS, AND ALCOHOL

SUMMARY HARTFORD, J. T., & T. SAMORAJSKI (1982). Alcoholism in the geriatric population. Journal of the American Ger- Elderly people are the fastest-growing segment iatric Society, 30(1), 18–24. of worldpopulation andconsume about 25 percent HEALTH CARE FINANCING ADMINISTRATION,OFFICE OF NA- of all the medicines prescribed. Their capacity to TIONAL COST ESTIMATES. (1990). National health ex- handle medication differs from that of the young penditures, 1988. Health Care Financing Review, 11, because of age-relatedchanges in various systems 1–41. of the body. Alcohol abuse among older people (as HOROWITZ, L. D. (1975). Alcohol andheart disease. in any other) can leadto falls, fractures, andother Journal of the American Medical Association, 232(9), similar medical complications. The addition of 959–960. medications (prescription and over-the-counter) to IKELS, C. (1991). Aging anddisabilityin China: Cultural alcohol drinking can lead to disastrous complica- issues in measurement andinterpretation. Social Sci- tions andeven premature death.However, in the ence Medicine, 32(6), 649–665. absence of any indications to the contrary such as JINKS, M. J., & R. R. RASCHKO (1990). A profile of alcohol the taking of the medications discussed above, andprescription drugabuse in a high-risk commu- drinking a small quantity of alcohol may be benefi- nity-basedelderlypopulation. Drug Intelligence Clin- cial in some elderly persons. In case of doubt, the ical Pharmacology, 24(10), 971–975. elderly and their families or caregivers are encour- KORRAPATI, Madhu R., C. M. LOI, & Robert E. VESTAL agedto seek the adviceof the pharmacist or family (1992). Adverse drug reactions in the elderly. Drug physician andto follow the guidelinesgiven in Ta- Therapy, 22(7), 21–30. ble 3. LOI, C. M., & Robert E. VESTAL (1988). Drug metabo- lism in the elderly. Pharmacological Therapy, 36 (1), (SEE ALSO: Social Costs of Alcohol and Drug Abuse) 131–149. MONANE, M., S. MONANE, & T. SEMLA (1997). Western BIBLIOGRAPHY Journal of Medicine, 167 (4), 233–237, followedim- mediately by comment 238–239. ADAMS, W. L. (1995). Interactions between alcohol and MONTAMAT, S. C., B. J. CUSACK, & Robert E. VESTAL other drugs. International Journal of the Addictions, (1989). Management of drug therapy in the elderly. 30 (13–14), 1903–1923. New England Journal of Medicine, 321(5), 303–309. ATKINSON, RonaldM. (1984). Substance use andabuse RIGLER, S. K. (2000). Alcoholism in the elderly. Ameri- in late life. In Alcohol and drug abuse in the old age. can Family Physician, 61(6), 1710–1716, 1883– Washington, D.C.: American Psychiatric Press. 1884, 1887–1888. BROCK, D. B., J. M. GURALNIK, & J. A. BRODY (1996). RIZACK, M. A., & C. D. M. HILLMAN (1987). Adverse in- Demography andepidemiologyof aging in the United teractions of drugs. In The Medical Letter handbook States. In E. L. Schneider & J. W. Rowe (Eds.), of adverse drug interactions. New York: Medical Let- Handbook of the biology of aging, 4th ed. San Diego: ter. Academic Press. RUMMANS, T. A., J. M. EVANS,L.E.KRAHN, & K. C. BUSH, T. M., T. L. SHLOTZHAUER, & K. IMAI (1991). FLEMING (1995). Delirium in elderly patients: Evalu- Nonsteroidal anti-inflammatory drugs: Proposed ation andmanagement. Mayo Clinic Proceedings, guidelines for monitoring toxicity. Western Journal of 70(10), 989–998. Medicine, 155(1), 39–42. SCHONFELD, L., & L. W. DUPREE (1991). Antecedents of DUFOUR, M. C., L. ARCHER, & E. GORDIS (1992). Alcohol drinking for early and late-onset elderly alcohol abus- andthe elderly. Clinical Geriatric Medicine, 8(1), ers. Journal of the Study of Alcoholism, 52(6), 587– 127–141. 592. GERBINO, P. P. (1982). Complications of alcohol use SCOTT, R. B. (1989). Alcohol effects in the elderly. Com- combined with drug therapy in the elderly. Journal of prehensive Therapy, 15(6), 8–12. the American Geriatric Society, 30(11 Supplement), SCOTT, R. B., & M. C. MITCHELL (1988). Aging, alcohol, S-88–S-93. andthe liver. Journal of the American Geriatric Soci- GREENBLATT, D. J., E. M. SELLARS, & R. I. SHADER ety, 36(3), 255–265. (1982). Drug disposition in old age. New England SPENCER, G. (1989). Projections of the population of the Journal of Medicine, 306(18), 1081–1088. United States, by age, sex, and race: 1988 to 2080. AGONIST-ANTAGONIST (MIXED) 63

Current Population Reports, series P-25, no. 1018, BIBLIOGRAPHY U.S. Bureau of the Census. Washington, D.C.: U.S. ROSS, E. M. (1990). Pharmacodynamics: Mechanisms of Government Printing Office. drug action and the relationship between drug con- STEIN, B. E. (1994). Avoiding drug reactions: Seven steps centration andeffect. In A. G. Gilman et al (Eds.), in writing prescriptions. Geriatrics, 49(9), 28–30, Goodman and Gilman’s the pharmacological basis of 33–36. therapeutics, 8th ed. New York: Pergamon STEWART, R. B. & J. W. COOPER (1994). Drugs and Ag- NICK E. GOEDERS ing, 4(6), 449–461. VESTAL, Robert E., & B. J. CUSACK (1996). Pharmacol- ogy andaging. In E. L. Schneider& J. W. Rowe (Eds.), Handbook of the biology of aging, 4th ed. San AGONIST-ANTAGONIST (MIXED) A Diego: Academic Press. mixedagonist-antagonist is a drugor receptor li- gandthat possesses pharmacological properties VESTAL, Robert E., A. J. J. WOOD, & D. J. SHAND (1979). Reduced ␤-adrenoreceptor sensitivity in the elderly. similar to both AGONISTS andA NTAGONISTS for cer- Clinical Pharmacology Therapy, 26(2), 181–186. tain RECEPTOR sites. Well-known mixedagonist- antagonists are drugs that interact with OPIOID VESTAL, Robert E., et al. (1977). Aging andethanol me- (morphine-like) receptors. Pentazocine, nalbuph- tabolism. Clinical Pharmacologic Therapy, 21(3), ine, butorphanol, andB UPRENORPHINE are all 343–354. mixedagonist-antagonists for opioidreceptors. WEKSLER, M. E. (1990). Protecting the aging immune These drugs bind to the ␮ (mu) opioidreceptor to system to prolong quality of life. Geriatrics, 45(7), compete with other substances (e.g., MORPHINE) 72–76. for this binding site; they either block the binding MADHU R. KORRAPATI of other drugs to the ␮ receptor (i.e., competitive ROBERT E. VESTAL antagonists) or produce a much smaller effect than REVISED BY JAMES T. MCDONOUGH,JR. that of ‘‘full’’ agonists (i.e., they are only partial agonists). Therefore, these drugs block the effects of high doses of morphine-like drugs at ␮ opioid AGONIST An agonist is a drug or an endoge- receptors, while producing partial agonist effects at ␬ ␦ nous substance that binds to a RECEPTOR (it has (kappa) and/or (delta) opioid receptors. Some affinity for the receptor binding site) and produces of the mixedopioidagonist-antagonists likely pro- a biological response (it possesses intrinsic activ- duce analgesia (pain reduction) and other mor- ity). The binding of a drug agonist to the receptor phine-like effects in the CENTRAL NERVOUS SYSTEM by binding as agonists to ␬ opioidreceptors. produces an effect that mimics the physiological In many cases, however, there is an upper limit response observedwhen an endogenoussubstance (ceiling) to some of the central nervous system ef- (e.g., hormone, NEUROTRANSMITTER) binds to the fects of these drugs (e.g., respiratory depression). same receptor. In many cases, the biological re- Furthermore, in people physically addicted to mor- sponse is directly related to the concentration of the phine-like drugs, the administration of a mixed agonist available to bindto the receptor. As more opioidagonist-antagonist can producean absti- agonist is added, the number of receptors occupied nence (WITHDRAWAL) syndrome by blocking the ␮ increases, as does the magnitude of the response. opioidreceptor andpreventing the effects of any ␮ The potency (strength) of the agonist for producing agonists (i.e., morphine) that may be in the body. the physiological response (how much drug is Pretreatment with these drugs can also reduce or needed to produce the effect) is related to the prevent the euphoria (high) associatedwith subse- strength of binding (the affinity) for the receptor quent morphine use, since the ␮ opioidreceptors andto its intrinsic activity. Most drugsbindto more are competitively antagonized. Therefore, the than one receptor; they have multiple receptor mixedopioidagonist-antagonists are believedto interactions. have less ABUSE LIABILITY than full or partial opioid receptor agonists. (SEE ALSO: Agonist/Antagonist (Mixed); Antago- As more andmore subtypes of receptors are nist) discovered in other NEUROTRANSMITTER systems 64 AIDS

(there are now more than five serotonin receptor BRIEF HISTORY subtypes andfive dopaminereceptor subtypes), it Early in the 1940s, wives startedattendingAA is quite likely that mixedagonist-antagonist drugs meetings andsoon began to informally meet to- will be identified that act on these receptors as well. gether. By the late 1940s, there were so many fam- ily members at AA affairs that the AA Boardof BIBLIOGRAPHY Trustees had to decide how to manage this valuable but perplexing influx. Since relatives of AA mem- GILMAN, A. G., ET AL.(EDS.). (1990). Goodman and bers hadalreadybegun to holdtheir own meetings, Gilman’s the pharmacological basis of therapeutics, the boardrecommendedthatAA meetings be only 8th ed. New York: Pergamon. for alcoholics but that whenever family members NICK E. GOEDERS askedto participate they shouldbe listedat the AA General Service office as a resource. Several AA wives began their own clearinghouse committee to coordinate the approximately ninety groups al- AIDS See Alcohol andAIDS; Complications: ready in existence. Soon there was a separate net- Route of Administration; Injecting Drug Users and work distinct and apart from AA itself. Because HIV; Substance Abuse andAIDS; NeedleandSy- they were closely relatedto AA, however, they de- ringe Exchanges andHIV/AIDS cided to shorten the first two letters of ‘‘alcoholic,’’ andthe first four letters of ‘‘anonymous’’ into Al-Anon. This has been their name ever since. AL-ANON Al-Anon is a fellowship very simi- In 1950, the anonymous Bill W., a founder of AA, persuaded his wife Lois to get involved with the lar to ALCOHOLICS ANONYMOUS (AA), but it is for family members andfriendsof alcoholics. Although fledgling Al-Anon. The rapidly accumulating lists in the General Service office were turnedover to her formally totally separate from the fellowship of AA, andto an associate, Anne B., who contactedthose it has incorporatedinto its groups the AA Twelve on the list, ‘‘andsoon they hadmore work than Steps andTwelve TraditionsandAA’s beliefs and they couldhandle’’(Wing, 1992:136). For two organizational philosophy, but it has directed them years, the two conducted their activities at Stepping towardhelping families of alcoholics cope with the Stones, the suburban home of Bill W. andLois. In baffling anddisturbingexperiences of living in 1952 they movedto New York City, where volun- close interaction with an active alcoholic. In this teer workers couldbe more easily recruited.By sense, it is a satellite organization of AA (Rudy, 1989, there were over 28,000 weekly Al-Anon 1986). Proselytizing organizations, such as AA, of Family Groups, which included Alateen, world- necessity attempt to reduce, even eliminate, the ties wide. ‘‘With each meeting averaging 12–15 mem- of newcomers with other significant persons and bers, an estimatedtotal of 336,000–420,000 visits groups who are not members. Rather than attempt to Al-Anon meetings occur each week’’ (Cermak, to sever those bonds for prospective AA members, 1988:92). Using data from a 1984 random sample AA evolvedAl-Anon as a way to includefamilies of groups conducted by the Al-Anon fellowship, it into a parallel organization, andthus also initiate was estimatedthat a quarter of a million people them into the beliefs and practices of AA. In addi- visit an Al-Anon meeting each week. tion, as AA expanded and more alcoholics became ‘‘recovering’’ ones, close relatives became aware AL-ANON’S STRATEGY that their own personal problems couldbe reduced Al-Anon strives to direct its members’ attention by applying AA principles to themselves andwork- away from the active alcoholic with whom they at- ing the Twelve Step program, even though they tempt to interrelate, andtowardtheir own behavior were not alcoholic. In 1980, there were 16,500 andemotions. In many ways, their personalities Al-Anon groups worldwide, including 2,300 resemble those of alcoholics: they repeatedly at- ALATEEN groups of children of alcoholics (Maxwell, tempt to control the feelings andbehaviors of the 1980). alcoholics in their midst by simple force of personal ALATEEN 65

will—much as alcoholics attempt to control their HUPPERT, S. (1976). The role of Al-Anon groups in the drinking by the sheer force of their individual will. treatment program of a V.A. alcoholism unit. Hospi- In both instances, a denial syndrome emerges in tal and Community Psychiatry, 27, 693–697. their emotional makeup that protects their compul- MAXWELL, M. (1980). Alcoholics Anonymous. In E. sive drive toward continued control. In sum, family Gomberg, H. R. White, & J. Carpenter (Eds.), Alco- members often become codependent—as obsessed hol, science, and society revisited (pp. 295–305). Ann with the alcoholics’ behavior as he or she is with the Arbor: University of Michigan Press. bottle (Huppert, 1976). RUDY, D. R. (1986). Becoming alcoholic: Alcoholics For example, the alcoholic’s spouse or partner Anonymous and the reality of alcoholism. Carbon- has often vainly attemptedto control the drinking. dale: Southern Illinois University Press. Except for brief periods, most pleas have been re- WING, N. (1992). Grateful to have been there: My 42 jectedandmost promises have not been kept. Of- years with Bill and Lois and the evolution of Alcohol- ten, while the alcoholic has continuedto drinkand ics Anonymous. Park Ridge, IL: Parkside Publishing. enjoy the brief emotional payoffs of intoxication, HARRISON M. TRICE the spouse or other caretaker must try to cope for both of them by running the household, rearing the children, and working steadily to earn a living. If ALATEEN Alateen is a division of the the alcoholic does show signs of improvement in a Al-Anon Family Group. Its members typically are treatment center, the spouse or life partner may teenagers whose lives have been impactedby some- resent it deeply, since strangers have done more in a one else’s problem drinking. Roughly, 59 percent short periodthan all the partner’s efforts over the are age 14 or younger, while 26 percent are ages 15 years. To alcoholics’ partners andrelatives it ap- to 16 and15 percent are age 17 or more. The pears as if they have not been wise enough, or problem drinkers in their lives are predominantly determined enough, or superhuman enough, to get one or both parents, but brothers andsisters are not the alcoholics in their lives to stop drinking. uncommon. Al-Anon attempts to introduce the Twelve Steps The prevailing story about the origin of Alateen of AA into the lives of family members as a way of is quite straightforward. Legend has it that in 1957 minimizing the resentments andobsessive-control a 17 year oldin California was attendingA LCOHOL- behavior they typically display. Al-Anon empha- ICS ANONYMOUS (AA) andA L-ANON meetings with sizes an adaptation of AA’s first step: ‘‘We admit we his parents. His father hadjust gotten sober in AA are powerless to control an alcoholic relative, that andhis mother was an active member of Al-Anon. we are not self-sufficient.’’ Such a step is an admis- Although the teenager decided that the Twelve sion that it is a waste of time to try to control what is Steps of AA were helping him, his mother suggested beyondtheir capacities. Accordingto this strategy, that insteadof attendingAA meetings he start a it is no longer necessary for them to deny that their teenagedgroup andpattern it after Al-Anon. The control efforts are powerless, andthis relieves them young man foundfive other teenagedchildrenof from the enormous sense of accumulatedburden alcoholic parents and, while the adult groups met and guilt. In addition, it allows acceptance of out- upstairs, he goth them together downstairs. sider treatment and its possible success. As other teenagers came forwardfrom Al-Anon groups, the idea spread and it is estimated that (SEE ALSO: Adult Children of Alcoholics; Codepen- dence; Families and Drug Use; Treatment Types: today about 3,500 Alateen groups meet worldwide. Twelve Steps) In formal terms, however, these groups are an im- portant andan integral part of Al-Anon Family Groups. They are coordinated from the Al-Anon BIBLIOGRAPHY Family Group Headquarters in New York City and AL-ANON FAMILY GROUP HEADQUARTERS. (1984). Al-An- tiedclosely to their public-information programs. on faces alcoholism (2nded.)New York: Author. Thus, Alateen uses AA’s Twelve Steps, but alters CERMAK, T. (1989). Al-Anon andrecovery. In M. step twelve to simply read‘‘carry the message to Galanter (Ed.), Recent developments in alcoholism, others,’’ rather than ‘‘to other alcoholics.’’ Alateen Vol. 7 (pp. 91–104). New York: Plenum Press. groups meet in churches andschoolrooms, often in 66 ALCOHOL AND AIDS the same building as Al-Anon, but in a different ALCOHOL AND AIDS Alcohol andAIDS room. (acquired immunodeficiency syndrome) from in- Although there are a few exceptions, an active, fection with HIV (human immunodeficiency virus) adult member of Al-Anon usually serves as a spon- are each separately agents that cause suppression sor. Also, members of Alateen can choose a per- of immune function. Therefore regular use of alco- sonal sponsor from other Alateen members or from hol by people infectedwith HIV shouldbe more Al-Anon members. suppressive than either alone. Some of the most Alateen enables its members to openly share interesting questions about infection with HIV in- their experiences andto deviseways of coping with cluding the following: Why does progression to the problem of living closely with a relative who has AIDS after HIV infection vary in length of time a drinking problem. The strategy is to change their from under 1 year to 15 years of more? Does inhibi- tion of mental functions by heavy alcohol use in- own thinking about the problem-drinking relative. crease risky sexual behaviors andthus the chance Alateen teaches that alcoholism is like diabetes—it of becoming infectedwith HIV? Does alcohol use or cannot be cured, but it can be arrested. Members abuse affect the production of the virus or the learn that they did not cause it, and they cannot invasion of cells by the virus? control it or cure it. Scolding, tears, or persuasion, Conventional wisdom based on long experience for example, are useless. Rather, ‘‘they learn to take is that alcohol’s relaxation of sexual inhibition will care of themselves whether the alcoholic stops or increase risky sexual behaviors in those who use not’’ (Al-Anon Family Groups, 1991:5). They ap- alcohol even in moderation (2–3 drinks a day). ply the Twelve Steps to themselves—to combat Risky behaviors include unprotected vaginal or their often obsessive thinking about controlling al- anal intercourse with more than one partner, un- coholic relatives andto help them stop denying protectedintercourse with intravenous drugusers, those relatives’ alcoholism. In addition, they adapt who have a high risk of HIV infection, andun- and apply AA’s Twelve Traditions to the conduct of protectedoral sex with potentially protectedin- their groups. For example, they practice anonym- fectedpartners. Anyone who has usedintravenous ity, defining it not as secrecy, but as privacy and the drugs or had sex with more than one person is at lowering of competitiveness among members. A significant risk of infection with HIV andother 1990 survey of Alateen members indicated an in- pathogens. crease in the number of black, Hispanic, andother Cocaine andother drugsof abuse are commonly minority members. usedalong with alcoholic beverages. They appear In essence, Alateen uses the strategy of AA itself to synergize in terms of affecting behavior, thereby to learn how to deal with obsession, anger, feelings enhancing the risk of HIV infection shouldone be of guilt, anddenials.Newcomers, like newcomers exposed. In addition, studies in the laboratory have in AA, gain hope when they bondwith other teen- shown that alcohol use increases the susceptibility agers to help one another cope with alcoholic par- of cells to HIV, increasing the likelihoodthat an invading HIV virus will successfully cause disease. ents andother relatives with drinkingproblems Animal studies involving mice with AIDS show that (Al-Anon Group Headquarters, Inc., 1973). alcohol andcocaine clearly suppress immune func- tion, moreso than AIDS alone. During alcohol and (SEE ALSO: Adult Children of Alcoholics; Codepen- cocaine use, mice infectedwith the virus that causes dence; Families and Drug Use; Treatment Types: AIDS are much more susceptible to cancer and Twelve Steps) pathogens, anddiesooner. While epidemiological studies in humans have BIBLIOGRAPHY been inconclusive, animal models and test tube studies with human cells clearly demonstarte that AL-ANON FAMILY GROUPS. (1991). Youth and the alco- alcohol increases the immune damage resulting holic parent. New York: Author. from retrovirus infection. Alcohol may lower resis- AL-ANON FAMILY GROUPS. (1973). Alateen—hope for tance to disease and tumors in AIDS patients, may children of alcoholics. New York: Author. accelerate development of AIDS by those who are HARRISON M. TRICE HIV infected, may increase HIV production by ALCOHOL- AND DRUG-FREE HOUSING 67 cells, andmay increase cellular susceptibility to Amendments Act of 1988 and become subject to HIV infection. zoning laws that prohibit treatment programs in AIDS patients suffer from various opportunistic residential neighborhoods. The result would be the pathogens, which normally do not grow sufficiently systematic exclusion of such residences from the to cause disease in immunologically normal people. safe andeconomically stable areas most conducive Alcohol andcocaine exacerbate the immune dys- to recovery. Under provisions of the Fair Housing function in studies with mice. They also increase Amendments Act, no regulation of any ADF resi- the extent of colonization in mice with AIDS by two dence is legal unless such requirements are imposed opportunistic parasites, Giardia and Cryptosporid- on all private residences in the surrounding com- ium. Normal mice andhumans are not as are essen- munity with the same zoning. tially resistant to such parasites. Alcohol is a Such protections aside, ADF housing is a crea- cofactor that accentuates immune damage result- ture of the marketplace. For it to be affordable, ing from the HIV retrovirus. public sponsorship of some sort must close the gap between market rents or mortgage costs andwhat residents can reasonably pay. A bewildering variety BIBLIOGRAPHY of affordability strategies for rent, property, and WATSON R. R. & GOTTESFELD, Z. Neuroimmune effects construction-cost subsidies has been worked out for of alcohol andits role in AIDS. Advances In Neu- individual ADF housing projects, but very few cit- roimmunology 3 (1993): 151–162. ies or other local jurisdictions have established for- WATSON,R.R.ET AL. Alcohol, immunomodulation, and mal policies to create andto sustain ADF housing. disease. Alcohol and Alcoholism 29 (1996): 131–139. Even so, for three principal reasons, interest in WATSON, R. R., ED. Nutrition and AIDS II. CRC Press in affordable ADF housing has increased remarkably Press, 2000. in the last few years. First, local units of govern- RONALD ROSS WATSON ment, special boards, and districts, are under pres- sure to make provisions for low-income housing. Second, recent studies indicate that affordable ADF housing helps homeless andvery low-income peo- ALCOHOL- AND DRUG-FREE HOUS- ple maintain sobriety following initial successes in ING Alcohol- anddrug-free(ADF) housing, also treatment/recovery programs. Third, ADF housing called sober housing,orsober living environments, now figures prominently in discussions of using or alcohol-free living centers, provides domestic ac- ‘‘social-model’’ recovery programs as vehicles for commodation for people who choose to live in an the cost-efficient deployment of treatment and re- environment that is free of alcohol and/or drugs. covery services. The search for economical ways to ADF housing is ordinary housing, located in resi- provide such services has led health-care system dentially zoned areas, distinguished only by the planners to reduce or eliminate the use of expensive residents’ shared commitment not to use alcohol or residential-treatment programs. In conjunction other drugs. with outpatient treatment andadjuncthealth and By definition, ADF housing excludes formal social services, affordable ADF housing increas- treatment or recovery services on the site. The ingly is viewedas an alternative. philosophic premise of ADF housing is that the ADF housing follows three simple tenets: sober living environment is itself the ‘‘service’’ for (1) residents must remain alcohol and drug free; residents. ADF housing provides a setting for daily (2) rent must be paidon time; and(3) residents living that supports residents’ efforts to maintain must abide by provisions of the landlord-tenant sobriety among themselves. agreement. This agreement may stipulate only that As a practical matter, the presence of on-site tenants must refrain from disruptive behavior that human services wouldsubject ADF residencesto provides grounds for eviction for cause in local state or local licensing of staff andto certification of ordinances (typically these are violence or threats their facilities. Under such circumstances, resi- of violence, illegal activity, destruction of property, denceswouldbe treatment facilities andno longer andperpetuation of unduenuisances). However, it ADF housing. As such, they wouldlose protections may also impose house rules that dictate curfews, afforded to ADF housing by the Fair Housing limit overnight guests, restrict automobile owner- 68 ALCOHOL- AND DRUG-FREE HOUSING ship, delegate house chores, andso forth. As long as predictability, and good order. Entrance and evic- the tenant’s participation in the regulatedhouse- tion policies are critical in this respect. holdis voluntary, andas long as the rules donot ADF housing is not magically exempt from our violate civil rights, ADF housing may be highly meaner or more self-serving impulses towardex- structuredandclosely governed. clusiveness. However, in well-run residences, en- An ADF residence can be program-affiliated or trance decisions focus only on the capacity of an free-standing. Program-affiliated sober houses are individual to benefit from the house milieu. Such tiedto the treatment andrecovery orientations of decisions, in which residents usually play an impor- particular organizations. Residents are likely to tant part (if only to exercise rights of refusal), con- come from the sponsoring program, andso will sider the structure and character of the house ‘‘pro- have been exposedto the sponsor’s proceduresand gram’’ in relation to the needs of a potential values. Accordingly, the residence will reflect the resident. Thus, a prospective resident with an ex- philosophy andpractices of the parent organiza- pressedneedor desirefor a highly structuredenvi- tion. Free-standing houses operate more along the ronment wouldbe discouragedfrom entering a lines of conventional residences and rely exclusively house with little structuredactivity. All recovering on self-government. people can benefit from ADF housing, regardless of Sober housing can be run by staff or residents. their treatment histories or other circumstances. Staff-run houses operate under the direct manage- But as ADF housing represents a spectrum of possi- ment of owners, program operators, or housing bilities for group living, particularly concerning the management firms. Site managers are compensated extent to which the environment is regulated, its andoften are recovering people who have several potential consumers must finda goodfit. Variety in ADF housing is therefore essential. more years of sobriety than the residents of the Residents are free to live in sober housing as long house. (It shouldbe emphasizedthat for obvious as they follow house rules. Any fixedtime limit on legal reasons, they are not ‘‘treatment personnel’’ length of tenancy is contrary both to the spirit and andtheir activities donot comprise formal service (in most communities) to the laws of residency. interventions.) In resident-run houses, residents However, those few who violate basic house rules take full responsibility for all aspects of house oper- must leave. Although management or a residents’ ation relatedto maintaining sobriety: admissions, council makes the final determination that basic maintenance of the house’s social environment, dis- house rules have been broken, violations usually ciplinary action, community relations, andphysical are obvious in a well-run house. If formal proceed- maintenance. ings are necessary, the only question to be settledis Resident-run ADF houses may be democratic or whether the violation actually occurred; thereafter, oligarchic. Democratic houses may be highly egali- commencement of the eviction process is auto- tarian—the residents have equal votes and share matic. Residents usually understand well the penal- equally in houses duties, as in OXFORD HOUSES—or ties for violations; those who know they will be they may be stratified, formally or informally, by evictedoften choose to leave immediately. residents’ seniority in sobriety or by other measures Violation of sobriety policy is the most common of status. Some therapeutic communities, such as reason for a tenant’s eviction or voluntary separa- Delancey Street in San Francisco, California, are tion from ADF housing. ADF houses vary some- oligarchic. In general, larger resident-run programs what in their toleration of drinking and drug use. tendto be more oligarchic in nature, though some Nearly all take a ‘‘no-slip’’ approach, in which a provide many opportunities for resident participa- single episode of drinking or using means that the tion in management andoperation of the house, as person must leave. Some permit individuals to slip does Beacon House in San Pedro (Los Angeles), once or twice before being evicted. Residents gener- California. ally findthat firm no-drinking,no-using policies The interests of landlords, owners, and program promote a sense of equity andmaintain tranquility operators notwithstanding, the rules of ADF house- in the house. holds seek to protect a sober environment. For their Some houses prefer a ‘‘client-centered’’ policy own peace of mind, residents often prefer places that permits the drinker/user to remain in contact that impose restrictions in the service of restraint, with counselors andotherwise receive help without ALCOHOL- AND DRUG-FREE HOUSING 69 having to leave the residence. The risk in such a ciofugal’’ spaces whose circulation systems empha- policy is that repeated drinking or using episodes size separation andisolation. Sociofugal circulation among residents will disturb the social environment systems keep people apart by using long corridors of the house. Some multicomponent programs with such as those foundin hotels androoms isolatedby very large facilities handle this issue by asking the stairs and such. Sociofugal spaces are dull, de- drinker/user to move from the sober housing com- pressing, andsometimes disorientingor frightening ponent of the program to the detoxification or pri- to anxious people who cannot easily see what is mary-recovery unit. Some ADF residences that per- going on in the building. Developers of successful mit off-site but not on-site drinking or using have ADF residences understand the influences of archi- foundthis policy to work well to reducechronic tecture. Specializeddesignwill play an important intoxication among those for whom continuous so- role in the future development of ADF housing, briety is not a realistic expectation. particularly affordable ADF housing for single par- Eviction proceedings are time consuming and ents or couples with children, who require func- filled with legal procedures that have been designed tionally different and far more space than do single to protect andextendthe rights of the resident.A people. signed landlord-tenant agreement that specifically It is not clear how quickly or in which specific proscribes drinking and/or using offers the stron- directions ADF housing development will proceed. gest starting point for eviction; but an eviction pro- The Anti-Drug Abuse Act of 1988 provided that cess can sometimes drag on for weeks or months every state receiving federal block grant funds for even in the most clear-cut cases. Successful ADF alcohol andother drugprograms establish a re- houses rely on resident participation in manage- volving fundof at least 100,000 dollarsto make ment. (A residents’ manual provides a model for start-up loans for sober housing. This was a foot in peer-based response to a resident’s drinking or the door for ADF projects, although the relatively drug use.) paltry funds involved have not provided much le- ADF housing works best when residents them- verage by themselves. selves actively maintain the collective sobriety of In addition, government at all levels—federal, their home. Management’s task is to create a living state, or local—has a strong tendency to regulate environment in which sobriety is respectedand and standardize the activities it supports and to maintainedby the residents.Frequent contact be- demand accountability to its agencies rather than tween management andresidents,both informally to other relevant constituencies, such as consumers andthrough regular house meetings, providesa of sober housing. Any governmental attempt to medium for interaction that quickly identifies a res- regulate the environment of sober housing raises ident who has been drinking or using. Secretiveness far-reaching questions about the invasion of pri- andthe absence of communication are important vacy, for ADF housing is by definition ordinary and signs that something isn’t right. protected from oversight not extended to other do- Architectural design plays a central role in creat- mestic households. The philosophy of ADF hous- ing an ADF housing environment that promotes ing, andmore practically, its necessary andsalu- both open social interaction andmutual account- tary diversity, is not compatible with intrusive ability. The basic floor plan of the residence makes regulation. a critical contribution. ‘‘Open’’ circulation systems Still, considerable potential exists for an explo- in buildings bring people into contact with one an- sion of interest andactivity. As noted,ADF resi- other. Examples are open-plan houses in which dences may play an important role in the reform of space flows from one room into another; areas that the system of services for people with alcohol and have nooks andsideareas where people can sit or drug problems. Although interest in sober housing stop to chat; andcentrally locatedcorridorswith originatedin the search for ways to support home- wide openings directly into the rooms they serve. less andvery low-income people completing resi- Spaces that invite social contact are called‘‘so- dential treatment and recovery programs, the use- ciopetal.’’ They subtly but powerfully encourage ful scope of sober housing may be much broader. people to socialize, to greet each other, to notice one Combinedwith various services in the surrounding another during the day. Sociopetal spaces are community, perhaps it is a goodalternative to ex- lively, engaging places, in stark contrast with ‘‘so- pensive, traditional forms of residential treatment. 70 ALCOHOL: Chemistry andPharmacology

Private insurance companies andhousing entrepre- Chemistry and Pharmacology Chemical neurs already are developing sober living arrange- determination has discovered five separate forms of ments that are attractive to the middle and upper alcohol that have little molecular variation, but classes, as well as to low-income people. enough variation to produce substantial differences It is also possible that sober residences appeal to in their characteristics. Occurring naturally many more people than those actively engagedin through the fermentation of fruits, vegetables and treatment or recovery programs. Just as some uni- grains exposedto the bacteria in the air, alcohol versity dormitories have become sober housing for production can be expedited by producing condi- self-selected students, perhaps sober residences will tions conducive to the environmental needs of the become part of a larger trendto reconfigure domes- alcohol producing organisms. The form of alcohol tic living arrangements to fit our changedfamily produced intentionally for use is ethyl alcohol, also demography and our changing styles of life. In the calledethanol. heyday of the temperance movement, the United People do not drink pure ethanol. Most drinks States was littered with dry hotels and boarding with alcoholic content do not exceed an 8 percent houses that cateredto a preference of style, not concentration, such as beer. Most wines do not merely or only to prohibitionist sentiment. It is not exceed15 percent, andmost liquors are still below hardto imagine a future in which likemindedciti- 50 percent, or, in the terms of the UnitedStates, zens cause ‘‘dry’’ households to reappear. 100 proof by weight or volume. Furthermore, alco- holic beverages are often diluted by water before (SEE ALSO: Treatment, History of ) they are consumed.

BIBLIOGRAPHY CHEMISTRY

MCCARTY, D., ET AL. (1993). Development of alcohol and Ethanol has a very simple molecular structure, drug-free housing. Contemporary Drug Problems, 20, C2H6O. It is composedof only two carbon atoms, 521–539. six hydrogen atoms, and one oxygen atom, yet its MOLLOY, J. P. (1990). Self-run, self-supported houses for precise mechanism of action is not fully under- more effective recovery from alcohol and drug addic- stood. Although it is commonly believed that etha- tion. DHHS Publication no. ADM 90-1678. Rockville, nol is useful in a number of physical ailments (as MD: Office of Treatment Improvement. medicinal alcohol, the medieval elixir of life), in OXFORD HOUSE,INC. (1988). The Oxford House manual. reality its uses are not therapeutic—andits chronic Great Falls, VA: Author. use is toxic. WITTMAN, F. D. (1993). Affordable housing for people with alcohol andother drugproblems. Contemporary EFFECTS ON THE BODY AND Drug Problems, 20, 541–609. THERAPEUTIC USES FRIEDNER D. WITTMAN Ethanol is a general central nervous system de- JIM BAUMOHL pressant, producing sedation and even sleep at higher doses. The degree of this depression is pro- portional to its concentration in the blood; how- ALCOHOL This section contains articles on ever, this relationship is more predictable when some aspects of alcohol, andthe following topics ethanol levels are rising than three or four hours are covered: Chemistry and Pharmacology; Com- later, when bloodlevels are the same but ethanol plications; History of Drinking; and Psychological levels are falling. This variance occurs because dur- Consequences of Chronic Abuse. For discussions of ing the first fifteen or twenty minutes after an etha- alcoholism, its treatment, andwithdrawalsymp- nol dose, the peripheral venous blood is losing etha- toms, see the section entitled Alcoholism; Treat- nol to the tissues while the brain has equilibrated ment; and Withdrawal. See also the articles Alco- with arterial bloodsupply. Thus, brain levels are holics Anonymous (AA) and Treatment Types: initially higher than the venous bloodlevels, and Twelve Steps. Other articles on relatedtopics are since all bloodsamples for ethanol determinations listedthroughout the Encyclopedia. are taken from a peripheral vein, the ethanol con- ALCOHOL: Chemistry andPharmacology 71 centrations are appreciably lower than a few hours skin disinfectant. Ethanol can lessen the severity of later, when the entire system has achievedequilib- dermatitis, reduces sweating, cools the skin during rium. a fever and, when added to ointments, helps other The reticular activating system of the brain stem drugs penetrate the skin. These therapeutic uses for is the most sensitive area to ethanol’s effects; this ethanol are for acute problems only. accounts for the loss of integrative control of the Until recently, it hadbeen felt that the chronic brain’s higher functions. Anecdotal reports of a drinking of ethanol led only to organ damage. Re- stimulating effect, especially at low doses, are likely cent evidence suggests that low or moderate intake due to the depression of the mechanisms that nor- of ethanol (1–2 drinks per day) can indirectly re- mally control speech andother behaviors that duce the risk of heart attacks. The doses must be evolvedfrom training or prior experiences. How- low enough to avoidliver damage.This beneficial ever, there may be a genetic basis for this initial effect is thought to be due to the elevation of high- stimulating effect, since rodents differing geneti- density lipoprotein cholesterol (HDL-C) in the cally show differences in the degree of initial stimu- bloodwhich, in turn, slows the developmentof lation or excitement. Upon drinking a moderate arteriosclerosis and, presumably, heart attacks. amount of ethanol, humans may quickly pass This relationship has not been proven, but has been through the ‘‘stimulating’’ phase. Memory, the culledfrom the results of several epidemiological ability to concentrate, andinsight are affectednext studies. whereas confidence often increases as moods swing Several mechanisms have been proposedto ex- from one extreme to another. If the dose is in- plain how oral ethanol exerts its effects. One is creased, then neuromuscular coordination becomes thought to be its ability to alter the fluidity of cell impaired. It is at this point that drinkers may be membranes—particularly neurons. This distur- most dangerous, since they are still able to move bance alters ion channels in the membrane result- about but reaction times andjudgmentare im- ing in a reduction in the propagation of neuronal paired—and sleepiness must be fought. The ability transmission. The anesthetic gases share this prop- to drive an automobile or operate machinery is erty with ethanol. Furthermore, it has been shown compromised. With higher doses, general (sleep) or that the degree of membrane disordering is directly surgical (unconsciousness) anesthesia may de- proportional to the drug’s lipid solubility. It has velop, but respiration is dangerously depressed. also been arguedthat such membrane effects occur Ethanol is believedby many to have a number of only at very high doses. More recently, scientists medicinal (therapeutic) uses; these are mostly have reportedthat ethanol may augment the activ- basedon anecdotalreports andhave few substan- ity of the neurotransmitter GABA by its actions on a tiatedclaims. One example of a well-known but receptor site close to the GABA receptor. The effect misguided use is to treat hypothermia—exposure of this action is to increase the movement of chlo- to freezing conditions. Although the initial effects ride across biological membranes. Again, this effect of an alcoholic beverage appear to ‘‘warm’’ the wouldalter the degreeto which neuronal transmis- patient, ethanol actually dilates blood vessels, sion is maintained. causing further loss of body heat. Another example is its effects on sleep— it is believedthat a nightcap PHARMACOKINETICS AND relaxes one andputs one to sleep. Acute adminis- DISTRIBUTION tration of ethanol may decrease sleep latency, but this effect dissipates after a few nights. In addition, Ethanol is quickly andrapidlyabsorbedfrom waking time during the latter part of the night is the stomach (about 20%) andfrom the first section increased, and there is a pronounced rebound in- of the small intestines (called the duodenum). Thus somnia that occurs once the ethanol use is discon- the onset of action is relatedin part to how fast it tinued. Except as an emergency treatment to re- passes through the stomach. Having foodin the duce uterine contractions and delay birth, the stomach can slow absorption because the stomach therapeutic use of oral ethanol is confinedto treat- does not empty its contents into the small intestines ing poisoning from methanol andethylene glycol. when it is full. However, drinking on an empty Most of ethanol’s therapeutic benefits are derived stomach leads to almost instant intoxication be- from applying it to the skin, since it is an excellent cause the ethanol not absorbedin the stomach 72 ALCOHOL: Chemistry andPharmacology passes directly to the small intestines. Maximal ory loss, sleep disturbances, seizures, and psy- bloodlevels are achievedabout thirty to ninety choses. Some of these neuropsychiatric syndromes, minutes after ingestion. Ethanol mixes with water such as Wernicke’s encephalopathy, Korsakoff’s quite well, andso once it enters the bodyit travels psychosis, andpolyneuritis can be debilitating. to all fluids and tissues, including the placenta in a Other, less obvious problems also occur during pregnant woman. After about twenty to thirty min- chronic ethanol consumption. The chronic drinker utes for equilibration, bloodlevels are a goodesti- usually fails to meet basic nutritional needs and is mate of brain levels. Ethanol freely enters all blood often deficient in a number of essential vitamins, vessels, including those in the small air sacs of the which can also leadto brain andnerve damage. lungs. Once in the lungs, ethanol exchanges freely Chronic drinking also causes damage to a num- with the air one breathes, making a breath sample a ber of major organs. Permanent alterations in brain goodestimate of the amount of ethanol in one’s function have already been discussed. By far, one of body. A breathalyzer device is often used by police the most important causes of death in alcoholics officers to detect the presence of ethanol in an indi- (other than by accidents) is liver damage. The liver vidual. is the organ that metabolizes ingestedandbody Between 90 and98 percent of the ethanol doseis toxins; it is essential for natural detoxification. Al- metabolized. The amount of ethanol that can be cohol damage to the liver ranges from acute fatty metabolizedper unit of time is roughly propor- liver to hepatitis, necrosis, andcirrhosis. Single tional to the individual’s body weight (and proba- doses of ethanol can deposit droplets of lipids, or bly the weight of the liver). Adults can metabolize fat, in the liver cells (calledhepatocytes). With an about 120 mg/kg/hr which translates to about accumulation of such lipid, the liver’s ability to thirty ml (one ounce) of pure ethanol in about three metabolize other body toxins is reduced. Even a hours. Women generally achieve higher alcohol weekend drinking binge can produce measurable bloodconcentrations than domen, even after the increases in liver fat. It was foundthat liver fats same unit dose of ethanol, because women have a doubled after only two days of drinking; blood eth- lower percentage of total body water but also be- anol levels rangedbetween twenty andeighty mg/ cause they may have less activity of alcohol-metab- dl, suggesting that one need not be drunk in order olizing enzymes in the wall of the stomach. The to experience liver damage. enzymes responsible for ethanol and acetaldehyde Alcohol-induced hepatitis is an inflammatory metabolism—alcohol dehydrogenase and aldehyde condition of the liver. The symptoms are anorexia, dehydrogenase, respectively—are under genetic fever, andjaundice.The size of the liver increases, control. Genetic differences in the activity of these andits ability to cleanse the bloodof other toxins is enzymes account for the fact that different racial reduced. Cirrhosis is the terminal and most danger- groups metabolize ethanol and acetaldehyde at dif- ous type of liver damage. Cirrhosis results after ferent rates. The best-known example is that of many years of intermittent bouts with hepatitis or certain Asian groups who have a less active variant other liver damage, resulting in the death of liver of the aldehyde dehydrogenase enzyme. When they cells andthe formation of scar tissue in their place. consume alcohol, they accumulate higher levels of Fibrosis of the bloodvessels leadingto the liver can acetaldehyde than do Caucasian males, for exam- result in elevatedbloodpressure in the veins ple; this causes a characteristic response called aroundthe esophagus, which may rupture and ‘‘flushing,’’ actually a type of hot flash with redden- cause massive bleeding. Ultimately, the cirrhotic ing of the face andneck. Some experts believe that liver fails to function andis a major cause of death the relatively low levels of alcoholism in such Asian among alcoholics. Although only a small percent- groups may be linkedto this genetically based age of drinkers develop cirrhosis, it appears that a aversive effect. continuous drinking pattern results in greater risk than does intermittent drinking, and an immuno- logical factor may be involved. TOXIC EFFECTS The role of poor nutrition in the development of Chronic consumption of excessive amounts of some of these disorders is well recognized but not ethanol can leadto a number of neurological disor- very well understood. Ethanol provides 7.1 kilocal- ders, including altered brain size, permanent mem- ories of energy per gram. Thus, a pint of whiskey ALCOHOL: Chemistry andPharmacology 73 provides around 1,300 kilocalories, which is a sub- tivity to ethanol andmay be quite extensive. The stantial amount of raw energy, although devoid of development of tolerance can take just a few weeks any essential nutrients. These nutritional distur- or may take years to develop, depending on the bances can exist even when foodintake is high, amount andpattern of ethanol intake. As with because ethanol can impair the absorption of vita- other central nervous system depressants, when the mins B1 andB 12 andfolic acid.Ethanol-related dose of ethanol is increased to achieve the desired nutritional problems are also associatedwith mag- effects (e.g., sleep), the margin of safety actually nesium, zinc, andcopper deficiencies.A chronic decreases, as the dose comes closer to producing state of malnutrition can produce symptoms that toxicity andthe brain’s control of breathing be- are indistinguishable from chronic ethanol abuse. comes depressed. Fetal alcohol syndrome (FAS) was recognized Like tolerance, dependence on ethanol can de- and described in the 1980s. Children of chronic velop after only a few weeks of consistent intake. drinkers are born deformed; the abnormality is The degree of dependence can be assessed only by characterizedby reducedbrainfunction as evi- measuring the severity of the withdrawal signs and denced by a low IQ and smaller than usual brain symptoms observedwhen ethanol intake is termi- size, slower than normal growth rates, characteris- nated. Victor and Adams (1953) provided perhaps tic facial abnormalities (widely spaced eyes and one of the best descriptions of the clinical aspects of flattenednasal area), other minor malformations, ethanol dependence. Patients typically arrive at the anddevelopmentalandbehavioral problems. Fetal hospital with the ‘‘shakes,’’ sometimes so severe malnutrition caused by ethanol-induced damage to that they cannot perform simple tasks by them- the placenta can also occur, andfetal immune selves. During the next twenty-four hours of their function appears to be weakened, resulting in the stay in the hospital, an alcoholic might experience child’s greater susceptibility to infectious disease. hallucinations, which typically are not too distress- Depending on the population studied, the rate of ing. Convulsions, however, which resemble those in FAS ranges from 1 in 300 to 1 in 2,000 live births; people with epilepsy, may occur in susceptible indi- however, the incidence is 1 in 3 infants of alcoholic viduals about a day after the last drink. Convul- mothers. Even today, it is not known if there is a sions usually occur only in those who have been safe lower limit of ethanol that can be consumedby drinking extremely large amounts of ethanol. If the pregnant women without risk of having a child convulsions are severe, the individual may die. with FAS. The lowest reportedlevel of ethanol that Many somatic effects, such as nausea, vomiting, resultedin FAS was about 75 ml (2.5 oz.) per day diarrhea, fever, and profuse sweating are also part during pregnancy. Among alcoholic mothers, if of alcohol withdrawal. Some sixty to eighty-four drinking during pregnancy is reduced, then the hours after the last dose, there may be confusion severity of the resulting syndrome is reduced. anddisorientation;more vividhallucinations may begin to appear. This phase of withdrawal is often TOLERANCE, DEPENDENCE, calledthe deliriumtremens, or DTs. Before the AND ABUSE days of effective treatment, a mortality rate of 5 to 15 percent was common among alcoholics whose Tolerance, a feature of many different drugs, withdrawal was severe enough to cause DTs. develops rather quickly to many of ethanol’s effects after frequent exposure. When tolerance develops, TREATMENT FOR the dose must be increased to achieve the original ALCOHOL DEPENDENCE effect. Ethanol is subject to two types of tolerance: tissue (or functional) tolerance andmetabolic (or The first step in treating alcoholics is to remove dispositional) tolerance. Metabolic tolerance is due the ethanol from the system, a process calleddetox- to alterations in the body’s capacity to metabolize ification. Since rapidtermination of ethanol (or any ethanol, which is achievedprimarily by a greater other central nervous system depressant) can be life activity of enzymes in the liver. Metabolic tolerance threatening, people who have been using high doses only accounts for 30 to 50 percent of the total shouldbe slowly weanedfrom the ethanol by giving response to alcohol in experimental conditions. Tis- a less toxic substitute depressant. Ethanol itself sue tolerance, however, decreases the brain’s sensi- cannot be usedbecause it is eliminatedfrom the 74 ALCOHOL: Complications

body too rapidly, making it difficult to control the HOFFMAN, F. G. (1975). A handbook on drugs and alco- treatment. Although barbiturates were once em- hol abuse: The biomedical aspects. New York: Oxford ployedin this capacity, the safer benzodiazepines University Press. have become the drugs of choice. Not only do they WEST,L.J.(ED.). (1984). Alcoholism and related prob- prevent the development of the potentially fatal lems: Issues for the American public. Englewood convulsions, but they reduce anxiety and help pro- Cliffs, NJ: Prentice-Hall. mote sleep during the withdrawal phase. New med- SCOTT E. LUKAS ications are constantly being testedfor their abili- REVISED BY ANDREW J. HOMBURG ties to aidin the treatment of alcohol withdrawal. Once a person has become abstinent, various methods can be used to maintain abstinence and Complications Through their ethanol (alco- encourage sobriety—some are pharmacologic and hol) content, alcoholic beverages significantly af- others are through social-support networks or for- fect the body’s cellular function as well as its cogni- mal psychological therapies. One type of treatment tive actions. Many of these effects are the involves making drinking an adverse toxic event for consequence of a complex set of biochemical reac- the individual, by giving a drug such as DISULFIRAM tions, long-term exposure to ethanol with an accu- (Antabuse) or citratedC ALCIUM CARBIMIDE, which mulation of damage that is manifested in diverse inhibits the metabolism of acetaldehyde and causes ways, or the result of increasedincidenceor severity facial flushing, nausea, andrapidheartbeat. When of major disease states, including AIDS, CANCER,or ethanol is ingestedby someone on disulfiram,the heart disease. However, some effects of ethanol are acetaldehyde levels rise very high, very quickly. immediate and do not require prolonged exposure, Disulfiram has not been successful in maintaining nor are they induced as the end product of many abstinence in all patients, however. physiological changes. For example, ethanol in- Many support groups are available to help peo- duces changes in cell membranes’ fluidity by mix- ple remain abstinent. ALCOHOLICS ANONYMOUS ing with the lipids there. The membrane changes (AA) is one of the most widely known and avail- inhibit neurological functions andthus can cause able; it is structuredarounda self-help philosophy. car ACCIDENTS. All of these can occur with a single The AA program emphasizes total avoidance of exposure and thus could be considered a direct alcohol andany medication.Insteadit relies on a effect of the ethanol in alcoholic beverages. ‘‘buddy’’ or ‘‘sponsor’’ system, providing support partners who are personally experiencedwith alco- ALCOHOL METABOLISM holism andalcoholism recovery. A number of other Ethanol Absorption and Metabolism. types of psychological andbehavioral approaches Because the ethanol molecule has a hydroxyl group, to treatment also exist. its metabolism involves dehydrogenase enzymes. After some metabolism in the stomach andintes- (SEE ALSO: Accidents and Injuries from Alcohol; tine, it is transportedto the liver for further metab- Alcoholism; Fetus, Effects of Drugs on; Complica- olism. Alcohol dehydrogenase produces acetalde- tions; Social Costs of Alcohol and Drug Abuse) hyde, which causes many of the indirect effects attributedto ethanol. Because females metabolize BIBLIOGRAPHY alcohol less efficiently in the stomach wall than males, their exposure can be higher, with more GILMAN, A. G., ET AL.(EDS.). (1990). Goodman and direct consequences, from the same amount of al- Gilman’s the pharmacological basis of therapeutics, cohol consumption. Ethanol is also metabolizedby 8th ed. New York: Pergamon. the liver cells’ MEOS system. Ethanol also affects GOLDSTEIN, A., ARONOW, L., & KALMAN, S. M. (1974). the transportation of proteins across membranes in Principles of drug action: The basis of pharmacology. the cell. Thus aldehyde dehydrogenase’s transpor- New York: Wiley. tation into the mitochondria from the cell’s cyto- GOLDSTEIN, D. B. (1983). Pharmacology of alcohol. New plasm is retarded. This reduces the oxidation of York: OxfordUniversity Press. acetaldehyde to acetic acid, and increases ethanol’s ALCOHOL: Complications 75 indirect effects by altering its metabolism and that crease internal conflicts andblock inhibitions, of its metabolites. Acetaldehyde is very reactive thereby making social behaviors more extreme. with proteins. Thus increasedlevels result in dam- Free Radical Generation by Alcohol. Free age to proteins with which it reacts. As many are radicals are a highly reactive oxygen species. They vital for cell function, cell death or dysfunction are important components of the body’s host de- occurs. This damage persists for the life of the fense, yet in high levels can cause tissue damage. protein or cell. Cytochrome P-450 is an oxidizing system that gen- Alcohol and Nutrition. Alcohol has major erates free radicals from ethanol. The reactive oxy- effects when consumedfrequently or in high gen species include superoxide and hydrogen per- amounts by affecting the frequency andquality of oxide. They react with DNA, protein, and lipids. foods consumed. This directly affects the amounts Products of the free radical reactions include lipid of vitamins andminerals that are consumedand peroxides; thus alcohol’s production of free radicals available for absorption. The long-term conse- indirectly initiates cancer, heart disease, and other quences involve undernutrition, nutritional defi- major health problems. Free radicals are produced ciencies, andultimately malnutrition. Ethanol also in higher levels when ethanol and acetaldehyde directly affects the absorption of vitamin A, begin to accumulate in cells and saturate dehydro- betacarotene (a vitamin A precursor), vitamin B genases. Then other products, such as free radicals 1 andcocaethylene (when cocaine is present), are (thiamine), folate, vitamin E, vitamin D, andfo- produced. late. Vitamins are critical for many enzymatic reac- Cholesterol and Fatty-Acid Production from tions, so ethanol causes indirect effects by altering Alcoholic Beverages. Excessive ethanol intake vitamin levels. Acute alcohol ingestion changes leads to formation of ethanol- and fatty-acid-con- many vitamin metabolic pathways. Folate andvi- taining ethyl esters, produced by synthases. Thus tamin A metabolism can cause increasedurinary tissues containing large amounts of synthases, such excretion. Thiamine deficiency is responsible for a as the heart, would be more likely to be damaged. severe neurological consequence of excessive alco- These products can adversely affect protein synthe- hol use—WERNICKE’S SYNDROME. sis, alter cell membranes that contain large amounts of normal lipids, and suppress energy pro- ACTIONS OF ALCOHOL ON THE BRAIN duction by the cells’ mitochondria. Cholesterol es- terase connects cholesterol to fatty acids, thus pro- The molecular site of alcohol’s action on neurons ducing fatty-acid cholesterol esters. When ethanol is unknown. Alcohol may work by perturbing lipids is present, the esterase produces fatty-acid ethyl in the cell membrane of the NEURON, interacting esters with a reduction of cholesterol. Ethanol con- directly with the hydrophobic region of neuronal sumption modifies components of cell membranes, membrane proteins, or interacting directly with a phospholipids, through the phospholipase D. The lipid-free enzyme protein in the membrane. Etha- importance of these changes is poorly defined and nol alters the function of neuron-specific proteins. understood. For example, evidence suggests that the activity of Cocaethylene and Drug Metabolism. When the chloride ion channel linked to the A-type recep- alcohol andcocaine are ingestedtogether, the EUROTRANSMITTER tor of the GABA N increases dur- ‘‘high’’ is accentuated. Ethanol can react with CO- ing exposure to intoxicating amounts of alcohol. CAINE via the enzyme cocaine esterase, producing a Acute exposure to alcohol effects the actions of potentially toxic product, COCAETHYLENE. This en- GLUTAMATE, the major excitatory transmitter in zyme inactivates cocaine in the absence of ethanol. the mammalian central nervous system. Chronic Metabolism of cocaine andother drugsoccurs in exposure to alcohol can result in TOLERANCE for large part via cytochrome P-450 IIEI. It is in- andP HYSICAL DEPENDENCE on the drug. Tolerance creasedby chronic alcohol consumption. This cyto- is recognizedas a chronic drinker’sability to con- chrome oxidizes ethanol in the liver as well as many sume increasing amounts of alcohol without dis- other compounds, including cocaine and the pain playing gross signs of intoxication. Alcohol’s effects killer acetaminophen. Oxidative products of cyto- on stress may be regulatedby the combination of its chrome P-450 are more toxic than the parent com- effect on information processing. Thus it can de- pounds, and thus can accentuate liver damage. 76 ALCOHOL: Complications

Metabolism of Protein. Consumption of alco- outside the cell membrane by signal transduction. holic beverages affects the metabolism of ethanol These signals regulate the functions of the various andother alcohols, andalters the NADH/NAD ra- cell types, affecting overall physiology of the body. tio—the ratio of reduced nicotinamide adenine di- Important enzymes in this process include phos- nucleotide to oxidized nicotinamide adenine dinu- pholipases. Ethanol acts like hormones andsignal cleotide—which influences lipid, vitamin, and molecules, changing membrane phospholipases, protein metabolism, membrane composition and which shouldmodifycell function. function, andenergy production.Such changes lead to indirect effects including cell damage, un- ALCOHOL TRAUMA, ACCIDENTS, AND dernutrition, and weight loss. Chronic alcohol bev- BEHAVIORAL EFFECTS erage use reduces type II muscle fibers, reducing the capacity for prolongedmuscle activity andthus Alcohol is directly involved in injuries by al- the ability to exercise, run, or do physical work. tering neurological function in ways that leadto Loss of this fiber produces muscle pain, weakness, motor vehicle ACCIDENTS, plane crashes, drown- and damage. Reduced type II fibers may be due to ings, SUICIDE, andhomicide.It appears to play a lower RNA, which wouldindicateless protein syn- role in both unintentional andintentional injuries. thesis. Nearly one-fourth of suicide victims, one-third of Metabolism of Lipids and Fats. Fat andlipid homicide victims, and one-third of unintentional functions andmetabolism are alteredby alcohol injury victims have high BLOOD ALCOHOL consumption. High alcohol intakes result in CONCENTRATIONS. Alcohol was a factor in half of changes in the ratio of NADH/NAD , which fatal traffic crashes and5 percent of all deaths.It rduces breakdown of fats and lipids. The accumu- causes premature mortality (not including deaths lated lipids are stored in the liver, producing a fatty from indirect, biochemical changes induced by liver. The NADH/NAD ratio also inhibits synthe- long-term exposure). sis of cholesterol andrelatedsteroidhormones. Alcohol and Auto Accidents. Alcohol con- Thus production of progesterone and androstene- sumption directly and promptly impairs many per- dione are reduced by alcohol use. Such changes ceptual, cognitive, andmotor skills neededto oper- may be the cause of hypogonadism in males who ate motor vehicles safely. Although in 1989 traffic consume alcohol chronically. Lipoprotein lipase is fatalities involving at least one intoxicateddriveror inhibitedby ethanol, thus reducingremoval of long nonoccupant (pedestrian or other) decreased by acyl chains from lipids. In heart muscle this reduces half, 22,413 people were killedin alcohol-related available energy andcouldbe a component of heart motor vehicle crashes, representing approximately disease. Lipoproteins are transport molecules for half of all traffic fatalities. The decrease in alcohol’s fats, including cholesterol, in plasma fluids. Alcohol involvement may be partially attributedto changes increases both low- andhigh-densitylipoproteins, which couldbe beneficial anddamaging,respec- in MINIMUM DRINKING AGE LAWS.WOMEN drivers tively, to the heart. are involvedin half as many alcohol-relatedcar Lipids in the Function and Composition of accidents as men. Impaired drivers arrested are Cell Membranes. Membranes have lipids and significantly more hostile; they have greater psy- proteins as major components. Ethanol clearly af- chopathic deviance, nontraffic arrests, and fre- fects lipids and membranes directly and indirectly. quency of impaired driving, and they drink more Alcohol affects cell membranes directly by its entry than drunk drivers caught in roadblocks. Thus, into them. Its physical characteristics modify ar- impaired driving and alcohol-related accidents are rangement of lipids in the cell membrane, and part of problematic behaviors that can be directly hence shouldaffect cell function directly.For ex- modified by ethanol. ample, electrolyte balance within all cells is pro- Alcohol and Airplane Accidents. Alcohol duced by sodium and potassium ion transportation. has not been shown to have causeda U.S. commer- High alcohol intake reduces the ion transporters, cial airline accident. However, it plays a direct and which causes cells to take up water andthus to prominent role in general aviation accidents. Pilot swell, affecting function. In addition, cells respond function is impairedby cognitive, perceptual, and to hormones andother chemicals in the plasma psychomotor changes due to ethanol use. Positional ALCOHOL: History of Drinking 77 alcohol nystagmus may contribute to many avia- Furthermore, the roles that alcohol plays differ, not tion crashes involving spatial disorientation. only from one culture to the next but even within a Alcohol and Water Accidents. Alcohol is as- culture over time. A single chemical compound, sociated with between half and two-thirds of adult used (or sometimes emphatically avoided) by a sin- drownings. Alcohol is also important in water-re- gle species, has resultedin a complex array of cus- latedspinal cordinjuries. toms, attitudes, beliefs, values, and effects. A brief Alcohol and Sexual Behavior. Via neurolog- review of the history of this relationship illustrates ical changes, alcohol impairs rational thought, thus both unity anddiversityin the ways people have decreasing behavioral inhibitions. Alcohol is an ex- thought about andtreatedalcohol. Special atten- cuse for behavior that violates social norms. Prob- tion is paidto the UnitedStates as a case studyof lem drinking behavior is associated with sexually particular interest to many readers. transmitteddisease. Alcohol and Violence. High alcohol con- THE QUESTION OF ORIGINS sumption reduces inhibition, impairs moral judg- Ethanol, the form of alcohol desired for use to ment, andincreases aggression; thus there is produce favorable effects, is both created naturally, greater likelihoodof homicideor assault resulting in the fermentation of exposedfruits, vegetables, from fights. Frequently, alcohol use has occurredin andgrains that have become overripe, andthrough situations that emerge spontaneously from per- the intervention of people who accelerate the pro- sonal disputes. Alcohol is linked to a high propor- cess by controlling the conditions of fermentation. tion of violence, with perpetrators more often under If we assume that it is ethanol that produces a host the influence of alcohol than victims. Very high of presumedfavorable effects, as well as alcohol- rates of problem drinking are reported among both relatedproblems, then the logic of labeling some property andviolent offenders. drinks ‘‘alcoholic’’ can be justified. It is important to remember, however, that labels are merely a (SEE ALSO: Accidents and Injuries from Alcohol; social convention. No matter how great its alcohol Complications) content may be, wine is thought of as ‘‘food’’ in much of France andItaly—as is beer in Scandina- BIBLIOGRAPHY via andGermany. Similarly, in the UnitedStates,

SECRETARY OF HEALTH AND HUMAN SERVICES. (1993). many people who regularly drink beer in consider- Eighth special report to the U.S. Congress on alcohol able quantities do not think of themselves as using and health. Washington, DC: U.S. Government Print- alcohol. Some fruit juices, candies, and desserts ing Office. come close to having enough alcohol to be so la- beled, but they are not. Thus many of the concerns WATSON, R. R. (1995). Alcohol and accidents. Totowa, N.J.: Humana Press. that people have about alcohol relate more to their expectations than to the actual pharmacological or WATSON, R. R. (1995). Alcohol and hormones. Totowa, N.J.: Humana Press. biochemical impact that the substance wouldhave on the human body. WATSON, R. R. (1992). Alcohol and neurobiology.I.Re- ceptors, membranes and channels. Boca Raton, FL: According to the Bible, one of the first things CRC. Noah did after the great Flood was to plant a vineyard(Genesis 9:21). Accordingto the RONALD R. WATSON predynastic Egyptians, the great god Osiris taught people to make beer, a substance that hadgreat religious as well as nutritional value for them. Simi- History of Drinking The key to the impor- larly, early Greeks credited the god Dionysus with tance of alcohol in history is that this simple sub- bringing them wine, which they drank largely as a stance, presumably present since bacteria first con- form of worship. In Roman times, the godBacchus sumedsome plant cells nearly 1.5 billion years ago, was thought to be both the originator of wine and has become so deeply embedded in human societies always present within it. It was a goddess, that it affects their religion, economics, age, sex, Mayahuel, with 400 breasts, who supposedly politics, andmany other aspects of human life. taught the Aztecs how to make pulque from the sap 78 ALCOHOL: History of Drinking

but the distribution of local styles of wine vessels serves as a guide to the flow of commerce in antiq- uity. It wouldbe misleadingto think of early wines and beers as similar to the drinks we know today. In a rough sense, the distinction between them is that a wine is generally derived from fruits or berries, whereas a beer or ale comes from grain or a grain-basedbread.Until as recently as A.D. 1700, both were often relatively dark, dense with sedi- ments, andextremely uneven in quality. Usually Police and alleged moonshiners pose with one of handcrafted in small batches, home-brewed beers the two giant stills taken during the raid at a tendto be highly nutritious but to last only a few downtown Pittsburgh office building, July 22, days before going sour (i.e., before all the ferment- 1922. ( Bettmann/CORBIS) ing sugars andalcohol are depletedandbecome vinegar). By contrast, homemade wines have rela- of the century plant; that mildbeer is still impor- tively little in the way of vitamins or minerals but tant in the diet of many Indians in Mexico, where it can last a long time if adequately sealed. is often referredto as ‘‘the milk of our Mother.’’ In In Egypt between 2700 and1200 B.C., beer was each of these instances, whether the giver was male not only an important part of the daily diet; it was or female, alcohol was viewedas supernatural, re- also buriedin royal tombs andofferedto the dei- flecting deep appreciation of its important roles in ties. Many of the paintings andcarvings in Egyp- nourishing andcomforting people. tian tombs depict brewing and drinking; early Anthropologists often treat myths as if they were papyri include commercial accounts of beer, a fa- each people’s own view of history, but clearly it ther’s warning to his student son about the danger wouldbe difficultto take all myths at face value. of drinking too much, praises to the god who We cannot know when or where someone first sam- brought beer to earth, andother indicationsof its pledalcohol, but we can imagine that it might well importance andeffects. have been just an attempt to make the most of an The earliest written code of laws we know, from overripe fruit or a souredbowl of gruel. The taste, Hammurabi’s reign in Babylon around2000 B.C., or the feeling that resulted, or both, may have been devoted considerable attention to the production pleasant enough to prompt repetition andthen andsale of beer andwine, includingregulations experimentation. Probably it happenednot just about standard measures, consumer protection, once but various times, independently, at a number andthe responsibilities of servers. of different places, just as did the beginnings of In ancient Greece andRome (roughly 800 B.C.– agriculture. A.D. 400), there was wider diffusion of grape-grow- ing north andwestwardin Europe, andwine was important for medicinal and religious purposes, al- PREHISTORY AND ARCHEOLOGY though it was not yet a commonplace item in the Although it is impossible to say where or when diet of poor people. The much-touted sobriety of Homo sapiens first sampledalcohol, there is firm the Greeks is presumably basedon their custom of evidence, from chemical analysis of the residues diluting wine with water and drinking only after foundin pots datingfrom 3500 B.C., that wine was meals, in contrast to neighboring populations who already being made from grapes in Mesopotamia often sought drunkenness through beer as a tran- (now Iran). This discovery makes alcohol almost as scendental state of altered consciousness. Certainly oldas farming, and,in fact, beer andbreadwere heavy drinking was an integral part of the religious first produced at the same place at about the same orgies that, commemorating their deities, we now time from the same ingredients. We know little call ‘‘Dionysiac’’ (or, in the case of Rome, about the gradual process by which people learned ‘‘Bacchic’’). The temperate stereotype also over- to control fermentation, to blenddrinks,or to store looks the infamous chronic drunkenness of Alexan- andship them in ways that kept them from souring, der the Great. Born in Macedon, in 356 B.C., he ALCOHOL: History of Drinking 79 managedto conquer most of the known worldin his Asia, we know most about China, where as early as time, by 325 B.C., bringing what are now Egypt and 2000 B.C. grain-basedbeer andwine were usedin most of the Middle East under the rule of Greece ceremony, offered to the gods, and included in before he died in 323 B.C. royal burials. Most of North America andOceania, Romans were quick to point out how their rela- curiously, appear not to have hadany alcoholic tive temperance contrastedwith the boisterous beverages until contact with Europeans. heavy drinking of their tribal neighbors in all direc- Alcohol in classical times servedas a disinfectant tions, whom they devalued as the bearded ones, andwas thought to strengthen the blood,stimulate ‘‘barbarians.’’ To a remarkable degree, the geo- nursing mothers, andrelieve various ills, as well as graphic spreadof Latin-basedlanguages andgrape to be an ideal offering to both gods and ancestral cultivation coincided with the spread of the Roman spirits. Obviously, drink and drinking had highly Empire through Europe andthe accompanying dif- positive meanings for early peoples, as they do now fusion of the Mediterranean diet—rich in carbohy- for many non-Western societies. dratesandlow in fats andprotein—with wine as the usual beverage. In striking contrast were non- FROM 1000 TO 1500 Latin speakers, who were less reliant on breadand pasta andwithout olive oil; they drankbeers and The Middle Ages was marked by a rapid spread meads, with drunkenness more common. Plato of both Christianity andIslam. Large-scale politi- considered wine an important adjunct to philo- cal andeconomic integration spreadwith them to sophical discussion, and St. Paul recommended it many areas that hadpreviously seen only local as an aidto digestion. warring factions, andsharp social stratification be- The Hebrews establisheda new pattern around tween nobles andcommoners was in evidenceat the time of their return from the Babylonian exile, courts andmanors, where foodanddrinkwere andthe construction of the SecondTemple (c. 500 becoming more elaborate. National groups began B.C.). Relatedto a new systematizing of religious to appear, with cultural differences (including pre- practices was a strong shift towardfamily rituals, ferred drinks and ways of drinking) increasingly in which the periodic sacred drinking of wine was notedby travelers, of whom there were growing accompaniedby a pervasive ethic of temperance, a numbers. Excessive drinking by poor people was pattern that persists today and often marks drink- often criticizedbut may well have been limitedto ing by religious Jews as different from that of their festive occasions. With population increases, towns neighbors. Early Christians (many of whom had andvillages proliferated,andtaverns became im- been Jews), praisedthe healthful andsocial benefits portant social centers, often condemned by the of wine while condemning drunkenness. A majority wealthy as subverting religion, political stability, of the many biblical references to drinking are andfamily organization. But for peasants and clearly favorable, andJesus’ choice of wine to sym- craftspeople, the householdwas still often the pri- bolize his bloodis perpetuatedin the solemn rite of mary economic unit, with home-brewedbeer being the Eucharist, which has become central to practice a major part of the diet. in many Christian churches as Holy Communion. During this period, hops, which enhanced both In the Iron Age in France (c. 600 B.C.), distinc- the flavor and durability of beer, were introduced. tive drinking vessels found in tombs strongly sug- In Italy andFrance, wine became even more popu- gest that political leadership involved the redis- lar, both in the diet and for expanding commerce. tribution of goods to one’s followers, with wine an Distillation hadbeen known to the Arabs since important symbol of wealth. Archeologists have about 800, but among Europeans, a small group of learnedso much about the style andcomposition of clergy, physicians, andalchemists monopolized pots made in any given area that they can often that technology until about 1200, producing spirits trace routes andtimes of trade,military expansion, as beverages for a limitedluxury market andfor or migrations by noting where fragments of drink broader use as a medicine. Gradual overpopulation containers are found. Although we know little was haltedby the Black Death (a pandemicof bu- about Africa at that time, we assume that mild bonic plague), andschisms in the Catholic church fermentedhome brews (such as banana beer) were resultedin unrest andpolitical struggles later in commonplace, as they were in Latin America. In this period. 80 ALCOHOL: History of Drinking

Across northern Africa andmuch of Asia, popu- FROM 1500 TO 1800 lations, among whom drinking and drunkenness Wealth andextravagance were manifest in the hadbeen lavishly andpoetically praisedas valu- rapidly growing cities of Europe, but so were pov- able ways of altering consciousness, became tem- erty andmisery, as class differencesbecame even perate andsometimes abstinent, in keeping with more exaggerated. The Protestant Reformation, the tenets of Islam and the teachings of Buddha and which set out to separate sacredfrom secular of Confucius. China and India both had episodes of realms of life, seemedto justify an austere morality prohibition, but neither country was consistent. In that included injunctions against celebratory the Hindu religion, some castes drank liquor as a drunkenness. If the body was the vessel of the sacrament, whereas others scornedit—vividproof spirit, which itself was divine, one should not dese- that a culture, in the anthropological sense (as a set crate it with long-term heavy drinking. Puritans of beliefs andpractices that guideone through liv- viewedintoxication as a moral offense—although ing), is often much smaller than a religion or a they drank beer as a regular beverage and appreci- nation, although we sometimes tendto think of atedliquor for its supposedwarming, social, and those larger entities as more homogenous than they curative properties. Public drinking establishments really are. evolved, sometimes as important town meeting As the Middle Ages gave way to the Renaissance, places andsometimes as the workers’ equivalent of both the population andthe economy expanded social clubs, with better heat andlighting than at throughout most of Europe. Because the Arabs home, with news andgossip, games andcompan- (who hadruledfrom 711 to 1492) hadbeen ex- ionship. COFFEE,TEA, andC HOCOLATE were also pelledfrom Spain andPortugal, they cut off over- introduced to Europe at this time, and each became landtraderoutes to Asia; European maritime ex- popular enough to be the focus of specializedshops. ploration therefore resultedin increasing But each was also suspect for a time, while physi- commerce all aroundthe coasts of Africa. The cians debated whether they were dangerous to the so-calledAge of Exploration ledto the startling health; clergy debated their effects on morality; and encounter with high civilizations andother tribal political andbusiness leadersfearedthat retail out- peoples who hadlong occupiedNorth America, lets wouldbecome breedingplaces of crime, labor Central America, andSouth America. Ironically, unrest, and civil disobedience. Brandies alcoholic beverages appear to have been totally un- (brantwijns, liquor distilled from wines to be ship- known north of Mexico, although a vast variety of pedas concentrates) spreadamong the aristocracy, beers, chichas, pulques, andother fermentedbrews andchampagne was introducedas a luxury bever- were important in Mexico as foods, as offerings to age (wine), as were various cordials and liqueurs. the gods and to ancestral spirits, and as shortcuts to Brewing andwine-making grew from cottage in- religious ecstasy—if we assume that Native Ameri- dustries to major commercial ventures, incorporat- cans then livedmuch as those who were soon to be ing many technical innovations, quality controls, described by the European conquerors and mis- andother changes. sionaries. The ‘‘gin epidemic’’ in mid-eighteenth-century Throughout sub-Saharan Africa, we assume, London is sometimes cited as showing how urban home-brewedbeers were plentiful nutritious, and crowding, cheap liquor, severe unemployment, and symbolically important, as they came to be de- dismal working conditions combined to produce scribedin later years. widespread drinking and dissolution, but the vivid During the Middle Ages, drinking was treated as engravings by William Hogarth may exaggerate the a commonplace experience, little different from problem. At the same time, the artist extolledbeer eating, anddrunkennessappears to have been in- as healthful, soothing, andeconomically sound.In frequent, toleratedin association with occasional France, even peasants began to drink wine regu- religious festivals andof little concern in terms of larly. In 1760, Catherine the Great set up a state health or social welfare. Alcoholic beverages them- monopoly to profit from Russia’s prodigious thirst, selves were becoming more diverse but still were andSwedenfollowedsoon after. thought to be invigorating to humans, appreciated Throughout Latin America andparts of North by spirits, andimportant to sociability. America, the Spanish andPortuguese con- ALCOHOL: History of Drinking 81 quistadors found that indigenous peoples already parts of their traditional ways of life. Detailed in- hadhome brews that were important to them for formation about the patterns of belief andbehavior sacred, medicinal, and dietary purposes. The Aztecs associated with drinking among the diverse popu- of Mexico derived a significant portion of their nutri- lations of Asia andAfrica vividlyillustrates that tional intake from pulque but reserveddrunkenness alcohol results in many kinds of comportment— as the prerogative of priests andoldmen. Cultures depending more on sociocultural expectations than throughout the rest of the area similarly usedchicha any qualities inherent in the substance. or beer made from maize, manioc, or other materi- In what is now the UnitedStates, colonial drink- als. The Yaqui (in what is now Arizona) made a wine ing patterns reflectedthose of the countries from from cactus as part of their rain ceremony, and which immigrants hadcome. Rum (distilledfrom specially made chicha was used as a royal gift by the West Indies sugar production) became an impor- Inca of Peru. Religious andpolitical leadersfrom the tant item in international trade, following routes colonial powers were ambivalent about what they dictated by the economic rules of the British perceivedas the risks of public drunkennessandthe Empire. In the infamous Triangle Trade, captive profits to be gainedfrom producingandtaxing alco- black Africans were shippedto the West Indiesfor holic beverages. A series of inconsistent laws and sale as slaves. Many workedon plantations there, regulations, including sometime prohibition for In- producing not only refined sugar, a sweet and valu- dians, were probably short-lived experiments, af- able new faddish food, but also molasses, much of fectedby such factors as local revolts anddifferent which was shippedto New England.Distillers there opinions among religious orders. turnedit into rum, which was in turn shippedto As merchants from various countries competed West Africa, where it couldbe tradedfor more to gain commercial advantage in trading with the slaves. During the American Revolution (1775/6– various Native American groups of North America, 1783), however, that trade was interrupted and liquor quickly became an important item. It has North Americans shiftedto whiskey. Farmers along become popular to assume that Native Americans what was then the frontier, still east of the Missis- are genetically vulnerable to alcohol, but some sippi, were gladto have a profitable way of using tribes (such as Hopi andZuni) never acceptedit, surplus corn that was too bulky to bring to distant and others drank with moderation. The Seneca, in markets. After the war, when the first federal excise New York state, are an interesting case study, be- tax was imposed(on whiskey) in 1790, to help cut cause they went from having no contact with alco- the debt of the new United States, producers’ anger hol through a series of stages culminating in a about a tax increase was expressedin the Whiskey religious ban. When brandy first arrived, friends Rebellion of 1794. To quell the uprising, federal wouldsave it for an unmarriedyoung man, who troops (militia) were usedfor the first time. At woulddrinkit ceremoniously to help in his re- about the same time, Benjamin Rush, a notedphy- quiredritual quest for a vision of the animal that sician andsigner of the Declaration of Indepen- wouldbecome his guardianspirit. In later years, dence, started a campaign against long-term heavy drinking became secular, with anyone drinking and drinking as injurious to health. boisterous brawling a frequent outcome. In 1799, Evidently, alcohol plays many roles in the his- when a tribal leader, who was already alcoholic, tory of any people, andchanges in attitudescan be hada very differentkindof vision, he promptly abrupt, illustrating again the importance that so- preachedabstention from alcohol, an endto war- cial constructions of reality have in relation to fare, anddevotionto farming—all of which remain drinking. important today in the religion that is named after him, Handsome Lake. THE 1800s Throughout the islands of the Pacific, local pop- ulations reacted differently to the introduction of The large-scale commercialization of beer, wine, alcohol, sometimes embracing it enthusiastically and distilled liquor spread rapidly in Europe as andsometimes rejecting it. Eskimos were generally many businesses andindustriesbecame interna- quick to adopt it, as were Australian Aborigines, to tional in scope. Large portions of the European the extent that some interpret their heavy drinking proletariat were no longer tiedto the landfor sub- as an attempt to escape the stresses of losing valued sistence, andnew means of transportation facili- 82 ALCOHOL: History of Drinking tatedvast migrations. The industrialrevolution reditary social status, and a wide variety of bever- was not an event but a long process, in which, for ages, of apparatus associatedwith drinking,and many people, work became separatedfrom home. even of public drinking establishments accentuated The arbitrary pace imposedby wage work con- such class differences. trasted markedly with the seasonal pace of tradi- Near the endof the century, another wave of tional agrarianism. sentiment against alcohol grew, as large numbers of In some contexts neighbors still drank while immigrants (many of them Catholic andanything helping each other—as, for example, in barn-rais- but ascetic) were seen by Protestant Yankees as ing or reciprocal labor exchange during the harvest. trouble—competing for jobs, changing the political But for the urban masses, leisure and a middle class climate, andchallenging oldvalues. Coupledwith emergedas new phenomena. Drinking, which be- this attitude was enthusiasm for ‘‘clean living,’’ came increasingly forbidden in the workplace as with an emphasis on natural foods, exercise, fresh dangerous or inefficient, gradually became a leisure air andwater, loose-fitting clothing, anda number activity, often timedto mark the transition between of other fads that have recently reappeared on the the workday and home life. As markets grew, foods scene. became diverse, so that beers and ciders (usually Native American populations, in the meantime, hard) lost their special value as nourishing and en- suffered various degrees of displacement, exploita- ergizing. tion, andannihilation, sometimes as a result of In Europe, political boundaries were approxi- deliberate national policy and sometimes as a result mately those of the twentieth century; trains and of local tensions. The stereotype of the drunken steamships changed the face of trade; and old ideas Indian became embedded in novels, news accounts, about social inequality were increasingly chal- andthe public mind,although the image appliedto lenged. Alcohol lost much of its religious impor- only a small segment of life among the several tance as ascetic Protestant groups, andeven fervent hundred native populations. Some Indians re- Catholic priests in Ireland, associated crime, family mainedabstinent andsome returnedto abstinence disruption, unemployment, and a host of other so- as part of a deliberate espousal of indigenous val- cial ills with it, andtaxation andother restrictions ues—for example, in the Native American Church, were broadly imposed. In Russia, the czar ordered using PEYOTE as a sacrament, or in the sun dance or prohibition, but only briefly as popular opposition the sweat lodge, using asceticism as a combined mountedandgovernment revenues plummeted. religious andintellectually cleansing precept. Those who paidspecial attention to physical and From Asia, Africa, andOceania, explorers, mental illnesses were quick to link disease with traders, missionaries, and others brought back in- long-term heavy drinking, although liquor re- creasingly detailed descriptions of non-Western mainedan important part of medicinefor various drinking practices and their outcomes. It is from curative purposes. A few institutions sprang up late such ethnographic reports—often sensa- in the nineteenth century to accommodate so-called tionalized—that we can guess about the earlier inebriates, although there was little consensus distribution of native drinks and can recognize new about how or why drinking created problems for alcoholic beverages as major commodities in the some people but not for others, nor was there any commercial exploitation of populations. Although systematic research. some of the sacramental associations of traditional A wave of mounting religious concern that has beverages were transferredto new ones, the in- been calledthe ‘‘great awakening’’ swept over the creasing separation of brewing from the home, the UnitedStates early in the 1800s, and,by 1850, a expansion of a money-basedeconomy, andthe ap- dozen states had enacted prohibition. Antialcohol parent prestige value of Western drinks all tended sentiment was often associatedwith opposition to to diminish the significance of home brews. In Afri- slavery. The local prohibition laws were repealedas can mines, Latin American plantations, andeven the Civil War andreligious fervor abated,andhard some U.S. factories, liquor became an integral part drinking became emblematic of cowboys, miners, of the wage system, with workers requiredto accept lumberjacks, andother colorful characters associ- alcohol in lieu of some of their cash earnings. In atedwith the expandingfrontier. Distinctions of some societies where drinking had been unknown wealth became more important than those of he- before Western colonization, the rapidspreadof ALCOHOL: History of Drinking 83 alcohol appears to have been an integral part of a studies showed how important they were in terms complex process that eroded traditional values and of ideology, for vows, communicating with super- authority. natural beings, honoring ancestors, andotherwise building social and symbolic credit—among native THE TWENTIETH CENTURY societies not only in Africa but also in Latin Amer- ica andAsia. Closer attention to the social dynam- It has been saidthat the average person’s life in ics of drinking and other aspects of culture showed 1900 was more like that of ancestors thousands of that the impact of contact with Western cultures is years earlier than like that of most people today. not always negative andthat for many peoples the The assertion certainly applies to the consumption role of alcohol remaineddiverseandvital. of liquor. Pasteurization, mass production, com- In the UnitedStates, a combination of religious, mercial canning andbottling, andrapidtransport jingoistic, andunsubstantiatedmedicalclaims re- all transformedthe public’s view of beer andwine sultedin the enactment of nationwideprohibition in the twentieth century. The spreadof ideasabout in 1919. Often called‘‘the noble experiment,’’ the individualism and secular humanism loosened the Eighteenth Amendment to the Constitution was the holdof traditionalreligions on the moral precepts first amendment to deal with workaday behavior of of large segments of the population. New assump- people who have no important public roles. It tions about the role of the state in support of public forbade commercial transaction but said nothing health andsocial welfare now color our expecta- about drinking or possession. Most authorities tions about drinking and its outcomes. Mass media agree that, during the early years, there was rela- andinternational conglomerates are actively en- tively little production of alcoholic beverages and gagedin the expansion of markets, especially into not much smuggling or home production. It was developing countries. not long, however, before illegal sources sprang up. WorldWar I promptednational austerity pro- Moonshiners distilled liquor illegally, and bootleg- grams in many countries that curtailedthe diver- gers smuggledit within the U.S. or from abroad. sion of foodstuffs to alcoholic beverages but didn’t Speakeasies sprang up as clandestine bars or cock- quite reach the full prohibition for which the tail lounges, anda popular counterculture devel- UnitedStates became famous. Absinthe was opedin which drinkingwas even more fashionable thought to be medically so dangerous that it was than before prohibition. Some entrepreneurs be- bannedin several European countries, andIceland came immensely wealthy andbrashly confident bannedbeer but not wine or liquor. Swedenexperi- andseemedbeyondthe reach of the law, whether mentedwith rationing, andthe czar again tried because of superior firepower or corruption or both. prohibition in Russia. The worldwide economic de- The government hadbeen suffering from the loss of pression of the 1930s appears to have slowedthe excise taxes on alcohol, which accountedfor a large growth of alcohol consumption, which grew rapidly part of the annual budget. The stock-market crash, during the economic boom that followed World massive unemployment, the crisis in agriculture, War II. The Scandinavian countries, beset by a and worldwide economic depression aggravated an pattern of binge drinking, often accompanied by already difficult situation, and civil disturbances violence, trieda variety of systems of regulation, spreadthroughout the country. Some of the same including state monopolies, high taxation, and se- influential people who hadpressedstrongest for verely restrictedplaces andtimes of sale, before prohibition reversedtheir stands,andthe Twenty- turning to large-scale social research. first Amendment, the first and only repeal to affect While several Western countries were expanding the U.S. Constitution, did away with federal prohi- their spheres of influence in sub-Saharan Africa, bition in 1933. Although the national government they agreedbriefly on a multinational treaty that retainedclose control over manufacturing anddis- outlawedthe sale of alcoholic beverages there, al- tribution to maximize tax collection, specific regu- though they did nothing to curtail production of lations about retail sales were left up to the states. domestic drinks by various tribal populations. A An odd patchwork of laws emerged, with many flurry of scientific analyses of indigenous drinks states remaining officially dry, others allowing local surprisedmany by demonstratingtheir significant option by counties or towns, some imposing a state nutritional value, andmore detailedethnographic monopoly, some requiring that drinks be served 84 ALCOHOL: History of Drinking with foodandothers expressly prohibiting it, some gradually fallen since; beer sales also appear to insisting that bars be visible from the street and have passedtheir peak even more recently. These others the opposite, andso forth. The last state to reductions occurred, despite increasing advertising, vote itself wet was Mississippi, in 1966, andmany along with a return of the ‘‘clean living’’ movement communities remain officially dry today. The older andanother shift towardphysical exercise, less- federal law prohibiting sales to Indians was not processedfoods,andconcern for health. Linked repealeduntil 1953, andmany Indianreservations with the reduction in drinking, what some ob- and Alaska native communities remain dry under servers call a ‘‘new temperance movement’’ has local option. emerged, in which individuals not only drink less The experience of failedprohibition in the U.S. but call for others to do the same; the decline would is famous, but a similar combination of problems be enforcedby laws andregulations that would with lawlessness, corruption, andrelatedissues led increase taxes, index liquor prices to inflation, di- to repeal, after shorter experiments, in Iceland, minish numbers andhours of sales outlets, require Finland, India, Russia, and parts of Canada, dem- warning labels, ban or restrict advertising, and oth- onstrating again that such drastic measures seem erwise reduce the availability of alcohol. Such a not to work except where supportedby consensus ‘‘public health approach’’ is by no means limitedto andreligious conviction (e.g., SaudiArabia, Iran, the U.S.; its popularity is growing throughout Eu- andEthiopia). It is ironic that some Indianreserva- rope andamong some groups elsewhere, even as tions with prohibition have more alcohol-related alcohol consumption continues to rise in Asia and deaths than those without. A more salutary recent many developing countries. factor is the growth of culturally sensitive programs of prevention andtreatment that are being devel- CURRENT IMPLICATIONS oped, often by the communities themselves, for In- dian and other minority populations. A quick review of the history of alcohol lends a In the middle decades of the twentieth century, a fresh perspective to the subject. The vast literature number of alcoholics formeda mutual-help group, on ethnographic variation among populations modeled on the earlier Washingtonians, and demonstrates the different ways in which peoples, ALCOHOLICS ANONYMOUS has grown to be an inter- widely separated geographically and historically, national fellowship of individuals whose primary have usedandthought about alcohol. The ideaof purpose is to keep from drinking. At about the alcohol as being implicatedin a set of problems is same time, scientists from a variety of disciplines peculiar to the recent past andis not yet generally startedstudyingvarious aspects of alcohol, andour acceptedin many areas. knowledge has grown rapidly. Because of the large What some observers call the ‘‘new temperance constituency of recovering alcoholics, the subject movement’’ andothers call ‘‘neoprohibitionism’’ is has become politically acceptable, andthe disease a recent phenomenon that grew out of Scandina- concept has overcome much of the moral stigma vian social research. The conclusion, on the basis of that usedto attach to alcoholism. Establishment of transnational comparisons, was that there ap- a National Institute on Alcohol Abuse andAlcohol- pearedto be some relationship between the amount ism in 1971 signaleda major government commit- of alcohol people drink and a broad range of what ment to the field, and its incorporation among the the researchers called‘‘alcohol-relatedproblems’’ National Institutes of Health in 1992 indicates that (including spouse abuse, child neglect, social vio- concerns about wellness have largely displaced lence, psychiatric illness, a variety of organic dam- theological preoccupations. ages, andtraffic fatalities). The vague andgeneral Consumption of all alcoholic beverages in- findings gradually came, through a process of creasedgraduallyin the U.S. from repeal until the misquotation andparaphrasing, to be treatedas a early 1980s, with markedincrease following World pseudoscientific iron-clad law, to the effect that War II, although it never reachedmore than one- problems are invariably proportionate to consump- thirdof what is estimatedfor the corresponding tion, so that the most effective way to diminish perioda century earlier. Around1980, sales of problems wouldbe to cut drinking.This approach spirits started dropping and have continued to do is sometimes calledthe ‘‘control of consumption so. A few years later, wine sales leveledoff andhave model,’’ or the ‘‘single distribution model’’ (refer- ALCOHOL: History of Drinking 85

ring to the fact that heavy drinkers are on the same BADRI, M. B. (1976). Islam and alcoholism. Indianapolis: distribution-of-consumption curve as low and American Trust Publications. moderate drinkers, with no clear points that would BARROWS, S., & ROOM R. (EDS.). (1991). Drinking: Be- objectively divide the groups). havior and belief in modern history. Berkeley: Univer- This movement is not restrictedto the U.S. and sity of California Press. Scandinavia, however. The World Health Organi- BARROWS, S., ET AL.(EDS.). (1987). The social history of zation of the United Nations called for a worldwide alcohol: drinking and culture in modern society. reduction, by 25 percent, of alcohol consumption Berkeley, CA: Alcohol Research Group, Medical Re- during the last decade and a half of the twentieth search Institute of San Francisco. century, recommending that member countries BLOCKER, J. S. (1980). American temperance move- adopt similar policies. Throughout most of central ments: Cycles of reform, 2nded.Boston: Twayne. andwestern Europe andNorth America, sales have BLUM, R. H. (1974). Society and drugs I. Social and fallen markedly, although the opposite trend can be cultural observations. San Francisco: Jossey-Bass. seen in much of the third world. An ironic develop- CHANG,K.C.(ED.). (1977). Food in Chinese cultures: ment has been recent loosening of controls in Scan- Anthropological and historical perspectives. New Ha- dinavian countries, traditionally the exemplars of ven: Yale University Press. that approach, while controls are being introduced EAMES, A. (1993). Blood, sweat, and beer. Berkeley, CA: andprogressively tightenedin southern Europe, Milk andHoney Press. GOMBERG, E. L., ET AL.(EDS.). (1982). Alcohol, science, where drinking has traditionally been an integral and society revisited. Ann Arbor: University of Michi- part of the culture. gan Press. The European Community standardization of GUSFIELD, J. (1986). Symbolic crusade: Status politics tariffs may result in further changes soon. A more and the American temperance movement, 2nded. realistic way of lessening whatever problems may Urbana: University of Illinois Press. be relatedto alcohol consumption wouldappear to HAMER, J., & STEINBRING,J.(EDS.). (1980). Alcohol and be the ‘‘sociocultural model’’ of prevention, em- native peoples of the north. Lanham, MD: University phasizing, on the basis of cross-cultural experience, Press of America. that people can learn to drink differently, to expect HATTOX, R. S. (1985). Coffee and coffeehouses: The different outcomes from drinking, and actually to origins of a social beverage in the medieval Near East. findtheir expectancies fulfilled.This program University of Washington Near Eastern Studies 3, wouldnot be quick or easy, requiring intensive Seattle. public education, but it seems more feasible than HEATH, D. B. (1994). International handbook on alcohol simply curtailing availability—in which case those and culture. Westport, CT: Greenwood. who enjoy moderate drinking would be inconve- HEATH, D. B., & COOPER, A. M. (1981). Alcohol use in niencedbut those who insist on drinkingheavily world cultures: A comprehensive bibliography of an- wouldcontinue to doso. Concern over policy is not thropological sources. Toronto: Addiction Research only directed at helping individuals who may have Foundation. become dependent; it also has the aim of making LENDER, M., & MARTIN, J. (1987). Drinking in America: life safer andmore pleasant for all. The history of A social-historical explanation, rev. ed. New York: alcohol indicates that problems are by no means Free Press. inherent in the substance but, rather, are mediated MACANDREW, C., & EDGERTON, R. B. (1969). Drunken by the individual user and by social norms. comportment: A social explanation. Chicago: Aldine. MAIL,P.D.,&MCDONALD, D. R. (1980). Tulapai to (SEE ALSO: Beers and Brews; Temperance Move- Tokay: A bibliography of alcohol use and abuse ment; Treatment, History of ) among Native Americans of North America. New Ha- ven: Human Relations Area Files Press. MARSHALL, M. (1979). Beliefs, behaviors, and alcoholic BIBLIOGRAPHY beverages: A cross-cultural survey. Ann Arbor: Uni- AUSTIN, G. A. (1985). Alcohol in Western society from versity of Michigan Press. Antiquity to 1800: A chronological history. Santa MCGOVERN, P., ET AL.(EDS.). (1993). The origins and Barbara, CA: ABC-Clio Information Services. ancient history of wine. New York: Gordon & Breach. 86 ALCOHOL: Psychological Consequences of Chronic Abuse

MUSTO, D. (1989). The American disease: Origins of nar- linkedto nutritional deficienciesfrom long-term cotic control, rev. ed. New York: Oxford University heavy drinking. Press. A major difficulty in describing the effects of O’BRIEN, J. M., & ALEXANDER, T. W. (1992). Alexander chronic alcohol abuse is that many factors interact the Great: The invisible enemy. New York: Routledge. with such consumption, resulting in markedindi- PAN, L. (1975). Alcohol in colonial Africa. Helsinki: vidual variability in the psychological conse- Finnish Foundation for Alcohol Studies. quences. In addition, defining both what consti- PARTANEN, J. (1991). Sociability and intoxication: Alco- tutes chronicity andabusive drinkingin relation to hol and drinking in Kenya, Africa, and the modern resulting behavioral problems is not simply a func- world. Helsinki: Finnish Foundation for Alcohol tion of frequency andquantity of alcohol consump- Studies. tion. For some individuals, drinking three to four drinks per day for a few months can result in severe RORABAUGH, W. (1987). The alcoholic republic: An consequences, while for others, six drinks per day American tradition. New York: OxfordUniversity for years may not have any observable effects. One Press. reason for this variability is relatedto genetic dif- ROUCHE´ , B. (1960). Alcohol: The neutral spirit. Boston: ferences in the effects of alcohol upon an individ- Little, Brown. ual. While not all of the variability can be linkedto ROYCE, J. E. (1989). Alcohol problems and alcoholism: A genetic predispositions, it has been demonstrated comprehensive survey, 2nded.New York: Free Press. that the interactions between individual genetic SEGAL, B. M. (1990). The Drunken society: Alcohol characteristics andenvironmental factors are im- abuse and alcoholism in the Soviet Union. New York: portant in determining the effects of chronic alco- Hippocrene. hol consumption. SEGAL, B. M. (1987). Russian drinking: Use and abuse of Other factors to consider when assessing the ef- alcohol in pre-revolutionary Russia. New Brunswick, fects of chronic drinking relate to the age and sex of NJ: Rutgers Center of Alcohol Studies. the drinker. In the United States, heavy chronic SIEGEL, R. K. (1989). Intoxication: Life in pursuit of drinking occurs with the greatest frequency in artificial paradise. New York: Dutton. white men, ages nineteen to twenty-five. For the SNYDER, C. R. (1958). Alcohol and the Jews: A cultural majority of individuals in this group, heavy drink- study of drinking and sobriety. Glencoe, IL: Free ing declines after age twenty-five to more moderate Press. levels andthen decreasesto even lower levels after WADDELL,J.O.,&EVERETT,M.W.(EDS.). (1980). age fifty. As might be expected, the type and extent Drinking behavior among southwestern Indians: An of psychological consequences depend on the age of anthropological perspective. Tucson: University of the chronic drinker. Research has indicated that Arizona Press. younger problem drinkers are more likely to per- WALLACE, F. C. (1970). The death and rebirth of the form poorly in school, have more arrests, andbe Seneca. New York: Knopf. more emotionally disturbed than older alcoholics. WEIL, A. (1986). The natural mind: A new way of look- Also, younger drinkers have more traffic accidents, ing at drugs and the higher consciousness, rev. ed. which may result from a combination of their Boston: Houghton Mifflin. heavy drinking and increased risk-taking behavior. Many of the more serious consequences of chronic DWIGHT B. HEATH alcohol use occur more frequently in older drink- REVISED BY ANDREW J. HOMBURG ers—individuals in their thirties and forties; these include increased cognitive and mental impair- ments, divorce, absenteeism from work, and sui- Psychological Consequences of Chronic cide. Chronic drinking in women tends to occur Abuse Chronic alcohol abuse (heavy drinking more frequently during their late twenties and con- over a long period) can lead to numerous adverse tinuing into their forties—but the onset of alcohol- effects—to direct effects such as impaired atten- related problems appears to develop more rapidly tion, increasedA NXIETY, depression, and increased in women than in men. In a study of ALCOHOLICS risk-taking behaviors—andto indirectaffects such ANONYMOUS members, women experiencedserious as impairedcognitive abilities, which may be problems only seven years after beginning heavy ALCOHOL: Psychological Consequences of Chronic Abuse 87 drinking, as compared to an average of more than The interaction between the social setting and eleven years for men. the individual, the current level of alcohol intoxica- Black andHispanic men in the UnitedStates tion, andpast drinkinghistory all play a role in the tendto show prolongedchronic drinkingbeyond psychological consequences of chronic heavy the white male’s reduction period during his late drinking. It is impossible to determine which twenties. Thus, for many of the effects of chronic changes in behavior result only from the use of drinking discussed below, age, sex, and duration of alcohol. drinking are important factors that mediate psy- Depression. One major psychological conse- chological consequences. quence resulting from heavy chronic drinking for a subpopulation of alcohol abusers (predominantly women) is the feeling of loss of control over one’s NEGATIVE CONSEQUENCES life, commonly manifestedas depression.(While In the early 1990s, it was estimatedthat between not conclusive, some studies suggest that the men- 7 and 10 percent of all individuals drinking alco- strual cycle may be an additional factor for this holic beverages will experience some degree of neg- population.) In many cases, increaseddrinkingoc- ative consequences as a result of their drinking curs as the depression becomes more intense. It has pattern. Most people believe that chronic excessive been postulatedthat the increaseddrinkingis an drinking results in a variety of behavioral conse- attempt to alleviate the depression. Unfortunately, quences, including poor work/school performance since this ‘‘cure’’ usually has little success, a vicious andinappropriate social behavior. These two be- drinking cycle ensues. While no specific causality havioral criteria are usedin most diagnosticproto- can be assumed, research on suicide has indicated cols when determining if a drinking problem exists. that chronic alcohol abuse is involvedin 20 to 36 Several surveys have foundthat heavy chronic percent of reportedcases. The level of suicidein drinking does produce a variety of school- and job- depressed individuals with no alcohol abuse is relatedproblems. A survey of personnel in the U.S. somewhat lower—about 10 percent. At this time, it armed services found that for individuals consid- is not clear if the chronic drinking results in depres- eredheavy drinkers,22 percent showedjob-per- sion or if the depression is a pre-existing psychopa- formance problems. Health professionals also show thology, which becomes exacerbatedby the drink- ing behavior. The rapidimprovement of depressive high rates of alcohol problems, with a late 1980s symptoms seen in the majority of alcoholics within British survey indicating that physicians experience a few weeks of detoxification (withdrawal) suggests such problems at a rate of 3.8 times that of the that, for many, depressive symptoms are reflective general population. A variety of surveys have con- of toxic effects of alcohol. Regardless of the mecha- sistently shown that chronic excessive drinking nism, it appears that the combination of depression leads to loss of support by moderate-drinking fam- and drinking can be a potent determinant for in- ily and friends. The dissolution of marriage in cou- creasing the potential to commit suicide. ples in which only one member drinks is estimated Aggression. For another subpopulation of to be over 50 percent. Often the interpersonal prob- chronic alcohol abusers (mainly young men), an lems that surrounda problem drinkercan leadto increase in overall aggressive behaviors has been family violence; a 1980s study found that more reported. Again, there is an indication that these than 44 percent of men with alcohol problems ad- individuals represent a group that has an under- mittedto physically abusing their wives, children, lying antisocial personality disorder, which is exac- or significant-other living partners. Survey data erbatedby chronic alcoholic drinking. also indicate that people who use alcohol frequently Sex Drive. Although it is often assumedthat are more likely to become involvedwith others who alcohol increases sexual behavior, chronic excessive share their drinking patterns—particularly those use has been foundto decreasethe level of sexual who do not express concern about the individual’s motivation in men. In some gay male populations, excessive andalteredbehavior that results from where high alcohol consumption is also associated drinking. This increased association with fellow with increasedhigh-risk sexual activity, this de- heavy drinkers as one’s main social-support net- crease in sex drive does not appear to result; how- work can itself result in increasedalcohol use. ever, for many chronic male drinkers, a long-term 88 ALCOHOL BEVERAGE CONTROL

consequence of heavy drinking is reduced sexual CAHALAN, D. (1970). Problem drinkers: A national sur- arousal anddrive.This may be the combinedresult vey. San Francisco: Jossey-Bass. of the decreased hormonal levels produced by the FISHBURNE, P., ABELSON, H. I., & CISIN, I. (1980). Na- heavy drinking and the decline of social situations tional survey on drug abuse: Main findings. Washing- where sexual opportunities exist. ton, DC: U.S. Government Printing Office. Cognitive Changes. Perhaps the best-docu- ROYCE, J. E. (1989). Alcohol problems and alcoholism, mentedchanges in psychological function resulting rev. ed. New York: Free Press. from chronic excessive alcohol use are those related VAILLANT, G. (1983). The natural history of alcoholism. to cognitive functioning. While no evidence exists Cambridge: Harvard University Press. for any overall changes in basic intelligence, spe- HERMAN H. SAMPSON cific cognitive abilities become impairedby chronic NANCY L. SUTHERLAND alcohol consumption. These most often include REVISED BY ANDREW J. HOMBURG visuo-spatial deficits, language (verbal) impair- ments, andin more severe cases, memory impair- ments (alcoholic amnestic syndrome). A specific ALCOHOL BEVERAGE CONTROL See form of dementia, alcoholic dementia, has been DistilledSpirits Council described as occurring in a small fraction of chronic alcohol abusers. The pattern andnature of the cognitive effects, as measuredon neuropsychiatric- assessment batteries in chronic alcohol abusers, ex- ALCOHOL DEPENDENCE SYNDROME hibit a wide variety of individual patterns. Also, up See Diagnosis of Drug Abuse; Disease Concept of to 25 percent of chronic alcoholics testedshow no Alcoholism andDrug Abuse detectable cognitive deficits. Although excessive al- cohol use has been clearly implicatedin such defi- cits, a variety of coexisting lifestyle behaviors might ALCOHOLICS ANONYMOUS (AA) This be responsible for the cognitive impairments ob- is a fellowship of problem drinkers, both men and served. For example, poor eating habits leading to women, who voluntarily join in a mutual effort to vitamin deficiencies result in cognitive deficits simi- remain sober. It was startedin the UnitedStates in lar to those observedin some alcohol abusers. Head the 1930s andhas been maintainedby alcohol- trauma from accidents, falls, and fights (behaviors troubledpeople who hadthemselves ‘‘hit bot- frequent in heavy drinkers) may also produce simi- tom’’—they haddiscoveredthatthe troubles asso- lar cognitive deficits. Therefore, it is extremely dif- ciatedwith their drinkingfar outweighedany plea- ficult to determine the extent to which alcohol sures it might provide. AA serves, without abuse is directly responsible for the impairments— professional guidance, a significant minority of the or if they are a result of the many alterations in population of alcoholics in the UnitedStates. Vari- behaviors that become part of the heavy-drinker ous professionally orientedtreatments serve other lifestyle. significant minorities of alcoholics. The specific psychological consequences of AA is not the only hope for alcoholics; nor is it chronic drinking are complex and variable, but everything they need. Nevertheless, its program there is clear evidence that chronic abuse of alcohol andmeetings have restoredthousandsof alcoholics results in frequent andoften disastrousproblems to abstinence, both in the UnitedStates andin for the drinker and for those close to him or her. many other countries. In 1992, the General Service Office of AA, locatedin New York City, reporteda (SEE ALSO: Aggression and Drugs: Research Issues; worldwide total of 87,403 AA groups, 48,747 of Complications) them in the United States, with an additional 1,783 in U.S. correctional facilities, and5,173 in Canada, leaving 31,700 in other countries. The report esti- BIBLIOGRAPHY mated there were almost 2 million individual mem- AKERS, R. (1985). Deviant behavior: A social learning bers in these groups worldwide; over half approach. Belmont, CA: Wadsworth. (1,079,719) livedin the UnitedStates. ALCOHOLICS ANONYMOUS (AA) 89

THE TWELVE STEPS OF are no dues or fees for membership; AA is self- ALCOHOLICS ANONYMOUS supporting andis not associatedwith any sect, denomination, political group, or other organiza- AA’s program for remaining sober is calledthe tion. It neither endorses nor opposes any causes. Twelve Steps. They are: These points, andother basic descriptionsof AA, 1. We admitted we were powerless over alcohol— appear on the first page of AA’s monthly magazine, that our lives hadbecome unmanageable. The Grapevine. Although AA is not set up as a 2. Came to believe that a Power greater than centralizedorganization, a commonly sharedset of ourselves couldrestore us to sanity. traditions guides their meetings and treatment 3. Made a decision to turn our will and our lives strategies. For example, one of the Twelve Tradi- over to the care of God as we understood Him. tions sets forth AA’s singleness of purpose—to help 4. Made a searching and fearless moral inventory alcoholics achieve andsustain sobriety; another of ourselves. tradition underscores the necessity for the anonym- 5. Admitted to God, to ourselves, and to another ity of members, as a way to avoidpersonality infla- human being the exact nature of our wrongs. tion andto promote humility. Over time, the 6. Were entirely ready to have God remove all Twelve Traditions have come to be as vital a part of these defects of character. AA as the Twelve Steps. They are: 7. Humbly askedHim to remove our shortcom- 1. Our common welfare shouldcome first; per- ings. sonal recovery depends upon A.A. unity. 8. Made a list of all persons we had harmed, and 2. For our group purpose there is but one ulti- became willing to make amends to them all. mate authority . . . a loving Godas He may 9. Made direct amends to such people wherever express Himself in our group conscience. Our possible, except when to do so would injure leaders are but trusted servants. . . . They do them or others. not govern. 10. Continuedto take personal inventory and 3. The only requirement for A.A. membership is a when we were wrong promptly admit it. desire to stop drinking. 11. Sought through prayer andmeditationto im- 4. Each group shouldbe autonomous except in prove our conscious contact with God as we matters affecting other groups or A.A. as a understood Him, praying only for knowledge whole. of His will for us andpower to carry that out. 5. Each group has but one primary purpose . . . to 12. Having hada spiritual awakening as the result carry its message to the alcoholic who still of these steps, we triedto carry this message to suffers. alcoholics andto practice these principles in all 6. An A.A. group ought never endorse, finance, or our affairs. lendthe A.A. name to any relatedfacility or The steps are basedon suggestions gleanedfrom outside enterprise, lest problems of money, the collective experiences of members about how property andprestige divertus from our pri- they achievedsobriety—andthen maintainedit. In mary purpose. this sense, AA is a collectivity of mutual help groups 7. Every A.A. group ought to be fully self- more than it is discrete individuals engaging in self- supporting, declining outside contributions. help. At meetings both open to the public and 8. Alcoholics Anonymous shouldremain forever ‘‘closed’’ (for members only), the Twelve Steps are nonprofessional, but our service centers may closely examined, and members frankly tell their employ special workers. own versions of their drinking histories—their AA 9. A.A., as such, ought never be organized; but we ‘‘stories’’—anddescribehow the AA program may create service boards or committees di- helpedthem to achieve sobriety. rectly responsible to those they serve. Membership in AA depends on an individual’s 10. Alcoholics Anonymous has no opinion on out- declaration of intention to stop drinking. An AA side issues; hence the A.A. name ought never group comes into being when two or more be drawn into public controversy. ‘‘drunks’’ join together to practice the AA program. 11. Our public relations policy is basedon attrac- ‘‘Loners’’ are relatively few, but some exist. There tion rather than promotion; we needalways 90 ALCOHOLICS ANONYMOUS (AA)

maintain personal anonymity at the level of two strategies. One was to take his story to other press, radio, and films. alcoholics andthe other was to become an evange- 12. Anonymity is the spiritual foundation of all list, because of his spiritual experience. Even traditions ever reminding us to place principles though he brought many alcoholics home with him before personalities. andpreachedat them, he utterly failedandalmost returnedto drinkinghimself. But his account un- Written in 1939, Alcoholics Anonymous (Alco- derscores how he came to realize that ‘‘to talk with holics Anonymous WorldServices, 1939, 1955, another alcoholic, even though I failedwith him, 1976) is the basic text that outlines the experiences was better than to do nothing’’ (W.W., 1949, of the first 100 members in staying sober. It is p. 374). fondly referred to as ‘‘The Big Book.’’ Two other experiences accumulated. He discov- ered that some medical authorities considered alco- ORIGINS holism a disease. Almost instantly, he replaced evangelism with science. Finally, in an effort to The unlikely coming together of the two recoup some financial losses, he pursueda slim cofounders of AA, ‘‘Bill W.’’ and ‘‘Dr. Bob’’ (Wil- business opportunity in Akron, Ohio, on May 11 liam Griffith Wilson, a stockbroker, andRobert and12, 1935. An Episcopalian minister there put Holbrook Smith, a surgeon)—both pronouncedal- him in contact with an OxfordGroup member who, coholics—is probably the most concrete event in in turn, arrangedfor a meeting the next daywith AA’s origins. Anonymity was basic, but there were Dr. Bob. Abandoning his evangelical approach, he other factors, among them Bill W.’s experiences usedhis newly foundscientific/diseaseapproach prior to contact with Dr. Bob. Hadit not been for with the doctor. An immediate rapport developed the readiness these experiences generated in Bill W. between the two men, andthey talkeduntil late to interact in a unique way with Dr. Bob, their into the night. Dr. Bob was, in effect, Bill W.’s first initial meeting might have turnedout to be the follower (Trice & Staudenmeier, 1989). Dr. Bob fifteen-minute encounter the doctor had initially hadonly one ‘‘slip’’ duringthe next month, but planned. soon thereafter the two began working together on First, Bill W. hadreacheda point of profound other alcoholics, using the sickness/scientific ap- hopelessness. Second, he had had a chance encoun- proach. By August 1936, AA meetings, within an ter with an olddrinkingfriend—Ebby T.—who OxfordGroup context, were being heldboth in despite strong and similar feelings of hopelessness Akron andNew York City. Soon, however, both Bill hadachievedconsiderablesobriety. Third,Ebby T. W. and Dr. Bob decided to sever their relationship attributedthis accomplishment to the Oxford with the OxfordGroups, andthe small AA groups Group, a nondenominational movement with no were on their own. By 1940, their newly formed membership lists, rules, or hierarchy. It embraced boardof trustees listedtwenty-two cities in which specific ideas that would soon find their way into groups were well establishedandholdingweekly AA practice: For example, members alone were meetings. Soon thereafter, The Saturday Evening powerless to solve their own problems; they must Post, a popular magazine with a wide circulation, carefully examine their behavior andtry to make publishedan article simply entitled‘‘Alcoholics restitution to others they had damaged; and they Anonymous.’’ It provedto be a compelling media practicedhelping others, resisting personal prestige event for the AA program, anda floodof positive in the process. responses andnew groups resulted.Ever since Next, a severe relapse hadforcedBill W. into a then, AA growth has steadily expanded. hospital, where he hadvisits from Ebby T. and Two coordinating groups have acted to link to- where Bill W. longedfor the sobriety Ebby seemed gether the thousands of AA local groups in the to have. Following a cry of lonely desperation and UnitedStates andabroad.In AA’s first year the agony, he reports that ‘‘the result was instant, elec- founders, along with members of the first New York tric, beyond description. The place lit up, blinding City group, formeda tax-free charitable trust with white . . . came the tremendous thought. ‘You are a a boardof trustees composedof both alcoholic and free man’’’ (W.W., 1949, p. 372). As a result of nonalcoholic members. It actedas a mechanism for these accumulated experiences, Bill W. decided on the collection andmanagement of voluntary contri- ALCOHOLICS ANONYMOUS (AA) 91 butions andas a general repository of the collective that our lives hadbecome unmanageable.’’ The experience of all AA groups. newcomers also will probably become associated Today the board of trustees consists of fourteen with an AA guide, who may soon become the new- alcoholic andseven nonalcoholic members who comer’s sponsor. Quick action by the AA group— meet quarterly. At an annual conference, specific closeness of initial contact—to include the new- regions elect the alcoholic boardmembers for four- comer increases the likelihoodof affiliation (Son- year terms. The boardappoints the nonalcoholic nenstuhl & Trice, 1987). This expresses itself in members for a maximum of three terms of three pressing any obviously interestednewcomer into a years each. An annual conference was established challenge of ‘‘ninety meetings in ninety days.’’ In in 1955 at AA’s Twentieth Anniversary Conven- effect, the receiving group seeks to keep a close tion. It expresses to the trustees the opinions and watch over the newcomer, gently forcing the person experiences of AA groups throughout the move- to forego other commitments andincrease commit- ment. A General Service office (GSO) in New York ments to the AA program. City interprets andimplements the deliberationsof Decisive thirdandfourth phases are the accep- these two groups on a daily basis. tance of telling one’s drinking story, with the begin- ning phrase, ‘‘I’m Chris X andI’m an alcoholic.’’ THE PROCESS OF AFFILIATION Throughout the initial weeks andmonths, new- comers are gently andsometimes bluntly pressedto Affiliation is a process, not a single, unitary hap- realize that they are alcoholics. They are encour- pening within AA. Its elements andphases act to agedto ‘‘go public’’ andtell their stories before the select andmake readycertain alcoholics andprob- entire group at an open meeting. In numerous in- lem drinkers for affiliation, leaving behind others stances, newcomers may already have decided that with less readiness. The process begins before the they are alcoholic. In other cases, it may be a problem drinker ever goes to a meeting (Trice, lengthy process of self-examination before this 1957). If the person has heardfavorable hearsay identity transformation occurs. In still others, it about AA; if long-time drinking friendships have may never transpire, making them suspect as real faded; if no will-power models of self-quitting have AAs. In any event, the public telling of one’s story is existed in the immediate background; and if the an act of commitment that symbolizes a conversion drinker has formed a habit of often sharing trou- of self into a genuine AA member. Members counsel bles with others—the stage is set for affiliation. It is newcomers on the appropriate first time to tell their further enhancedif, upon first attendingmeetings, stories, andtheir narrations are cause for many the person has had experiences leading to the deci- congratulations. Much applause typically attends sion that the troubles associatedwith drinkingfar this open act of commitment. outweigh the pleasures of drinking (i.e., ‘‘hitting A final phase involves the literal execution of the bottom’’). Typically, this means that affiliates, con- program’s twelfth step: ‘‘Having hada spiritual trastedwith nonaffiliates, hada longer andmore awakening as a result of these Steps, we triedto severe history of alcoholism—andthose with more carry this message to alcoholics, andto practice severe alcohol problems are more likely to make these principles in all our affairs.’’ In essence, doing consistent efforts to affiliate than are those with less twelfth-step work exemplifies one of AA’s basic severe problems (Trice & Wahl, 1958; Emerick, philosophies, namely, one is never recoveredfrom 1989b). the disease; one is only ‘‘recovering.’’ As a conse- Five other specific phases follow from those quence, a member can maintain sobriety only by forces that make for commitment to the AA pro- remaining active in AA andby steadilyengaging in gram: (1) first-stepping, (2) making a commit- carrying the program to those who are still active ment, (3) accepting one’s problem, (4) telling one’s alcoholics. In short, by doing twelfth-step work, story, and (5) doing twelfth-step work (Rudy, members reinforce their membership andthe new 1986). First-stepping involves the initial contact definition of self. with AA; it often entails orientation meetings that Throughout this affiliation process, another dy- dwell on the group’s notions of alcoholism as a namic is also at work—‘‘slipping,’’—a relapse into disease and on step one in the twelve-step program: drinking by a recovering AA member. After re- ‘‘We admitted we were powerless over alcohol . . . viewing six relevant studies, plus a summary of his 92 ALCOHOLICS ANONYMOUS (AA) own fieldwork with AA, Rudy (1980, p. 728) re- attractedto AA andits program. Overall, these portedthat among both newly committedand findings appear to be consistent with the role de- longer-term members ‘‘slipping is a common oc- mands made on members. For example, the currence, but it is possible that it serves a function sociability andaffiliativeness themes foundamong in A.A. . . . [It is] a deviant behavior and the func- those who do affiliate, as compared to nonaffiliates, tion of this deviance is boundary maintenance.’’ seem to match the heavy group interactions expec- The response of most AA members to another’s tedof members. slipping is sympathy and understanding, senti- All things considered, affiliation with AA is a ments that in turn enhance group solidarity. In distinctively selective process that fits only a dis- essence, ‘‘their abstinence is dependent on interac- tinct minority of those in the alcohol-abusing popu- tion with those who slip’’ (Rudy, 1980, p. 731). lation. Although the exact proportion of the popu- lation helpedby AA is unknown, even AA’s critics WHO AFFILIATES? recognize that it is substantial. Other specific types of therapies may do proportionally somewhat bet- What are the characteristics of those who do ter or worse, but a reasonable estimate wouldbe undergo the affiliation processes, contrasted with that AA is associatedwith fairly typical improve- those who do not, even though exposed to the ment rates. possibility? Demographic variables such as age, so- Current studies strongly suggest that AA appeals cial class, race, employment status, andparental to a highly specific andselect segment and,by socio-economic status have been consistently found doing so, further suggest that other therapies are to be unrelated to membership (Trice & Roman, also selective as to their appeal. These points un- 1970; Emerick, 1989). These findings provide con- derscore the need for service providers to be aware siderable certainty about the existence of often- of the diverse makeup of the problem-drinking allegeddemographicbarriers to AA affiliation— population. Assessment andservices needto be far they, in effect, fail to deter affiliation. more individualized than they have been, so that Less certainty can be attributedto significant assignments may be made to the most appropriate psychological characteristics that have been found organizations, institutions, or therapies. to encourage affiliation. As in evaluations of psy- chotherapies in general (Eysenck, 1952; Rachman THERAPEUTIC MECHANISMS & Wilson, 1980), researchers cannot predict with any certainty who will affiliate. Despite this, certain As with psychotherapies in general, the effec- personality features have been systematically tiveness of AA has not been convincingly estab- foundto distinguish between affiliates and lished. For example, some problem drinkers drop nonaffiliates (Ogborne & Glaser, 1981; Ogborne, out after the first two or three AA meetings. Never- 1989). theless, for those who remain, AA has unique and distinctive features that contribute to its therapeu- Several studies have suggested that, among other tic effectiveness. things, A.A. members can be distinguished from By definition, as problem drinkers move into other heavy drinkers with respect to personality addiction, alcohol comes to be central to their lives. andperceptual characteristics. . . . The authors How can this centrality be reduced and a new con- suggest that A.A. affiliation is associatedwith au- ception of alcohol be put in its place? AA experi- thoritarianism andconformist tendencies,high af- ences provide a new orientation, not only to alco- filiation needs, proneness to guilt, religiosity, ex- hol, but to self andto others. ‘‘One of A.A.’s great ternal control and field dependency [Ogborne, strengths lies in the quality of its social environ- 1989, p. 59]. ment: the empathetic understanding, the accep- Ogborne (1989) also reports on two additional tance andconcern which alcoholics experience studies that support the belief that AA attracts there which, along with other qualities, make it individuals with certain emotional makeups. easier to internalize new ways of feeling, thinking, Ogborne’s overall findings were that alcohol-trou- anddoing’’(Maxwell, 1982). Even brief exposure bledpersons who expressedgroup adherence,ex- to AA introduces the alcoholic to the idea that self- troversion, submissiveness, andconservatism were regulation seems to be rarely achievedalone by ALCOHOLICS ANONYMOUS (AA) 93 self-reliance andwillpower. Its basic premise de- exposure to AA andits unique but widelypubli- scribes the compelling sense of ego powerlessness— cizedor modifiedtherapeuticmechanisms. (Sev- but immediately offers the potent substitute of a eral organizations in the alcohol or drug recovery viable community that provides individual atten- fieldhave been working along similar but modified tion, an explanation of alcoholism, andsimple pre- lines.) It is impossible to estimate the numbers of scriptions for sobriety. ‘‘In a community that shares those helpedby such exposure, but they are surely the same distresses and losses, accepts its members’ numerous and should not be discounted. vulnerabilities andapplaudsandrewardssuc- cesses, A.A. provides a stabilizing, sustaining, and CRITICAL EVALUATIONS ultimately, transforming group experience’’ (Khantzian & Mack, 1989, 76). Probably the most widespread and long-stand- Within the AA community, there are group- ing critical assessment of AA centers aroundthe basedspecific therapeutic strategies unlikely to ex- question of the selective nature of membership. ist in professionally directed psychotherapy. Exam- Thus, critic Stanton Peele (1989, 57) bluntly in- ples include (1) empirically based hope; (2) direct sists: ‘‘In fact, research has not foundA.A. to be an attack on denials; (3) practical guidelines for effective treatment for general populations of alco- achieving sobriety; and(4) one-to-one sponsor- holics.’’ Again, however, neither has any given pro- ship. When problem drinkers first attend meetings fessional psychotherapeutic methodbeen foundto they are immediately aware of others who have be effective for general populations of the psy- confrontedtheir very problem, andthey hear these choneurotic. In 1981, Ogborne andGlaser pre- people speak about dramatic improvements in their dicted that evidence will soon be found for the lives via the AA program. Moreover, the AA pro- effectiveness of AA, but ‘‘it will be limitedto a gram consistently reminds them that denial of the particular, identifiable subgroup of persons with realities surrounding their drinking is a major bar- alcohol problems.’’ This concern hadbeen ex- rier to any change. Telling one’s story, either pub- pressedsince the 1950s (Trice & Staudenmeier licly or in closedsessions, helps to dissolvethe en- 1989), andmore evidenceof AA’s selective nature trencheddenialsystems that wardoff therapeutic came from Walsh et al. (1991). changes. Walsh andher colleagues randomized227 em- The Twelve Steps are structuredphases that ployedproblem drinkersinto compulsory inpatient provide an organized approach to the confusions treatment, compulsory attendance at AA, and a and frustrations of an individual’s attempt to cope choice of options. During a two-year follow up, the with alcohol problems. This is especially so when researchers usedmeasures of performance with members reach the developmental stage where drinking and drug use to gauge effectiveness. They twelfth-step work is indicated. They dramatically concluded that the hospital group fared best and see themselves as they once hadbeen, andthis that the group assignedto AA faredleast well. reinforces their needto ‘‘work the program.’’ In Many of those randomly assigned to AA probably addition, simple, practical guidelines are repeated lackedthe readinessandthe emotional makeup as group-testedways to avoidusing alcohol as an that appear to be requiredfor affiliation. Matching adjustment technique: ‘‘First things first,’’ ‘‘one patients to specific treatments has been advocated day at a time,’’ ‘‘easy does it,’’ and practical advice for many years (Ogborne & Glaser 1981; Pattison about how to work the program. 1982), and the Walsh study certainly indicates the AA typically arranges for the informal sponsor- importance of matching in the case of AA. ship of newcomers—who often identify with and Emerick (1989) has broadened the array of crit- closely relate to their sponsors. Sponsors are recov- icisms of AA to include (1) that AA has denounced ering alcoholics typically available at all hours of in the media scientific discoveries that contradict its the day and night for phone or in-person discus- ‘‘formal ideology’’ and dogma: (2) AA has brought sions andcrises. These valuable treatment strate- pressures to bear in an effort to suppress various gies are voluntary andfree of any monetary cost or psychological findings. Emerick quickly acknowl- financial obligation. Drinkers who drop out or who edges, however, that ‘‘it is these very characteristics reject active membership in AA may nevertheless . . . that provide for AA’s strength and effectively be substantially helpedby primary or secondary preserve its boundaries and identity’’ (p. 5). This 94 ALCOHOLICS ANONYMOUS (AA) criticism boils down to charges that AA is anti- 1991). Regarding the charge that AA is overly reli- intellectual andantiprofessional. Second,harmful gious, numerous close observers, including the effects may come to those who ‘‘do not fit comforta- present writer, have concluded that religion plays a bly in the organization’’ (p. 9). These harmful ef- minor role in the practical day-to-day effort of AAs fects include beliefs that ‘‘slipping’’ inevitably leads to ‘‘work the program.’’ to loss of control, making for more problems than otherwise. Some members may despair and lose ADAPTATION OF AA TO hope when they discover they do not mesh with OTHER DISORDERS AA’s norms andbeliefs. Third,there is a risk of becoming ‘‘AA addicts’’ who spend so much time Despite the criticisms that have been directed andenergy on the AA program that they neglect against AA, its format andbeliefs have nevertheless other areas of life such as family andjob. Fourth, been applied to a wide variety of other addictions AA groups may contain alcohol-troubledpersons and behavior disorders. For example, NARCOTICS who also suffer from other psychiatric disorders— ANONYMOUS (NA) (estimatedin 1979 to have about i.e., schizophrenia and anxiety disorders—that 700 groups in practically every U.S. state andin should be directly treated, but are covered up by several other countries) first appliedthe AA pattern AA ideologies. Finally, AA members may develop to drug addicts at the U.S. PUBLIC HEALTH SERVICE dual overlapping relationships inside AA that are HOSPITAL at Lexington, Kentucky, in 1947. In ultimately harmful, i.e., a newcomer becomes the 1948, andin 1953, groups of AA members who lover of an establishedmember, or a sponsor enters were also drug addicts formed an independent NA into an unfortunate business partnership with a group in New York City andin Sun Valley, Califor- sponsoree. nia. The resemblance to AA was made even more Other negative judgments of AA that have been remarkable by the fact that the magazine that had voicedat one time or another are that it is tilted made AA well-known (The Saturday Evening Post) towardbeing a religion by too much emphasis on a also gave NA a national audience through a lengthy ‘‘higher power’’; local groups are not nearly as ac- piece that playedup similarities with AA (Ellison, cepting of drunks as advertised; it suffers from too 1954). much adulation and consequently often becomes a Similarly, AA’s beliefs andstrategies have been ‘‘dumping ground’’ at which companies and courts adapted to help people with a broad spectrum of require compulsory attendance; and it insists that other problems, including excessive buying, sexual members come to accept the label of ‘‘alcoholic’’— excesses or deviations, gambling, child abuse, a label that continues to be highly stigmatic outside overdependence on others, eating disorders, and AA andtendsto repel many of those who are in- excessive shame and guilt. In addition, AL-ANON clinedto affiliate. family groups andA LATEEN groups have adapted Understandably, these criticisms have fueled al- AA’s philosophy to family, children, and friends of ternative groups that claim to help members cope problem drinkers. Many others could be cited. Vet- with alcohol problems but without many of the eran AA members point to this great proliferation beliefs andrituals of AA. Apparently, many of the as evidence that AA’s influence goes well beyond its members of these groups are AA dropouts. Beyond impact on AA members. They argue that this wide- this observation, no systematic research efforts spread adaptation to other disorders demonstrates have been mountedto determinehow affiliation is the essential value andappeal of the AA program. achieved, and with what kinds of problem drinkers these alternatives to AA are effective. For example, (SEE ALSO: Alcoholism; Gambling as an Addiction; RATIONAL RECOVERY (RR), SECULAR ORGANIZA- Treatment) TION FOR SOBRIETY (SOS), andW OMEN FOR SOBRI- ETY (WFS) have all claimedto be alternative self- BIBLIOGRAPHY help groups for alcoholics. They tendto reject the notion that alcoholism is a disease and advocate ALCOHOLICS ANONYMOUS. (1939, 1955, 1976). Alcohol- insteadpersonal responsibility. Also, they under- ics Anonymous: The story of how many thousands of score individual willpower rather than AA’s belief men and women have recovered from alcoholism. New in a higher power (Gelman, Leonard, & Fisher, York: Alcoholics Anonymous WorldService. ALCOHOLISM: Abstinence versus ControlledDrinking 95

ALCOHOLICS ANONYMOUS WORLD SERVICE. (1993). A.A. TRICE, H. M. (1957). A study of the process of affiliation directory, 1992–1993. New York: Author. with A.A. Quarterly Journal of Studies on Alcohol, 18, ELLISON, J. (1954). These drug addicts cure one another. 38–54. Saturday Evening Post, 227 (6, Aug. 7), 22—23; TRICE, H. M., & STAUDENMEIER, W. J., JR. (1989). A 48–52. socio-cultural history of Alcoholics Anonymous. In M. EMERICK, C. (1989a). Overview: Alcoholics Anonymous. Galanter (Ed.), Recent developments in alcoholism: In M. Galanter (Ed.). Recent developments in alcohol- Treatment research. Vol. 7. New York: Plenum. ism: Treatment research. Vol. 7. New York: Plenum. TRICE, H. M., & WAHL, R. (1958). A rank order analysis EMERICK, C. (1989b). Alcoholics Anonymous: Member- of the symptoms of alcoholism. Quarterly Journal of ship characteristics andeffectiveness as treatment. In Studies on Alcohol, 19, 636–648. M. Galanter (Ed.), Recent developments in alcohol- WALSH, D. C., & ASSOCIATES (1991). A randomized trial ism: Treatment and research. Vol. 7. New York: Ple- of treatment options for alcohol-abusing workers. num. New England Journal of Medicine, 325, 775–782. EYSENCK, J. (1952). The effects of psychotherapy: An W., W. (1949). The society of Alcoholics Anonymous. evaluation. Journal of Consulting Psychology, 16, American Journal of Psychiatry, 106, 370–376. 319–324. HARRISON M. TRICE GELMAN, D., LEONARD, E., & FISHER, B. (1991). Clean andsober andagnostic. Newsweek, July 8, 62–63. KHANTZIAN, E. J., & MACK, J. E. (1989). Alcoholics Anonymous andcontemporary psychodynamicthe- ALCOHOLISM This section contains articles ory. In M. Galanter (Ed.) Recent developments in al- on some aspects of chronic drinking: Abstinence coholism: Treatment research. New York: Plenum. versus Controlled Drinking and Origin of the Term. MAXWELL, M. (1982). Alcoholics Anonymous. In E. For further information on this subject, see Disease Gomberg, H. R. White, & A. Carpenter (Eds.), Alco- Concept of Alcoholism and Drug Abuse andthe hol, science and society revisited. Ann Arbor: Univer- sections on Complications,onTreatment andon sity of Michigan Press. Withdrawal. OGBORNE, A. C. (1989). Some limitations of Alcoholics Anonymous. In M. Galanter (Ed.), Recent develop- ments in alcoholism: Treatment research. New York: Abstinence versus Controlled Drinking Plenum. The position of ALCOHOLICS ANONYMOUS (AA) and OGBORNE, A. C., & GLASER, F. B. (1981). Characteristics the dominant view among therapists who treat al- of affiliates of Alcoholics Anonymous: A review of the coholism in the UnitedStates is that the goal of literature. Journal of Studies on Alcohol, 42 (7), 661– treatment for those who have been dependent on 679. alcohol is total, complete, andpermanent absti- PATTISON, E. M. (1982). Selection of treatment for alco- nence from alcohol. holics. New Brunswick, NJ: Rutgers Center of Alcohol Abstinence was at the base of Prohibition (legal- Studies. izedin 1919 with the Eighteenth Amendment)and PEELE, S. (1989). Diseasing of America: Addiction treat- is closely relatedto prohibitionism—the legal pro- ment out of control. Lexington, MA: Lexington Books. scription of substances andtheir use. RACHMAN, S. J., & WILSON, G. T. (1980). The effects of Although temperance originally meant mod- psychological therapy, 2nded.New York: Pergamon. eration, the nineteenth-century TEMPERANCE RUDY, D. R. (1986). Becoming alcoholic: Alcoholics MOVEMENT’s emphasis on complete abstinence Anonymous and the reality of alcoholism. Carbon- from alcohol andthe mid-twentiethcentury’s expe- dale, IL: Southern Illinois University Press. rience of the ALCOHOLICS ANONYMOUS movement RUDY, D. R. (1980). Slipping andsobriety: The functions have strongly influencedalcohol- anddrug-abuse of drinking in A.A. Journal of Studies on Alcohol, 41, treatment goals in the UnitedStates. Moral and 727–732. clinical issues, however, have been irrevocably SONNENSTUHL, W. J., & TRICE, H. M. (1987). The social mixed. construction of alcohol problems in a union’s peer The disease model of alcoholism and drug ad- counseling program. Journal of Drug Issues, 17 (3), diction, which insists on abstinence, has incorpo- 223–254. ratednew areas of compulsive behavior—such as 96 ALCOHOLISM: Abstinence versus ControlledDrinking overeating andsexual involvements. In these cases, (1988) reporteda 57 percent continuous absti- redefinition of abstinence from total avoidance to nence rate for private clinic patients who were ‘‘the avoidance of excess’’ (what we would other- stably marriedandhadsuccessfully completed wise term moderation) is required. detoxification and treatment—but results in this Abstinence can also be usedas a treatment- study covered only a six-month period. outcome measure, as an indicator of its effective- In other studies of private treatment, Walsh ness. In this case, abstinence is defined as the num- et al. (1991) foundthat only 23 percent of alco- ber of drug-free days or weeks during the treatment hol-abusing workers reportedabstaining regimen—andmeasures of drugin urine are often throughout a two-year follow-up, although the usedas objective indicators. figure was 37 percent for those assignedto a hospital program. According to Finney and CONTROLLED DRINKING Moos (1991), 37 percent of patients reported they were abstinent at all follow-up years 4 By extension, for all those treatedfor alcohol through 10 after treatment. Clearly, most re- abuse, including those with no dependence symp- search agrees that most alcoholism patients toms, moderation of drinking (termed controlled drink at some point following treatment. drinking, or CD) as a goal of treatment is rejected 2. What proportion of alcoholics eventually (Peele, 1992). Instead, providers claim, holding out achieve abstinence following alcoholism treat- such a goal to an alcoholic is detrimental, fostering ment? a continuation of denial and delaying the alco- Many patients ultimately achieve abstinence holic’s needto accept the reality that he or she can only over time. Finney andMoos (1991) found never drink in moderation. One painful example of that 49 percent of patients reportedthey were this is the case of Audrey Kishline, author of Mod- abstinent at four years and54 percent at ten erate Drinking: The New Option for Problem years after treatment. Vaillant (1983) found Drinkers, and founder of the group Moderation that 39 percent of his surviving patients were Management. In the summer of 2000, Kishline abstaining at eight years. In the Randstudy,28 pleaded guilty to a vehicular homicide incident in percent of assessedpatients were abstaining af- which she killeda father andhis twelve-year-old ter four years. Helzer et al. (1985), however, daughter when she drove the wrong way on a reportedthat only 15 percent of all surviving Washington State highway. Her bloodalcohol level alcoholics seen in hospitals were abstinent at 5 at the time of the accident was 0.26—three times to 7 years. (Only a portion of these patients were the legal limit. specifically treatedin an alcoholism unit. Absti- In Britain andother European andCommon- nence rates were not reportedseparately for this wealth countries, controlled-drinking therapy is group, but only 7 percent survivedandwere in widely available (Rosenberg et al., 1992). The fol- remission at follow-up.) lowing six questions explore the value, prevalence, 3. What is the relationship of abstinence to con- andclinical impact of controlleddrinkingversus trolled-drinking outcomes over time? abstinence outcomes in alcoholism treatment; they Edwards et al. (1983) reported that con- are intended to argue the case for controlled drink- trolleddrinkingis more unstable than absti- ing as a reasonable andrealistic goal. nence for alcoholics over time, but recent studies have foundthat controlleddrinkingincreases 1. What proportion of treated alcoholics abstain over longer follow-up periods. Finney and Moos completely following treatment? (1991) reporteda 17 percent ‘‘social or moder- At one extreme, Vaillant (1983) founda 95 ate drinking’’ rate at six years and a 24 percent percent relapse rate among a group of alcoholics rate at ten years. In studies by McCabe (1986) followedfor eight years after treatment at a andNordstro ¨m andBerglund(1987), CD out- public hospital; andover a four-year follow-up comes exceeded abstinence during follow-up of period, the Rand Corporation found that only 7 patients fifteen andmore years after treatment percent of a treatedalcoholic population ab- (see Table 1). Hyman (1976) earlier founda stainedcompletely (Polich, Armor, & Braiker, similar emergence of controlleddrinkingover 1981). At the other extreme, Wallace et al. fifteen years. ALCOHOLISM: Abstinence versus ControlledDrinking 97

4. What are legitimate nonabstinent outcomes for Vaillant (1983) labeledabstinence as drinking alcoholism? less than once a month andincludinga binge The range of nonabstinence outcomes be- lasting less than a week each year. tween unabatedalcoholism andtotal abstinence The importance of definitional criteria is evi- includes (1) ‘‘improved drinking’’ despite con- dent in a highly publicized study (Helzer el al., tinuing alcohol abuse, (2) ‘‘largely controlled 1985) that identified only 1.6 percent of treated drinking’’ with occasional relapses, and alcoholism patients as ‘‘moderate drinkers.’’ (3) ‘‘completely controlleddrinking.’’Yet some Not included in this category were an additional studies count both groups (1) and (2) as contin- 4.6 percent of patients who drank without prob- uing alcoholics andthose in group (3) who en- lems but who drank in fewer than thirty of the gage in only occasional drinking as abstinent. previous thirty-six months. In addition, Helzer 98 ALCOHOLISM: Abstinence versus ControlledDrinking

et al. identified a sizable group (12%) of former alcoholics who drank a threshold of seven drinks four times in a single month over the previous three years but who reportedno ad- verse consequences or symptoms of alcohol de- pendence and for whom no such problems were uncoveredfrom collateral records.Nonetheless, Helzer et al. rejectedthe value of CD outcomes in alcoholism treatment. While the Helzer et al. study was welcomed by the American treatment industry, the Rand results (Polich, Armor, & Braiker, 1981) were publicly denounced by alcoholism treatment advocates. Yet the studies differed primarily in that Randreporteda higher abstinence rate, using a six-month window at assessment (com- paredwith three years for Helzer et al.). The studies found remarkably similar nonabstinence outcomes, but Polich, Armor, andBraiker (1981) classifiedboth occasional andcontinu- ous moderate drinkers (8%) and sometimes frequent as abstinence after eight years for un- heavy drinkers (10%) who had no negative treatedalcoholic felons who had‘‘unequivocal drinking consequences or dependence symp- histories of alcoholism’’ (see Table 1). Results toms in a nonabstinent remission category. from the 1989 Canadian National Alcohol and (Randsubjects hadbeen highly alcoholic andat Drug Survey confirmedthat those who resolve a intake were consuming a median of seventeen drinks daily.) drinking problem without treatment are more The harm-reduction approach seeks to mini- likely to become controlleddrinkers.Only 18 mize the damage from continued drinking and percent of five hundred recovered alcohol abus- recognizes a wide range of improved categories ers in the survey achievedremission through (Heather, 1992). Minimizing nonabstinent re- treatment. About half (49 percent) of those in mission or improvement categories by labeling remission still drank. Of those in remission reduced but occasionally excessive drinking as through treatment, 92 percent were abstinent. ‘‘alcoholism’’ fails to address the morbidity as- But 61 percent of those who achievedremission sociatedwith continueduntrammeleddrinking. without treatment continueddrinking(see Ta- 5. How do untreated and treated alcoholics com- ble 2). pare in their controlled-drinking and abstinent- 6. For which alcohol abusers is controlled-drink- remission ratios? ing therapy or abstinence therapy superior? Alcoholic remission many years after treat- Severity of alcoholism is the most generally ment may depend less on treatment than on acceptedclinical indicatorof the appropriate- post-treatment experiences, andin some long- ness of CD therapy (Rosenberg, 1993). Un- term studies, CD outcomes become more promi- treatedalcohol abusers probably have less se- nent the longer subjects are out of the treatment vere drinking problems than clinical milieu, because patients unlearn the abstinence prescription that prevails there (Peele, 1987). populations of alcoholics, which may explain By the same token, controlleddrinkingmay be their higher levels of controlleddrinking.But the more common outcome for untreatedremis- the less severe problem drinkers uncovered in sion, since many alcohol abusers may reject nonclinical studies are more typical, outnum- treatment because they are unwilling to abstain. bering those who ‘‘show major symptoms of al- Goodwin, Crane, & Guze (1971) found that cohol dependence’’ by about four to one (Skin- controlled-drinking remission was four times as ner, 1990). ALCOHOLISM: Abstinence versus ControlledDrinking 99

Despite the reportedrelationship between se- trolleddrinkersand20 percent abstinent (from verity andCD outcomes, many diagnosedalco- fifty-nine initial patients) at 5 to 6 year fol- holics do control their drinking, as Table 1 re- low-up. Outcome type was not relatedto sever- veals. The Randstudyquantifiedthe ity of dependence. Nor was it for Nordstro¨m and relationship between severity of alcohol depen- Berglund(1987), perhaps because they ex- dence and controlled-drinking outcomes, al- cluded ‘‘subjects who were never alcohol depen- though, overall, the Randpopulation was a se- dent.’’ verely alcoholic one in which ‘‘virtually all Nordstro¨m andBerglund,like Wallace et al. subjects reportedsymptoms of alcohol depen- (1988), selectedhigh-prognosis patients who dence’’ (Polich, Armor, and Braiker, 1981). were socially stable. The Wallace et al. patients Polich, Armor, andBraiker foundthat the hada high level of abstinence; patients in most severely dependent alcoholics (eleven or Nordstro¨m andBerglundhada high level of more dependence symptoms on admission) were controlleddrinking.Social stability at intake the least likely to achieve nonproblem drinking was negatively relatedin Rychtarik et al. to con- at four years. However, a quarter of this group sumption as a result either of abstinence or of who achievedremission didso through limitedintake. Apparently, social stability pre- nonproblem drinking. Furthermore, younger dicts that alcoholics will succeed better whether (under 40), single alcoholics were far more they choose abstinence or reduced drinking. But likely to relapse if they were abstinent at eigh- other research indicates that the pool of those teen months than if they were drinking without who achieve remission can be expanded by hav- problems, even if they were highly alcohol-de- ing broader treatment goals. pendent (Table 3). Thus the Rand study found a Rychtarik et al. foundthat treatment aimed strong link between severity andoutcome, but a at abstinence or controlleddrinkingwas not far from ironcladone. relatedto patients’ ultimate remission type. Some studies have failed to confirm the link Booth, Dale, andAnsari (1984), on the other between controlled-drinking versus abstinence hand, found that patients did achieve their se- outcomes andalcoholic severity. In a clinical lected goal of abstinence or controlleddrinking trial that included CD and abstinence training more often. Three British groups (Elal-Law- for a highly dependent alcoholic population, rence, Slade, & Dewey, 1986; Heather, Roll- Rychtarik et al. (1987) reported18 percent con- nick, & Winton, 1983; Orford & Keddie, 1986) 100 ALCOHOLISM: Abstinence versus ControlledDrinking

have foundthat treatedalcoholics’ beliefs about possibility of controlleddrinking—also play a role, whether they couldcontrol their drinkingand sometimes the dominant role, in determining suc- their commitment to a CD or an abstinence- cessful outcome type. Finally, reduced drinking is treatment goal were more important in deter- often the focus of a harm-reduction approach, mining CD versus abstinence outcomes than where the likely alternative is not abstinence but were subjects’ levels of alcohol dependence. Mil- continuedalcoholism. ler et al. (in press) found that more dependent drinkers were less likely to achieve CD outcomes (SEE ALSO: Alcohol; Disease Concept of Alcoholism but that desired treatment goal and whether one and Drug Abuse; Relapse Prevention; Treatment) labeledoneself an alcoholic or not indepen- dently predicted outcome type. BIBLIOGRAPHY

BOOTH, P. G., DALE, B., & ANSARI, J. (1984). Problem SUMMARY drinkers’ goal choice and treatment outcomes: A pre- As of 2000, there is no conclusive evidence to liminary study. Addictive Behaviors, 9, 357–364. show that one single methodof treatment is consis- EDWARDS, G., ET AL. (1983). What happens to alcohol- tently more successful than another (Project ics? Lancet, 2, 269–271. MATCH). One of the largest (U.S.) clinical experi- ELAL-LAWRENCE, G., SLADE,P.D.,&DEWEY,M.E. ments—sponsoredby the National Institute on Al- (1986). Predictors of outcome type in treated problem cohol Abuse andAlcoholism—shows that of the drinkers. Journal of Studies on Alcohol, 47, 41–47. three major treatments studied (cognitive-behav- FINNEY, J. W., & MOOS, R. H. (1991). The long-term ioral therapy [CBT], twelve-step facilitation [TSF], course of treatedalcoholism: 1. Mortality, relapse and andmotivational enhancement therapy [MET]), remission rates andcomparisons with community none emergedthe clear ‘‘winner.’’ controls. Journal of Studies on Alcohol, 52, 44–54. A group of 952 outpatients (some still drinking) GOODWIN, D. W., CRANE, J. B., & GUZE, S. B. (1971). and774 patients (previously receiving residential/ Felons who drink: An 8-year follow-up. Quarterly day hospital treatment) participated in the study, Journal of Studies on Alcohol, 32, 136–147. that spannedover twelve weeks. The two groups HEATH, D. B. (1992). Prohibition or liberalization of al- were each divided into three separate groups, each cohol and drugs? In M. Galanter (Ed.), Recent devel- group receiving one of the three treatments. opments in alcoholism: Alcohol and cocaine. New Particpants were polledimmediatelyafter treat- York: Plenum. ment andagain every three months for a year in an HEATHER, N. (1992). The application of harm-reduction effort to document their subsequent progress. Pa- principles to the treatment of alcohol problems. Paper tients of all three treatments exemplifiedgoodand presentedat the ThirdInternational Conference on sustainedresults. In all, only 10 percent of the the Reduction of Drug-Related Harm, Melbourne, participants dropped out of the study itself; two- Australia, March. thirds finished the treatment(s). The percentage of HEATHER, N., ROLLNICK, S., & WINTON, M. (1983). A days abstinent (PDA) rose in all three groups by 60 comparison of objective andsubjective measures of percent (from 20 to 80 percent), andsufferedonly alcohol dependence as predictors of relapse following minimal decline in the next year. treatment. Journal of Clinical Psychology, 22, 11–17. Controlleddrinking(CD) is one of a number of HELZER,J.E.ET AL. (1985). The extent of long-term approaches with an important role to play in alco- moderate drinking among alcoholics discharged from holism treatment. CD, as well as abstinence, is an medical and psychiatric treatment facilities. New En- appropriate goal for the majority of problem drink- gland Journal of Medicine, 312, 1678–1682. ers who are not alcohol-dependent (though there is HYMAN, H. H. (1976). Alcoholics 15 years later. Annals no proven scientific methodto determinewho can of the New York Academy of Science, 273, 613–622. andwho cannot stop drinkingafter one or two LENDER, M. E., & MARTIN, J. K. (1982). Drinking in drinks). In addition, while controlled drinking be- America. New York: Free Press. comes less likely the more severe the degree of alco- LICENSE TO DRINK:CAN BOOZERS LEARN MODERATION?A holism, other factors—such as age, values, andbe- TRAGEDY REKINDLES DEBATE ABOUT A CONTROVERSIAL liefs about oneself, one’s drinking, and the PROGRAM. (2000) Time, 156, 47. ALCOHOLISM: Origin of the Term 101

MCCABE, R. J. R. (1986). Alcohol-dependent individuals TREATMENT OF ALCOHOLISM–PART II. (2000) Harvard 16 years on. Alcohol & Alcoholism, 21, 85–91. Mental Health Letter 16. MILLER,W.R.ET AL. (1992). Long-term follow-up of VAILLANT, G. E. (1983). The natural history of alcohol- behavioral self-control training. Journal of Studies on ism. Cambridge: Harvard University Press. Alcohol, 53, 249–261. WALLACE, J., ET AL. (1988). 1. Six-month treatment out- NORDSTRO¨ M, G., & BERGLUND, M. (1987). A prospective comes in socially stable alcoholics: Abstinence rates. study of successful long-term adjustment in alcohol Journal of Substance Abuse Treatment, 5, 247–252. dependence. Journal of Studies on Alcohol, 48,95– WALSH, D. C., ET AL. (1991). A randomized trial of treat- 103. ment options for alcohol-abusing workers. New En- ORFORD, J., & KEDDIE, A. (1986). Abstinence orcon- land Journal of Medicine, 325, 775–782. trolled drinking: A test of the dependence and persua- STANTON PEELE sion hypotheses. British Journal of Addiction, 81, REVISED BY KIMBERLY A. MCGRATH 495–504. PEELE, S. (1992). Alcoholism, politics, and bureaucracy: The consensus against controlled-drinking therapy in America. Addictive Behaviors, 17, 49–61. Origin of the Term The term alcoholism is of relatively recent date; knowledge of the adverse PEELE, S. (1987). Why do controlled-drinking outcomes vary by country, era, and investigator?: Cultural con- effects of heavy alcohol (ethanol) consumption is ceptions of relapse and remission in alcoholism. Drug not. A proverb describes alcohol as ‘‘both man- and Alcohol Dependence, 20, 173–201. kind’s oldest friend and oldest enemy.’’ Alcohol PEELE, S., BRODSKY, A., & ARNOLD, M. (1991). The truth occurs in nature, and humans have long known about addiction and recovery. New York: Simon & how to ferment plants to create it; both its moderate Schuster. and excessive use have therefore occurred since POLICH, J. M., ARMOR, D. J., & BRAIKER, H. B. (1981). prehistory. The Bible cautions: ‘‘Do not look at The course of alcoholism: Four years after treatment. wine when it is red, when it sparkles in the cup and New York: Wiley. goes down smoothly. At the end it bites like a PROJECT MATCH RESEARCH GROUP (1997). Matching al- serpent and stings like an adder’’ (Proverbs 23:31– coholism treatments to client heterogeneity: Project 32). A drunken Noah (Genesis 9:20–28) is one of a AUTCH post-treatment drinking outcomes. Journal long line of such literary descriptions. In the classi- of Studies on Alcohol, 58, 7-29. cal era of the Greeks and the Romans we have PROVET,PH.D., P. (2000). Why addiction cannot be drunks in the Character Sketches of Theophrastus, moderate. Alcoholism & Drug Abuse Weekly, 12, no. in the Satyricon of Petronius Arbiter, and in the 30: 5. Epistles of Seneca. In the 1600s, we have Shake- ROSENBERG, H. (1993). Prediction of controlled drinking speare’s porter in Macbeth (Act II, Scene 3) and by alcoholics and problem drinkers. Psychological others. Bulletin, 113, 129–139. Viewing the long-term adverse effects of alcohol ROSENBERG, H., MELVILLE, J., LEVELL,D.,&HODGE, as a disease is a concept that also predates the J. E. (1992). A ten-yearfollow-up surveyof accept- term alcoholism. Benjamin Rush (1745–1813) ability of controlled drinking in Britain. Journal of and Thomas Trotter (1760–1832), both physi- Studies on Alcohol, 53, 441–446. cians, wrote extensively in this vein, using words RYCHTARIK, R. G., ET AL. (1987). Five-six-yearfollow-up such as drunkenness; their elder contemporary of broad spectrum behavioral treatment for alcohol- Benjamin Franklin (1706–1790) produced a glos- ism: Effects of training controlled drinking skills. sary of 228 synonyms in use in 1737 for ‘‘being Journal of Consulting and Clinical Psychology, 55, underthe influence of alcohol.’’ It was not until 106–108. 1849 that the Swedish physician and temperance SKINNER, H. A. (1990). Spectrum of drinkers and inter- advocate Magnus Huss (1807–1890) first used the vention opportunities. Journal of the Canadian Medi- word alcoholism in his book Alcoholismus Chro- cal Association, 143, 1054–1059. nicus (The Chronic Alcohol-disease). Huss’s term, SUBAK-SHARPE, G. J. (1995). The Columbia University used originally in a descriptive sense to denote the College of Physicians and Surgeons Complete Home consequences of the prolonged consumption of Medical Guide. New York: Crown Publishers, Inc. large quantities of alcohol, has come to connote a 102 ALCOHOLISM: Origin of the Term

disease, believed by some to result in such ALCOHOLISM, the largest public interest group in consumption. this area, was a project of the same movement. Huss meant by the term chronic alcoholism Their successful efforts may be the reason that the ‘‘those pathologic symptoms which develop in such term alcoholism developed and sustained a popu- persons who over a long period of time continually larity in the United States beyond anything it use wine or other alcoholic beverages in large quan- achieved in Europe and even in Scandinavia, where tities’’ and stated that it ‘‘corresponds with chronic it was first used. poisoning.’’ His book is filled with detailed case histories illustrating the various symptoms that MEANING BROADENS might occur. Sweden was at that time highest in the list of countries that consumed liquors, and Huss, As the term alcoholism became widely used, its as attending physician to the Serafim Clinic In meaning broadened. In a 1941 review of treatment, Stockholm, had ample opportunity to observe ten definitions of chronic alcoholism and sixteen cases. The London Daily News of December8, definitions of alcohol addiction were collected from 1869, carried a story on ‘‘the deaths of two persons the international literature. Originally used by from alcoholism,’’ which according to the Oxford Huss to refer to a disease that consisted of the English Dictionary was the first popular use of the consequences of alcohol consumption, alcoholism word in English. From that time on, its use in both came in time to represent a disease that caused high the professional and the popular literature greatly levels of alcohol consumption (Jellinek, 1960). A expanded. This is partly because of the natural variant theory attempts to preserve the original process that popularizes usage of certain words and meaning: High levels of alcohol consumption re- partly because of deliberate activities on behalf of sulted in consequences of various kinds, particu- the term alcoholism. larly in terms of damage to the central nervous The period of national prohibition in the United system, which damage in turn caused the high lev- States (1919–1933) was accompanied by a lack of els of consumption to continue (Vaillant, 1983). attention to the consequences of alcohol consump- That is, the term alcoholism evolved overtime from tion, for understandable reasons. Such consump- a primarily descriptive term to a largely explana- tion was illegal—permanently, it was assumed— tory concept. An example of a definition of alcohol- and as a result, it was thought that there would be ism with clearexplanatoryintent is one that R. C. little in the way of consequences. Indeed, such con- Rinaldi and colleagues produced in 1988 through sequences as cirrhosis of the liver did decline an elaborate consensus exercise (a Delphi process) abruptly during this period. But as enthusiasm for among eighty American experts, who defined the prohibition waned, and especially after it was term as ‘‘a chronic, progressive, and potentially repealed, a need to promote treatment became in- fatal biogenetic and psychosocial disease charac- creasingly evident. One group involved in this pro- terized by tolerance and physical dependence man- motion used alcoholism as the key word in their ifested by a loss of control, as well as diverse per- efforts, and accordingly were called the alcoholism sonality changes and social consequences.’’ As a movement by sociologists who subsequently studied counterpoint to this line of development, a growing their work. In an early statement of this movement, and increasingly influential literature holds that Anderson (1942) predicted that ‘‘When the dis- problems developing in the context of alcohol con- semination of these ideas is begun through the sumption do not constitute a disease at all existing media of public information, press, radio, (Fingarette, 1988). and platform, which will consider them as news, a The greater interest taken in alcohol consump- new public attitude can be shaped.’’ It was also felt tion and its consequences as a result of the popu- that the term, together with the disease connota- larization of the term alcoholism has been grat- tions attached to it, would encourage the involve- ifying as well as useful. But the broadening of ment of physicians in its study and treatment. The meaning of the term, with much attendant contro- medical profession was viewed as critical to the versy among the advocates of various definitions, success of the effort to increase the nation’s concern has become problematic. For example, in a review about the consequences of alcohol consumption. of alternative definitions, Babor & Kadden (1985) The formation of the NATIONAL COUNCIL ON concluded: ‘‘Clearly, the past and present lack of ALCOHOLISM: Origin of the Term 103 consensus concerning the definition of alcoholism more of the latter than of the former (Institute of and the criteria for its diagnosis does not provide a Medicine, 1990, chapter 9). To reduce the burden solid conceptual basis to design screening proce- upon society effectively, both kinds of populations dures for early detection or casefinding.’’ Because must be dealt with. An exclusive concentration on of its imprecise meaning, the term alcoholism has alcoholism may cause this reality to be overlooked. for some time now been dropped from the two Costly Consequences. The term alcoholism majorofficial systems of diagnosis of diseases, the retains, and probably will always retain, its place in INTERNATIONAL CLASSIFICATION OF DISEASES of the general, nontechnical speech as an indicator of seri- World Health Organization and the DIAGNOSTIC ous problems that are the consequences of pro- AND STATISTICAL MANUAL of Mental Disorders of longed heavy alcohol consumption. Its continued the American Psychiatric Association. A recent popularity has some advantages, for the public- comprehensive study of treatment deliberately health consequences of such alcohol consumption avoided the use of the word alcoholism as too nar- are horrendous. The presence of a convenient row in its focus, while suggesting that the word was shorthand term for this fact in the public con- not incompatible with the phrase that it chose to sciousness—alcoholism—serves as a continuing use—alcohol problems—to refer to any problem reminder of this major unfinished item on the pub- occurring in the context of alcohol consumption lic-health agenda. Certainly, there is a legitimate (Institute of Medicine, 1990, pp. 30–31). place in Western society for the use of alcohol. But with equal certainty, too many individuals fail to COMPLEX PROBLEMS use alcohol wisely orwell. These recent attempts to be precise in the use of The ravages that prolonged exposure to alcohol words represent a return to the more straightfor- produces in the human body are manifold, as Huss ward, descriptive use of alcoholism by its origina- well understood; they include neurological prob- tor, Huss. Two major realities contributing to this lems (damage to the central and peripheral nervous change of direction have been widely recognized systems), cirrhosis (fibrosis and shrinking) of the since Huss first used the term in the 1840s. One is liver, hypertension (high blood pressure), and that the problems people experience are complex, many forms of cancer, particularly of the digestive including those that may arise in the context of tract, to name but a few. If to these are added the alcohol use. Although alcohol may be a factorin consequences of short-term but intense exposure to some such problems—even an important factor— alcohol and the intoxication it produces, one can it is not often the full explanation forthem. Multi- include a high proportion of all accidents, burns, all ple factors, including heredity, early environment, types of violence including suicide, and especially cultural factors, personality factors, situational fac- automobile crashes, as well as the common behav- tors, and others, contribute to the development of ioral effects of intoxication with which we are all human problems and must be considered in their too familiar. Small wonder that almost 30 percent resolution. This formulation should not be taken to of all admissions to hospitals in the United States minimize the important role of alcohol in such are of persons with severe alcohol problems; yet problems or to say that the reduction or elimination most of these problems go unrecognized, and the of alcohol consumption may not be a critical factor in the resolution of problems in particular individu- individuals go untreated. About 50 percent of als. The other reality has to do with the extremely American women have or have had a parent, blood broad spectrum of problems that arise in the con- relative, or spouse to whom they would apply the text of alcohol consumption. Although a substantial term alcoholism; the figure is closer to 40 percent proportion of these problems arise from those who for men. The difficulties that this creates are le- drink too much over a long period of time and who gion—and its remediation would be a remarkable usually have multiple problems (those to whom the step forward. term alcoholism is usually applied), an even greater burden of problems arises from those who drink too (SEE ALSO: Addiction: Concepts and Definitions; much over short periods of time, and who have only Disease Concept of Alcoholism; Treatment, History a few problems. The simple reason is that there are of ) 104 ALKALOIDS

BIBLIOGRAPHY VAILLANT, G. E. (1983). The natural history of alcohol- ism: Causes, patterns, and paths to recovery. Cam- ANDERSON, D. (1942). Alcohol and public opinion. bridge: Harvard University Press. An ingenious at- (1942). Quarterly Journal of Studies on Alcohol, 3, tempt to discoverwhat happens to people with severe 376. An early manifesto of the alcoholism movement. alcohol problems by tracing their histories over long BABOR, T. F., & KADDEN, R. (1985). Screening for alco- periods of time. hol problems: Conceptual issues and practical consid- FREDERICK B. GLASER eratiions. In N. C. Chong & H. M. Cho (Eds.), Early identification of alcohol abuse. Washington, DC: U.S. Government Printing Office. ALKALOIDS This is the general term for any BYNUM, W. F. (1968). Chronic alcoholism in the first half number of complex organic bases that are found in of the 19th century. Bulletin of the History of Medi- nature in seed-bearing plants. These substances are cine, 42, 160–185. An excellent review of medical usually colorless but bitter to the taste. Alkaloids thought about alcohol problems at the time of Magnus often contain nitrogen and oxygen and possess im- Huss. portant physiological properties. FINGARETTE, H. (1988). Heavy drinking: The myth of Examples of alkaloids include not only quinine, alcoholism as a disease. Berkeley: University of Cali- atropine, and strychnine but also CAFFEINE,NIC- fornia Press. A comprehensive summary of the evi- OTINE,MORPHINE,CODEINE, and COCAINE. There- dence against the disease concept of alcoholism. fore, many drugs that are used by humans for both HUSS, M. (1852). Chronische Alkoholskrankheit oder Al- medical and nonmedical purposes are produced in coholismus Chronicus (Alcoholismus chronicus or the nature in the form of alkaloids. Naturally occurring chronic alcohol disease). Translated by G. van dem receptors for many alkaloids have also been identi- Busch into German from the Swedish, with revisions fied in humans and otheranimals, suggesting an by the author. Stockholm and Leipzig: C. E. Fritze. evolutionary role for the alkaloids in physiological Original published 1849. processes. INSTITUTE OF MEDICINE. (1990). Broadening the base of NICK E. GOEDERS treatment for alcohol problems. Washington, DC: Na- tional Academy Press. A detailed contemporary re- view of all aspects of treatment. ALLERGIES TO ALCOHOL AND INSTITUTE OF MEDICINE. (1987) Causes and conse- DRUGS In addition to ALCOHOL,OPIATES, and quences of alcohol problem: An agenda for research. BARBITURATES, some street drugs have been re- Washington, DC: National Academy Press. A compre- ported to induce allergic reactions. These allergic hensive look at some basic issues in the field that phenomena are most frequently mediated by reac- includes extensive chapters on the medical, social, and tions of the immune system known as immediate psychological consequences of alcohol consumption. hypersensitivity and delayed hypersensitivity. Im- mediate hypersensitivity is mediated by the serum JELLINEK, E. M. (1960). The disease concept of alcohol- ism. Highland Park, NJ: Hillhouse Press. The classic protein immunoglobulin E(IgE), whereas delayed hypersensitivity is mediated by thymus-derived book on the disease concept. If read carefully, it is lymphocytes (the white blood cells called T cells). more skeptical than credulous. Immediate Hypersensitivity. The symptoms RINALDI, R. C., STEINDLER, E. M., WILFORD, B. B., & and signs associated with IgE-mediated immune GOODWIN, D. (1988). Clarification and standardiza- reactions are urticaria (hives); bronchospasm that tion of substance abuse terminology. Journal of the produces wheezing; angioedema (swelling) of face American Medical Association, 259, 555–557. and lips orfull-blown anaphylaxis (a combination TURNER, T. B., BORKENSTEIN, R. F., JONES, R. K., & of all the above symptoms and lowering of blood SANTORA,P.B.(EDS.) (1985). Alcohol and highway pressure). Abdominal pain and cardiac arrhyth- safety. Supplement no. 10 to the Journal of Studies on mias (irregular heartbeat) may also occur with an- Alcohol. New Brunswick, NJ: Rutgers University Cen- aphylaxis. Any orall of these symptoms occurwhen terof Alcohol Studies. Coversmultiple aspects of this IgE, which has previously been synthesized by a complex and highly important area. sensitized lymphocyte, fixes to mast cells orba- ALLERGIES TO ALCOHOL AND DRUGS 105 sophils in the skin, bronchial mucosa, and intesti- was precipitated in some asthmatic patients by nal mucosa. This cell-fixed IgE then binds the anti- administration of ethanol, and contact hypersensi- gen that triggers the release of the following—the tivity to 50 percent ethanol solution was produced histamine, the slow-reacting substance of anaphy- in 6 percent of subjects tested. These allergic re- laxis (SRSA), the bradykinin, and the other media- sponses differ from the ‘‘flush’’ reaction exhibited tors that induce these symptoms. Examples of this in individuals (especially Asians) with acetalde- type of allergic reaction are the allergic responses to hyde dehydrogenase abnormalities. eitherbee stings orto penicillin. Similarsymptoms may also occurwhen media- ALLERGIES TO OPIATES, tors are released by mast cells in response to chemi- BARBITURATES, AND STREET DRUGS cal orphysical stimuli. This is called an anaphylactoid reaction. In this instance, the mast There have been reports of MORPHINE-induced cell orbasophil is directlyactivated by the chemical hives in some people, and studies show that mor- to release mediators without having to bind to IgE. phine can cause histamine release directly from Examples of this type of reaction are responses to cells without binding to specific receptors on cells. intravenous contrast material, such as IVP dye, or Anaphylaxis may also occurwith eithermorphine the hives induced by exposure to cold. orC ODEINE, and IgE antibodies against morphine Delayed Hypersensitivity. Reactions occur and codeine have been found in patients experienc- when antigenic chemicals stimulate T lymphocytes ing anaphylaxis. Thus, the OPIATES can mediate and induce their proliferation. T effector cells are allergic reaction by either mechanism, and the an- then recruited into the tissue site. These effector tagonist drug NALOXONE will not reverse these re- cells bind the antigen and subsequently release ef- actions. There are also reports of HEROIN causing fectormolecules, such as the interleukins,the che- bronchospasm. motactic factors, and the enzymes. These effector Some instances of anaphylaxis associated with molecules induce an inflammatory response in the the medical administration of opiates or local anes- area and may also induce formation of granuloma thesia during surgery are due to the often included (a mass of inflamed tissue) by macrophages and preservative methylparaben, rather than to the opi- inflammatory cells. Symptoms of delayed hyper- ate itself. Anaphylaxis may occurwith morethan sensitivity reactions are skin rashes, which may be one local anesthetic and/oranalgesic compound in red, pruritic (itchy), or bullous (blistered) in na- the same patient because of the methylparabens. ture. Granulomas can cause lymph node enlarge- Numerous reports exist for anaphylactoid reac- ment and nodules in the skin orin organs.Exam- tions following the use of BARBITURATES forthe ples of this response are poison ivy, cosmetic induction of anesthesia. The drugs themselves may allergies, Erythema Nodosum or Sarcoidosis. induce histamine release. This may also be medi- ated through a true allergic IgE mediated response in some patients. Skin rashes also occur frequently ALLERGIC RESPONSE TO ALCOHOL following barbiturate usage. This may be a hyper- True anaphylactic or anaphylactoid reactions to sensitivity reaction, or it may be a pseudo-allergic ALCOHOL (ethanol) are rare. Most reactions to in- reaction. gested alcoholic beverages are secondary to other Street drugs have been reported to induce chemicals in the beverage such as yeasts, met- asthma and oranaphylaxis. Bronchospasmmay abisulfite, papain, or dyes. However, there are re- occurin patients smoking C OCAINE orin those in- ports of true allergic reactions in which the offend- jecting heroin. This may occur more often in pa- ing agent was shown to be the ethanol itself. tients who have a previous history of asthma. The Symptoms of anaphylaxis have been reported to asthma may persist after the subjects have stopped occurin severalsubjects following ingestion of beer smoking cocaine. Pulmonary edema (fluid in the and/or wine, and these symptoms were reproduced lungs) may also occurwith F REEBASING cocaine. in one patient by administration of 95 percent eth- These side effects are not likely to be mediated by anol. Hives have been reported with ethanol inges- the immune system. However, a hypersensitivity tion, and hives on contact with ethanol have been pneumonitis to cocaine has been described and is reported for some Asian patients. Bronchospasm associated with elevated levels of IgE. MARIJUANA 106 AMANTADINE

does not appearto increasethe incidence of either CAINE withdrawal and cocaine dependence are asthma oranaphylaxis. thought to be related to abnormalities in the dopa- mine systems of the brain, and these are thought to (SEE ALSO: Complications) contribute to relapse, amantadine has been exam- ined as a treatment possibility. BIBLIOGRAPHY Afterchroniccocaine use, many patients’ dopa- mine systems eitherfail to releasesufficient dopa- ETTINGER, N. A., & ALBIN, R. J. (1989). A review of the mine orareinsensitive to the dopamine that is respiratory effects of smoking cocaine. American released. This relative dopamine deficit is believed Journal of Medicine, 87, 664. to be responsible for the dysphoria of cocaine with- FAKUDA, T., & DOHI, S. (1986). Anaphylactic reaction to drawal. It was hoped that amantadine would re- fentanyl or preservative. Canadian Anesthetists’ Soci- lieve their dysphoria and reduce relapse back to ety Journal, 33, 826. cocaine abuse by increasing the release of dopa- HICKS, R. (1968). Ethanol, a possible allergen. Annals of mine in the brains of cocaine-dependent patients. Allergy, 26, 641. Amantadine has been effective in reducing depres- KARVOREN, J., & HANNUKSELA, M. (1976). Urticaria from sive symptoms in patients with neurological disor- alcoholic beverages. Acta Allergan, 31, 167. ders such as Parkinson’s disease, which is due to KELSO, J., ET AL. (1990). Anaphylactoid reaction to etha- the death of dopamine-producing cells in the brain; nol. Annals of Allergy, 64, 452. however, no solid evidence exists that it is helpful in MCLELLAND, J. (1986). The mechanism of morphine in- preventing continued cocaine use or relapse to co- duced urticaria. Archives of Dermatology, 122, 138. caine use afterdetoxification. PRZYBILLA, B., & RING, J. (1983), Anaphylaxis to ethanol and sensitization to acetic acid. Lancet, 1, 483. (SEE ALSO: Treatment: Cocaine; Withdrawal: Co- REBHUN, J. (1988). Association of asthma and freebase caine) smoking. Annals of Allergy, 60, 339. THOMAS R. KOSTEN RILBET, A., HUNZIKER,N.,&BRAUN, R. (1980) Alcohol contact urticaria syndrome. Dermatologica, 161, 361. RUBIN, R., & NEUGARTEN, J. (1990). Codeine associated asthma. American Journal of Medicine, 88, 438. AMERICAN ACADEMY OF ADDICTION SETO, A., ET AL., (1978). Biochemical correlates of etha- PSYCHIATRY (AAAP) The American Acad- nol-induced flushing in Orientals. Journal in the emy of Addiction Psychiatry (7301 Mission Road, Studies of Alcohol, 39,1. Suite 252, Prairie Village, KS 66208; 913-262- SHAIKH, W. A. (1970). Allergy to heroin. Allergy, 45, 6161; http://www.aaap.org/) is a not-for-profit 555. scientific and professional organization whose SHANABAN, E. C., MARSHALL,A.G.,&GARRETT,C.P.U. members specialize in the clinical treatment of ad- Adverse reactions to intravenous codeine phosphate. dictive disorders and related research and educa- Anesthesia, 38, 40. tion. The AAAP originated in 1985 as the American TING, S., ET AL. (1988). Ethanol induced urticaria: A case Academy of Psychiatrists in Alcoholism and Addic- report. Ann. Allergy, 60, 527. tions (AAPAA). In 1996, the organization renamed WILKINS,J.K.,&FORTNER, G. (1985). Ethnic contact itself the American Academy of Addiction Psychia- urticaria to alcohol. Contact Dermatology, 12, 118. try. MARLENE ALDO-BENSON The AAAP strives to provide psychiatrists, mental health professionals, and students a close- knit environment where members have opportu- nities to collaborate, network, and educate one AMANTADINE Amantadine is a medication another. The AAAP also seeks to increase public (Symmetrel) that is believed to be an indirect awareness of addiction psychiatry in the treat- DOPAMINE agonist; this means that it releases the ment and prevention of substance-use disorders neurotransmitter dopamine from nerve terminals by publishing policy statements, working with in the brain. Since some of the symptoms of CO- lawmakers, and cosponsoring programs such as AMERICAN SOCIETY OF ADDICTION MEDICINE (ASAM) 107

National Alcohol Screening Day. In an effort to well as the annual business meeting and an awards further promote the field of addiction psychiatry, ceremony. the AAAP will assist medical schools that are ap- plying to the Accreditation Council on Graduate (SEE ALSO: American Society of Addiction Medi- Medical Education foraccreditationof theirad- cine) diction psychiatry subspecialty programs. Other FAITH K. JAFFE stated goals of the organization include promoting REVISED BY NANCY FAERBER availability of the highest-quality treatment for all who need it; promoting excellence in clinical practice in addiction psychiatry; providing con- tinuing education foraddiction professionals;dis- AMERICAN INDIANS AND DRUG USE seminating new information in the field of addic- See Ethnicity and Drugs tion psychiatry; and encouraging research on the etiology, prevention, identification, and treatment of addictions. Membership in the AAAP exceeds one thousand AMERICAN SOCIETY OF ADDICTION and is organized into nine national and interna- MEDICINE (ASAM) The American Society of tional geographic areas. Psychiatrists who work Addiction Medicine (4601 North Park Avenue, Ar- with alcoholism and addiction in theirpractices cade Suite 101, Chevy Chase, MD 20815; 301- and are members of the American Psychiatric Asso- 656-3920; http://www.asam.org) is a not-for- ciation and/orthe Canadian PsychiatricAssocia- profit organization of physicians in all medical spe- tion are eligible to become General Members in the cialties and subspecialties who devote a significant AAAP. Faculty members and nonpsychiatrist pro- part of their practice to treating patients addicted fessionals who have contributed to the field of ad- to, orhaving problemswith, alcohol, nicotine, and diction psychiatry may join as Affiliate Members. other drugs. The society strives to have addiction There are additional membership categories for recognized as a medical disorder by health insur- medical students, residents, retired psychiatrists, ance and managed care providers, and the medical and international members. Psychiatrists who have community at large. Many of its members are ac- made significant contributions to the field through tively involved in medical education, research, and clinical work, teaching, research, or administration public policy issues concerning the treatment and may, upon recommendation of the executive com- prevention of addiction. mittee, be elected Fellows. ASAM’s roots can be traced to the early 1950s, Physicians already certified as specialists in psy- when Dr. Ruth Fox organized regular meetings at chiatry by the American Board of Psychiatry and the New York Academy of Medicine with other Neurology (ABPN) can earn further credentials in physicians interested in alcoholism and its treat- the subspecialty of addiction psychiatry by passing ment. These meetings led to the establishment, in the ABPN Examination forSubspecialty Certifica- 1954, of the New York City Medical Society on tion in Addiction Psychiatry. The AAAP offers ad- Alcoholism, which eventually became the Ameri- diction psychiatry review courses to assist in pre- can Medical Society on Alcoholism (AMSA). An- paring for certification. otherstate medical society devoted to addiction as a The official journal of the AAAP is the American subspecialty, the California Society for the Treat- Journal on Addictions, a peer-reviewed clinical ment of Alcoholism and OtherDrugDependencies, publication that is published quarterly. The organi- was established in the 1970s. By 1982, the Ameri- zation also publishes a quarterly newsletter, AAAP can Academy of Addictionology was incorporated, News. Subscriptions to both the journal and news- and all these groups united within AMSA the fol- letter are included with membership. lowing year. Because the organization was con- The AAAP hosts an annual meeting and sympo- cerned with all drugs of addiction, not only alcohol, sium, which includes workshops, presentations of and was interested in establishing addiction medi- papers, poster sessions, committee meetings, and cine as part of mainstream medical practice, the area meetings designated by geographic region, as organization was renamed the American Society on 108 AMERICAN SOCIETY FOR THE PREVENTION OF TEMPERANCE

Alcoholism and OtherDrugDependencies, which graduate fellowships in alcoholism and drug abuse, was soon changed to the American Society of Ad- and has developed guidelines forthe trainingof diction Medicine (ASAM) in 1989. In 1988, the physicians in this area of medical practice. American Medical Association (AMA) House of MARC GALANTER Delegates admitted ASAM as a voting memberand JEROME H. JAFFE in 1990, the AMA recognized addiction medicine as REVISED BY NANCY FAERBER a medical specialty. In the late 1990s, ASAM and the American Managed Behavioral Healthcare As- sociation (AMBHA) began an ongoing collabora- AMERICAN SOCIETY FOR THE PRE- tion to publish statements of consensus on various VENTION OF TEMPERANCE See issues such as the effective treatment of addictive Temperance Movement; Women’s Christian Tem- disorders and credentialing of clinical profes- perance Movement (WCTM) sionals, among others. The stated mission and goals of ASAM are to increase access to and improve the quality of addic- tions treatment; educate physicians, medical stu- AMOBARBITAL Amobarbital (Amytal) is dents, and the public; promote research and pre- one of the many different members of the BARBITU- vention; and establish addiction medicine as a RATE family of central nervous system depressants specialty recognized by the American Board of used to produce relaxation, sleep, anesthesia, and Medical Specialties. anticonvulsant effects. In terms of the duration of By the late 1990s, membership in the society its effects, it is considered an intermediate-acting exceeded 3,500, with chapters in all 50 states, as barbiturate. When taken by mouth, its sedating effects take about 1 hourto develop and last about well as overseas. Membership consists of private- 6 to 8 hours, although it takes considerably longer and group-practice physicians, corporate medical forall the drugto leave the body. directors, residents, and medical students, as well In addition to its use as a sedative, amobarbital as retired physicians. ASAM-certified members is occasionally used in psychiatric evaluation in with at least 5 years’ active participation in the so-called ‘‘Amytal interviews,’’ to relax patients in society, as well as involvement in related organiza- order to help them recall memories or information tions and activities, may become Fellows. that has been repressed due to trauma. This tech- Educational activities of the society are con- nique was sometimes called narcoanalysis or ducted through publications, courses, and clinical narcotherapy. and scientific conferences. Publications include, among others, a bimonthly newsletter, ASAM News; the Journal of Addictive Diseases, published DOSAGE AND ADMINISTRATION quarterly; the ASAM Principles of Addiction Medi- Amobarbital may be given orally, intra- cine, a comprehensive reference guide; and the Pa- muscularly, or intravenously for the treatment of tient Placement Criteria for the Treatment of Sub- insomnia oranxiety. The adult dosage forsedation stance-Related Disorders, a clinical guide for is 15 to 50 milligrams but 65 to 200 milligrams for matching adult and adolescent patients to appro- sleep. Fortreatingconvulsions, the adult dose is 65 priate levels of care. Courses include the Ruth Fox to 200 milligrams, with a maximum dose of 500 Course for Physicians; Medical Review Officer milligrams. (MRO) certification training; and in-depth studies Amobarbital should not be given to patients of addiction medicine. An annual medical-scientific with a history of addiction; personal or family his- conference includes scientific symposia, clinically tory of porphyria; severe kidney, liver, or lung dis- oriented courses and workshops, and presentations ease; or hypersensitivity to barbiturates. of submitted papers. Amobarbital is incompatible with a number of In its continued effort to establish the legitimacy medications, including dimenhydrinate, phenyt- of addiction medicine as a subspecialty within oin, hydrocortisone, insulin, morphine, cimetidine, medicine, ASAM administers a 6-hour certification pancuronium, streptomycin, tetracycline, examination, is a primary sponsor of medical post- vancomycin, and penicillin G. It may decrease the AMOTIVATIONAL SYNDROME 109 effectiveness of birth control pills containing estro- Withdrawal. The symptoms of withdrawal gen. It has also been shown to increase the risk of from amobarbital or any barbiturate may be severe birth defects if taken during pregnancy. oreven fatal if the patient has been taking the drug in large doses (800 mg/day). The barbiturate with- PSYCHIATRIC USE drawal syndrome is similar to delirium tremens. Within 12 to 20 hours after withdrawal, the patient The use of amobarbital in ‘‘Amytal interviews’’ becomes restless and weak. During the second and has declined since the mid–1990s because of its third days, 75 percent of patients develop convul- relatively low success rate. One medical text pub- sions, which may progress to status epilepticus and lished in the mid–1990s noted that the amount of death. From the third to the fifth day, untreated clinically useful information obtained by this withdrawal syndrome is marked by delirium, hal- method is quite limited. Amobarbital interviews lucinations, insomnia, fever, and dehydration. To appear to be useful primarily in distinguishing be- prevent withdrawal syndrome, patients are treated tween psychosis and delirium. Psychotic patients with a dose of phenobarbital equivalent to one- usually improve with amobarbital, whereas deliri- third of the daily dose of amobarbital on which they ous patients get worse. are dependent. This initial dose of phenobarbital is decreased by 30 milligrams per day until the pa- DEPENDENCY AND ABUSE tient’s system is clearof drugs. Amobarbital has been largely replaced by ben- zodiazepine medications as a sedative because of BIBLIOGRAPHY the high risk of abuse. It has been dropped from the BEERS, M. H., AND BERKOW, R., EDS. (1999).The Merck 1999 edition of the Physicians’ Desk Reference, manual of diagnosis and therapy, 17th ed. which implies that it is no longermanufacturedin Whitehouse Station, NJ: Merck Research Laborato- the United States. As of 2000, it is still available in ries. Canada. Although amobarbital has been less popu- BROPHY, J. J. (1994). Psychiatric disorders. In: L. M. lar with addicted patients than the more rapidly Tierney et al. (Eds.), Current medical diagnosis & acting barbiturates (secobarbital and pentobarbi- treatment, 33rd ed. Norwalk, CT: Appleton & Lange. tal), it is still sold on the street as ‘‘blues’’ or HARDMAN, J. G., AND LIMBIRD, L. E., EDS. (1996). Good- ‘‘rainbows’’ (combinations of amobarbital and man and Gilman’s the pharmacological basis of ther- secobarbital). A daily dose of 500 to 600 milli- apeutics, 9th ed. New York: McGraw-Hill. grams is considered sufficient to produce depen- MEDICAL ECONOMICS COMPANY (1999). Physicians’ desk dence. The time necessary to produce dependence reference, (PDR), 53rd edition. Montvale, NJ. Author. is estimated at 30 days. It has often been noted that WILSON, B. A., SHANNON, M. T., AND STANG, C. L., EDS. the symptoms of barbiturate dependence resemble (1995). Nurses drug guide, 3rd ed. Norwalk, CT: those of chronic alcoholism, though barbiturate Appleton & Lange. withdrawl is more often associated with life-threat- SCOTT E. LUKAS ening complications than alcohol withdrawl. REVISED BY REBECCA J. FREY

EMERGENCY TREATMENT Overdose. Although the toxic dose of am- AMOTIVATIONAL SYNDROME This obarbital varies according to height, weight, and term refers to a hypothetical effect produced by other factors, 1 gram taken by mouth usually pro- drugs, especially MARIJUANA, whereby individuals duces serious poisoning in an adult. Two to 10 lose interest or the ability to engage in activities grams are usually a fatal dose. Emergency treat- motivated by normal psychological processes. It is ment is supportive, including oxygen administra- associated with lethargy, a severe reduction in ac- tion if necessary, fluid therapy and other standard tivities, unwillingness to work, failure to meet re- treatment for shock, and forced diuresis if the pa- sponsibilities, and neglect of personal needs in- tient has normal kidney function. This procedure cluding hygiene and nutrition (despite efforts by speeds the excretion of the barbiturate in the urine. others to help and despite statements by the indi- 110 AMPHETAMINE viduals that they wish they could get started in crease alertness during battle and night watches, to these activities). increase endurance, and to elevate mood. It has The experimental evidence of the existence of been estimated that approximately 200 million this syndrome has been mixed, but it is generally Benzedrine (amphetamine) tablets were dispensed believed that amotivation is rarely caused by a drug to the U.S. armed forces during World War II. In alone; it is instead the result of a complex interac- fact, much of the research on performance effects of tion among the effects of the drug, the personality the amphetamines was carried out on enlisted per- and experience of the individual, and the context in sonnel during this period, as the various countries which the drug is repeatedly administered. In addi- sought ways of maintaining an alert and productive tion, there is some confusion as to whether this armed force. Although amphetamine was found to syndrome is seen only during drug intoxication and increase alertness, little data were collected sup- is therefore transient or whether it is a more perma- porting its ability to enhance performance. nent consequence that persists for a long period of Since 1945, use of the amphetamines and CO- time following cessation of drug use. CAINE appears to have alternated in popularity, with several stimulant epidemics occurring in the (SEE ALSO: Cannabis sativa; Complications) United States. There was a major epidemic of am- CHRIS-ELLYN JOHANSON phetamine and methamphetamine abuse (both oral and intravenous) in Japan right after the war. The epidemic was reported to have involved, at its peak, some half-million users and was related to the re- AMPHETAMINE Amphetamine was first lease with minimal regulatory controls of huge synthesized in 1887, but its central nervous system quantities of surplus amphetamines that had been (CNS) stimulant effects were not noted at that time. made foruse by the Japanese military.Despite this After rediscovery, in the early 1930s, its use as a experience, there were special regulations govern- respiratory stimulant was established and its prop- ing their manufacture, sale, or prescription in the erties as a central nervous system stimulant were United States until 1964 (Kalant, 1973). described. Reports of abuse soon followed. As had The first major amphetamine epidemic in the occurred with cocaine products when they were United States peaked in the mid-1960s, with ap- first introduced in the 1880s, amphetamine was proximately 13.5 percent of the university popula- promoted as being an effective cure for a wide tion estimated, in 1969, to have used amphet- range of ills without any risk of addiction. The amines at least once. By 1978, use of the medical profession enthusiastically explored the amphetamines had declined substantially, con- potentials of amphetamine, recommending it as a trasting with the increase of cocaine use by that cure for everything from alcohol hangover and de- time. The majoramphetamine of concernin the pression to the vomiting of pregnancy and weight United States in the 1990s is methamphetamine, reduction. These claims that it was a miracle drug with pockets of ‘‘ice’’ (smoked methamphetamine) contributed to public interest in the amphetamines, abuse. and they rapidly became the stimulant of choice— Amphetamines are now controlled under Sched- since they were inexpensive, readily available, and ule II of the CONTROLLED SUBSTANCES ACT. Sub- had a long duration of action. stances classified within this schedule are found to Derivatives of amphetamine, such as have a high potential for abuse as well as currently METHAMPHETAMINE, were soon developed and both accepted medical use within the United States. Am- oral and intravenous preparations became avail- phetamine, methamphetamine, cocaine, able for therapeutic uses. Despite early reports of METHYLPHENIDATE, and phenmetrazine are all an occasional adverse reaction, enormous quan- stimulants included in this schedule. tities were consumed in the 1940s and 1950s, and their liability for abuse was not recognized. During MEDICAL UTILITY World War II, the amphetamines, including meth- amphetamine, were widely used as stimulants by Amphetamines are frequently prescribed for the the military in the United States, Great Britain, treatment of narcolepsy, obesity, and for childhood Germany, and Japan, to counteract fatigue, to in- ATTENTION DEFICIT DISORDER. They are clearly ef- AMPHETAMINE 111

ficacious in the treatment of narcolepsy, one of the cocaine have been suggested forthe treatmentof first conditions to be successfully treated with these depression, although the evidence to support their drugs. Although patients with this disorder can efficacy does not meet current standards demanded require large doses of amphetamine for prolonged by the U.S. Food and Drug Administration. periods of time, attacks of sleep can generally be prevented. Interestingly, tolerance does not seem to PHARMACOLOGY develop to the therapeutic effects of these drugs, and most patients can be maintained on the same The amphetamines act by increasing concentra- dose foryears. tions of the neurotransmitters DOPAMINE and Although the amphetamines have been used ex- NOREPINEPHRINE at the neuronal synapse, thereby tensively in the treatment of obesity, considerable augmenting release and blocking uptake. It is the evidence exists for a rapid development of toler- augmentation of release that differentiates amphet- ance to the anorectic (appetite loss) effects of this amines from cocaine, which also blocks uptake of drug, with continued use having little therapeutic these transmitters. Humans given a single moder- effect. These drugs are extremely effective appetite ate dose of amphetamine generally show an in- suppressants, but after several weeks of use the crease in activity and talkativeness, and they report dose must be increased to achieve the same appe- euphoria, a general sense of well-being, and a de- tite-suppressant effect. People remaining on the crease in both food intake and fatigue. At higher amphetamines for prolonged periods of time to de- doses repetitive motor activity (i.e., stereotyped be- crease food intake can reach substantial doses, re- havior) is often seen, and further increases in dose sulting in toxic side effects (e.g., insomnia, irrita- can lead to convulsions, coma, and death. This bility, increased heart rate and blood pressure, and class of drugs increases heart rate, respiration, dia- tremulousness). Therefore, these drugs should stolic and systolic blood pressure, and high doses only be taken for relatively short periods of time can cause cardiac arrhythmias. In addition, the (4–6 weeks). In addition, long-term follow-up amphetamines have a suppressant effect on both studies of patients who were prescribed amphet- rapid eye movement sleep (REM)—the stage of amines forweight loss have not found any advan- sleep associated with dreaming—and total sleep. tage in using this medication to maintain weight The half-life of amphetamine is about ten hours, loss. Data indicate that weight lost underamphet- quite long when compared to a stimulant like co- amine maintenance is rapidly gained when am- caine, which has a half-life of approximately one phetamine use is discontinued. In addition to the hour, or even methamphetamine which has a half- lack of long-term efficacy, the dependence- life of about five hours. producing effects of amphetamines make them a The amphetamine molecule has two isomers: the -isomers. There is marked stereo (מ)-and l (ם)-poorchoice of maintenance medication forthis d problem. selectivity in theirbiological actions, with the The use of amphetamines in the treatment of d-isomer (dextroamphetamine) considerably more attention deficit disorders in children, remains ex- potent. Forexample, it is morepotent as a locomo- tremely controversial. It has been found that the torstimulant, in inducing stereotypedbehavior amphetamines have a dramatic effect in reducing patterns, and in eliciting central nervous system restlessness and distractibility as well as lengthen- excitatory effects. The isomers appear to be equipo- ing attention span, but there are side effects. These tent as cardiovascular stimulants. The basic am- include reports of growth impairment in children, phetamine molecule has been modified in a number insomnia, and increases in heart rate. Those pro- of ways to accentuate various of its actions. For moting theiruse point to theirpotential benefits example, in an effort to obtain appetite suppress- and they advocate care in limiting treatment dose ants with reduced cardiovascular and central ner- and duration. Opponents of their use, while agree- vous system effects, structural modifications ing that they provide some short-term benefits, yielded such medications as diethylproprion and conclude that these do not outweigh theirdisad- fenfluramine, while other structural modifications vantages. Amphetamine therapy has also been at- have enhanced the central nervous system stimu- tempted, but with little success, in the treatment of lant effects and reduced the cardiovascular and Parkinson’s disease, and both amphetamine and anorectic actions, yielding medications such as 112 AMPHETAMINE methylphenidate and phenmetrazine. These sub- Animals given unlimited access to amphetamine stances share, to a greater or lesser degree, the will self-administer it reliably, alternating days of properties of amphetamine. high intake with days of low intake. They become restless, tremulous, and ataxic, eating and sleeping TOXICITY little. If allowed to continue self-administering the drug, most will take it until they die. Animals main- A majortoxic effect of amphetamine in humans tained on high doses of amphetamines develop tol- is the development of a schizophrenia-like psycho- erance to many of the physically and behaviorally sis after repeated long-term use. The first report of debilitating effects, but they also develop irrevers- an amphetamine psychosis occurred in 1938, but ible damage in some parts of the brain, including the condition was considered rare. Administration long-lasting depletion of dopamine. It has been of amphetamine to normal volunteers with no his- suggested that the prolonged anhedonia seen after tories of psychosis (Griffith et al., 1968) resulted in long-term human amphetamine use may be related a clear-cut paranoid psychosis in five of the six to this, although the evidence forthis is not very subjects who received d-amphetamine forone to strong. five days (120–220 mg/day), which cleared when the drug was discontinued. Unless the user contin- BEHAVIORAL EFFECTS ues to take the drug, the psychosis usually clears within a week, although the possibility exists for Nonhumans. As with all PSYCHOMOTOR prolonged symptomology. This amphetamine psy- STIMULANT drugs, at low doses animals are active chosis has been thought to represent a reasonably and alert, showing increases in responding main- accurate model of schizophrenia, including symp- tained by other reinforcers, but often decreasing food intake. Higherdoses producespecies-specific toms of persecution, hyperactivity and excitation, repetitive behavior patterns (stereotyped behav- visual and auditory hallucinations, and changes in ior), and further increases in dose are followed, as body image. In addition, it has been suggested that in humans, by convulsions, hyperthermia, and there is sensitization to the development of a stimu- death. Tolerance (loss of response to a certain dose) lant psychosis—once an individual has experi- develops to many of amphetamine’s central effects, enced this toxic effect, it is readily reinitiated, and cross-tolerance among the stimulants has been sometimes at lowerdoses and even following long demonstrated in rats. Thus, for example, animals drug-free periods. tolerant to the anorectic effects of amphetamine Amphetamine abusers taking repeated doses of also show tolerance to cocaine’s anorectic effects. the drug can develop repetitive behavior patterns Although there is tolerance development to many of which persist for hours at a time. These can take amphetamine’s effects, sensitization develops to the form of cleaning, the repeated dismantling of amphetamine’s effects on locomotoractivity. Thus, small appliances, orthe endless picking at wounds with repeated administration, doses of amphet- on the extremities. Such repetitive stereotyped pat- amine that initially did not result in hyperactivity terns of behavior are also seen in nonhumans ad- or stereotypy can, with repeated use, begin to in- ministered repeated doses of amphetamines and duce those behaviors when injected daily for sev- other stimulant drugs, and they appear to be re- eral weeks. In addition, there is cross-sensitization lated to dopaminergic facilitation. Cessation of am- to this effect, such that administration of one stim- phetamine use afterhigh-dose chronicintake is ulant can induce sensitization to anotherone. In generally accompanied by lethargy, depression, contrast to cocaine, however (in which an increased and abnormal sleep patterns. This pattern of be- sensitivity to its convulsant effects develops with havior, opposite to the direct effects of amphet- repeated use), amphetamines have an anticon- amine, does not appearto be a classical abstinence vulsive effect. syndrome. The symptoms may be related to the Learned behaviors, typically generated by oper- long-term lack of sleep and food intake that accom- ant schedules of reinforcement, are generally affec- pany chronic stimulant use as well as to the cate- ted by the amphetamines in a rate-dependent fash- cholamine depletion that occurs as a result of ion. Thus, behaviors that occur at relatively low chronic use. rates in the absence of the drug tend to be increased AMPHETAMINE 113 at low-to-moderate doses of amphetamine, while medal’’ and any other. Unfortunately, such data behaviors occurring at relatively high frequencies have led athletes to take stimulants prior to athletic tend to be suppressed by those doses of amphet- events, particularly those in which strenuous activ- amine. In addition, with high doses most behaviors ity is required over prolonged periods (e.g., bicycle tend to be suppressed. As is seen with other stimu- racing), leading to hyperthermia, collapse, and lants, such as cocaine, environmental variables and even death in some cases. behavioral context can play a role in modulating The mood-elevating effects of the amphetamines these effects. Forexample, behaviorunderstrong are generally believed to be related to their abuse. stimulus control shows tolerance to repeated am- Their use is accompanied by reports of increased phetamine administration much more rapidly than self-confidence, elation, frequently euphoria, does behaviorunderweak stimulus control.In ad- friendliness, and positive mood. When amphet- dition, if the amphetamine-induced behavioral dis- amine is administered repeatedly, tolerance devel- ruption has the effect of interfering with reinforce- ops rapidly to many of its subjective effects (such ment delivery, tolerance to that effect develops that the same dose no longerexertsmuch of an rapidly. Tolerance does not develop to the amphet- effect). This means that the usermust take increas- amine-induced disruptions when reinforcement ingly larger amounts of amphetamine to achieve density is increased or remains the same. the same effect. As with nonhuman research sub- Amphetamines can serve as reinforcers in jects, there is however, little or no evidence for the nonhumans and, as described above, can produce development of tolerance to amphetamine’s rein- severely toxic consequences when available in an forcing effects. unlimited fashion. However, when available for a Experienced stimulant users, given a variety of few hours a day, animals will take them in a regular stimulant drugs, often cannot differentiate among fashion, showing little or no tolerance to their rein- cocaine, amphetamine, methamphetamine, and forcing effects. methlyphenidate—all of which appearto have sim- Humans. A substantial numberof studies ilar profiles of action. Since these drugs have differ- have been carried out evaluating the effects of am- ent durations of action, however, it becomes easier phetamines on learning, cognition, and other as- to make this differentiation over time. pects of performance. The data indicate that under most conditions the amphetamines are not general ABUSE performance enhancers. When there is improve- ment in performance associated with amphetamine In the United States in the 1950s, nonmedical administration, it can usually be attributed to a amphetamine use was prevalent among college stu- reduction in the deterioration of performance due dents, athletes, truck drivers, and housewives. The to fatigue orboredom.Attention lapses that impair drug was widely publicized by the media when very performance after sleep deprivation appear to be little evidence of amphetamine toxicity was avail- reduced by amphetamine administration; however, able. Pills were the first form to be widely abused. as sleep deprivation is prolonged, this effect is re- Use of the drug expanded as production of amphet- duced. A careful review of the literature in this area amine and methamphetamine increased signifi- (Laties & Weiss, 1981) concluded that improve- cantly, and abusers began to inject it. An extensive ment is more obvious with complex, as compared black market in amphetamines developed, and it with simple, tasks. has been estimated that 50 to 90 percent of the In addition, in trained athletes, whose behavior quantity commercially produced was diverted into shows little variability, only very small improve- illicit channels. In the 1970s, manufacture of am- ments can be seen. Laties and Weiss have argued phetamines was substantially curtailed, amphet- persuasively, however, that the small changes in amines were placed in Schedule II of the Controlled performance induced by amphetamines can result Substances Act, and abuse of these substances was in the 1 to 2 percent improvement that may make substantially reduced. Perhaps only by coinci- the difference in a close athletic competition. Al- dence, as amphetamine use declined, cocaine use though the facilitation in performance after am- increased. phetamine does not appearto be substantial, it is The amphetamines, as with otherstimulants, sufficient to ‘‘spell the difference between a gold are generally abused in multiple-dose cycles (i.e., 114 AMPHETAMINE EPIDEMICS

binges), in which people take the drug repeatedly (Eds.), Handbook of psychopharmacology. New for some period of time, followed by a period in York: Plenum. which they take no drug. Amphetamines are often GRIFFITH, J. D., ET AL. (1970). E. Costa and S. Garattini taken every three or four hours for periods as long (Eds.), Amphetamines and related compounds. New as three or four days, and dosage can escalate dra- York: Raven Press. matically as tolerance develops. Like cocaine GRILLY, D. M. (1989). Drugs and human behavior. binges, these amphetamine-taking occasions are Needham, MA: Allyn & Bacon. followed by a ‘‘crash’’ period in which the user KALANT, O. J. (1973). The amphetamines: Toxicity and sleeps, eats, and does not use the drug. Abrupt addiction. Springfield, IL: Charles C. Thomas. cessation from amphetamine use is usually accom- LATIES,V.G.,&WEISS, B. (1981). Federation proceed- panied by depression. Mood generally returns to ings, 40, 2689–2692. normal within a week, although craving for the MARIAN W. FISCHMAN drug can last for months. There is little evidence for the development of physical dependence to the amphetamines. Al- though some experts view the ‘‘crash’’ (with leth- Am- argy, depression, exhaustion, and increased appe- AMPHETAMINE EPIDEMICS phetamine, METHAMPHETAMINE, and related com- tite) that can follow a few days of moderate-to-high pounds have relatively brief abuse histories, dating dose use as meeting the criteria for a withdrawal from the 1930s and 1940s. Similar to the other syndrome, others believe that the symptoms can majorP SYCHOMOTOR STIMULANT of abuse, CO- also be related to the effects of chronic stimulant use. When using stimulants people do not eat or CAINE, the amphetamines are addictive, and a sleep very much and, as well, catecholamine deple- number of cycles of epidemic use have occurred in tion may well be contributing to these behavioral the United States and in othercountries.Unlike changes. cocaine, however, the amphetamines do not occur in nature and can only be synthesized in a labora- tory—a distinction that significantly influences the TREATMENT manufacture, distribution, and abuse patterns of As of the mid-1990s, little information is avail- the drugs. able about the treatment of amphetamine abusers, and no reports of successful pharmacological inter- EARLY USE IN THE UNITED STATES ventions exist in the treatment literature. As with cocaine abuse, the most promising non- Amphetamines were initially synthesized in pharmacological approaches include behavioral 1887, with methamphetamine being developed ap- proximately thirty years later. The rise in the popu- therapy, RELAPSE PREVENTION, rehabilitation (e.g., vocational, educational, and social-skills training), larity of the amphetamines parallels that experi- and supportive psychotherapy. Unlike cocaine, enced during the introduction of cocaine. however, minimal clinical trials with potential Exaggerated publicity and fallacious claims about treatment medications for amphetamine abuse amphetamines, combined with medical optimism have been carried out. The few that have been concerning potential uses and a lack of understand- attempted report no success in reducing a return to ing of abuse, contributed to a dramatic increase in amphetamine use. public interest in amphetamines. In 1933, Central Nervous System stimulant actions of amphet- amines were reported, about the same time that (SEE ALSO: Amphetamine Epidemics; Pharmacoki- netics; Treatment) reports of their effectiveness in treating narcolepsy and Parkinson’s disease were released. When the American Medical Association (AMA) approved the BIBLIOGRAPHY use of amphetamines for these disorders, a mild ANGRIST, B., & SUDILOVSKY, A. (1978). Central nervous warning was added that ‘‘continuous doses higher system stimulants: Historical aspects and clinical ef- than recommended’’ might cause ‘‘restlessness and fects. In L. L. Iversen, S. D. Iverson, & S. H. Snyder sleeplessness,’’ but physicians were assured that AMPHETAMINE EPIDEMICS 115

‘‘no serious reactions had been observed.’’ Between had used amphetamines returned home with drug 1932 and 1946 the pharmaceutical industry devel- habits. In addition, during the 1940s and 1950s oped more than three dozen generally accepted enormous quantities of these drugs were prescribed clinical uses foramphetamines, among them the in the civilian population without concern for any treatment of schizophrenia, morphine and codeine addictive effects, as the drugs continued to be mar- addiction, tobacco smoking, heart block, head inju- keted to treat obesity, narcolepsy, hyperkinesis, ries, infantile cerebral palsy, radiation sickness, low and depression. College students, athletes, truck blood pressure, seasickness, and persistent hiccups. drivers, and housewives began using amphet- It was not until several decades later that the addic- amines for nonmedical purposes, primarily to in- tive properties and psychiatric complications of crease energy, decrease the need for sleep, lose amphetamines were fully recognized by the medi- weight, and elevate mood. Pharmaceutical produc- cal community. tion reached 3.5 billion tablets (about 20,000 stan- dard dosage units per thousand U.S. residents) in U.S. PATTERNS AND TRENDS 1958 and 10.0 billion tablets by 1970. In compari- son, the medical use of amphetamines in 1996-98 In the 1940s and 1950s amphetamines were averaged approximately 1.8 standard dosage units prescribed liberally and soon surpassed cocaine as perthousand U.S. population. an illicit stimulant widely available on the street. One consequence of excessive production and The increase in the popularity of amphetamines widespread popularity of amphetamines was the was influenced by easy availability, low cost, and diversion of pharmaceutical-grade drugs to illegal long duration of effect (eight to twelve hours). Be- traffic and use. Drugs sold on the black market tween the 1930s and the 1970s the public could came from or would otherwise have gone to phar- obtain amphetamines, such as Benzedrine, in a maceutical companies, wholesalers, druggists, and variety of over-the-counter (OTC) nasal inhaler physicians. Probably over half (and potentially 90 preparations. Abuse involved breaking open the percent) of the total commercial product was di- inhalers and ingesting directly or soaking the fillers verted into the black market. In 1966, the Food in alcohol orcoffee. Although inhaleruse may have and Drug Administration (FDA) estimated that introduced hundreds of thousands of Americans to more than 25 tons of amphetamine were illegally amphetamine abuse, this type of abuse was most distributed (Fischman, 1990). One market for the prevalent in prison populations and among deviant product was composed of long-distance truck driv- groups. The ability to cause euphoria, dysphoria, ers who found that amphetamines allowed them to and psychic stimulation resulted in removal of am- work for extended periods without resting. The all- phetamine-like drugs from OTC inhaler prepara- night restaurants and truck stops served as a distri- tions in 1971. However, amphetamine products re- bution network that spanned the entire country. mained available in pill, capsule, orinjectable By the mid-1960s, the need forinterventionand form. legislative controls over amphetamine production During World War II, methamphetamine and and distribution was clear. The Drug Abuse Con- amphetamine were widely used by the American, trol Amendments of 1965, passed by Congress, British, German, and Japanese military as insom- required increased record keeping throughout the niacs and as stimulants to increase alertness during system of manufacture, distribution, prescription, battle and night watches; they were used as well by and sale. However, diversion of pharmaceutical war-related industries to enhance worker produc- amphetamine to illicit use continued. The CON- tivity. Perhaps as many as 200 million tablets and TROLLED SUBSTANCES ACT (CSA) was passed in pills were supplied to American troops during the 1970. It further established the legal foundation of war. The U.S. armed services authorized the issue the government’s fight against drug abuse, and of amphetamines on a regular basis beginning with placed amphetamine and some related stimulant the Korean conflict, escalating to well over 225 drugs in Schedule II—acknowledging the drugs’ million standard-dose tablets dispensed between high potential forabuse, development of psycho- 1966 and 1969. logical or physical dependency, and restricted med- R. R. Monroe and A. H. Drell (1947) reported ical use. In 1971 the Justice Department began that at the end of World War II, some soldiers who imposing quotas on legal amphetamine production. 116 AMPHETAMINE EPIDEMICS

A significant shift from abuse of oral prepara- until 1974, specimens were on average less than 30 tions to abuse of the intravenous form occurred percent methamphetamine. From 1975 through during the 1960s. Intravenous methamphetamine 1983 the composition of methamphetamine in abuse, described by S. M. Pittel and R. Hofer samples increased from 60 to over 95 percent. For (1970), was particularly prevalent in the Haight- the street samples submitted as stimulants, includ- Ashbury district of San Francisco, where ‘‘speed,’’ ing those submitted as amphetamine, methamphe- the street name for amphetamine and methamphe- tamine, orspeed, methamphetamine made up a tamine, began to replace hallucinogenic drugs, relatively small percentage between 1972 and such as LSD, in popularity. Escalating doses of 1979, but increased to approximately 60 percent in methamphetamine were taken, often as a series of 1983. These data demonstrate the increasing pre- injections overseveraldays orweeks—what came dominance of methamphetamine in the speed mar- to be known as a ‘‘speed run.’’ Exhaustion, then ket during this time period. Prior to the increase in depression, accompanied the end of a run, followed quality of street speed, the products sold as meth- by readministration of the drug to mitigate the un- amphetamine orspeed wereusually a combination pleasant side effects and regain the previous eu- of phenylpropanolamine hydrochloride, ephedrine, phoria and high—thus the cycle of high to low to and caffeine and referred to as ‘‘look-alike’’ speed. high. Initially the drugs were diverted from phar- The term referred to the similarity of appearance of maceutical supplies. Later, some unscrupulous these drugs and of central nervous system effects. physicians who were already prescribing intrave- Other constituents also found in products pur- nous methamphetamine to treat heroin addiction ported to be speed included pseudoephedrine and became involved in illegal prescriptions. In 1963, cocaine. injectable ampules of methamphetamine were vol- Since the mid-1980s, virtually all substances untarily removed by manufacturers from sale to marketed illicitly as amphetamine or by street retail pharmacies in California. terms, such as ‘‘speed,’’ ‘‘crystal,’’ ‘‘crank,’’ ‘‘go,’’ Speed use escalated during the 1960s, with the ‘‘go-fast,’’ ‘‘zip,’’ or‘‘cristy,’’contain methamphe- Haight-Ashbury district serving as a focal point. tamine. By analyzing contaminants found in street With this escalation came an increase in violence methamphetamine samples, researchers have de- and the diffusion of manufacturing and distribu- termined that clandestine manufacture of metham- tion of speed from Haight-Ashbury to other areas phetamine, rather than diversion of pharmaceuti- along the West Coast (Smith, 1970). Outlaw mo- cal products, now supplies the illicit marketplace. torcycle gangs became heavily involved in metham- According to the U.S. Drug Enforcement Adminis- phetamine manufacture and gained control of its tration (DEA), methamphetamine has been the clandestine production and distribution. Within most prevalent clandestinely manufactured con- the subculture, serial speed users became known as trolled substance in the United States, and one of ‘‘speed freaks.’’ A public campaign was initiated to the only widely abused controlled substances that inform users of the hazards associated with speed can be made in the home. Along with the increase use. Partly as a result of the ‘‘speed kills’’ cam- in methamphetamine laboratory seizures was a lo- paign, amphetamine and methamphetamine use calized resurgence of methamphetamine abuse— dropped sharply after 1972. From 1972 through since the clandestine manufacture of the metham- 1977, the characteristics of the drug-taking popu- phetamine in a community facilitates the develop- lation changed from heavy users to predominantly ment of a market for the drug. Clandestine labs also light-to-moderate users, and a growing proportion create other hazards for the community since the were women. materials used (precursors, reagents, and solvents) Changes in Clandestine Manufacture. are hazardous in the hands of inexperienced chem- Because of increasing controls on the prescribing ists, who may cause explosions and fires. Also, each and marketing of amphetamine, the clandestine pound of methamphetamine produced creates up manufacture of methamphetamine became more to five pounds of hazardous wastes, and the opera- widespread. The availability of illicitly synthesized tors (who rarely own the property) commonly dis- methamphetamine varied greatly during the 1970s cardthe wastes on ornearthe site, creatinglong- and 1980s. Analyses of street samples of drugs lasting chemical contamination of the area. The purported to be methamphetamine revealed that number of laboratories seized declined in the early AMPHETAMINE EPIDEMICS 117

1990s, largely because of the passage and enforce- ment of the Chemical Diversion and Trafficking Act of 1988, which placed under federal control the distribution of twelve precursor and eight essential chemicals used in the production of illicit drugs, including phenyl-2-propanone, the major metham- phetamine precursor in use at the time. In the late 1980s, however, the clandestine methamphetamine chemists brought into produc- tion a more efficient synthesis process utilizing ephedrine or pseudoephedrine as the precursor chemical. As knowledge of this process spread, in some cases not only by word of mouth, but also via turing and distribution process. Although motorcy- the growing medium of the Internet, the number of cle gangs continued to control a share of the clandestine labs began to increase again. In 1997, market, in 1995 well-established Mexico-based 98 percent of all clandestine laboratories seized by polydrug trafficking organizations began manufac- the Drug Enforcement Administration (DEA) were turing and distributing methamphetamine. Im- producing methamphetamine and, in 1999 more porting precursor chemicals and reagents into or than 7,000 clandestine methamphetamine labs through Mexico, these organizations established were seized, along with over 2,250 kg of metham- ‘‘superlabs’’ in Mexico and in southern California phetamine. Figure 1 shows that the amount of that were capable of producing ten pounds or more methamphetamine seized domestically increased of high-purity methamphetamine in one to two substantially from 1990 through 1999. While most days. These superlabs are in marked contrast to the of the labs seized early in the 1990s were in Califor- more numerous and widely distributed ‘‘mom-and- nia, Texas, orOregon,in 1998 the DEA seized labs pop’’ labs producing several ounces that may be set in almost every state in the nation, with 371 labs up in a motel room, a car trunk, or on a kitchen seized in Missouri. counter. By 1999, it was estimated that superlabs Another factor increasing the spread of metham- were producing approximately 85 percent of the phetamine was a change in control of the manufac- methamphetamine in the U.S. mainland. Portions of the Crime Control Act of 1990 and the Chemical Diversion Control Act of 1993, as well as the Com- prehensive Methamphetamine Control Act of 1996, were all enacted to counter the changes in the syn- thetic process, the changes in the trafficking pat- terns, the emergence of superlabs, and the prolifer- ation of mom-and-pop labs forthe clandestine manufacture of methamphetamine. Changes in Indicators of Abuse. The DRUG ABUSE WARNING NETWORK (DAWN), a nationally based surveillance system that monitors emergency medical consequences and deaths related to drug use, reflected a stable trend across the United States from the mid-1970s until the mid-1980s. Over seven hundred hospitals in twenty-one metropoli- tan areas and a panel of hospitals outside of these Figure1 areas report to DAWN. During the mid-1980s Number of Clandestine Methamphetamine sharp increases in nonfatal emergency-room epi- Laboratories Seized in the United States, 1981– sodes began to appear, largely in metropolitan 1991 areas on the West Coast. Increases in drug-use SOURCE: U.S. Department of Justice (1992). indicators were also reported for methampheta- 118 AMPHETAMINE EPIDEMICS mine through the Community Epidemiology Work From 1992 to 1997, both the absolute number of Group (CEWG), a network of state and local drug- admissions reporting methamphetamine or am- abuse experts representing twenty cities and metro- phetamine as the primary drug of abuse and the politan areas across the United States. percentage of such admissions, relative to treat- Total methamphetamine and amphetamine ment admissions for all substances, more than tri- mentions in DAWN rose from earlier levels during pled. The most common route was inhalation, but 1988 and 1989, decreased during 1990 and 1991, almost 30 percent of admissions reported injecting then rose sharply during the early 1990s to reach the drug. an erratic higher plateau for the rest of the decade The demographic profile of methamphetamine (see figure 2). Among DAWN emergency-room abusers in several studies that looked at different cases, the most common route of administration of populations in the late 1980s and through the methamphetamine was intravenous. Methamphe- 1990s showed the majority of abusers to be pre- tamine accounted for approximately 3.0 percent of dominantly Caucasian, low to middle income, the total DAWN drug mentions in 1994 and just high-school educated young adults generally rang- under 2.5 percent in 1998, compared with 16.0 ing in age from 20 to 35, with slightly more males percent and 17.5 percent for cocaine during 1984 than females. However, by the end of the 1990s, and 1998, respectively. there were indications of growing numbers of women and Hispanic abusers. Routes of adminis- The Treatment Episode Data Set (TEDS) col- tration tend to vary from locale to locale and from lects information nationwide on admissions to drug subgroup to subgroup, and include injecting intra- and alcohol treatment facilities that report to state venously, smoking (inhaling vaporized drug), and administrative data systems. Data on Primary, sec- snorting. Methamphetamine abusers carry an in- ondary, and tertiary substances of abuse, their creased risk of both Hepatitis B and HIV infections, route of administration, frequency of use, and age predominantly through sharing of needles and in- at first use are among the data collected. In 1997, creased unsafe sex practices. TEDS captured data on an estimated 67 percent of Other U.S. Trends. At the same time that in- all U.S. drug and alcohol treatment admissions. creases were being noted in methamphetamine use on the mainland of the United States, a new phe- nomenon was developing in Hawaii. Sharp rises in law-enforcement activity and in clients entering treatment because they smoked a new dosage form of methamphetamine were recorded between 1986 and 1989. The street names for this drug were ice, crystal, shabu (Japanese), and batu (Filipino for rock), and it looked like a large, usually clear crys- tal resembling broken fragments of glass or rock candy. Ice is of high purity (90 to 100 percent) and the d-isomer(the morepsychoactive molecu- lar form) of methamphetamine hydrochloride salt. In Hawaii it is almost always smoked in a glass pipe. The hydrochloride salt is sufficiently volatile Figure2 to vaporize in a pipe so that it can be inhaled. This Trends in Methamphetamine-Related route of administration allows rapid absorption Emergencies, 1986–1991 into the bloodstream, with onset of effects similar SOURCE: The Drug Abuse Warning Network (DAWN). a to those experienced with intravenous NOTE: Estimates for 1986–1987 are provisional. The administration. estimates are based on a nonrandom sample of hospital emergency rooms in the coterminous U.S. The use of ice was first detected by Hawaiian bEstimates for1988–1991 arebased on a treatment programs during the summer of 1986, representative sample of nonfederal short-stay with more widespread use occurring into the hospitals with 24-hour emergency rooms in the 1990s. By 1997, The Treatment Episode Data Set coterminous U.S. reported that in Hawaiian drug and alcohol treat- AMPHETAMINE EPIDEMICS 119 ment admissions, methamphetamine/amphet- INTERNATIONAL PATTERNS amine was the most commonly reported single pri- AND TRENDS mary substance of abuse, accounting for almost one The use and abuse of amphetamines has also quarter of all admissions. This epidemic, which was occurred in countries outside the United States, al- described in an outbreak investigation and fol- though the absence of significant epidemiologic in- low-up field study conducted by the NATIONAL formation in many countries and the lack of stan- INSTITUTE ON DRUG ABUSE, involved a population dardization in data collection and analysis make varying widely in age and ethnic background and multinational comparisons difficult. Based on included both sexes. The ice-using treatment popu- available data, amphetamine use and abuse ap- lation was studied and reflected a younger popula- pear to be an endemic problem worldwide and, as tion, with a higher representation of women and a in the United States, other countries reflect pat- larger proportion of Hawaiian/part Hawaiian than terns that are episodic, localized, population-spe- other drug users in treatment in the state. Ice was cific, and rooted in multiple etiologies. Senay (1991) cites a numberof studies conducted princi- typically smoked in runs, or periods of continuous pally in the 1970s and first half of the 1980s that use, averaging three to eight days, with one or two document this phenomenon. Amphetamine epi- days between runs, during which the user would demics have been evident in several countries dur- ‘‘crash’’ into deep, prolonged sleep. Users reporting ing the past fifty years and continue to be the pri- this pattern became rapidly addicted and experi- mary concern in some. The experience of three of enced numerous adverse medical, social, and phys- these, Japan, Sweden, and Thailand, are described iologic consequences. Precipitants of the epidemic briefly, but are described at greater length else- included both a law enforcement campaign that where (Kalant 1973, Klee 1997, Chaiyawong, effectively eradicated large portions of the Hawai- 1999). ian marijuana or pakalolo crop, and well-orches- Japan. Methamphetamine has been the single trated marketing campaigns by Asian ice distribu- most prevalent drug of abuse in Japan since the tors holding out ice as a replacement drug. 1940s. Based on indicators from law-enforcement Until the late 1980s, the ice form of methamphe- data, epidemic patterns appeared at several periods tamine came only from Asia, specifically Hong during that time. The increase of methamphetamine abuse in Ja- Kong, Korea, Japan, Taiwan, Thailand, and the pan during the 1940s and early 1950s has been Philippines. Attempts to smuggle ice from Taiwan attributed to the wholesale appearance of the drug and Korea into Hawaii can be documented back to in the black market following World War II. Both the mid-1980s by the Drug Enforcement Adminis- amphetamine and methamphetamine were avail- tration (DEA). The importation and distribution of able to Japanese forces during the war and became ice in Hawaii has been linked to Asian and Hawai- widely used by the beleaguered civilian population ian criminal organizations and gangs. By 1989, following military defeat. In response to the esca- limited distribution of ice had occurred on the West lation in abuse, Japan’s Stimulants Drug Law of Coast of the United States. In the following year, 1951 was enacted and the eventual decline in abuse increased amounts of ice were found in California was attributed to the effectiveness of the penal and subsequently in otherlimited locations. The provisions of the law and subsequent control of the increase in availability of ice was believed to stem raw materials used to produce the drug. After a from clandestine laboratories operating in Califor- hiatus of fifteen years, Japan’s methamphetamine nia. During 1990, domestically manufactured ice abuse began to increase again and continued at relatively elevated levels through the mid-1980s. began to be supplied to distributors in Hawaii and That epidemic was associated with illicit produc- seven clandestine ice laboratories were seized na- tion of the drug and trafficking by criminal organi- tionwide, six of them in California. This domestic zations—Yakuza and Boryokudan. The downturn production was compensating for a disruption of in recent years is being attributed to the implemen- the major Asian trafficking organizations smugg- tation of a stimulant-abuse prevention campaign ling ice from South Korea. that was begun in 1979. 120 AMPHETAMINE EPIDEMICS

Sweden. Amphetamines also have been at the CONCLUSION forefront of the drug-abuse problem in Sweden In the United States, the overall magnitude of since the 1930s. According to a 1988 report from use and abuse of amphetamines, including meth- the Swedish Council forInformationon Alcohol amphetamine, is relatively minor compared with and Other Drugs, abuse of amphetamines increased the prevalence of other illicit drugs, such as mari- during the three decades following their introduc- juana and cocaine. The National Household Survey tion to the market as an over-the-counter (OTC) on Drug Abuse (NHSDA), a nationally representa- medication and their widespread promotion as a tive survey of the household population age 12 and treatment for a variety of health conditions. While older, estimates that by 1998, 4.4 percent had ever the prevalence of heavy, dysfunctional use during used stimulants—including amphetamines, meth- that era has been disputed, amphetamine abuse amphetamine, and other prescription stimulants continues as a predominant problem in Sweden, (U.S. Department of Health and Human Services, especially among injection drug users. 1998). The NHSDA also estimated that 0.7 percent of the household population had used stimulants Thailand. Thailand had a 1998 population of during 1998 and 0.3 percent had used them during just over60 million, with low unemployment (3.5 the month prior to the interview. These numbers percent) and high literacy (94 percent). A major are in contrast to 35.8 percent estimated to have transit route for heroin from Laos and Burma, the ever used any illicit drug, 33.0 percent who re- country began experiencing a large shift in drug use ported any use of marijuana, and 10.6 percent who patterns during the 1990s. The drug began to be had ever used cocaine. However, data from the more widely used in the late 1980s, as the synthesis national HIGH SCHOOL SENIOR SURVEY, Monitoring from ephedrine came into practice. In the late The Future, indicate that among twelfth graders 1990s, production had changed from being cen- surveyed each year since 1975, annual and past- tralized in the hands of large crime syndicates run- 30-day use of stimulants such as methampheta- ning superlabs, to being shared with a multitude of mines have always been substantially higherthan small mom-and-pop labs—a pattern opposite that use of cocaine. These differences in magnitude in of the United States. Substantial increases have no way diminish the impact of the health conse- been seen in a number of use indicators. Figure 3 quences and social problems, both at the individual and at the community level, resulting from am- shows changes in the percentage of patients report- phetamine epidemics in the United States and in ing drug use in the thirty days prior to admission othercountries. for methamphetamine and heroin during the pe- In the United States, abuse of amphetamine and riod 1993 to 1997. methamphetamine dates back to the early part of the twentieth century. During the ensuing years, abuse of amphetamine and methamphetamine has become endemic throughout this country, with fo- cal problematic areas. Survey data and ethno- graphic information indicate a concentration of abuse in cities along the West Coast and in Hawaii that has been moving east and north across the United States. Historically, the typical composite methamphetamine userwas white, male, young adult, and with a low to middle income, but this picture may be changing. As was experienced in the Hawaiian ‘‘ice’’ outbreak, and as seen recently in California, methamphetamine users can include di- verse ethnic and socioeconomic groups. Metham- phetamine is reported by the Drug Enforcement Figure 3 Administration (DEA) to be the most common Methamphetamine Abuse in Japan, 1951–1985 product of illicit drug laboratories in the United AMPHETAMINE EPIDEMICS 121

States. With extensive production and distribution KALANT O. J., ED. (1973). The amphetamines: toxicity systems in place—and potentially serious medical, and addiction. 2nd edition Toronto: University of psychological, and social consequence to abuse— Toronto Press. these drugs continue to pose a significant public KLEE, H., ED. (1997). Amphetamine misuse: Interna- health threat. tional perspectives on current trends. Singapore: The literature suggests that abuse of amphet- Harwood Academic Publishers/Gordon and Breach amines has been and remains an endemic problem Science Publishers. among diverse populations in countries throughout MILLER, M. A., AND KOZEL, N. J., EDS. (1991). Metham- the world, at times reaching epidemic proportion. phetamine abuse: epidemiologic issues and consider- Measurement of the scope of drug abuse, trend ations. NIDA Research Monographs, 115. Rockville, analysis, and valid cross-cultural comparisons are MD:U.S.DepartmentofHealthandHuman fraught with difficulties. However, based on his- Services. tory, it is clear that the prevention of future epi- MONROE, R. R., AND DRELL, H. H. (1947). Oral use of demics requires the implementation of an effective stimulants obtained from inhalers. Journal of the program of international drug-abuse surveillance, American Medical Association 135: 909-14. communication, and early intervention. MORGAN, J. P. (1979). The clinical pharmacology of am- phetamine. In D. E. Smith, D. R. Wesson, et al. (eds.), (SEE ALSO: Epidemics of Drug Abuse; Ethnicity and Amphetamine Use, Misuse and Abuse (pp. 3-10). Bos- Drugs) ton: G.K. Hall. MORGAN, P. (1994). Researching Hidden Communities: BIBLIOGRAPHY A Quantitative Comparative Study of Methampheta- mine Use in Three Sites. In National Institute on Drug AMA COUNCIL ON DRUGS. (1963). New drugs and devel- Abuse, Epidemiologic Trends in Drug Abuse, Decem- opments in therapeutics. Journal of the American ber 1993 (pp.402-10). Rockville, MD: U.S. Depart- Medical Association 183: 362-63. ment of Health and Human Services. ANDERSON, R., AND FLYNN, N. (1997). The Methamphe- PITTELL, S. M., AND HOFER, R. (1970). The transition to tamine-HIV connection in northern California. In H. Klee (Ed.), Amphetamine misuse: International per- amphetamine abuse. In E. H. Ellinwood, and S. spectives on current trend. (pp.181-96). Singapore: Cohen (eds.), Current concepts on amphetamine Harwood Academic Publishers/Gordon and Breach abuse. Washington, DC: U.S. Government Printing Science Publishers. Office. PUDER, K. S., KAGAN, D. V., AND MORGAN, J. P. (1988). BEEBE, D. K., AND WALLEY, E. (1995). Smokable meth- amphetamine ‘‘ice’’: An old drug in a different form. Illicit methamphetamine: analysis, synthesis, and American Family Physician 51: 449-53. availability. Am J Drug Alcohol Abuse 14: 463-73. OBSON AND RUCE CHAIYAWONG, A. (1999). Methamphetamine and other R , P., B , M. (1997). A comparison of drug abuse patterns in Thailand. In National Institute ‘visible’ and ‘invisible’ users of amphetamine, cocaine on Drug Abuse, International Epidemiology Work- and heroin: two distinct populations? Addiction 92: groupon Drug Abuse . Rockville, MD: NIH Publica- 1729-36. tion 00-4530. U.S. Government Printing Office. SENAY, E. C. (1991). Drug abuse and health: a global DERLET, R. W., AND HEISCHOBER, B. (1990). Metham- perspective. Drug Safety 6: 1-65. phetamine: stimulant of the 1990s? West J Med 153: U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES,SUB- 625-28. STANCE ABUSE AND MENTAL HEALTH SERVICES ELLINWOOD, E. H. (1969). Amphetamine psychosis: a ADMINISTRATION,OFFICE OF APPLIED STUDIES. (1999). multidimensional process. Seminars in Psychiatry 1: Summary of Findings from the 1998 National House- 208-26. hold Survey on Drug Abuse. Web page, [accessed 21 FRANK, R. S. (1983). The clandestine drug laboratory August 2000]. Available at http://www.samhsa.gov/ situation in the United States. J Forensic Sciences 28: OAS/NHSDA/98SummHtml/TOC.htm. 18-31. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES,SUB- GRINSPOON, L., AND HEDBLOM, P. (1975). The speed STANCE ABUSE AND MENTAL HEALTH SERVICES culture: amphetamine use and abuse in America. ADMINISTRATION,OFFICE OF APPLIED STUDIES. (1999). Cambridge, MA: Harvard University Press. Treatment Episode Data Set (TEDS) 1992-1997. 122 AMSTERDAM, DRUG USE IN

Web page, [accessed 20 August 2000]. Available at particular, modulating DOPAMINE RECEPTORS and http://wwwdasis.samhsa.gov/teds97/teds97.htm. concentrations. The result of this manipulation is WEAVER, R. (1998). Intelligence: Trafficking Organiza- that the animals will increase or decrease their rate tions. In Office of National Drug Control Policy, The of administration of drugs. Thus, the amygdala National Methamphetamine Drug Conference Pro- makes a significant contribution to the study of ceedings (pp. 29-34). Washington, D.C.: Office of cocaine-taking behavior. National Drug Control Policy. The amygdala also contributes to the rewarding WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- properties of ETHANOL. Studies have examined the ICY. (1998). 1998 National Drug Control Policy. effect of altering neurotransmission in the amyg- Washington, DC: Office of National Drug Control dala on ethanol self-administration. Similar to the Policy. findings reported for cocaine, modulation of the amygdala causes animals to change theirrateof MARISSA MILLER ethanol administration. NICHOLAS KOZEL The amygdala is also involved in the effects of REVISED BY MARTIN H. LEAMON chronic drug exposure on the brain. Small changes in neurochemicals in the extended amygdala sug- gest that it may be mediating chronic drug action. AMSTERDAM, DRUG USE IN See These studies indicate that changes in the amyg- Netherlands, Drug Use in dala after long-term drug exposure may contribute to relapse. Together, the amygdala and nucleus accumbens AMYGDALA The amygdala, a region of the may be the main brain regions that underlie the brain, is part of the limbic system. The limbic sys- brain changes associated with drug (particularly tem is a group of similar brain structures related cocaine) addiction. functionally. They provide the basis for emotion STEPHANIE DALLVECCHIA-ADAMS and motivated behaviors including REWARD-re- lated events. The amygdala is located in the tempo- ral lobe and consists of several different parts. It AMYL NITRATE See Inhalants plays a role in various brain functions including epilepsy, emotion, learning and memory, and drug abuse. In particular, the role of the extended amygdala AMYTAL See Amobarbital has become an area of recent investigation. The extended amygdala refers to a group of brain struc- tures that extend from the amygdala to the NU- ANABOLIC STEROIDS Anabolic steroids CLEUS ACCUMBENS; these brain regions are believed are synthetic versions of the naturally occurring to participate in the general reward circuitry of the male sex hormone, testosterone. They are more brain. The MESOLIMBIC DOPAMINE SYSTEM sends properly called anabolic-androgenic steroids projections to the amygdala; these axons arise from (AASs), because they have both bodybuilding (an- the dopamine cells in the VENTRAL TEGMENTAL abolic) effects and masculinizing (androgenic) ef- AREA. fects. The masculinizing effects of testosterone The amygdala has long been established as an cause male characteristics to appear during pu- important area mediating stimulus-reward associa- berty in boys, such as enlargement of the penis, hair tions. This behavioris believed to play an impor- growth on the face and pubic area, muscular devel- tant role in the seeking and using of drugs of abuse, opment, and deepened voice. Females also produce especially COCAINE. An informative way to study natural testosterone, but ordinarily in much drug abuse in animal models is through the SELF- smalleramounts than males. ADMINISTRATION of drugs that are abused by hu- AASs are sometimes referred to simply as ste- mans. Rats can be trained to self-administer co- roids. Steroid means only that a substance either caine, and then the experimenter can interfere with resembles cholesterol in its chemical structure or is the neurochemical transmission in the amygdala in made from cholesterol in the body. Thus, AASs are ANABOLIC STEROIDS 123 one kind of steroid. (They are not to be confused as a pill or injection (it is subject to rapid break- with an entirely different group of steroids called down in the body). Bodybuilders may have begun corticosteroids—of which prednisone and cortisone using AASs to build muscle size and strength as are examples—which are commonly used to treat early as the 1940s. Olympic athletes started to use illnesses such as arthritis, colitis, and asthma. In these drugs in the 1950s. Most of this use went contrast to anabolic steroids, corticosteroids can undetected, however, because the technology of cause muscle tissue to be wasted.) AASs are also drug testing did not allow reliable detection of referred to as ergogenic drugs, which means per- AASs in the urine until the 1976 Olympic Games. formance-enhancing. Street or slang terms for Even so, anabolic steroids did not become a house- AASs include ‘‘roids’’ and ‘‘juice.’’ hold word until Canadian sprinter, Ben Johnson, Soon after testosterone was first isolated and tested positive forAASs at the Seoul Olympic synthesized in the laboratory in 1935, a number of Games in 1988. In the same year, a study reported synthetics were created to be used as medicines. that 6.6 percent of American male high school The synthetic forms were developed because natu- seniors had tried AASs. This study made it clear ral testosterone did not work very long when given that elite athletes were not the only ones taking 124 ANABOLIC STEROIDS these drugs. By 1991, AASs were added by federal law to the list of Schedule III of the Controlled Substances Act. Schedule III Controlled Substances are recognized to have value as prescribed medi- cines, but also have a potential forabuse that may lead to eitherlow to moderatephysical dependence orhigh psychological dependence. Table 1 lists the names of some AASs that bodybuilders have used. Hundreds of AASs have been synthesized, and more comprehensive lists exist (Wright & Cowart, Figure 1 1990; Yesalis, 2000). Testosterone Molecule. Two naturally occurring steroids, dehy- The numbers refer to carbon atoms, and the droepiandrosterone (DHEA) and androstenedione, hydrogen and hydroxyl groups are at carbon 17. are used by the body to make testosterone and estrogen (Corrigan, 1999). The benefits and ad- MEDICAL AND NONMEDICAL USES verse effects of synthetic DHEA and androstenedi- AASs are prescribed by physicians to treat a one are mostly unknown, but they are commonly variety of medical conditions (Bagatell & Bremner, believed to have anabolic and androgenic effects. 1996). The most accepted use is fortreatingboys Unlike other AASs, DHEA and androstenedione are and men unable to produce normal levels of their neither regulated by the Food and Drug Adminis- own testosterone, a condition known as testoster- tration nor listed as controlled substances in the one deficiency orhypogonadism. AASs arealso United States. DHEA has been sold over-the-coun- used to treat a rare skin condition called hereditary teras a nutritionalsupplement in the United States angioedema, certain forms of anemia (deficiency of since 1994, even though the International Olympic red blood cells), advanced breast cancer, and endo- Committee, many U.S. sports organizations, and metriosis (a painful condition in females in which some countries such as Australia ban it. tissue usually found only in the uterus develops in other body parts). AASs are also combined with GENERAL CHEMICAL STRUCTURE female hormones to treat distressing symptoms that Testosterone has a four-ring structure composed can accompany menopause. Experimentally, AASs of nineteen carbon atoms. Accordingly, the carbon have been used to treat a condition in which bone atoms are labeled by number from one to nineteen loss occurs (osteoporosis), to treat impotency and (see Figure 1). Many synthetic forms of testoster- low sexual desire, and as a male birth control pill. one are made by adding either an alkyl group or an In addition, AASs have been used in the treatment ester to the seventeen-carbon atom. An alkyl group of Acquired Immune Deficiency Syndrome (AIDS) is a chain of carbon and hydrogen atoms. An ester to stimulate appetite, weight gain, strength, and is formed by reacting an acidic chain of carbon and improvements in mood. Most of these medical uses hydrogen atoms to the -OH group on the seven- are uncommon, either because the conditions are teen-carbon atom. In general, when an alkyl group rare (such as angioedema) or because other treat- is added to the seventeen-carbon atom, the result- ments are preferred (such as erythropoeitin for ing drug can be taken as a pill; however, these anemia). Nevertheless, AASs are important medi- so-called seventeen-alkylated AASs are relatively cines to have available. toxic to the liver and are more likely to cause nega- Nonmedically, AASs are used to enhance athlet- tive effects on cholesterol levels. By contrast, when ic performance, physical appearance, and fighting an ester is formed at the seventeen-carbon atom, an ability. Since society endows people who look phys- injectable form of testosterone is created that is less ically fit and attractive with many benefits and toxic to the liverand cholesterollevels. OtherAASs recognition, some individuals see AASs as a means are created by making modifications at other car- to those benefits. Three groups of AAS users have bon atoms. been described: ANABOLIC STEROIDS 125

However, there are serious limitations to how these studies were done and what they could show. In general, most researchers agree that AASs can work in some individuals to enhance muscle size and strength when combined with a proper exercise program and diet (Bagatell & Brenner, 1996; Bhasin et al., 1996). By contrast, AASs probably do not improve performance of aerobic or endurance activities (Yesalis, 2000).

CONSEQUENCES OF USE AASs have been associated with a variety of undesirable effects. The most severe consequence attributed to their use is death. One study of mice given AASs revealed a shortened life span (Bronson & Matherne, 1997). In humans, the distinction be- tween fatalities that occuramong relativelyhealthy athletes who use AASs and patients with illnesses (such as anemia) who are prescribed AASs is im- portant, because ill patients are already at a higher risk for an early death. Nevertheless, reported Most illegal anabolic steroids are sold at gyms, deaths in nonmedical steroid users (such as athletes competitions, and through mail order operations; and aesthetes) have occurred from liver disease, some of those commonly encountered are cancer, heart attacks, strokes, and suicide (Yesalis, pictured. (Drug Enforcement Administration) 2000; Pope & Brower, 2000). Clearly, anyone us- ing AASs should have theirhealth monitoredby a 1. The athlete group aims to win at any cost. The physician. athlete also believes, sometimes correctly, that Psychiatric Effects. Anotherserious,life- the competition is using AASs. The anticipated threatening consequence has been violent aggres- rewards to the athlete are the glory of victory, sion toward other people. Both the medical litera- social recognition and popularity, and financial ture and newspapers contain reports of previously incentives (college scholarships, major league mild-mannered individuals who committed mur- contracts). derand lesserassaults while taking AASs (Thiblin 2. The aesthete group aims to create a beautiful et al., 1997). Although reports of severe violence body, as if to make the body into a work of art. generate both alarm and widespread attention, the Aesthetes may be competitive bodybuilders, or total number of such reports is small. Moreover, the aspiring models, actors, or dancers. They put effects of AASs on violent behaviorvarywidely theirbodies on display to obtain admirationand depending on the social circumstances and the financial rewards. characteristics of the individual. Nevertheless, most 3. This group of AAS users seeks to enhance their but not all studies in humans have found that high ability to fight orintimidate. They include body doses of AASs increase feelings and thoughts of guards, security guards, prison guards, police, aggressiveness (Yesalis & Cowart, 1998). Although soldiers, bouncers, and gang members. These an increase in feelings and thoughts of violence people depend on fighting for their very sur- does not always lead to violent behavior, it can be vival. very distressing to the individual and to those around him or her. ‘‘Roid rage’’ is a slang expres- Whether AASs actually work to improve per- sion used to describe the aggressive feelings, formance and appearance has been debated. In- thoughts, and behaviors of AAS users. variably, users believe AASs do work, but some Otherpsychiatriceffects of AASs include mood scientific studies have failed to show an effect. swings and psychosis (Pope & Brower, 2000). AAS 126 ANABOLIC STEROIDS users commonly report that they feel energetic, liver. Death can occur from bleeding if one of the confident, and even euphoric during a cycle of use. sacs ruptures. Finally, liver tumors may occur in 1 They may have a decreased need for sleep or find it to 3 percent of individuals (including athletes) us- difficult to sleep because of theirhigh energylevel. ing high doses of the seventeen-alkylated AASs for Such feelings may give way to feeling down, de- more than two years (Yesalis, 2000). Rare cases of pressed, irritable, and tired between cycles of use. liver tumors have been reported with other types of With continued use of high AAS doses, moods may AASs as well. Some of the tumors are cancerous, shift suddenly, so that the userfeels on top of the and although more than half of the tumors disap- world one moment, irritable and aggressive the peared when AASs were stopped, others resulted in next, and then depressed or nervous. The appetite death. may also swing widely with cycles of use (Wright & Potential to Affect the Heart. AASs can cause Cowart, 1990). During a cycle on AASs, huge changes in cholesterol levels (Yesalis, 2000). Low quantities of food may be consumed to support the amounts of a certain kind of cholesterol (high-den- body’s requirements for muscle growth and energy. sity lipoprotein cholesterol) in the blood are known During the ‘‘off cycles,’’ appetite may diminish. to increase the risk of heart attacks. AASs, espe- The term ‘‘psychosis’’ means that a person can- cially the seventeen-alkylated ones, cause a lower- not distinguish between what is real and what is ing of this so-called good form of cholesterol. When not. Forexample, a personmay believe that other AASs are stopped, however, cholesterol levels re- people intend harm when no real threat exists; or a turn to normal. Another risk factor for heart at- person may believe that an impossible, life-threat- tacks and strokes is high blood pressure. Studies ening stunt can be performed with no problem. have shown that AASs can cause small increases in Such false beliefs are called delusions. The psy- blood pressure, which return to normal when AASs chotic person may also experience hallucinations, are stopped. As a result of strenuous exercise, many such as hearing a voice that is not there. Fortu- athletes develop an enlarged heart that is not harm- nately, most psychiatric effects of AASs tend to ful. Some, but not all studies, suggest that AAS disappearsoon afterAASs arestopped, although a users can develop a harmful enlargement of the depressed mood may last for several months. Obvi- heart. As noted previously, heart attacks and ously, when suicides, homicides, orlegal conse- strokes have been reported in AAS users, but stud- quences from assault have occurred, they cannot be ies are needed to determine if AAS users have a reversed simply by stopping one’s use of AASs. higher risk of heart attacks and strokes than non- Effects on the Liver. AASs can affect the liver users (Yesalis, 2000). in various ways, but the seventeen-alkylated AASs Sexual Side Effects. AASs can alterthe levels are more toxic to the liver than other AASs. Most of several sex-related hormones in the body, result- commonly, AASs cause the liver to release extra ing in many adverse effects (Wright & Cowart, amounts of enzymes into the bloodstream that can 1990; Yesalis & Cowart, 1998). In males, the pros- be easily measured by a blood test. The liver en- tate gland can enlarge, making it difficult to zymes usually return to normal levels when AASs urinate; the testes shrink; and sterility can occur. are stopped. The liver also releases a substance The effects on the prostate, the testes, and sterility called bilirubin, which in high amounts can cause reverse when AASs are stopped; however, at least the skin and eyes to turn yellow (a condition called one case of prostate cancer has been reported, an jaundice). As many as 17 percent of patients exception to reversibility. Males can also develop treated with the seventeen-alkylated AASs develop enlarged breast tissue from taking AASs, an effect jaundice (Yesalis, 2000). Nonmedical AAS users medically termed ‘‘gynecomastia’’ (it is referred to can also develop jaundice. Although untreated by male users as ‘‘bitch tits’’). Gynecomastia occurs jaundice can be dangerous and even fatal, jaundice because testosterone is chemically changed in the usually disappears within several weeks of stopping body to the female hormone, estrogen. Thus, the AASs. Jaundice can also signal otherdangerous male user experiences higher amounts of estrogen conditions of the liver, such as hepatitis, so a physi- than normal. Painful lumps in the male breast may cian should always treat it. Another condition that persist after stopping AASs, and they sometimes occurs among patients treated with AASs is peliosis require surgical removal. Females, however, may hepatis, in which little sacs of blood form in the undergo shrinkage of their breasts, as a response to ANABOLIC STEROIDS 127 higher amounts of male hormone than normal. Steroid users commonly take other drugs, each Menstrual periods become irregular and sterility with theirown risks,to manage the unpleasant side can occurin females as well. Deepened voice and an effects of steroids, to increase the body-building enlarged clitoris are effects in females, which do not effects, and/orto avoid detection by urinetesting always reverse after stopping AASs. Women may (Wright & Cowart, 1990). For example, estrogen also develop excessive hairgrowthin typically mas- blockers, such as tamoxifen or clomiphene, are culine patterns, such as on the chest and face. taken to prevent breast enlargement. Water pills Finally, both males and females may experience (diuretics) are taken both to dilute the urine prior increases and decreases in their desire for sex. to drug testing and to eliminate fluid retention so Other Effects. In children of both sexes before that muscles will look more defined. Human chori- the onset of puberty, AASs can initiate the charac- onic gonadotropin (HCG) is an injectable, non- teristics of male puberty and cause the bones to steroidal hormone that stimulates the testicles to stop growing prematurely. The latter effect can produce more testosterone and to prevent them result in shorter adult heights than would otherwise from shrinking. Human growth hormone is another occur. AASs can cause premature baldness in some nonsteroidal hormone that is taken to increase individuals, and it can cause acne. The acne is muscle and body size. reversible with cessation of AASs. Other possible Addictive Potential. As with otherdrugsof effects include small increases in the number of red abuse, dependence on AASs occurs when a user blood cells, worsening of a condition called sleep reports several of the following symptoms: Inability apnea (in which afflicted persons stop breathing for to stop or cut down use, taking more drugs than short intervals during sleep), and worsening of intended, continued use despite having negative effects, tolerance, and withdrawal. ‘‘Tolerance’’ re- muscle twitches (known as tics) in those who are fers to needing more of a drug to get the same effect predisposed. that was previously obtained with smaller doses, or Patterns of Illicit Use. AASs are commonly of having diminished effects with the same dose. In smuggled from countries where they are obtained terms of the anabolic effects, tolerance was demon- over-the-counter without a prescription, and then strated in animals in the 1950s. In recent studies, sold illegally in the United States. Dealers and users 12 to 18 percent of nonmedical AAS users reported typically connect in weight-lifting gyms. Users re- tolerance (Yesalis, 2000; Copeland et al., 2000). port that AASs are relatively easy to obtain. Whether tolerance develops to the mood-altering Steroids are taken as pills, through skin patches, effects of AASs is unknown. Withdrawal refers to and by injection (Bagatell & Bremner, 1996). In- the uncomfortable effects users experience when jection occurs into large muscle groups (buttocks, they stop taking AASs. As noted previously, many thigh, orshoulder)orunderthe skin, but not into of the undesirable effects reverse when AASs are veins. Cases of acquired immune deficiency syn- stopped, however, others can begin—such as de- drome (AIDS) have been reported in steroid users pressed mood, fatigue, loss of appetite, difficulty due to needle sharing. Steroids are often taken in sleeping, restlessness, decreased sex drive, head- cycles of six to twelve weeks on the drugs, followed aches, muscle aches, and a desire for more AASs by six to twelve weeks off. At the beginning of a (Copeland et al., 2000). The depression can be- cycle, small doses are taken with the intent to build come so severe that suicidal thoughts occur. The to larger doses, which are then tapered at the end of risk of suicide described previously is thought to be a cycle. Illicit users typically consume ten to one highest during the withdrawal period. hundred times the amounts ordinarily prescribed Studies indicate that between 14 and 57 percent for medical purposes, requiring them to combine or of nonmedical AAS users develop dependence on ‘‘stack’’ multiple steroid drugs. The actual dose AASs (Yesalis, 2000), and rare cases have been cannot always be determined, however, because reported in women (Copeland et al., 2000). These illicit steroids may contain both falsely labeled and studies support the addition of AASs to the list of veterinary preparations. (Drugs purchased on the Schedule III controlled substances. Nevertheless, illicit market do not always contain what the labels AASs may differ from other drugs of abuse in indicate, and law-enforcement officials have several ways. First, neither physical nor psycholog- confiscated vials contaminated with bacteria.) ical dependence on AASs has been reported to oc- 128 ANALGESIC cur when AASs are prescribed for treating medical Moreover, some individuals may develop depen- conditions. This differentiates the AASs from the dence on AASs, making it difficult forthem to stop opioid pain killers and the sedative-hypnotics. Sec- using. Stopping use can also produce distressing ond, dependence may develop primarily to the withdrawal symptoms, the worst of which is suici- muscle-altering effects of AASs, rather than the dal depression. Finally, studies of the long-term mood-altering effects. Some researchers have ques- effects of using AASs are lacking, so safety cannot tioned whetherAASs producedependence at all, be assumed with the high-dose use of these drugs. because most definitions of dependence require that drugs be taken primarily for their mood-al- BIBLIOGRAPHY tering effects. Third, AAS users appear more preoc- cupied with theirbodies and how they look than do BAGATELL, C. J., and BREMMER, W. J. (1996). Drug ther- users of other drugs of dependence. apy: Androgens in men—uses and abuses. New En- gland Journal of Medicine, 334, 707-714. SUMMARY BHASIN,S.,ET AL. (1996). The effects of su- praphysiological doses of testosterone on muscle size The anabolic-androgenic steroids are related to and strength in normal men. New England Journal of the male sex hormone, testosterone. They have Medicine, 335, 1-7. both masculinizing and bodybuilding effects. AASs BRONSON, F. H., and MATHERNE, C. M. (1997). Exposure are useful to treat a variety of mostly uncommon to anabolic-androgenic steroids shortens life span of medical conditions. They are sometimes used for male mice. Medicine and Science in Sports and Exer- the nonmedical purposes of enhancing athletic per- cise, 29, 615-619. formance and physical appearance. Most research- COPELAND, J., PETERS, R., and DILLON, P. (2000). Ana- ers agree with users that AASs can increase muscle bolic-androgenic steroid use disorders among a sam- size and strength in some individuals when com- ple of Australian competitive and recreational users. bined with a proper exercise program and diet. Drug and Alcohol Dependence, 60, 91-96. Many are also concerned about the potential for CORRIGAN, A. B. (1999). Dehydroepiandrosterone and harmful effects with AASs, especially when the pat- sport. Medical Journal of Australia, 171(4), 206-208. terns of illicit use are considered. Drugs obtained POPE, JR., H. G., and BROWER, K. J. (2000). Anabolic- on the illicit market may be contaminated, falsely androgenic steroid abuse. In B. J. Sadock and V. A. labeled, ormay contain substances not approved Sadock (Eds.), Comprehensive textbook of psychiatry for human use. Multiple steroid and nonsteroidal (pp. 1085-1095). Philadelphia: Lippincott Williams drugs are combined, and AAS doses may exceed & Wilkins. therapeutic doses by ten to one hundred times. Al- WRIGHT, J. E., and COWART, V. S. (1990). Anabolic ste- though the seventeen-alkylated AASs are com- roids: altered states. Carmel, IN: Benchmark Press. monly used because pills are more convenient than THIBLIN, I., KRISTIANSSON, M., and RAJS, J. (1997). Ana- injections, they are more toxic to the liver and bolic androgenic steroids and behavioural patterns cholesterol levels than the injectable testosterone among violent offenders. Journal of Forensic Psychia- esters. Nevertheless, injections carry their own risks try, 8, 299-310. from improper injection techniques to dirty and YESALIS, C. E., ED. (2000). Anabolic steroids in exercise shared needles. and sport. Champaign, IL: Human Kinetics. The most serious side effects of AASs seem rela- YESALIS, C. E., and COWART, V. S. (1998). The steroids tively uncommon, such as deaths ornear-deaths game. Champaign, IL: Human Kinetics. from liver disease, heart attacks, strokes, cancer, suicide, and homicidal aggression. Most other side KIRK J. BROWER effects appear to be reversible when AASs are stopped, such as altered cholesterol levels, some livereffects, most psychiatriceffects, testicular ANALGESIC Analgesics are drugs used to shrinkage, sterility, high blood pressure, and acne. control pain without producing anesthesia or loss of Exceptions to reversibility include lumps in the consciousness. Analgesics vary in terms of their male breast, deepened voice and enlarged clitoris in class, chemical composition, and strength. Mild an- females, and cessation of bone growth in children. algesics, such as aspirin (e.g., Bayer, Bufferin), ace- ANORECTIC 129 tominophen (e.g., Tylenol), and ibuprofen (e.g., Anhedonia may be idiopathic (of unknown Advil), work throughout the body. More potent cause), may occur as a side effect of certain drugs agents, including the OPIATES codeine and mor- (forexample, the NEUROLEPTICS), which act as do- phine, work within the central nervous system (the pamine-receptor antagonists, or may be an aspect brain and spinal cord). The availability of the more of certain psychiatric disorders, such as depression. potent analgesics is more carefully regulated than It is conjectured that a state of anhedonia may that of aspirin and other similar analgesic/anti- occur during the ‘‘crash’’ that follows a prolonged inflammatory agents that are sold in drugstores bout of drug self-administration, particularly CO- OVER-THE-COUNTER. The more potent opiate CAINE oramphetamine-like stimulants. agents typically require prescriptions to be filled by pharmacists. BIBLIOGRAPHY An important aspect of analgesics is that they work selectively on pain, but not on other types of DACKIS, C. A., and GOLD, M. S. (1985). New concepts in sensation, such as touch. In this regard, they are cocaine addiction: The dopamine depletion hypothe- easily distinguished from anesthetics which block sis. Neuroscience Biobehavioral Review, 9, 469–477. all sensation. Local anesthetics, such as those used WISE, R. A. (1985). The anhedonia hypothesis: Mark III. in dental work, make an area completely numb for Behavior and Brain Science, 8, 178–186. several hours. General anesthetics typically are WISE, R. A. (1982). Neuroleptics and operant behavior: used to render patients unconscious for surgery. The anhedonia hypothesis. Behavior and Brain Sci- ence, 5, 39–87. (SEE ALSO: Pain: Drugs Used in Treatment of ) ANTHONY PHILLIPS

BIBLIOGRAPHY

HARDMAN, J. G., ET AL.EDS. (1996). The Pharmacologi- ANIMAL RESEARCH See Research, Ani- cal Basis of Therapeutics, 9th ed. New York: mal Model McGraw-Hill. GAVRIL W. PASTERNAK ANORECTIC This term derives from Greek ,oregein, meaning ‘‘not to reach for’’; later ם a) ANESTHETIC See Inhalants anorektos) and it refers to a substance that reduces food intake. It came into use in English about 1900. Anorectic agents (also referred to as anorexics, an- ANGEL DUST See Phencyclidine (PCP); orexegenics, or appetite suppressants) fall into a Slang and Jargon number of categories according to the brain neuro- transmitter system through which they work. Central nervous system (CNS) stimulants that ANHEDONIA This term refers to a clinical act through the noradrenergic and dopaminergic condition in which a human oran experimental systems include COCAINE, amphetamine-like com- animal cannot experience positive emotional states pounds, mazindol, and phenylpropanalamine. Se- derived from obtaining a desired or biologically rotonergic compounds include fenfluramine, fluox- significant stimulus. Generally, certain stimuli etine, and sertraline. Several endogenous peptides serve as positive reinforcers in normal individuals (within the body) also have anorectic actions, in (e.g., food, water, the company of friends). ‘‘Posi- that they inhibit food intake—these include chole- tive reinforcement’’ is a descriptive term used by cystokinin, glucagon, and the bombesin-like behavioral scientists to denote an increase in the peptides. probability of a behavior that is contingent on the Not all agents that can suppress appetite are presentation of biologically significant stimuli, such medically approved for such use. For example, co- as food orwater. caine is approved only as a local anesthetic. 130 ANOREXIA

(SEE ALSO: Amphetamine) these persons became addicted, often without even TIMOTHY H. MORAN realizing it. They merely used the narcotic so stead- ily that they didn’t experience withdrawal. These addicts were typically white, lived in the country- side, continued to function satisfactorily at work or ANOREXIA This term means a ‘‘loss of ap- at home, could afford the cheap drugs they used, petite,’’ especially when prolonged, and came into and caused no trouble to anyone else. English in the 1620s from Latin usage, based on At the age of fourteen, Anslinger started working orexis [appetite]). Anorexia ם [Greek stems (a [no forthe Pennsylvania Railroadwhile taking high generally leads to loss of weight due to a of loss of school courses in his free hours. Without a high appetite; anorexia nervosa is an appetite disorder associated with severe weight loss. Eating disorders school diploma, he managed in 1913 to entera of this type and those associated with compulsive Pennsylvania State College two-year program in eating are, in some ways, behavioral equivalents of engineering and business management, while con- drug abuse. tinuing to work part-time for the railroad and also playing the piano forsilent movies. By 1915, he was a railroad detective, and one summer day he (SEE ALSO: Overeating and Other Excessive Behav- iors) had to assist an Italian railroad worker who had been beaten and left unconscious nearthe tracksby TIMOTHY H. MORAN an organized-crime gangster. In 1917, he volunteered to help the American effort in World War I and worked for the U.S. Army ANSLINGER, HARRY JACOB, AND U.S. as assistant to the Chief of Inspection of Equip- DRUG POLICY For almost a third of a century, ment. In 1918, Anslingerenteredthe U.S. diplo- from 1930 until 1962, one man, Harry Jacob matic service. His First post was Holland, where he Anslinger(1892–1975), had the dominant rolein was assigned as liaison to deposed KaiserWilhelm’s shaping and enforcing U.S. policy about the use of entourage; Wilhelm II was born in 1859, became drugs—other than alcohol and tobacco. Under- Emperor (Kaiser, that is Caesar) of Germany and standing his life and work is, therefore, a necessity King of Prussia in 1888 upon the death of his for understanding the evolution of federal drug pol- father, Frederick III, reigned as emperor and king icies through the end of the twentieth century. until 1918 when he fled to asylum in Holland, Anslinger was Commissioner of the U.S. Treasury where he lived a comfortable life as a country gen- Department Bureau of Narcotics from 1930 to tleman until his death in 1940. Anslinger’s assign- 1962, chief U.S. delegate to international drug ment in Holland lasted three years, and then in the agencies until 1970, and a leading proponent of summer of 1921, he was sent to Hamburg, Ger- repressive antidrug measures in the United many. In 1923 he was reassigned from Germany to States—and worldwide. Venezuela for a frustrating three-year stint as U.S. Anslingerwas bornin Altoona, Pennsylvania, vice-consul in La Guaira, the port for the capital May 20, 1892, the eighth of nine children in a Swiss city of Caracas (McWilliams, 1990). immigrant family. At the age of twelve, he was sent by a neighborto pick up a package of morphine THE FEDERAL BUREAU from the drugstore. Anslinger said that he never OF NARCOTICS forgot the screams of agony shrieked by the neigh- bor’s wife because of her withdrawal symptoms, or In 1920, the Prohibition Amendment had made how quickly she felt good upon getting a dose, or the importing, manufacture, or sale of alcoholic how easy it was fora twelve-year-oldboy to buy beverages illegal throughout the United States and morphine. Until the Harrison Act was passed in its possessions (a slight amount was permitted for 1914—about a decade afterthis incident which sacramental and medicinal purposes). Of course, haunted Anslinger for the rest of his life—there was illegal liquorbecame an instant success. In 1926, simply no federal law against selling or using nar- Anslingerbecame U.S. consul in Nassau in the cotics. They were inexpensive. Most persons started British Bahamas, which were then a principal loca- taking them as perfectly legal painkillers. A few of tion from which illegal alcohol was smuggled into ANSLINGER, HARRY JACOB, AND U.S. DRUG POLICY 131 the United States. Consul Anslingerwas quickly career), so they were ‘‘infectious’’ in the commu- recognized for his effective work in persuading the nity. British authorities to cooperate in curbing the flow Sometimes the Bureau of Narcotics warned that of intoxicating beverages. The Volstead Act (1919) an entire generation of American youth, including and the Harrison Act (1914), aimed respectively at young children, was imperiled; then, suddenly, enforcing Prohibition and controlling the distribu- drugs would be revealed as responsible for a wave tion of narcotic drugs, were both tax measures, and of juvenile delinquency and forthe menace of hence came within the jurisdiction of the U.S. Trea- ‘‘young hoodlums.’’ The Bureau announced its en- sury Department. Treasury soon borrowed forcement success in terms of the total number of Anslinger from the Department of State to serve in years of sentences imposed on drug offenders annu- its Prohibition Bureau, which then enforced both ally (‘‘3,248 years, 10 months, 18 days’’ for 1933); acts. On July 1, 1930, three years before Prohibi- SEIZURES OF DRUGS were announced at STREET tion ended, the drug-regulation functions were VALUE, which grossly inflated their price. Because shifted to a new Bureau of Narcotics; Anslinger was formal systems to measure levels of drug abuse named acting commissionerafterothercandidates were lacking, drug statistics could be and were were disqualified by scandal. President Herbert C. manipulated—skyrocketing when Anslinger Hoover made Anslinger’s appointment permanent wanted support or appropriations, plummeting on September23, 1930. when he wanted credit and praise. Indeed, even before Anslinger became commissioner of narcotics REPRESSIVE POLICIES in 1930, enforcement activities had resulted in an Drug addiction, particularly genuine addiction increase in federal prisoners and had led Congress to the OPIATES, had already been demonized when to establish two U.S. Public Health Service Hospi- Anslingercame on the scene: Addicts had been tals (one in Kentucky, one in Texas)to treat ad- labeled dope fiends in the public mind, and the dicted inmates. They were authorized in January illicit traffic had been attributed first to sinister 1919, but it was 1935 before the first of the two German agents during World War I, then to ter- actually opened. However, the major thrust of U.S. rifying Chinese tongs (secret societies). Clinics, set policy was control of supply and punishment of up to relieve the plight of addicts who had been cut users. off from their supplies by providing them with maintenance doses of HEROIN, were curbed by a MARIJUANA TAX ACT OF 1937 series of U.S. Supreme Court rulings, interpreted During his tenure as commissioner, Anslinger by the Treasury Department to prohibit heroin dominated the enactment of U.S. narcotics laws. In maintenance as a form of medical treatment. The clinics were closed, and by 1925 doctors had the mid-1930s, to puff the menace his Bureau was stopped prescribing to addicts. A black market had combating, he turned his attention to MARIJUANA begun to flourish parallel to that in alcohol. (CANNABIS SATIVA [hemp]), used at the time by a Anslinger favored an extremely punitive ap- few Spanish Americans, Caribbean Blacks, and in proach from the outset. He cultivated members of such limited circles as jazz musicians. A number of Congress and other politicians, providing all who responsible studies of the effects of marijuana (such served his interests with material to portray them- as one by the Hemp Commission in British India in selves as fierce drug-fighters. He relentlessly op- 1895) and its more potent form, hashish, had pro- posed ‘‘education’’ about the realities of drug use— nounced it relatively harmless—but that gave on the ground that it would encourage ‘‘youthful Anslingerand a few othersensationalists of the day experimenters.’’ His Bureau sounded one alarm af- no pause. Shocking accounts of heinous crimes ter another: For example, drugs caused users to induced by marijuana began emanating from the commit violent crimes (it was solemnly claimed, for Bureau; the theory that pot smoking was a danger- a while, that dangerous criminals took drugs to ous ‘‘gateway’’ to otheraddictions gained credence; sharpen their vicious courage in committing and a Bureau-sponsored film, Reefer Madness, was crimes) and that addicts induced others to become produced to popularize Anslinger’s visions of the addicted (each addict made seven others in his hazards of drug use. Viewed from the end of the 132 ANSLINGER, HARRY JACOB, AND U.S. DRUG POLICY twentieth century, this film convulses audiences as Federal lawmakers were somewhat inhibited, in classic kitsch. Anslinger’s day, by the fact that federal drug laws Anslinger orchestrated the passage of a bill in were based solely on Congress’s power to tax. Congress to place marijuana in the same highly States could enact penalties based on theirgeneral restricted categories as HEROIN and COCAINE. Presi- powers to punish crime, and some even prescribed dent Franklin Delano Roosevelt signed the bill on punishment forthe merestatus of being an ad- August 2, 1937. The drug soon came to account for dict—until the Supreme Court ruled that practice more enforcement activity than any other. Honest out in Robinson v. California (1963). Little atten- research on its toxic properties was stifled because tion was paid to ‘‘treatment’’ or ‘‘rehabilitation’’; the Bureau would not license its use by researchers addicts should eithergive up theirwicked habits, outside of government. Although its therapeutic and their spreading of the vice to others, or they value in alleviating nausea due to chemotherapy for should be isolated from society by ‘‘quarantine’’ cancer patients or for treating glaucoma is gener- somewhere. Toward the end of Anslinger’s tenure, ally recognized, it remains in the most strictly pro- attention turned to ‘‘civil commitment,’’ which hibited ‘‘dangerous drug’’ classification in the year sometimes in effect made the quarantine a life- 2000. sentence, at least when lawmakers provided scanty resources for rehabilitating those thus committed.

BOGGS ACT OF 1951 INTERNATIONAL DRUG POLICIES In the late 1940s, Anslingerlaunched an attack By 1930, when Anslingerhad become commis- on judges, claiming that the drug problem was sioner, the patterns of international controls had caused by too-lenient sentences imposed on drug also been largely set, with the United States urging offenders. This was picked up by Anslinger disci- stringent repression and most of the rest of the ples in Congress and resulted in legislation—the world remaining indifferent or resistant. (The basic Boggs Act, signed by President Truman on Novem- Hague Convention of 1912 would neverhave been ber 2, 1951, and amended by the Narcotics Control ratified by more than a few nations had not the Act, signed by President Eisenhower on July 18, United States insisted upon its inclusion in the 1956. These acts introduced severe mandatory Paris peace treaties, which created the League of minimum punishments following conviction, at Nations in 1921.) Although the United States never least two, five, and ten years in prison for repeated joined the League of Nations, U.S. representatives convictions, without probation or parole, and with were always given a voice in drug matters—and a mandatory life sentence—or death, at a jury’s Anslinger dominated international deliberations, discretion—for sale of heroin by an adult to a leading the U.S. delegations first to the drug-con- minor. trol agencies of the League of Nations and then to those of the United Nations (U.N.), even afterhis UNIFORM STATE LAWS resignation as U.S. commissioner. Anslinger’s annual Bureau reports to the U.S. The Narcotics Bureau had similarly pressured Treasury were also submitted as his official annual state legislatures to enact extreme drug laws, pro- reports to the League Opium Advisory Committee mulgating a Uniform Narcotic Drug Act through and its successor, the U.N. Commission on Narcotic the National Conference of Commissioners on Uni- Drugs. He could thus push his views in the United form State Laws in 1932, inducing the passage of States as recommendations endorsed by the inter- tough marijuana measures after 1937, and promot- national bodies and, simultaneously, present them ing ‘‘Little Boggs Acts’’ in the late 1950s. Some of to the latteras official statements of U.S. positions. the latter laws contained penalties even more severe Anslinger participated in the drafting of the than the federal law, and it became common prac- 1931 Narcotics Limitation Convention, which im- tice for Anslinger’s men and local prosecutors to posed controls on the production of drugs for le- shuffle drug offenders into either state or federal gitimate medical uses; he pressed for the 1936 courts, depending on where they would receive the Convention forSuppression of Illicit Tr affic, harsher sentences. which sought to persuade other nations to impose ANSLINGER, HARRY JACOB, AND U.S. DRUG POLICY 133 criminal sanctions on domestic distribution and 1989), and George Bush (1989–1993) intensified consumption. When World War II isolated Ge- the drug war, justifying such efforts with argu- neva and ended most of the functions of the ments initially developed by Anslinger. Congress, League of Nations based there, he arranged for too, continues to be influenced by Anslinger’s moving the international drug agencies to New views. Congressional rhetoric and penal statutes York City, where they continued to operate. After are more extreme in the year 2000 than those of the the war, he was the leading proponent of a Single Boggs era. Marijuana is still lumped with heroin Convention, finally approved in 1961, after ten and cocaine, and new alarms—the discovery of a years of drafting. It incorporated much of the CRACK-baby epidemic and the menace of ‘‘ice’’— U.S. law-enforcement orientation, including obli- are periodically trumpeted. Anslinger created and gations upon members to control crops and pro- set a pattern of aggressive drug suppression— duction, to standardize identification and packag- contrary to the initial purposes of the Harrison ing, and to impose severe criminal penalties on Act—and kept drug prohibition alive when the al- drug offenders. cohol ban, Prohibition, which had truly been in- Although the Single Convention was widely rat- tended, was repealed in 1933. Anslinger may in- ified, many signatories ignored its requirements. deed have been, as critical Congressman John M. Lacking enforcement sanctions, it had small effect. Coffee labeled him in 1938, ‘‘farand away the Some of Anslinger’s more radical proposals, such as costliest man in the world.’’ including the promotion of opium addiction in the Anslinger has often been portrayed as a racist definition of genocide, which he charged to enemies who promoted and enforced extremely severe laws like the People’s Republic of China and the Soviet against marijuana once he realized that it was fa- Union, won no international support, but they vored by blacks (as HASHISH, its use had been legal played well at home. in Muslim Africa, and the Spanish permitted its importation to the Americas along with the slaves). It is a fact that Anslingerpreventedthe showing in THE ANSLINGER LEGACY the United States of a Canadian film Drug Addict on grounds that it would encourage youthful exper- It is often asserted that Anslinger was forced out imentation with drugs. Keys & Galliher (2000) of the Federal Bureau of Narcotics by the Kennedy claim: ‘‘The historical record paints a different pic- administration. Actually, he offered his resignation ture of Anslinger’s reasoning and demonstrates on his seventieth birthday, May 20, 1962, but was what was really unacceptable to Anslinger and the asked by the Kennedy administration to remain as FBN [Federal Bureau of Narcotics]. Major themes acting commissioneruntil a successorcould be of the film, addicts are recruited from all races and found. He did so, and was pleased when his closest classes. . . . To emphasize this the film shows afflu- aide, Deputy Commissioner Henry L. Giordano, ent whites injecting drugs. . . .’’ If Anslinger indeed was appointed by President Kennedy as the new objected to the film forshowing affluent white ad- commissionerand promisedthat he would make dicts, one would logically suspect that he would no changes in policies established by Anslinger. object to the following passage forthe same reason: Kennedy also permitted Anslinger to remain as ‘‘Many of the big dealers in the business of narcotic U.S. representative to the United Nations, a post agony move in the most elite circles in both Europe he continued to hold until 1970. Anslinger, for his and America. One notorious international traf- part, spoke highly of the fact that Attorney Gen- ficker, responsible for the addiction of millions, . . . eral Robert Kennedy, the president’s younger with his edge of accent and his impeccable groom- brother, went after top figures in the Mafia, not ing, melted easily into the Park Avenue cocktail merely jailing addicts. After the Kennedy assassi- hour.’’ But Anslinger did not object to this descrip- nation in 1963, President Johnson (president from tion of an affluent Parisian drug lord. Indeed, he is 1963 to 1969) moved much of the federal drug- its author(Anslinger,1961). control apparatus from Treasury to the Depart- In hindsight, it is easy to say that in 1930 Amer- ment of Justice. ica would have benefited from a three-pronged ap- Yet Anslinger’s perspective seems to live on. proach to narcotics: punishment for organized Presidents Nixon (1969–1974), Reagan (1981– crime when it imported drugs, medical treatment 134 ANTABUSE

foraddicts, and honest education about the facts of BIBLIOGRAPHY drug use. But we must remember that Anslinger ANSLINGER,HARRY JACOB, and WILLIAM F. TOMPKINS was basically a high school dropout. He never re- (1953). The traffic in narcotics. New York: Funk & ceived a high school diploma or a degree from a Wagnalls; reprint, New York: Arno Press, 1980. four-year undergraduate college. He saw the world ANSLINGER,HARRY JACOB, with WILL OURSLER (1961). in one-dimensional black-and-white terms. He had The murderers: The story of the narcotics gangs. New seen the pain that addiction caused his neighbor’s York: Farrar, Straus & Cudahy. wife. He had seen the evil of organized crime. He ANSLINGER,HARRY JACOB, and J. DENNIS GREGORY had seen decisive American military force in World (1964). The protectors: The heroic story of the nar- War I destroy the evil empires, as they were per- cotics agents, citizens, and officials in their unending, ceived, of Germany and Austria-Hungary. He had unsung battles against organized crime in America seen the Allies fight crime and exact severe punish- and abroad. New York: Farrar, Straus. ment. (He could not have foreseen in 1930 that the BRECHER,EDWARD M., ET AL. (1972). Licit and illicit severity of this punishment was misguided and drugs: The Consumers Union report on narcotics, would lead to Hitlerand WorldWarII.) He wanted stimulants, depressants, inhalants, hallucinogens, to fight the evil of drug addiction. The solution and marijuana—including caffeine, nicotine, and al- seemed simple. Make everything connected with cohol. Boston: Little, Brown. drug use—sale, use, importation, manufacture— KEYS,DAVID PATRICK, and JOHN F. GALLIHER (2000). illegal; lock up everyone involved in any way with Confronting the drug control establishment: Alfred any drug for as long as possible, preferably for life. Lindesmith as a public intellectual. Albany: State He seems never to have realized that greater em- University of New York Press (SUNY series in phasis on treatment and education would have deviance and social control). KING,RUFUS (1974). The drug hang-up: America’s fifty- made drugs less profitable to organized crime, that year folly, 2nd ed. Springfield, Ill.: Charles C. his extreme criminalization policies created a niche Thomas. for international criminals to fill. The years 1930 LINDESMITH,ALFRED RAY (1965). The addict and the through 1962 in which he headed the FBN were not law. Bloomington: Indiana University Press. normal years, but rather consisted of three great MCWILLIAMS,JOHN C. (1990). The protectors: Harry J. crises in a row: the Depression, World War II, and Anslinger and the Federal Bureau of Narcotics, 1930– the beginning of the Cold War—all three of which 1962. Newark, Delaware: University of Delaware encouraged greater activism on the part of the fed- Press; London and Toronto: Associated University eral government. They were also the years in which Presses. blacks migrated from the rural South to the urban MUSTO, D. F. (1999). The American disease: Origins of North, where they were often tempted to ease their narcotics control. 3rd edition, New York: Oxford Uni- culture shock with narcotics that were expensive versity Press. (as they had not been forhis neighbor’swife when WALKER III, WILLIAM O. ED. (1996). Drugs in the West- Anslingerwas twelve and morphinewas legal), ern hemisphere: An odyssey of cultures in conflict. precisely because his Bureau’s enforcement drove Wilmington, Del.: Scholarly Resources (Jaguar Books the drugs underground. Anslinger has yet to receive on Latin America, no. 12). the benefit of a well-balanced biography. It is RUFUS KING hoped that an objective setting of his life against his REVISED BY JAMES T. MCDONOUGH,JR. times may one day be completed, thanks in part to the thirteen boxes of his papers which he left to Pennsylvania State University (McWilliams, ANTABUSE See Disulfiram 1990).

(SEE ALSO: Methadone Maintenance Programs; ANTAGONIST An antagonist is a drug that Treatment, History of, in the United States; U.S. binds to a RECEPTOR (i.e., it has affinity forthe Government Agencies) receptor binding site) but does not activate the ANTIDEPRESSANT 135 receptor to produce a biological response (i.e., it ANTIDEPRESSANT Antidepressants are a possesses no intrinsic activity). Antagonists are also diverse group of drugs that demonstrate a capacity called receptor ‘‘blockers’’ because they block the to produce improvement in the symptoms of clini- effect of AGONISTS. The pharmacological effects of cal depression, and they are used to treat the abnor- an antagonist therefore result in preventing ago- mal mood states that characterize depressive ill- nists (e.g., drugs, hormones, neurotransmitters) nesses. The word depression is used commonly to describe a state of sadness; but health professionals from binding to and activating the receptor. A com- use the term in a more restricted or defined manner petitive antagonist competes with an agonist for to describe several psychiatric disorders character- binding to the receptor. As the concentration of ized by abnormal moods. One of these is bipolar antagonist is increased, the binding of the agonist is disorder, in which periods of depression (marked progressively inhibited, resulting in a decrease in by dejection, lack of energy, inactivity, and sad- the physiological response. High antagonist con- ness) alternate with periods of manic behavior centrations can completely inhibit the response. (marked by abnormally high energy levels and in- This inhibition can be reversed, however, by in- creased activity). Another is major depression, creasing the concentration of the agonist, since the which is often a recurring problem characterized by agonist and antagonist compete forbinding to the severe and prolonged periods of depression without receptor. A competitive antagonist, therefore, shifts the manic swing. A third is dysthymia, a chronic the dose-response relationship for the agonist to the mood state characterized by depression and irrita- bility, which was once referred to as depressive right, so that an increased concentration of the neurosis. The signs and symptoms of depressive agonist in the presence of a competitive antagonist mood disorders may occur as part of other medical is required to produce the same biological response and psychiatric disorders (i.e., following stroke); as observed in the absence of the antagonist. a result of endocrine disorders; or as a consequence A second type of receptor antagonist is an irre- of excessive drug use. Often these abnormal mood versible antagonist. In this case, the binding of the states may not meet established criteria for one of antagonist to the receptor (its affinity) may be so the major psychiatric mood disorders, but they may strong that the receptor is unavailable for binding nevertheless respond to one of the antidepressant by the agonist. Other irreversible antagonists actu- drugs. ally form chemical bonds (e.g., covalent bonds) Antidepressants can also be useful in a number with the receptor. In either case, if the concentra- of medical and psychiatric disorders where depres- tion of the irreversible antagonist is high enough, sion is not the majorfeature.Forexample, some the number of receptors remaining that are avail- categories of antidepressants can be used to treat anxiety and panic disorders, and they are often able foragonist binding may be so low that a useful as adjunctive medications forchronicpain. maximum biological response cannot be achieved Antidepressant drugs are not generally helpful for even in the presence of high concentrations of the short-term depressed moods that are part of every- agonist. day life or for the normal period of grief that follows the loss of a loved one. (SEE ALSO: Naloxone; Naltrexone) New categories of antidepressants are being con- tinuously developed and tested. There are now at least five categories in use. These include tricyclic BIBLIOGRAPHY antidepressants, monoamine oxidase (MAO) inhib-

ROSS, E. M. (1990). Pharmacodynamics: Mechanisms of itors, lithium, nontricyclic antidepressants, and se- drug action and the relationship between drug con- rotonin-reuptake inhibitors (SSRIs). The chemical centration and effect. In A. G. Gilman, T. W. Rall, structures of some of these are shown below. The tricyclic antidepressants, which have been A. S. Nies, & P. Taylor(Eds.), Goodman and used for many years in the treatment of depression, Gilman’s the pharmacological basis of therapeutics, include such compounds as imipramine (Tofranil), 8th ed. New York: Pergamon. nortriptyline (Aventyl), and desipramine NICK E. GOEDERS (Norpramin). In addition to being used to treat 136 ANTIDOTE depression, imipramine is sometimes used to treat effect of SSRIs, they are usually given as a single alcoholism and cocaine withdrawal. Desipramine is dose in the morning. The SSRIs also have several also sometimes used to treat depression associated disadvantages, including a long response time (pa- with cocaine withdrawal. In terms of dosage, most tients may need to wait 4 weeks to see any improve- of the tricyclics can be given in a single dose at ment); the same failure rate as the older tricyclics bedtime. The tricyclics as a group, however, have (20–40percent of patients); side effects that in- two major drawbacks. First, the patient must take clude sexual dysfunction; and high cost ($2–3 per a specific tricyclic for a period of 2 to 4 weeks tablet). before signs of clinical effectiveness occur. Second, When a patient does not respond to a specific the tricyclics have a relatively narrow margin of antidepressant after a trial of 2 to 4 weeks, the safety, which means that it is easierfora depressed physician may prescribe another medication. If the patient to take an overdose. As a rule, physicians new drug is from the same group as the first antide- are cautious about prescribing tricyclic antidepres- pressant, the physician can rapidly decrease the sants if the patient appears to be at risk for suicide. dosage of the first drug while increasing the dosage The monoamine oxidase (MAO) inhibitors are of the second. If, however, the new antidepressant generally used as second-line drugs for depressed is from a different category, a ‘‘washout time’’ must patients who do not respond to tricyclics, because be allowed in order to prevent drug interactions. A they require certain dietary restrictions (patients washout period of 2 to 3 weeks is necessary when are not allowed liver, aged meats, most cheeses, red the patient is switched from an MAO inhibitor to a wine, soy sauce, etc.) The MAO inhibitors are, tricyclic; a period of 4 to 5 weeks is necessary when however, first-choice drugs for treatment of panic switching from an SSRI to an MAO inhibitor. disorder and of depression in the elderly. They include phenelzine sulfate (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate). BIBLIOGRAPHY These antidepressants may be given in either the AMERICAN PSYCHIATRIC ASSOCIATION. (1994). Diagnostic morning or the evening, depending on their effect and statistical manual of mental disorders, 4th ed. on the patient’s sleep. (DSM-IV). Washington, DC. Although lithium (Eskalith, Lithonate) is useful BALDESSARINI, R. J. (1991). Drugs and the treatment of in treating manic states and in preventing depres- psychiatric disorders. In: A. G. Gilman et al. (Eds.), sion in bipolar disorders, it is not generally used for Goodman and Gilman’s the pharmacological basis of other types of depression. Lithium may have seri- therapeutics, 8th ed. New York: Pergamon. ous side effects and may be toxic at high dosages. EISENDRATH, S. J. (1998). Psychiatric Disorders. In L. M. Exposure to lithium in early pregnancy is associ- Tierney et al. (Eds.), Current Medical Diagnosis & ated with an increased frequency of birth defects, Treatment, 37th ed. Stamford, CT: Appleton & and the long-term use of lithium damages kidney Lange. function. It also seems to have no significant value GEORGE R. UHL in treating cocaine dependence or alcoholism. VALINA DAWSON The serotonin reuptake inhibitors (SSRIs) are REVISED BY REBECCA J. FREY the newest category of antidepressant medications. They have become the most widely used drugs for depression; fluoxetine (Prozac) has been the best- selling antidepressant since the mid-1990s. Other ANTIDOTE A medication ortreatmentthat SSRIs include paroxetine (Paxil) and sertraline counteracts a poison or its effects. An antidote (Zoloft). A fourth drug, bupropion (Wellbutrin), is may work by reducing or blocking the absorption not an SSRI but is often grouped with them because of a poison from the stomach. It might counteract it is a newer antidepressant. The SSRIs have several its effects directly, as in taking something to neu- advantages: They can often nip mild depression ‘‘in tralize an acid. Or an antidote might work by the bud’’ before it develops into a major depressive blocking a poison at its receptor site. For example, episode. They can also be used to treat bulimia, a medication called naloxone will block opiates obesity, and obsessive-compulsive disorder as well such as heroin at its receptors and prevent deaths as depression. Since insomnia is a common side that occur because of heroin overdose. In a sense, ANTISOCIAL PERSONALITY 137

drug ANTAGONISTS can all be antidotes undersome BIBLIOGRAPHY circumstances, but not all antidotes are drug BALDESSARINI, R. J. (1990). Drugs and the treatment of antagonists. psychiatric disorders. In A. G. Gilman et al. (Eds.), Many cities have a telephone ‘‘poison hot line,’’ Goodman and Gilman’s the pharmacological basis of where information on antidotes is given. In case of therapeutics, 8th ed. New York: Peragamon. drug overdose or poisoning, it is advisable to call forexpertmedical help immediately. GEORGE R. UHL VALINA DAWSON

BIBLIOGRAPHY

KLAASSEN, C. D. (1990). Principles of toxicology. In ANTI-SALOON LEAGUE See Temperance A. G. Gilman, T. W. Rall, A. S. Nies, & P. Taylor Movement; Women’s Christian Temperance Move- (Eds.), Goodman and Gilman’s the pharmacological ment basis of therapeutics, 8th ed. (p. 58). New York: Per- gamon Press. MICHAEL J. KUHAR ANTISOCIAL PERSONALITY Antisocial personality disorder (ASP) is particularly germane to alcohol and drug abuse because it co-occurs in a large proportion of those who abuse alcohol or ANTIPSYCHOTIC Any of a group of drugs, drugs, and it confounds the diagnosis of, influences also termed neuroleptics, used medicinally in the the course of, and is an independent risk factor for therapy of schizophrenia, organic psychoses, the the development of alcohol or drug abuse disorder. manic phase of manic-depressive illness, and other Additionally, scientific evidence suggests that alco- acute psychotic illnesses. The prototype antipsy- hol and drug abuse complicated by ASP is more chotics are the phenothiazines, such as chlorpro- heritable than is substance abuse without ASP. mazine (Thorazine), and the butyrophenones such In the latest diagnostic classification system as haloperidol (Haldol). The antipsychotics are tri- DIAGNOSTIC AND STATISTICAL MANUAL-4th edition cyclic compounds, with chemical substitution at R1 (DSM-IV), ASP is defined as a disorder that begins and R2, which determine the selectivity and po- in childhood orearlyadolescence and continues tency of the neuroleptic. into adulthood; it is characterized by a general disregard for and violation of the rights of others. At least three of the following behaviors must have occurred in any twelve-month period of time before the age of 15, with two before age 13: running away from home overnight twice, staying out late at night despite parental rules to the contrary (before age 13), truancy (beginning before age 13), initiat- ing physical fights, using weapons in fights, cruelty Figure 1 to animals and to people, vandalism, forcing some- Antipsychotics one into sexual activity, arson, frequent lying to obtain favors or goods, frequently bullying, break- ing into someone’s house or car, and stealing from The ‘‘positive’’ symptoms of psychotic disorders, others (either passively like shoplifting, or aggres- such as hallucinations, can often be effectively sively, like mugging). In addition, three of the fol- treated with antipsychotics; the ‘‘negative’’ symp- lowing behaviors must have occurred since the age toms, such as withdrawal, are less effectively man- of 15: consistent irresponsibility (e.g., inability to aged by these drugs. Most of these drugs also have sustain consistent work behavior or to honor finan- effects on movement, and a good response to the cial obligations), failure to conform to social norms drugs’ antipsychotic effects must often be balanced by repeatedly engaging in arrestable behaviors, ir- against motorside effects. ritability and aggressiveness, deceitfulness (e.g., 138 ANTISOCIAL PERSONALITY frequent lying or conning of others), reckless be- served among those with antisocial behavior in haviors indicating disregard for safety of oneself or childhood. This finding has subsequently been rep- of others, impulsivity or failure to plan ahead, and licated in numerous other studies. lack of remorse for hurtful or manipulative behav- Data from several studies indicate that alcohol- iors. ism complicated by ASP orASP-like behaviorsmay A large percentage of alcohol and drug abusers be more heritable than non-ASP alcoholism. Evi- meet criteria for ASP. For example, in one multisite dence from a Swedish adoption study indicated the study of 20,000 community respondents, 15 per- adopted-out sons of fathers with ASP-like alcohol- cent of the alcoholic participants compared to 2.6 ism had a risk of alcoholism nine times that of percent of the population as a whole, met criteria adopted-out sons of otherfathers. for ASP. Comparable data from clinical samples The causes of ASP are not known, but data are indicate that from 16 percent to 49 percent of accumulating from neurochemical studies that pro- treated alcoholics met criteria for ASP. vide some clues. Neuropharmacological studies A substantial proportion of those with ASP also have established associations of aggressive, impul- abuse alcohol or drugs—three times as many men sive, hostile, and low socialization behaviors with with a diagnosis of ASP as without abuse alcohol low SEROTONIN levels. Another neurotransmitter, and five times as many abuse drugs. For females, DOPAMINE, is linked to novelty-seeking behavior. the association is even stronger—twelve times as The interactions among neurotransmitters have led many women with ASP as without abuse alcohol researchers to postulate an association of multiple and thirteen times as many abuse drugs. The strong neurotransmitter dysfunctions, with a loss of im- association between ASP and alcohol ordrugabuse pulse control and an increased appetite for novel may actually be caused by antisocial behaviors that occurwhen underthe influence of alcohol ordrugs experiences. judgment is impaired. It is possible, however, to distinguish primary abusers, those for whom the SUMMARY antisocial behaviors are a result of their substance ASP is a common concomitant of alcohol and use, from secondary abusers, for whom substance drug abuse that affects their course and treatment; abuse is just one manifestation of a wide spectrum it may represent a highly heritable subtype of such of antisocial behaviors. This differentiation is par- abuse. Although its etiology is unknown, evidence ticularly important in understanding the genetic from neuropharmacology studies has provided transmission of disease, where genetic factors re- sponsible for the co-morbid state might be trans- some leads. As with many personality disorders, mitted separately from those that cause substance there is no known treatment for ASP. It is an im- abuse. portant disorder to consider in alcohol and drug The course of alcohol or drug abuse is affected abuse. by ASP. Alcoholics with ASP have a more chronic and more severe course, an earlier onset of alcohol (SEE ALSO: Addictive Personality; Childhood Be- symptoms (forexample, averageage of onset of 20 havior and Later Drug Use; Conduct Disorder and compared to nearly 30 for those without ASP), as Drug Use) well as a significantly longer history of problem drinking. Furthermore, evidence is mounting that BIBLIOGRAPHY ASP alcoholics have poorer response to treat- ment—relapsing much earlier than alcoholics AMERICAN PSYCHIATRIC ASSOCIATION. (1994). Diagnostic without ASP—and they may respond only to cer- and Statistical Manual of Mental Disorders-4th ed. tain therapies. (DSM-IV). Washington, DC: Author. Antisocial behaviorproblemsin childhood have BEERS, M. H., & BERKOW, R. (Eds.) (1999). The Merck been identified as an independent risk factor in the Manual of Diagnosis and Therapy, 17th ed. development of alcoholism. One of the first studies Whitehouse Station, NJ: Merck Research Laborato- to document this was carried out by Robins (1962) ries. in a follow-up study of child-guidance clinic at- BUCHOLZ, K. K., et al.(2000). A latent class analysis of tendees; a marked excess of alcoholism was ob- antisocial personality disorder symptom data from a ANXIETY 139

multi-centre family study of alcoholism. Addiction, by feelings of apprehension or fear of losing con- 95, 553–567. trol, depersonalization and derealization, and diffi- CECERO, J. J., et al.(1999). Concurrent and Predictive culties in concentration. Strains around the per- Validity of Antisocial Personality Disorder Subtyping formance of social roles (e.g., spouse, parent, wage Among Substance Abusers. Journal of Nervous and earner) and certain life situations (e.g., separating Mental Disease, 187, 478–486. from parents when starting school or leaving home, COSTA, L, et al.(2000).Frontal P300 decrements, alcohol illness) can generate anxiety symptoms. Other fac- dependence, and antisocial personality disorder. Bio- tors can contribute to the etiology of anxiety, such logical Psychiatry, 47, 1064–1071.[/bibcit as use of alcohol, caffeine and otherstimulant HESSELBROCK, V. M., MEYER, R., & HESSELBROCK,M. drugs (e.g., amphetamine), a family history of anx- (1992). Psychopathology and addictive disorders: iety symptoms, ora biological predisposition.In The specific case of antisocial personality disorder. In certain cases, recurrent anxiety symptoms will lead C. P. O’Brien & J. H. Jaffe (Eds.). Addictive states. an individual to avoid certain situations, places, or New York: Raven Press. things (phobias). In many cases, an anxious emo- KELLEY, J. L., & PETRY, N. M. (2000). HIV risk behav- tional state can motivate positive coping behaviors iors in male substance abusers with and without anti- (e.g., anxiety that leads to studying foran exam). social personality disorder. Journal of Substance When the anxiety becomes excessive and impairs Abuse Treatment, 19, 59–66. functioning, it can lead to the development of psy- ROBINS, L. N., TIPP, J., & PRZYBECK, T. (1991). Antiso- chiatric illness. Individuals differ in their predispo- cial personality. In L. N. Robins & D. A. Regier sition to anxiety. (Eds.), Psychiatric disorders in America. New York: Different constellations of anxious mood, physi- Free Press. cal symptoms, thoughts, and behaviors, when ROBINS, L. N., BATES, W. M., & O’NEAL, P. (1962). Adult maladaptive, constitute various anxiety disorders. drinking patterns of former problem children. In D. J. Panic disorder is characterized by brief, recurrent, Pitman & C. R. Snyder(Eds.), Society, culture and anxiety attacks during which individuals fear drinking patterns. New York: Wiley. death orlosing theirmind and experienceintense THOMPSON, K. M., et al. (2000). The neglected link be- physical symptoms. People with obsessive compul- tween eating disturbances and aggressive behavior in sive disorder experience persistent thoughts that girls. Journal of the American Academy of Child and they perceive as being senseless and distressing Adolescent Psychiatry, 38, 1277–1284. (obsessions) and that they attempt to neutralize by YOSHINO, A., FUKUHARA, T., & KATO, M. (2000). Pre- performing repetitive, stereotyped behaviors morbid risk factors for alcohol dependence in antiso- (compulsions). The essential feature of phobic dis- cial personality disorder. Alcohol in Clinical Experi- orders (e.g., agoraphobia, social phobia, simple mental Research, 24, 35–38. phobia) is a persistent fear of one or more situa- tions orobjects that leads the individual to either KATHLEEN K. BUCHOLZ avoid the situations orobjects orendureexposure REVISED BY REBECCA J. FREY to them with great anxiety. Generalized anxiety disorder is diagnosed in individuals who persis- tently and excessively worry about several of their ANXIETY Anxiety refers to an unpleasant life circumstances and experience motor tension emotional state, a response to anticipated threat or and physiologic arousal. Anxiety disorders are the to specific psychiatric disorders. In anxiety, the an- psychiatric illness most frequently found in the ticipated threat is often imagined. Anxiety consists general population. of physiological and psychological features. The Anxiety states can result from underlying medi- physiological symptoms can include breathing dif- cal conditions, and therefore these conditions ficulties (hyperventilation, shortness of breath), should always be looked forwhen evaluating prob- palpitations, sweating, light-headedness, diarrhea, lematic anxiety. When anxiety develops into a psy- trembling, frequent urination, and numbness and chiatric illness, various forms of treatment are tingling sensations. The anxious person is usually available to reduce it. The choice of treatment often hypervigilant and startles easily. The subjective depends on the specific disorder. Medications may psychological experience of anxiety is characterized be used, including anxiolytics (e.g., BENZODIAZE- 140 APHRODISIAC

PINES, buspirone) and ANTIDEPRESSANTS (e.g., surements have demonstrated that ALCOHOL (a de- imipramine, fluoxetine). Psychotherapies offered pressant) actually decreases sexual responsiveness generally consist of cognitive-behavioral interven- in both men and women. This paradoxical effect tions (e.g., exposure therapy), but they can include was best expressed about 1605 by William Shake- psychotherapy of a supportive nature or more psy- speare in Macbeth, act 2, scene 3: chodynamically oriented approaches. Some people MACDUFF: with severe anxiety may turn to alcohol or What three things does drink espe- nonprescribed sedative-hypnotics for symptom re- cially provoke? lief, and this in turn may exacerbate the underlying PORTER: condition. Marry, sir, nose-painting, sleep, and urine. Lechery, sir, it provokes, (SEE ALSO: Causes of Substance Abuse: Psychologi- and unprovokes; it provokes the cal (Psychoanalytic) Perspective: Prescription desire, but it takes away the per- Drug Abuse) formance. . . .

BIBLIOGRAPHY Since the 1980s, COCAINE has gained popularity as a potential aphrodisiac, since its use purportedly AMERICAN PSYCHIATRIC ASSOCIATION. (1994). Diagnostic enhances the sexual experience; MARIJUANA and and Statistical Manual of Mental Disorders, 4th edi- AMYL NITRITE have had this reputation, in general, tion. Washington, DC: American Psychiatric Press. since the 1960s. Nevertheless, chronic cocaine BRAWMAN-MINTZER,O.,&LYDIARD, R. B. (1997). Gener- users, like chronic heroin users, often report a loss alized anxiety disorder. In A. Tasman, G. Kay, & J. A. of sexual interest and capability; therefore no ratio- Lieberman (Eds.), Psychiatry, 1st edition (pp. 1100– nale exists forthe use of alcohol orotherdrugsas 1118). Philadelphia, PA: W. B. Saunders Company. sexual stimulants. Quite the contrary, the use of SHEAR, M. K. (1997). Panic disorder with and without these substances can lead to a loss of sexual desire agoraphobia. In A. Tasman, G. Kay, & J. A. Lieber- and excitement and the development of a physical man (Eds.), Psychiatry, 1st edition (pp. 1020–1036). and/orpsychological dependence. Philadelphia, PA: W. B. Saunders Company. A prescription drug—yohimbine, derived from MYROSLAVA ROMACH the African yohimbe tree—seems to help cure some KAREN PARKER men of impotence. The data suggest that it may work as a placebo (psychologically), but urologists prescribe it nonetheless in the hope that the patient APHRODISIAC An aphrodisiac is a sub- can avoid more invasive treatments. The treatment stance that can be administered topically, inter- takes three to six months before there is an effect, nally, by injection, orby inhalation to stimulate and the natural form (available in health-food sexual arousal or to enhance sexual performance. stores), is not the form used therapeutically. The term is based on Aphrodite, the ancient Greek goddess of love and beauty, and it came into the BIBLIOGRAPHY English language during the early 1800s. Although no solid scientific evidence exists forany substances CHITWOOD, D. D. (1985). Patterns and consequences of that have selective effect on sexual function, many cocaine use. In Cocaine use in America: Epidemiologic foods and food combinations have a long-standing and clinical perspectives. NIDA Research Monograph reputation as aphrodisiacs—such as oysters, cav- No. 61, DHHS Publication no. (ADM)85–1414. iar, champagne, and truffles (a subterranean fun- Washington, DC: U.S. Government Printing Office. gus uprooted by pigs in the oak forests of France). ROOT, W. (1980). Food: An authoritative and visual Alcoholic drinks have also been considered to be history and dictionary of the foods of the world. New an aphrodisiac, since sexual behavior often occurs York: Simon & Schuster. after ‘‘cocktails,’’ during or after parties, or during WILSON, G. T. (1977). Alcohol and human sexual behav- periods of alcohol intoxication—but only if not too ior. Behavioral Research and Therapy, 15, 239–252. much alcohol has been consumed. Objective mea- NICK E. GOEDERS ARRESTEE DRUG ABUSE MONITORING (ADAM) 141

ARGOT When we talk about the argot of drug continued drug use more likely rather than less users, we mean their vocabulary or the collection of likely. slang words and phrases used by one drug user to Many of the terms that originally were part of communicate with another—often to the exclusion the argot of drug users have entered into more of non-users. In some instances, argot extends to common usage. Forexample, ‘‘dope’’ has become a the intonation orpitch used to speak wordsand general purpose term, widely used in relation to phrases. many types of drug; many people know that Argot fascinates sociologists, anthropologists, ‘‘weed’’ or ‘‘reefer’’ refers to marijuana while and others who study human behavior because the ‘‘acid’’ is LSD (lysergic acid diethylamide). This use of argot is an example of learned behavior that encyclopedia includes a glossary of terms in the helps identify members of one social group as op- article SLANG AND JARGON, which lists many exam- posed to another, Argot also marks off the bound- ples of argot that have become part of American aries of group membership: those of the in-group slang usage. use argot with ease, while outsiders use argot in- eptly ornot at all. (SEE ALSO: Slang and Jargon) In one study, we showed more than 2,000 drug users in Baltimore, Maryland, a photograph of BIBLIOGRAPHY someone injecting a drug into a vein, and we asked ‘‘What do you call this?’’ The vast majority, well MAURER, D. W., & VOGEL, V. H. (1973). Argot in nar- over 50 percent, said that it was a picture of some- cotic addicts. In L. M. Snyderet al. (Eds.), Narcotics one ‘‘firing up’’ and most of the others called it and Narcotic Addiction, 4th ed. (pp. 364–455). ‘‘shooting.’’ Most otherpeople in Baltimorespeak Springfield, IL: Charles C. Thomas Publisher. of ‘‘firing up’’ their furnaces or ‘‘shooting’’ baskets SMITH, A. M., ET AL. (1992). Terminology for drug injec- on a basketball court, but they do not think about tion practices among intravenous drug users in Balti- drug use when these terms are used. more. International Journal of the Addictions, 27, The argot of drug users also varies from place to 435–453. place and from time to time. A very small minority DAVID VLAHOV of the drug users in our study spoke of ‘‘main- lining’’ the drug, ‘‘spiking,’’ or ‘‘oiling’’ when they saw the picture of a drug injection into a vein. These are older terms for the same injecting behav- ARRESTEE DRUG ABUSE MONITOR- iornow called ‘‘firingup’’ and ‘‘shooting’’ by youn- ING (ADAM) The Arrestee Drug Abuse Moni- ger drug users. toring (ADAM) system evolved from the Drug Use In some ways, argot reflects the social structure Forecasting program (DUF). The National Insti- of groups: in-group members use the argot, while tute of Justice developed this monitoring system in others do not. However, if argot was used to serve 1987 (Wish and Gropper, 1990). DUF was devel- as a badge of membership in an in-group, then we oped on the premise that a large fraction of ar- might expect to hear argot in general conversations, restees not arrested for drug crimes (such as the no matterwho is present.Nonetheless, sociologists possession or sale of drugs) were drug users, and studying the use of argot often have been surprised that their drug use was linked to their criminality. to find that argot is spoken mainly between group Although many indicators were available to assess members but not as often when nonmembers are the level and nature of the nation’s drug-abuse present. problem, little reliable data was available for ar- Arguing from evidence of this type, some ob- restees, a particularly high-risk group in this re- servers claim that argot serves more to convey and gard. By 1989 the DUF program included twenty- reinforce identities within groups than to distin- fourcities. guish one group from another. That is, the process DUF protocol called for the collection of inter- of learning and using drug-related argot reinforces view and urinalysis data from arrestees. In each the process of joining in with others who use drugs. city, a goal of interviewing 225 adult male and 100 In some ways, this process might serve to supple- adult female arrestees each quarter was set. Ini- ment the reinforcing functions of drug use, making tially, no more than 20 percent of those included in 142 ARTS, DRUG USE AND the sample could be charged with a drug crime. could be applied to the arrestee population in a Male arrestees were eligible to participate if they given city, ADAM added twenty-six new cities to had been charged with a misdemeanor or felony, their programs, with a target goal of seventy-five. but all female arrestees were eligible for participa- tion. Urinalysis was conducted to test for the pres- BIBLIOGRAPHY ence of a number of drugs, including cocaine, mari- juana, opiates, PCP, amphetamines, NATIONAL INSTITUTE OF JUSTICE (1998). Arrestee Drug methamphetamines, and designer drugs. Inter- Abuse Monitoring: 1997 Annual report on adult and views were confidential and voluntary, and in most juvenile arrestees. Washington, D.C. sites high rates of compliance from arrestees were WISH, E. and GROPPER, B. (1990). Drug testing by the obtained. A national laboratory analyzed all urine criminal justice system: Methods, research and appli- samples, and federal drug-testing standards for cations. In M. TONRY and J. WILSON (Eds.) Drugs and false positives and drug confirmation were applied Crime. Chicago: University of Chicago Press, 321– to the testing procedure. 392. The DUF program had three specific goals: SCOTT H. DECKER (1) to forecast drug epidemics, (2) to understand ERIC D. WISH the nature of arrestee drug use, and (3) to provide drug treatment services for arrestees. Arrestees tested positive for drugs at very high levels: as many as 80 percent in some cities tested positive for ARTS, DRUG USE AND See Creativity and at least one illegal drug. The drug of choice in the Drugs late 1980s through the mid-1990s was cocaine, followed by marijuana and opiates. There was a notable increase in the use of marijuana in the mid- ASAM See American Society of Addiction 1990s and by the late 1990s some cities found that Medicine methamphetamines were the drug of choice among arrestees. These cities were located in the western and southwestern United States. In general, women ASIA, DRUG USE IN Asia is the world’s were more likely to test positive than men, and largest continent; India and China are its most arrestees in their late twenties were the age group populous countries. More than half the world’s most likely to test positive. In addition, women population lives in Asia. Thus we find considerable charged with the crime of prostitution were the variation in drug use and drug problems there, not group most likely to test positive for drugs. It was no surprise that arrestees charged with drug crimes only among the various countries but also within tested positive forillegal drugsat higherlevels than them. Unfortunately, the available information those charged with other offenses. However, indi- about drug use in Asia is sketchy and fragmentary; viduals arrested for property crimes such as bur- few good studies have been published. Epidemio- glary tested positive for drugs at levels comparable logical data are almost completely absent. The to those arrested for drug crimes. Individuals rapid social, economic, cultural, and political charged with violent crimes tested positive at the transformations are adding to the complexity of lowest levels, well below the average for the entire drug-use patterns and associated drug-related sample. There was considerable evidence of behav- problems in Asia and worldwide. This article pro- iors that placed arrestees at risk for HIV, including vides a broad overview of the historical, cultural, multiple sex partners, unprotected sex, and sharing political and economic forces that have shaped of needles. drug use in Asia. It should be kept in mind that In 1997, the National Institute of Justice current drug use in many parts of Asia is tied to revamped and renamed DUF (NIJ, 1998) as Ar- drug-production. Myanmar and Afghanistan pro- restee Drug Abuse Monitoring (ADAM). This duce most of the world’s illegal opium, while the change came in response to criticism about the Golden Triangle of Southeast Asia (Myanmar, sampling procedures used in DUF. In addition to a Thailand, and Laos) find users contracting HIV sampling plan that would yield findings which infections from contaminated needles. ASIA, DRUG USE IN 143

TEA Most people know the tea plant Camellia sinensis in the brewed form of TEA. Tea has been part of Asian culture for thousands of years. Its use seems to have originated in southeastern China. It is mentioned in the very early Chinese medical literature. To a large extent, the medical benefits of tea can be ascribed to the chemical theophylline, which depending on its use can have eithermildly calming orstimulating effects. The use of tea as a popular beverage and its production in large quan- tities has only been documented since the sixth cen- tury. The history of tea is also a history of interna- As part of a government-instituted program, tional trade. Japan was one of the first countries to students give samples of their urine to an official import tea from China, and tea became part of the to test for narcotic drugs at Yothinburanat Japanese culture. Chanoyu (the way of the tea) is a School in Bangkok, Thailand, March 4, 1998. meditation ritual introduced in Japan by Zen Bud- (AP Photo/Sakchai Lalit) dhist monks several hundred years ago, and elabo- rate tea ceremonies developed there. This tea cere- Arabian traders began exporting opium to India mony is still taught and practiced in modern Japan. and China about that time, and it also appeared in Tea became the primary stimulant beverage not trade shipments to Europe. Although accurate doc- only in China and Japan but also in India, Malay- umentation is scarce, some observers claim that sia, the Russian empire, and other Asian countries. opium use spread faster in precolonial and colonial In the 1700s, tea was imported directly to Great India, than in China. A British royal commission Britain and to the British colonies by the East India investigated Indian opium use in 1895 and claimed Company. Even today, there are tea-preferring that the people of India had not suffered detrimen- countries like Britain and coffee-preferring coun- tal effects from the taking of opium. The situation tries like Spain. The difference in preference goes was different in China. The British traded Indian- back to the time of colonial trading: Those coun- grown opium for Chinese tea and porcelain. This tries with tea-producing colonies drank tea, be- led to an increasing supply of opium in China, cause it was cheaperthan coffee; countrieswith associated with an increasing use of opium for rec- coffee-producing colonies drank coffee, because for reational purposes. During the nineteenth century a them it was cheaperthan tea. raging epidemic of opium smoking in China led to a situation of great concern to the Chinese govern- OPIUM ment. In an attempt to cut the supply of opium, the Aftertea, the drugmost often associated with Chinese government tried to close its ports to Brit- Asia is OPIUM. Opium is prepared from the opium ish trade. This resulted in the Opium wars (1839– poppy (Papaver somniferum), which grows well in 1842), but Britain won the war and the right to the alkaline limestone soil of Turkey and Iran, east continue trading opium to China. through Afghanistan and Pakistan to the northern The different responses of India and China to the mountainous areas of Myanmar (formerly Burma), availability of opium might be explained, to some Thailand, and Laos. The area forms a crescent, degree, by the way this drug was introduced to the thus the name GOLDEN CRESCENT. The mountain- population. In India, opium was introduced as a ous areas of Myanmar, Thailand, and Laos are medicinal plant, to be taken by mouth and swal- known as the Golden Triangle. lowed. In contrast, in China during the 1500s, Por- Medical historians have been able to document tuguese sailors had just introduced New World to- that Arabian physicians of Asia Minor extracted bacco smoking as a form of a recreational drug use. raw opium from the seed pods of the poppy and Many Chinese, who had just picked up tobacco used it to treat pain and diarrhea before A.D. 1000. smoking, substituted opium fortobacco. Thus 144 ASIA, DRUG USE IN opium was not only introduced as a nonmedicinal many social rules associated with its use are evi- recreational drug, but it was also introduced in a dence of its long-standing integration into Indian different route of administration. Drugs inhaled culture. Traditional Indian society was divided into through the lungs seem to produce faster and more hereditary classes or castes. The highest caste was severe dependence than those ingested through the to use white-flowered cannabis; the Kshatriya, the gastrointestinal tract. warriors, used the red-flowered plants; the farmers Effective government control of opium smoking and traders, the Vaishya caste, were to use the yel- in China did not become possible until late in the low-flowered plant; and the Shudra, servant caste, nineteenth and early twentieth centuries when Brit- used plants with dark flowers. ain, the United States, and other world powers The earliest Indian medical text, Sushruta signed international agreements to help curb samhita, apparently dating from pre-Christian worldwide supply and distribution networks. They times, differentiated three major ways of preparing cooperated because opium abuse spread and and administering Cannabis—BHANG, GANJA, and started to affect these countries directly. In 1930, charas. Bhang was a sweet drink prepared from the League of Nations Commission of Inquiry into the leaves and flowershoots, which also might be the Control of Opium Smoking in the Far East brewed as a tea. Ganja was the dried flowers, which reported that opium use had not been prohibited in was smoked. Charas was a cake compound from any Asian country except the Philippines. By 1950, the most resinous parts of the plant; this seems to this situation had changed dramatically. Many have been the upper-class favorite. While bhang, Asian countries placed high priority on narcotic- ganja, and charas are still used in India today, the control policies. Harsh penalties, including the form of preparation may not be quite the same as death penalty, had been reinstated for drug traf- the recipes in the Sushruta samhita. ficking and possession of opium and derivatives, like MORPHINE and HEROIN. Despite these government actions, opium and its BETEL NUT derivatives are still used widely in regions where they are grown. In 1990, Myanmar, Thailand, and In southern parts of Asia, mainly in India, Indo- Laos supplied about 56 percent of the heroin con- nesia, Malaysia, southern China, and also in East sumed in the United States. By 1999, Latin Amer- Africa, many people chew BETEL NUT (Areca cat- ica supplied most of the heroin to the United States, echu). The nut is prepared by wrapping it in a betel accounting for 82 percent of the heroin seized in the pepperleaf ( Piper belle) with a compound of lime U.S. The Southeast Asian opium crop, which was (calcium hydroxide or calcium carbonate) and on the rise in the early 1990s, suffered a sharp spices. Chewing this preparation produces mild decline due to adverse weather in the later 1990s. stimulating effects. At the same time, the saliva China has moved to contain opium trafficking. In becomes red and the mouth and teeth are stained 1998, China began a ‘‘Drug Free Communities’’ red. Mouth cancer may result. program to eliminate drug trafficking and abuse as The ancient Greek traveler and historian well as drug-related crime. Herodotus wrote about betel-nut chewing in 340 B.C. Although its use seems to be declining, an esti- CANNABIS mated 400 million persons are still dependent on this substance. Known in the United States mainly as the MARI- JUANA plant, Cannabis sativa may first have been cultivated in Asia in a region just north of Afghani- OTHER NATIVE DRUGS stan. From there it seems to have spread to China and India. It is mentioned in the early medical Students interested in ETHNOPHARMACOLOGY literature of China (e.g., in the Shenmong bencao) and cultural practices associated with drug use will as well as in India (e.g., in the Sushruta samhita). find many fascinating accounts in Asian history. Early nonmedical use has also been documented. One modern example involves the consumption of a Cannabis use seems to have become popular drink called KAVA, which is prepared from the especially in India and the Islamic countries. The roots of Piper methysticum. In Polynesia, Mi- ASIA, DRUG USE IN 145 cronesia, and Melanesia this drink is taken for rec- sponse to become intoxicated. In fact, South Ko- reational purposes, to calm and sedate the user. rean males suffer from the highest recorded preva- There are ancient drug-taking practices con- lence rates of alcohol abuse and dependence: An nected to FLY AGARIC, a sometimes deadly mush- estimated 44 percent of adult men have a history of room (Amanita mascaria) found in several coun- currently active or former alcohol abuse and/or de- tries. One way to reduce the toxicity of this pendence. The reasons for this very high rate are a mushroom is to feed it to a reindeer and drink the matterof speculation and should be a topic of reindeer urine, which contains intoxicating metab- intense study. As evidence of the considerable vari- olites of the chemicals found in the mushroom. ation in alcohol problems in Asia, Taiwan has one of the lowest rates of alcohol abuse and dependence in the world for both adult men and women. This STIMULANTS variation cannot be explained by differences in re- Some Asian countries have suffered epidemics of search methods, because the same methods have drug use in connection with legally produced drug been used in surveys of Taiwan and South Korea. products. An especially widespread epidemic of The difference must involve fundamental social and cultural differences, or fundamental biological AMPHETAMINE use started in Japan during World WarII and continued into the 1950s. A second differences in vulnerability to alcohol-related prob- wave of amphetamine use was reported in the late lems, ora combination. Alcohol use is not a new phenomenon in Asia. 1970s. Recently an epidemic of METHAMPHETA- The drinking of fermented beverages has been part MINE ‘‘(ice)’’ smoking spread across the Pacific into of Asian cultures since antiquity, as documented in Hawaii and other American states after earlier mi- the early classical literature of China (in the Shuj- cro-epidemics in Asia. ing and the Liji), India (in the Susruta samhita), and othercountries.The Susruta samhita describes ALCOHOL various stages of intoxication. In China, the fall of the Shang Dynasty in the eleventh century B.C. was The account of drug use in Asia would be incom- attributed to excessive use of alcohol by the em- plete without mention of alcoholic beverages. At peror and his followers. The same explanation was present, Asia is the continent with the lowest over- given forthe fall of laterdynasties. In China, differ- all per-capita consumption of ALCOHOL. In many ent forms of alcohol have been fermented from Asian countries, alcohol consumption is prohibited various kinds of grain. In other parts of Asia, alco- on religious grounds—because of the prohibitions holic beverages were based on a large variety of of Islam: the Koran forbids its use. Nonetheless, different substances, including rice in the case of even in the most conservative Islamic countries, Japanese sake; horse milk in the case of Kumys, an there is some alcohol dependence. Saudi Arabia for alcoholic beverage prepared by northern and cen- example, has an ALCOHOLICS ANONYMOUS (AA) or- tral Asian nomads; and toddy-palm sap in the case ganization and a modern hospital for drug and of arrack prepared in southern India and Indone- alcohol treatment. sia. In addition to religious and social restrictions on An early epidemic of drug use combining alcohol alcohol consumption, there are some important bi- with a drug called hanshi can be traced in the ological factors known to be related to genetic vari- ancient writings of the time of the fall and over- ation within the Asian population. Forexample, throw of the Chinese Han Dynasty—a time of rapid many Asian people have the ‘‘flushing syndrome’’ changes in society (second and third century A.D.). in response to alcohol that is associated with their The use of hanshi was associated with an uncon- particular configuration of aldehyde dehydroge- ventional ‘‘bohemian’’ lifestyle, disregard of social nase, an alcohol-metabolizing enzyme. One promi- norms, ‘‘disheveled hair,’’ and ‘‘incorrect cloth- nent sign is that theirfacial skin becomes flushed. ing.’’ The hanshi users were reported to claim that Although this response might work to discourage the drug helped open their minds and clarify their alcohol use, and thus protect against alcohol de- thinking. Although reports of this early epidemic pendence, many Asian people—especially men— are sketchy, hanshi is mentioned in several later are known to ‘‘drink through’’ the flushing re- medieval texts, mainly in relation to remedies that 146 ASPIRIN can be used to help treat its detrimental side effects. tea orthe illegal trafficof opium. Recently some At present it is not clear which chemical compound countries in Asia have reported an increase in was present in hanshi. POLYDRUG use among theiryoungerpopulation. Since the 1950s, a numberof Asian countries TOBACCO have also experienced a growth of what might best be called ‘‘drug tourism.’’ Travelers, mainly from Probably the most widespread twentieth-cen- the Western Hemisphere, have come to Asia to pur- tury epidemic in Asia is TOBACCO smoking. Today, chase and consume such drugs as opium, Canna- in most Asian countries, local, international, and bis, heroin, and magic mushrooms. For many, it especially American tobacco manufacturers are has come as a surprise that Asian countries respond marketing their products aggressively—in part be- with harsh penalties, as did Singapore in 1994, cause of declining demand in North America and in when a man from the Netherlands was hanged for part because of the increasing economic strength of possessing a large amount of heroin. It must be kept the Asian countries. One result has been an increase in mind that a long history of harsh penalties and in the consumption of tobacco products since the 1960s, especially the smoking of cigarettes. social sanctions against those who violate social Tobacco became a part of Asian culture from the conventions, including local drug regulations, are time it was imported by Europeans from their colo- part of Asian heritage—as well as the seemingly nies in the Americas during the 1600s. The exotic custom of drug use. ‘‘hubbly-bubbly,’’ orhookahs, of the Middle East and India were used for smoking tobacco. This was (SEE ALSO: Source Countries for Illicit Drugs) centuries before modern advertisement techniques were applied by the tobacco industry. But recently, BIBLIOGRAPHY tobacco-related diseases and deaths are becoming more prominent in the health statistics of Asia. This BUREAU OF INTERNATIONAL NARCOTICS AND LAW, U.S. DE- toll is connected directly to an increasing consump- PARTMENT OF STATE. (1999). International narcotics tion of tobacco products. Part of the tobacco is control strategy report (INCSR). Washington, DC. imported from the United States and other interna- HELZER, J. E., and CANINO, G. J. (1992). Alcoholism in tional suppliers. Some observers noticed similari- North America, Europe and Asia. New York: Oxford ties to the situation in the nineteenth-century, when University Press. British traders aggressively fought to keep the lu- HOBHOUSE, H. (1987). Seeds of change: Five plants that crative opium trade from being interrupted. Some transformed mankind. New York: Harper & Row. thus call for international agreements concerning SMART, R. G., and MURRAY, G. F. (1985). Narcotic drug tobacco trade, similar to those which helped curb abuse in 152 countries: Social and economic condi- the opium problem at the beginning of the twenti- tions as predictors. The International Journal of the eth century. International support seems to be Addictions, 20(5), 737–749. needed to help these countries reduce tobacco-re- SPENCER, C. P., and NAVARATNAM, V. (1981). Drug lated problems. abuse in East Asia. Kuala Lumpur: Oxford University Press. THE FUTURE WESTENMEYER, J. (1982). Poppies, pipes and people: Opium and its use in Laos. Berkeley: University of As commerce between countries has increased, California Press. so has the traffic in drugs. For centuries Asia has WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- had trading partners for its tea, opium, and Canna- ICY. (2000). National Drug Control Strategy: 2000 bis. In return it has received shipments of other Annual Report. Washington, D.C. goods, including pharmaceuticals. Sometimes these exchanges have been within Asia, as in the early CHRISTIAN G. SCHUTZ introduction of opium into China by Arabian REVISED BY FREDERICK K. GRITTNER traders, and the later commerce in opium between colonial India and China. Now trading is done on a worldwide scale, whether it is the legal trade with ASPIRIN See Pain: Drugs Used for ASSESSMENT OF SUBSTANCE ABUSE: DRUG ABUSE SCREENING TEST (DAST) 147

ASSERTIVENESS TRAINING See treatment. Most clients with alcohol-related prob- Cognitive Behavioral Therapy; Treatment; Treat- lems scored 5 or below, whereas the majority of ment Types clients with drug problems scored 6 or above on the 20-item DAST. The DAST-10 correlates very with the longerDAST-20 and has (0.98סhighly (r ASSESSMENT OF SUBSTANCE ABUSE: high internal consistency reliability for a brief scale DRUG ABUSE SCREENING TEST (DAST) (0.92 forthe total sample and 0.74 forthe drug- The assessment of drug use and related problems is abuse sample). important for both prevention and clinical care. Subsequent research has evaluated the DAST Measures that are both reliable and valid provide with various populations and settings including tools forhealth education, foridentifying problems psychiatric patients (Cocco & Carey, 1998; Maisto (early if possible) in health care and community et al., 2000; Staley & El Guebaly, 1990), prison settings, and forevaluating the effectiveness of inmates (Peters et al., 2000), substance-abuse pa- treatment. As well, this information is useful for tients (Gavin et al., 1989), primary care (Maly, matching individual needs and readiness for 1993), in the workplace (El-Bassel et al., 1997), change with tailored interventions. and adapted foruse with adolescents (Martinoet The Drug Abuse Screening Test (DAST) was al., 2000). Overall, these studies support the reli- designed to be used in a variety of settings to pro- ability and diagnostic validity of the DAST in di- vide a quick index of drug-related problems. The verse contexts. DAST yields a quantitative index of the degree of Advantages. consequences related to drug abuse. This instru- ment takes approximately 5 minutes to administer 1. The DAST is brief and inexpensive to adminis- and may be given in questionnaire, interview, or ter. Versions are being developed in different computerized formats. The DAST provides a brief, languages (French and Spanish). self-report instrument for population screening, 2. It provides a quantitative index of the extent of identifying drug problems in clinical settings and problems related to drug abuse. Thus, one may treatment evaluation. move beyond the identification of a drug prob- DAST-20 and DAST-10 Versions. The lem and obtain a reliable estimate of the degree DAST was modeled afterthe widely used Michigan of problem severity. Alcoholism Screening Test (Selzer, 1971). Mea- 3. The DAST has been evaluated and demon- surement properties of the DAST were initially strated excellent reliability and diagnostic valid- evaluated using a clinical sample of 256 drug-alco- ity in a variety of populations and settings. hol-abuse clients (Skinner, 1982). The 20-item 4. Routine administration of the DAST would pro- DAST has excellent internal consistency reliability vide a convenient way of recording the extent of (alpha) at 0.95 fortotal sample and 0.86 forthe problems associated with drug abuse, ensuring drug-abuse sample. Good discrimination is evident that relevant questions are asked of all clients/ among clients classified by theirreasonforseeking patients.

TABLE 1 DAST Interpretation Guide DAST-10 DAST-20 Action ASAM*

None 0 0 Monitor Low 1–2 1–5 Brief counseling Level I Intermediate (likely meets DSM** criteria) 3–5 6–10 Outpatient (intensive) Level I or II Substantial 6–8 11–15 Intensive Level II or III Severe 9–10 16–20 Intensive Level III or IV

* ASAM–American Society of Addiction Medicine Placement Criteria ** DSM-IV–American Psychiatric Association 148 ASSESSMENT OF SUBSTANCE ABUSE: HIV RISK ASSESSMENT BATTERY (RAB)

5. The DAST can provide a reference standard for Multi-Health Systems, Toronto (http// monitoring changes in the population over time, www.mhs.com); call 1-800-268-6011 in Canada as well as for comparing individuals in different or1-800-456-3003 in the United States. settings. Limitations. BIBLIOGRAPHY 1. Since the content of the DAST items is obvious, COCCO, K. M. and CAREY, K. B. (1998). Psychometric individuals may fake results. properties of the Drug Abuse Screening Test in psy- 2. Since any given assessment approach provides chiatric outpatients. Psychological Assessment, 10, an incomplete picture, there is a danger that 408-414. DAST scores may be given too much emphasis. EL-BASSEL, N., SCHILLING, R. F., SCHINKE, S., ET AL. Because the DAST yields a numerical score, this (1997). Assessing the utility of the Drug Abuse score may be misinterpreted. Screening Test in the workplace. Research on Social Work Practice, 7, 99-114 Administration, Scoring and Interpretation. GAVIN, D. R., ROSS, H. E., and SKINNER, H. A. (1989). The DAST may be administered in a questionnaire, Diagnostic validity of the DAST in the assessment of interview, or computerized format. The question- DSM-III drug disorders. British Journal of Addiction, naire version allows the efficient assessment of 84, 301-307. large groups. The DAST should not be adminis- MAISTO, S. A., CAREY, M. P. and CAREY, K. B., ET AL. tered to individuals who are presently under the (2000). Use of the Audit and the DAST-10 to identify influence of drugs, or who are undergoing drug alcohol and drug use disorders among adults with a withdrawal. Under these conditions the reliability severe and persistent mental illness. Psychological As- and validity of the DAST would be suspect. Re- sessment, 12, 186-192. spondents are instructed that ‘‘drug abuse’’ refers MALY, R. C. (1993). Early recognition of chemical de- to (1) the use of prescribed or over-the-counter pendence. Primary Care, 20, 33-50. drugs in excess of the directions and (2) any non- MARTINO, S., GRILO, C. M. and FEHON, D. C. (2000). medical use of drugs. The various classes of drugs Development of the Drug Abuse Screening Test for may include cannabis, (e.g., marijuana, hash), sol- adolescents (DAST-A). Addictive Behaviors, 25, vents or glue, tranquillizers (e.g., valium), barbitu- 57-70. rates, cocaine, stimulants, hallucinogens (e.g., PETERS, R. H., GREENBAUM, P. E., STEINBERG, M. L., ET LSD), or narcotics (e.g., heroin). Remember that AL. (2000). Effectiveness of screening instruments in the questions do not refer to the use of alcoholic detecting substance use disorders among prisoners. beverages. Journal of Substance Abuse Treatment, 18, 349-358. The DAST total score is computed by summing SKINNER, H. A. (1982). The Drug Abuse Screening Test. all items that are endorsed in the direction of in- Addictive Behaviors, 7, 363-371. creased drug problems. Guidelines for interpreting SKINNER, H. A. (1994). Computerized lifestyle assess- DAST scores and recommended action are given in ment manual. Toronto: Multi-Health Systems. Table 1. A score of 3 or more on the DAST-10 and STALEY, D., and EL GUEBALY, N. (1990). Psychometric 6 ormoreon the Dast-20 indicates the likelihood of properties of the Drug Abuse Screening Test in a substance abuse ordependence (e.g., DSM IV, psychiatric patient population. Addictive Behaviors, American Psychiatric Association). This diagnosis 15, 257-264. would need to be etablished by conducting a fur- therdiagnostic assessment. HARVEY A. SKINNER Availability. Copies of the DAST may be obtained from H. Skinner, (E-mail: harvey.skinner @utoronto.ca), or from the Centre for Addiction ASSESSMENT OF SUBSTANCE ABUSE: and Mental Health, 33 Russell Street, Toronto, On- HIV RISK ASSESSMENT BATTERY (RAB) tario, Canada M5S 1A8, telephone: 1-800-463- The Risk Assessment Battery (RAB) is a self- 6273 (http://www.camh.net). A computerized ver- administered questionnaire designed for use with sion of the DAST is included in the Computerized substance-using populations. It was developed to Lifestyle Assessment (Skinner, 1994) published by provide a rapid (less than 15 minutes) and confi- ASSESSMENT OF SUBSTANCE ABUSE: HIV RISK ASSESSMENT BATTERY (RAB) 149 dential, non interview method of assessing both unprotected sex even though these behaviors are needle use practices and sexual activity associated common in shooting galleries. Instead, these pe- with HIV transmission. ripheral behaviors may be more readily reported by The forty-five questions of the RAB are simply some respondents despite their reluctance to report worded and use discrete response categories. Re- primary transmission events such as sharing a sy- spondents are asked to ‘‘check off’’ the answer that ringe or unprotected sexual activity. best describes their behavior. There are no open- Scoring. Sixteen items from the RAB are used ended questions, minimizing the need forwriting in the computation of three scores: a drug-risk skills. A brief set of instructions is included on the score, a sex risk score, and a total score. These first page of the RAB. However, as with all self- scores are calculated by adding responses to se- administered questionnaires, it is particularly im- lected items. Forindividual questions, the values portant to provide the respondent with a proper range from zero to a maximum of 4. Higher values introduction and explanation of the form, its pur- for items reflect greater frequency of occurrence for pose, and how it is to be completed. A staff member the behavior. The eight-item drug-risk score has a should be available during administration of the range of 0 to 22. The range of the sex-risk score, test to screen for reading difficulties, answer ques- comprised of nine items, is 0 to 18. This simple tions as they arise, and ensure that the form is being scoring system was designed to capture frequency filled out properly. Given the very sensitive nature of engaging in each of the reported risk behaviors. of the information collected, it is also important Scores for the various items are not differentially that individuals administering the RAB address the weighted. This scoring strategy serves to guard issue of confidentiality. Although the more private against underestimates of risk resulting from the approach of the self-administered questionnaire tendency to under report participation in behaviors should reinforce the confidential nature of the as- known to be most likely to transmit the AIDS virus. sessment, it is very important that respondents un- As a self-administered questionnaire, the RAB derstand the confidentiality of their responses will offers an efficient tool for screening individuals who be protected. may be at risk for HIV infection. The RAB provides There are two global sections within the RAB: a measure of HIV-risk behaviors, which is broken 1) drug and alcohol use during the past 30 days, down into subscales for drug risk and sex risk and and 2) needle use and sexual behaviorduringthe combined to yield a measure of total risk. A number previous 6 months. Questions have been con- of studies conducted by the authors and others sug- structed to provide maximum coverage and sensi- gest that when properly administered, the RAB re- tivity to potential risk behaviors within these cate- sponses are equivalent to those collected via a per- gories. Since self-reports may be expected to sonal interview. Test-retest reliability has also been provide underestimates of behaviors that are so- found to be relatively high. Most importantly, the cially unaccepted, items have been assembled that RAB has demonstrated discriminant validity in dif- assess a wider range of behaviors associated with ferentiating between respondents engaging in dif- HIV infection. Thus, questions ask not only about ferent drug-use patterns and predictive validity in the behaviors directly responsible for viral trans- identifying seroconverters on the basis of higher- mission such as needle sharing and unprotected risk scores. sexual activity, but also those associated with such As the AIDS epidemic enters its third decade, it activities (e.g., needle acquisition, shooting gallery has become increasingly important to have valid, attendance, exchange of money ordrugsforsex). reliable, and cost-effective tools to monitor behav- The inclusion of these items is intended to identify iors associated with the transmission of HIV. It is individuals at increased risk of HIV exposure even no longer sufficient to direct prevention resources if transmission behaviors are not directly reported. toward populations at risk in a ‘‘shotgun’’ ap- However, endorsement of these ‘‘peripheral behav- proach to risk reduction. Such a strategy is costly iors’’ does not prove that transmission behaviors and inefficient since many individuals within risk have actually occurred. For example, an individual groups have instituted safer behaviors. Targeting who indicates that he orshe has visited a shooting risk-reduction interventions to specific segments of gallery on numerous occasions during the assess- the population at risk and evaluating their efficacy ment interval may not have shared a needle or had are necessary components in a well-planned ap- 150 ASSESSMENT OF SUBSTANCE ABUSE: MAST proach to HIV prevention. Measures of risk behav- much more common than full FAS. There are ana- ior, such as the RAB, are needed to target and tomic anomalies, called alcohol-related birth de- evaluate interventions in a more precise manner. fects (ARBD) and alcohol-related neurobehavioral disorder (ARND), a set of behavioral abnormalities BIBLIOGRAPHY in offspring prenatally exposed to substantial levels of alcohol. Other adverse pregnancy outcomes re- METZGER D., DEPHILIPPIS, D., DRULEY, P., O’BRIEN, C., lated to maternal drinking during pregnancy in- MCLELLAN, A. T., WILLIAMS, J., NAVALINE, H., AND clude miscarriage and stillbirth. DYANICK, S., WOODY, G. (1992). The impact of HIV A national goal to reduce the prevalence of FAS testing on risk for AIDS behaviors. In L. Harris by one half by decreasing maternal drinking was (Eds.), problems of drug dependence: nida research set in Healthy People 2000. Unfortunately, the monograph 119, Washington, D.C.: National Institute reported prevalence did not decrease through the on Drug Abuse. 297–298. 1990s, but, in fact, increased, possibly because of METZGER, D., WOODY, G., MCLELLAN, A., O’BRIEN, C., improved case finding. Regardless, it is likely that DRULEY, P., NAVALINE, H., DEPHILIPPIS, D., STOLLEY, heavy drinking in pregnancy did not decrease, de- P., and ABRUTYN, E. (1993). Human immunodefi- spite warning labels on all alcoholic beverages since ciency virus seroconversion among in- and out-of- 1989. treatment intravenous drug users: An 18-month pro- There is evidence that pregnant women are re- spective follow-up. Journal of Acquired Immune Defi- ceptive to advice from their health care providers, ciency Syndromes, 6, 1049–1056. particularly their physicians, to quit or at least cut DAVID S. METZGER down both drinking alcohol and smoking ciga- HELEN A. NAVALINE rettes. Given that generalized warnings, such as the GEORGE E. WOODY warning label, have not proven effective, a more focused approach would seem reasonable—this would focus prevention efforts on women who ASSESSMENT OF SUBSTANCE ABUSE: drink or are likely to drink enough during preg- nancy to damage their offspring. Such drinking has MAST See Appendix, Volume 4. been labeled ‘‘risk drinking.’’ The precise level of drinking that might damage the embryo/fetus is unknown, but is probably vari- ASSESSMENT OF SUBSTANCE ABUSE: able because of differing susceptibility and differ- T-ACE Heavy maternal drinking is a major ing exposures depending on exactly which adverse pregnancy risk and a significant public health effect is considered and when during pregnancy the problem. Fetal Alcohol Syndrome (FAS) was first exposure occurs (critical period). Solid estimates of reported as a recognizable clinical syndrome nearly risk drinking have decreased over the years, as thirty years ago. It is characterized by betterinterviewingand statistical techniques have 1) prenatal and/or postnatal growth restriction become available. It is now reasonable to use a 2) central nervous system (brain) abnormalities figure of about seven drinks per week, typically and massed on one ortwo days, but averagingabout 3) facial dysmorphology, i.e., an abnormal ap- one drink per day or 0.5 ounces of absolute alcohol pearing face characterized by underde- perday. This is the amount of absolute alcohol in velopment of the midface with small eyes, a one can of beer, one glass of wine or one mixed short nose and a long simple (flat) philtrum, the drink of standard size. This amount of alcohol intake, while unlikely to pose any health risk to the area below the nose and above the upper lip. mother, is enough to adversely affect the embryo/ As these children grow up, they are often mildly fetus. There is not convincing evidence of clinically mentally retarded, with average IQs of about 70 important effects on the offspring from an occa- and disabling behavioral abnormalities. In addi- sional drink during pregnancy. tion, there is a continuum of abnormalities among There are, as of yet, no laboratory tests, i.e., offspring exposed before birth to alcohol, but with- biological markers, which will reliably identify risk out the full syndrome—abnormalities that are drinking women. The only way to identify them is ASSET FORFEITURE 151

TABLE 1 The T-ACE Questionnaire Question Answer Score

T How many drinks can you hold (TOLERANCE)? 62 A Have people ANNOYED you by criticizing your drinking? Yes 1 C Have you felt you ought to CUT DOWN on your drinking? Yes 1 E Have you ever had a drink first thing in the morning to steady your nerves or get rid Yes 1 of a hangover (EYE-OPENER)?

The Tolerance Question is positive if the patient admits that she can hold, i.e., not get sick or lose consciousness, at least a sixpack of beer, a bottle of wine, or six standard drinks. As in the old song, (T) for two and two for (T) and, as in blackjack, each ACE is worth one. A total score of two or more is positive.

to obtain an appropriate history of drinking, but be at risk to drink too much during pregnancy and this is complicated by DENIAL—the woman doesn’t should be counseled. want to admit drinking to herself or to her doctor. A final point—screening for risk drinking is not Further, time is distinctly limited during prenatal enough. At the minimum a brief intervention to visits and there are many problems to identify and support the patient in becoming abstinent during address. Thus, a brief, simple questionnaire was pregnancy or at the minimum cutting way down is needed. Most brief questionnaires, such as the warranted, as is close follow-up. If alcohol abuse or CAGE, were developed and tested almost entirely dependence is present, consultation or referral may in male populations, and do not function well for be warranted. reproductive age women. The T-ACE questions were developed specifi- BIBLIOGRAPHY cally as a screening test for risk drinking. They CHANG, G., ET AL. (1998). Alcohol use and pregnancy: have been tested and validated overthe last decade Improving identification. Obstetrics and Gynecology, in women of multiple ethnicities, including white, 91, 892–898. African American and Native American, and in a RUSSELL, M., ET AL.(1996). Detecting risk drinking dur- range of socioeconomic statuses and geographic lo- ing pregnancy: A comparison of four screening ques- cations. The original questionnaire included the tionnaires. American Journal of Public Health, 86, question, ‘‘How many drinks does it take to make 1435–1439. you feel high?’’ as the (T)olerance question. An RUSSELL,M.ET AL. (1994). Screening for pregnancy answer of greater than two standard drinks was risk-drinking. Alcoholism: Clinical and Experimental considered positive. Several studies have now Research, 18, 1156–1166. shown that substituting the hold question, included SOKOL, R. J., ET AL. (1989). The T-ACE questions: Prac- in Table 1, instead of the high question, gives better tical prenatal detection of risk drinking. American results, improving the sensitivity of the T-ACE Journal of Obstetrics and Gynecology, 160, 863–870. questions. ROBERT J. SOKOL T-ACE is a screening test, so it was designed to pick up as high a proportion of risk drinkers as possible. This version picks up about nine in ten ASSET FORFEITURE Asset forfeiture is women who drink enough in pregnancy potentially the involuntary relinquishment of money or prop- to damage theirbaby. If the scoreis less than two, erty without compensation as a consequence of a i.e., the T-ACE is negative, it will correctly identify commission of a crime. Forfeiture laws authorize about seven in ten women who are not risk drink- prosecutors to file civil lawsuits asking a court for ers. It has a substantial false positive rate, i.e., permission to take property from a criminal defen- warning the clinician, though the patient is not, in dant that was eitherused in the crimeorwas the fact, a risk drinker. It has been speculated though fruit of a criminal act. Since the 1970s, federal that any woman who scores positive might, in fact, asset forfeiture laws have been used against drug 152 ASSET FORFEITURE dealers. By 2000, however, there were many in In a civil forfeiture proceeding, the government Congress and the legal community who urged re- must prove that the property is subject to forfeiture form of these forfeiture laws, as they have been because there is a substantial connection between often resulted in harsh and unfair outcomes for the property and the crime. If the defendant fails to innocent third parties. rebut this proof with sufficient evidence, the gov- In 1970, Congress enacted the Comprehensive ernment is allowed to keep the property. At the Drug Abuse Prevention and Control Act, also trial, the government’s standard of proof is by a known as the Forfeiture Act. The Forfeiture Act preponderance of the evidence, a lesser burden of authorized federal prosecutors to bring civil forfei- proof than the criminal standard of a reasonable ture actions against certain properties owned by doubt. persons convicted of federal drug crimes. The act The Forfeiture Act permits law enforcement was not used much because it limited forfeiture to agencies to receive a part of the proceeds from the property of persons convicted of participating property forfeiture. Prior to the 1984 amendments, in continuing criminal enterprises. In 1978, Con- all revenue derived from a federal asset forfeiture gress amended the law to allow forfeiture of any- was deposited into the U.S. Treasury general fund. thing of value used orintended to be used by a The 1984 law allowed federal law enforcement person to purchase illegal drugs. This expanded the agencies to keep all proceeds from confiscated act to allow the forfeiture of all proceeds and prop- property and to use the proceeds to support asset- erty traceable to the purchase of illegal drugs. The seizure programs. State and local law enforcement amended law authorized the federal government to agencies that turned over their seizure cases to proceed in rem against property. In rem forfeiture federal authorities received up to 80 percent of the profit after the property had been sold. Many legal proceedings are actions taken against the property, scholars criticized this feature of the law, arguing not the owner of the property. This allows the gov- that it detracts from the traditional police function ernment to remove property from persons suspec- of fighting crime and created incentives for police ted of a crime without ever charging them with a to pursue forfeitures that lacked probable cause. crime. Proponents of this budgetary scheme argue that Congress amended the Forfeiture Act again in drug activity is the source of much violent crime 1984 as part of the Comprehensive Crime Control and that the proceeds benefit community programs Act. The amendment authorized the federal gov- and increase the capacity to fight violent crime. ernment to pursue in rem forfeitures of land and Most states also have forfeiture laws upon con- buildings. Federal authorities may seize any real viction of certain crimes. These laws often mandate property purchased, used, or intended to be used to forfeiture of prohibited drugs, property used to facilitate narcotics trafficking. Although Congress contain, protect, or secure prohibited drugs, fire- appears to have intended the law to apply only to arms, and vehicles. In contrast to the federal law, drug manufacturing or storage facilities, federal many states require that profits from the sale of courts have interpreted the law to allow the seizure forfeited property be deposited in the state’s gen- of any real property, including fraternity houses, eral treasury fund. hotels, ranches, and private residences. In addition, Defendants have employed several defenses to courts have allowed forfeitures regardless of forfeiture and some have proved successful. If no- whether the property was used to store or manufac- tice and a hearing before a court do not precede the ture drugs. initial seizure, a defendant may argue that forfei- The process of seizing property under the Forfei- ture violates the Due Process Clause of the Fifth ture Act is straightforward. Forfeiture begins with and Fourteenth Amendments. If a forfeiture is dis- the constructive or actual seizure of property after a proportionate to the offense that gave rise to it, it warrant has been issued by a federal district court. may be found to violate the Eighth Amendment’s This warrant must be based on the reasonable be- Excessive Fines Clause. lief that the property was used in a crime subject to Congress has also responded to criticism by forfeiture, but this belief can be based on hearsay enacting an ‘‘innocent owner’’ defense in civil drug and circumstantial evidence. After the property is forfeiture cases. These are cases where forfeiture is seized, the court holds it until the case is resolved. sought without prosecution of the owner. A defen- ASSOCIATION FOR MEDICAL EDUCATION AND RESEARCH IN SUBSTANCE ABUSE (AMERSA) 153 dant in a civil forfeiture case may invoke this de- in the field of substance abuse. The organization was fense if the property was connected with illegal derived from an informal coalition of U.S. Federal drugs without the owner’s knowledge or consent. Career Teachers in alcoholism and drug abuse; Forexample, if the ownerof an automobile inno- these career teachers, one on the faculty of each of cently allows another person to borrow the car and fifty-five medical schools, were funded by the Na- that person commits a drug offense in the car, the tional Institute on Drug Abuse (NIDA) and the Na- owner can offer this defense and retain the car. tional Institute on Alcohol Abuse and Alcoholism As state and federal prosecutors intensified their (NIAAA) to promote enhanced teaching at their use of asset forfeiture laws, public grew. By the respective medical campuses. The Career Teachers early 1990s, the federal government was prosecut- Program, established in 1972, was regarded as a ing only 20 percent of the individuals from whom highly successful vehicle forhighlighting an issue of they seized property through forfeiture. According considerable importance in the medical curriculum. to Department of Justice statistics, over 28,000 As the program wound down (it came to an end in properties were seized in 1996, with a combined 1981), the participants felt it important to secure value of $1.264 billion. Critics have argued that the the continuation of theirmission and established government routinely violates the Fifth Amend- AMERSA as a national membership organization ment’s ban against taking property without due open to all medical faculty and faculty in allied process of law, largely because it sees forfeiture as health programs. an easy way to collect funds. Supporters have coun- In the yearof its establishment, AMERSA held tered that forfeiture has helped in the war on drugs its first national meeting, which was followed by by stripping criminals of their resources. meetings of increasing attendance in each suc- Congress finally responded by passing the Civil ceeding year. The national meetings have been the Asset Forfeiture Reform Act of 2000. It requires focus of federal participation in teaching programs federal prosecutors to show a substantial connec- and have focused on curriculum techniques and tion between the property and the crime. In addi- new research findings. tion, it allows the property to be released by the AMERSA established a quarterly publication, district court pending final disposition of the case Substance Abuse, in 1979, presenting educational when the ownercan demonstratethat possession by and research findings; it serves as a vehicle for the government causes a hardship to the owner. broadening the base of teaching in the members’ Moreover, the law allows owners of property to sue fields. In addition, a variety of curricula were estab- the government for any damage to the property if lished by members, with coordination through the the victim of the seizure prevails in a civil forfeiture AMERSA national headquarters (located in Provi- action. dence, Rhode Island) and augmented by the Center forMedical Fellowships in Alcoholism and Drug BIBLIOGRAPHY Abuse, located at New York University.

WEST’S ENCYCLOPEDIA OF AMERICAN LAW (1997). St. Paul, Full membership is available for all persons MN: Westgroup. holding faculty appointments in health-profes- O’MEARA, K. (2000). When feds say seize and desist. sional schools and/orto those involved in substance Insight on the News, Aug. 7. abuse education or research. Membership benefits include a free subscription to Substance Abuse; FREDERICK K. GRITTNER reduced rates at the annual conference; and a na- REVISED BY DONNA CRAFT tional voice that supports academic programs in universities, professional schools, and organiza- ASSOCIATION FOR MEDICAL EDUCA- tions that promote substance abuse education and TION AND RESEARCH IN SUBSTANCE research. ABUSE (AMERSA) The Association forMedi- The organization’s members work in a variety of cal Education and Research in Substance Abuse ways to effect theireducational ends. Much effortis (AMERSA) is a national organization of more than invested in developing curriculum and curriculum 300 medical and allied faculty, which was founded outlines for courses directed at a variety of disci- in 1976 for the promotion of education and research plines and various educational levels. In addition, 154 ATHLETES AND DRUGS most members work actively within their respective from the structured diagnostic interviews that have departments to develop subspecialty expertise—as been implemented in the past. Significant develop- in psychiatry and internal medicine. Efforts are ments have been made in these structured diagnos- also directed at schoolwide initiatives—as with tic interviews over more than two decades, but programs organized through the deans of medical along with these improvements have come prob- schools. lems. This alternative diagnostic method may have MARC GALANTER potential for strengthening the authority of child psychiatric diagnosis (Edelbrock, Crnic & Bohnert, 1999). ATHLETES AND DRUGS See Anabolic Children who qualify for a diagnosis of ADHD Steroids often, but not invariably, meet criteria also for a diagnosis of conduct disorder or oppositional de- fiant disorder. In addition, attention deficit disorder ATROPINE See Jimsonweed; Scopolamine does not always occurin conjunction with behav- and Atropine ioral hyperactivity. These latter individuals are as- signed the diagnosis of undifferential attention def- icit disorder. ATTENTION DEFICIT DISORDER Characteristically, youth with ADHD demon- Children and adolescents who ‘‘act out’’ their feel- strate an excessively high level of behavioral activ- ings, frustrations, and emotional conflicts are said ity across a wide variety of situations. The behav- to exhibit externalizing behavior. Within the ioral disturbance is most apparent, however, where framework of the American Psychiatric Associa- the appropriate level of behavioral activity should tion’s DIAGNOSTIC AND STATISTICAL MANUAL,3rd be low, such as in a classroom where focused task- edition, revised (DSM-III-R), once a certain level of oriented cognitive demands are placed on the severity is demonstrated, these youth qualify for youngster. In naturalistic settings, ADHD children, the umbrella diagnosis of disruptive behavior disor- although not overtly hyperactive, typically are im- der. Three disorders are encompassed within this pulsive, emotionally labile, restless, and general diagnostic category: (1) attention deficit/ distractable. They often act in a socially intrusive hyperactivity disorder (ADHD); (2) CONDUCT and inappropriate manner such that they are con- DISORDER (CD); and (3) oppositional defiant sidered to be immature. Consequent to poor fore- disorder. sight and poorimpulse control,combined with a It should be noted that in recent years some high behavior level, ADHD children frequently get controversy has developed concerning diagnostic into social difficulties with adults and peers, which techniques. It has been suggested that with the subsequently lead to rejection. Physical injury is introduction of the American Psychiatric Associa- common in ADHD because of poorself-control tion’s DIAGNOSTIC AND STATISTICAL MANUAL, (e.g., dashing across the street without looking). fourth edition (DSM-IV) in 1994, accurately diag- Because ADHD symptomatology is often present nosing ADHD in adults has become problematic in children with poor coordination, reading and ‘‘because of the vague nature of the criteria’’ in learning problems, and other neurodevelopmental DSM-IV (Higgins, 1999). Comparatively, in more disturbances, in the past labels such as ‘‘minimal recent studies, a different approach for adminis- brain damage’’ and ‘‘minimal brain dysfunction’’ trating the Diagnostic Interview Schedule for Chil- were assigned, although no neurologic pathology or dren (DISC), based on communication principles, injury was detectable. The terms ‘‘hyperactivity’’ has marked a shift from structured interviewing to and ‘‘hyperkinesis’’ were subsequently introduced; a more open communication model. This commu- however, these labels emphasize the motor aspects nication model is defined by three factors: (1) a of the disorder. The current diagnostic label— schematic representation of the areas to be covered; attention deficit disorder—circumvents these (2) a common language forthe categories,diagno- problems by focusing on the core etiological deter- sis, and criteria; and (3) the respondent was per- minant forthe multifaceted expressionof cognitive, mitted to chose the order of the diagnostic areas to behavioral, and emotional disturbances. For this be covered. This new method is a notable departure diagnosis to be assigned, the disorder must first be ATTENTION DEFICIT DISORDER 155 expressed before age 7, have at least a 6-month the developing fetus, malnutrition, exposure to duration, and not be the consequence of a pervasive toxins (especially alcohol), and medical illness dur- developmental disorder (American Psychiatric As- ing pregnancy augment the risk for ADHD symp- sociation, 1987). toms to appear. Circumstances around birth, espe- cially the occurrence of toxemia (toxins in the EPIDEMIOLOGY blood) orhypoxemia (not enough oxygen in the blood), increase the risk for neurological injury in Approximately 10 percent of boys and 3 percent the newborn, which ultimately could result in of girls in the general population qualify for a diag- symptoms of ADHD. During childhood develop- nosis of ADHD. The symptom presentation is dif- ment, many factors, particularly head trauma (by ferent between the genders, with girls being some- accident ormaltreatment),infection, toxic poison- what olderthan boys at the time of firstdiagnosis. ing, and malnutrition can produce ADHD symp- Girls manifest more mood changes, fears, and so- toms. Neurologic conditions (e.g., epilepsy) and cial withdrawal than boys but less aggressivity and neurodevelopmental disorders (e.g., dyslexia, impulsivity. Among children receiving psychiatric autism) are also commonly associated with some treatment, ADHD is estimated to be present in 40 symptoms of ADHD. Although all these lattercon- to 70 percent of inpatient cases and 30 to 50 per- ditions produce ADHD-type symptoms, according cent of outpatient cases. to DSM-III-R they must be excluded as etiologic factors to make the diagnosis of the ADHD syn- GENETIC ETIOLOGY drome. In other words, the diagnosis of ADHD is Behavior-activity level is a heritable trait of tem- assigned only where there is no neurodevelop- perament characterizing the human species. Indi- mental disability orinjury. viduals who are at the high end of this trait, com- pared to the average, are behaviorally highly active NATURAL HISTORY or hyperactive. Thus, although not necessarily im- plying pathology or a disorder, but rather normal Recognizing that there is substantial variability variation in behavioral disposition, high-end active in the etiology of ADHD, it is obvious that the individuals demonstrate a rapid behavioral tempo lifetime course and outcome is also highly variable. and greater vigor and forcefulness than the aver- Symptoms persist into adulthood in about 50 per- age. Forclinicians, it is importantto distinguish cent of cases. Under these circumstances, the per- between individuals with behavior-activity level as son is assigned a diagnosis of attention deficit dis- a temperament trait and extreme cases that com- order-residual type. prise psychological and psychiatric disorder. Formany individuals, extremelyhigh manifes- RELATION OF ADHD TO DRUG ABUSE tations of behavior-activity level has a genetic ba- Serious psychiatric disorder is common among sis. ADHD aggregates in families and twin studies adults with a history of ADHD. ANTISOCIAL show high concordance rates for this disorder. The PERSONALITY disorder, alcohol and substance neurobiological mechanisms underlying ADHD is abuse, depression, and anxiety are the most com- an active topic of research. As of the mid-1990s, we mon associated disorders. These associated disor- assume that the neurochemistry in such people is ders should not be viewed as invariant outcomes of likely to be disturbed; however, a candidate neuro- ADHD but rather as disturbances for which ADHD transmitter system has yet to be identified. Most youth are at increased risk. Whether any of these likely, multiple neurochemical systems are in- psychiatric outcomes are manifested depends on a volved. Neuroimaging studies have revealed low- ered brain metabolism, particularly in the frontal variety of factors besides ADHD, including the regions, in ADHD children (Zametkin et al., 1990). child’s self-esteem, opportunity for normal social- ization with peers, success in school, and level of social and family support (Tarter, 1988). NONGENETIC ETIOLOGY With respect to alcohol and other drug abuse, Injury to the brain, particularly in the anterior augmented risk appears to be circumscribed to region, can produce the symptoms of ADHD. For youth who have both ADHD and a conduct disor- 156 ATTENTION DEFICIT DISORDER der. The association, however, between ADHD and Lifestyle. Coordinated effort should be made substance abuse is complex. Alcohol and other to promote a healthy lifestyle, including scheduled drugs may be more subjectively rewarding for regulation of bedtime, meals, homework, and rec- ADHD youth and adults than in the general popu- reation. Nutrition is important; however, contrary lation. Drug use is commonly tied to a general to popular belief and anecdotal reports, there is no pattern of social deviancy and nonnormative peer substantive evidence linking diet orfood allergies affiliation. Where the ADHD person has been ostra- to the cause of ADHD. There is no scientific evi- cized by the normative peer group, the use of dence indicating that a special diet ornutritional alcohol/drugs may be just another manifestation of supplements can ameliorate ADHD. generalized maladjustment. Furthermore, alcohol/ Education. Informing parents and school per- drug use may be mediated by a coexisting psychiat- sonnel about the causes of ADHD and the nature of ric disorder, such as anxiety and depression, and the behavior disorder can constructively assist the thus reflect an attempt at self-medication. There- child by evoking empathy rather than anger. Thus, fore, although there is substantial evidence demon- family counseling and teachereducation areinte- strating an increased risk for alcohol/drug abuse in gral components of treatment to help maximize the ADHD youth, this association is complex and is child’s adjustment in the home and at school. contingent on many factors. Environmental Engineering. Structuring the environment so that the child is not easily distracted is an important intervention. In the TREATMENT home, this entails minimizing distracting stimula- Because the psychological manifestations of tion from radio or television, especially while the ADHD are multifaceted, it is necessary that com- youngster is doing homework. In the classroom, prehensive treatment interventions that encompass consideration should be given to the child’s seat multiple components be implemented (Danforth, location to enable the teacherto ensurethat the Barkley, & Stokes, 1991). child persists at tasks, is not distracted by other Pharmacotherapy. PSYCHOSTIMULANTS are students, or has no opportunity to be disruptive. therapeutically beneficial for approximately 75 Behavior Modification. Behavior-modifica- percent of ADHD children and adults. The most tion strategies are effective for training the young- commonly used medications are METHYLPHENI- sterto controlimpulses and to monitorbehavior DATE (Ritalin), d-AMPHETAMINE, and PEMOLINE cognitively. Behavior-modification methods, which (Cylert). Tricyclic antidepressants are also effective help the child, are also useful in teaching effective in many cases. These medications have been shown parenting skills. to be useful for reducing problem behavior of ADHD in more than 100 research studies; however, (SEE ALSO: Psychomotor Stimulant; Vulnerability they do not improve school performance or elimi- As Cause of Substance Abuse) nate a conduct disorder where this disturbance is present. BIBLIOGRAPHY Additionally, it is interesting to note that recent AMERICAN PSYCHIATRIC ASSOCIATION (2000). Attention studies of the effects of stimulant medication treat- Deficit Disorder—Part I. Harvard Mental Health Let- ment have produced disparate results. A 1998 ter, 17, issue 2. study by N. M. Lambert and C. S. Hortsough puts DANFORTH, R., BARKLEY, R., & STOKES, T. (1991). Ob- forward that stimulant medication treatment may servations of parent-child interactions with hyperac- be a ‘‘gateway to abuse’’, suggesting a connection tive children: Research and clinical implications. between stimulant treatment and adult dependence Clinical Psychology Review, 11, 703–727. on cocaine as well as tobacco. Alternately, a 1999 AMERICAN PSYCHIATRIC ASSOCIATION (1987). Diagnostic study by Joseph Biederman, Eric Mick, Stephen V. and statistical manual of mental disorders, 3rd ed. Faraone, T. Wilens, and T. Spencer found phar- Washington, DC. macotherapy to be responsible for a significant BIEDERMAN, J., MICK, E., & FARAONE, S. V. (2000). Let- reduction in substance abuse for young people with terto the Editor. Journal of Learning Disabilities, 33, ADHD (Beiderman, Mick & Faraone, 2000). 4, 314. Response to article by N. M. Lambert and AYAHUASCA 157

C. S. Hartsough (1998). Journal of Learning apparently several variations in the recipe for caapi Disabilites, 31, 533. and most of those who have studied it believe that EDELBROCK, C., CRNIC, K., & BOHNERT, A. (1991). Inter- each recipe produces somewhat different psychic viewing as Communication: An Alternative Way of effects. In 1929, the great pioneer of psychophar- Administrating the Diagnostic Interview Schedule for macology, Louis Lewin, published a monograph Children. Journal of Abnormal Child Psychology, describing the pharmacological actions and possi- 27(6), 447. ble therapeutic uses of Banisteria caapi, whose ac- GLICKEN, A. D. (1997). Attention deficit disorder and the tions he believed to be due to an active alkaloid, pediatric patient: a review. Physician Assistant, harmine. In early studies in patients with Parkin- 21(4), 101–112. sonism, harmine produced improvements in chew- HIGGINS, E. S. (1999). A Comparative Analaysis of Anti- ing, swallowing, and movement that lasted from depressants and Stimulants for the Treatment of two to six hours. Curiously, it was reported to have Adults with Attention-Deficit Hyperactivity Disorder. little orno psychic effects. It was latershown that Journal of Family Practice, 48(1), 15–16. harmine acts to inhibit the enzyme monoamine JENSEN, P. S., & EDELBROCK, C. (1999). Subject and oxidase, thereby raising levels of the neurotrans- Interview Characteristics Affecting Reliability of the mitters DOPAMINE and NOREPINEPHRINE. Diagnostic Interview Schedule for Children. Journal Mixtures containing Banisteriopsis caapi are of Abnormal Child Psychology, 27(6), 413. still in use among the indigenous peoples of the LAMBERT, N. M., & HARTSOUGH, C. S. (2000). Letterto Amazon. A tea brewed from it and the leaves of the Editor. Journal of Learning Disabilities 31, 533. Psychotria viridis has been used in shamanistic rit- Resonse to Biederman, Mick & Faraone, 2000. uals for hundreds of years in Colombia, Brazil, and NIGG, J. T. (1999). The ADHD Response-Inhibition Defi- Peru. In recent years, a number of people seeking cit as Measured by the Stop Task: Replication with alternatives to Western medicine, and for other rea- DSM-IV Combined Type, Extension, and Qualifica- sons, have participated in Santo Daime rituals, in tion. Journal of Abnormal Child Psychology, 27(5), which drinking ayahuasca is a central feature. The 393. tea is said to induce ecstatic states, during which TARTER, R. (1988). Are there inherited behavioral traits the participants claim to experience great insight. which predispose to substance abuse? Journal of Con- In southern Brazil, some psychotherapists and ho- sulting and Clinical Psychology, 56, 189–196. meopaths have been known to bring clients or pa- ZAMETKIN, A., ET AL. (1990). Cerebral glucose metabo- tients to participate in such rituals. lism in adults with hyperactivity of childhood onset. New England Journal of Medicine, 323, 1361–1366. (SEE ALSO: Hallucinogenic Plants; Hallucinogens) RALPH E. TARTER ADA C. MEZZICH BIBLIOGRAPHY REVISED BY CHRIS LOPEZ DEULOFEU, V. (1967). Chemical compounds isolated from Banisteriopsis and related species. In D. H. AVERSION THERAPY See Treatment Efron, B. Holmstedt, & N. S. Kline (Eds.), Ethnopharmacologic search for psychoactive drugs. AYAHUASCA In 1851, the botanist Richard Washington, DC: Public Health Service Publication Spruce observed natives along the Rio Negro in no. 1645. Brazil preparing a beverage from the roots of a LEWIN, L. (1964). Phantastica: Narcotic and stimulat- vine, which he called Banisteria caapi, of the fam- ing drugs. New York: Dutton. ily Malpighiaceae (it was recently designated Ban- SCHULTES, R. E. (1967). The place of ethnobotany in the isteriopsis caapi.) He laterobservedthe use of a ethnopharmacologic search for pychotomimetic similar drink in the Ecuadorian Amazon basin, drugs. In D. H. Efron, B. Holmstedt, & N. S. Kline, where it was called ayahuasca (from the Quechua (Eds.), Ethnopharmacologic search for psychoactive language, spoken in the Andes). He noted that the drugs. Washington, DC: Public Health Service Publi- brew was often a mixture of Banisteria caapi with cation no. 1645. the roots of another indigenous plant. There were JEROME H. JAFFE B

BAC See Blood Alcohol Concentration, Mea- quickly used to treat a number of disorders effec- sures of tively, their side effects were becoming apparent. The chief problem, an overdose, can result in res- piratory depression, which can be fatal. By the BARBITURATES Barbiturates refer to a mid-1950s, more than 70 percent of admissions to a poison-control center in Copenhagen, Denmark, class of general central nervous system depressants involved barbiturates. Additionally, it became ap- that are derived from barbituric acid, a chemical parent that the barbiturates were subject to abuse, discovered in 1863 by the Nobel Prize winner in which could lead to dependence, and that a serious chemistry (1905) Adolf von Baeyer (1835–1917). withdrawal syndrome could ensue when the drugs Barbituric acid itself is devoid of central depressant were abruptly discontinued. In the 1960s, the in- activity; however, German scientists Emil Her- troduction of a safer class of hypnotic drugs, the mann Fischer and Joseph von Mering made some B ENZODIAZEPINES reduced the need for modifications to its structure and synthesized barbiturates. barbital, which was found to possess depressant Barbiturates are dispensed in distinctly colored properties. Scientists had been looking for a drug to capsules making them very easy to identify by the treat anxiety and nervousness but without the de- lay public. In fact, users within the drug culture pendence-producing effects of OPIATE drugs such often refer to the various barbiturates by names as OPIUM,CODEINE, and MORPHINE. Other drugs associated with their physical appearance. Exam- such as bromide salts, CHLORAL HYDRATE, and ples of these names include blue birds, blue clouds, paraldehyde were useful sedatives, but they all had yellow jackets, red devils, sleepers, pink ladies, and problems such as toxicity or they left such a bad Christmas trees. The term goofball is often used to taste in patients’ mouths that they preferred not to describe barbiturates in general. All barbiturates take them. Fischer and von Mering noted that are chemically similar to barbital, the structure of barbital produced sleep in both humans and ani- which is shown in Figure 1. mals. It was introduced into chemical medicine in All barbiturates are general central nervous sys- 1903 and was soon in widespread use. tem depressants. This means that sedation, sleep, By 1913, the second barbiturate, PHENOBARBI- and even anesthesia will develop as the dose is TAL, was introduced into medical practice. Since increased. Some barbiturates also are useful in re- that time, more than 2,000 similar chemicals have ducing seizure activity and so have been used to been synthesized but only about 50 of these have treat some forms of epilepsy. The various barbitu- been marketed. Although the barbiturates were rates differ primarily in their onset and duration of

159 160 BARBITURATES

of sleep. Prolonged use of barbiturates causes rest- lessness during the late stages of sleep. Since the barbiturates remain in our bodies for some time after we awaken, there can be residual drowsiness that can impair judgment and distort moods for some time after the obvious sedative effects have disappeared. Curiously, some people are actually Figure 1 excited by barbiturates, and the individual may Barbital even appear inebriated. This paradoxical reaction often occurs in the elderly and is more common action, ability to enter the brain, and the rate at after taking phenobarbital. which they are metabolized. These differences are The general use of barbiturates as hypnotics achieved principally by adding or subtracting at- (SLEEPING PILLS) has decreased significantly, since oms to the two branches on position ࠻5 in Figure 1. they have been replaced by the safer benzodiaze- The barbiturates are classified on the basis of their pines. Phenobarbital and butabarbital are still duration of action, which ranges from ultrashort- available, however, as sedatives in a number of acting to long-acting. The onset of action of the combination medications used to treat a variety of ultrashort-acting barbiturates occurs in seconds inflammatory disorders. These two drugs also are and lasts a few minutes. The short-acting com- used occasionally to antagonize the unwanted over- pounds take effect within a few minutes and can stimulation produced by ephedrine, AMPHETAMINE, last four to eight hours, while the intermediate- and and theophylline. long-acting barbiturates can take almost an hour to Since epilepsy is a condition of abnormally in- take effect but last six to twelve hours. Table 1 lists creased neuronal excitation, any of the barbiturates the common barbiturates, their trade names, typi- can be used to treat convulsions when given in cal route of administration, and plasma half-life. anesthetic doses; however, phenobarbital has a se- The plasma half-life is a measure of how long the lective anticonvulsant effect that makes it particu- drug remains in the blood, but not how long the effects last, although it does provide a general indi- larly useful in treating grand mal seizures. This cation of when to expect the effects to wane (a half- selective effect is shared with mephobarbital and life of five hours means that one-half of the drug metharbital. Thus, phenobarbital is often used in will be removed from the system in five hours; one- hospital emergency rooms to treat convulsions such half of the remaining drug will be removed during as those that develop during tetanus, eclampsia, the next five hours, etc.). status epilepticus, cerebral hemorrhage, and poi- soning by convulsant drugs. The benzodiazepines are, however, gradually replacing the barbiturates EFFECTS ON THE BODY AND in this setting as well. THERAPEUTIC USES It is not completely understood how barbiturates Barbiturates affect all excitable tissues in the work but, in general, they act to enhance the activ- body. However, NEURONS are more sensitive to ity of GABA on GABA-sensitive neurons by acting their effects than other tissues. The depth of central at the same receptor on which GABA exerts its nervous system depression ranges from mild seda- effects (see Figure 2). GABA is a NEUROTRANSMIT- tion to coma and depends on many factors includ- TER that normally acts to reduce the electrical ac- ing which drug is used, its dose, the route of admin- tivity of the brain; its action is like a brake. Thus, istration, and the level of excitability present just barbiturates enhance the braking effects of GABA before the barbiturate was taken. The most com- to promote sedation. There is an area in the brain mon uses for the barbiturates are still to promote called the reticular activating system, which is re- sleep and to induce anesthesia. Barbiturate-in- sponsible for maintaining wakefulness. Since this duced sleep resembles normal sleep in many ways, area has many interconnecting or polysynaptic but there are a few important differences. Barbitu- neurons, it is the first to succumb to the barbitu- rates reduce the amount of time spent in rapid eye rates, and that is why an individual becomes tired movement or REM sleep—a very important phase and falls asleep after taking a barbiturate. BARBITURATES 161

PHARMACOKINETICS AND lipid; when the ultrashort-acting barbiturates are DISTRIBUTION given intravenously, they proceed directly to the The ultrashort-acting barbiturates differ from brain to produce anesthesia and unconsciousness. the other members of this class mainly by the After only a few minutes, however, these drugs are means by which they are inactivated. Methohexital redistributed to the fats in the rest of the body so and its relatives are very soluble in lipids (i.e., fatty their concentration is reduced in the brain. Thus, tissue). The brain is composed of a great deal of recovery from IV barbiturate anesthesia can be very fast. For this reason, drugs such as methohexi- tal and thiopental are used primarily as intrave- nous anesthetic agents and not as sedatives. The other longer-acting barbiturates must be metabolized by the liver into inactive compounds before the effects wane. Since these metabolites are more soluble in water, they are excreted through the kidneys and into the urine. As is the case with most drugs, metabolism and excretion is much quicker in young adults than in the elderly and infants. Plasma half-lives are also increased in pregnant women because the blood volume is ex- Figure 2 panded due to the development of the placenta and Barbiturates fetus. 162 BARBITURATES

TOLERANCE, DEPENDENCE, individual always includes a slow reduction in the AND ABUSE dose to avoid the dangers of rapid detoxification. Few, if any, illegal laboratories manufacture Repeated administration of any number of drugs barbiturates. Diversion of licit production from results in eventual compensatory changes in the pharmaceutical companies is the primary source body. These changes are usually in the opposite for the illicit market. Almost all barbiturate users direction of those initially produced by the drug take it by mouth. Some try to dissolve the capsules such that more and more drug is needed to achieve and inject the liquid under their skin (called skin- the initial desired effect. This process is called popping) but the toxic effects of the alcohols used TOLERANCE . There are two basic mechanisms for to dissolve the drug and the strong alkaline nature tolerance development: tissue tolerance and meta- of the solutions can cause lesions of the skin. Intra- bolic or pharmacokinetic tolerance. Tissue toler- venous administration is a rare practice among ance refers to the changes that occur on the tissue barbiturate abusers. or cell that is affected by the drug. Metabolic toler- Many barbiturate users become dependent to ance refers to the increase in the processes that some degree during the course of treatment for in- metabolize or break down the drug. This process somnia. This type of problem is called iatrogenic, generally occurs in the liver. Barbiturates are sub- because it is initiated by a physician. In some in- ject to both types of tolerance development. stances the problem will be limited to continued use Tolerance does not develop equally in all effects at gradually increasing doses at night, to prevent produced by barbiturates. Barbiturate-induced insomnia that is in turn due to withdrawal. How- respiratory depression is one example. Barbiturates ever, some individuals who are susceptible to the reduce the drive to breathe and the processes neces- euphoric effects of barbiturates may develop a pat- sary for maintaining a normal breathing rhythm. tern of taking increasingly larger doses to become Thus, while tolerance is quickly developing to the intoxicated, rather than for the intended therapeu- desired sedative effects, the toxic doses change to a tic effects (for example, to promote sleepiness). To lesser extent. As a result, when the dose is increased achieve these aims, the person may obtain prescrip- to achieve the desired effects (e.g., sleep), the mar- tions from a number of physicians and take them to gin of safety actually decreases as the dose comes a number of pharmacists—or secure their needs closer to producing toxicity. A complete cessation from illicit distributors (dealers). If the supply is of breathing is often the cause of death in barbitu- sufficient, the barbiturate abuser can rapidly in- rate poisoning (Rall, 1990). crease the dose within a matter of weeks. The upper If tolerance develops and the amount of drug daily limit is about 1,500 to 3,000 milligrams; taken continues to increase, then PHYSICAL DEPEN- however, many can titrate their daily dose to the DENCE can develop. This means that if the drug is 800 to 1,000 milligram range such that the degree suddenly stopped, the tissues’ compensatory effects of impairment is not obvious to others. The pattern become unbalanced and withdrawal signs appear. of abuse resembles that of ethyl (drinking) ALCO- In the case of barbiturates, mild signs of with- HOL, in that it can be daily or during binges that drawal include apprehension, insomnia, last from a day to many weeks at a time. This excitability, mild tremors, and loss of appetite. If pattern of using barbiturates for intoxification is the dose was very high, more severe signs of with- more typically seen in those who, from the begin- drawal can occur, such as weakness, vomiting, de- ning, obtain barbiturates from illicit sources rather crease in blood pressure regulatory mechanisms (so than those who began by seeking help for insomnia. that pressure drops when a person rises from a Barbiturates are sometimes used along with lying position, called orthostatic hypotension), in- other drugs. Often, the barbiturate is used to poten- creased pulse and respiratory rates, and grand mal tiate, or boost, the effects of another drug upon (epileptic) seizures or convulsions. DELIRIUM with which a person is physically dependent. Alcohol fever, disorientation, and HALLUCINATIONS may and HEROIN are commonly taken together in this also occur. Unlike withdrawal from the opioids, way. Since barbiturates are ‘‘downers,’’ they also withdrawal from central nervous system depres- are used to counteract the unwanted overstimu- sants such as barbiturates can be life threatening. lation associated with stimulant-induced intoxica- The proper treatment of a barbiturate-dependent tion. It is not uncommon for stimulant abusers (on BARBITURATES: COMPLICATIONS 163

COCAINE or amphetamines) to use barbiturates to PRESSANTS (‘‘downers’’). These drugs produce sed- combat the continued ‘‘high’’ and the associated ative, hypnotic, and anesthetic effects. Depending motor disturbances associated with heavy and con- on the dose used, any single drug in this class may tinued cocaine use. Also, barbiturates are used to produce sedation (decreased responsiveness), hyp- ward off the early signs of withdrawal from alcohol. nosis (sleep), and anesthesia (loss of sensation). A Treatment for barbiturate dependence is often small dose will produce sedation and relieve ANXI- conducted under carefully controlled conditions, ETY and tension; a somewhat larger dose taken in a because of the potential for severe developments, quiet setting will usually produce sleep; an even such as seizures. Under all conditions, a program of larger dose will produce unconsciousness. The sleep supervised withdrawal is needed. Many years ago, produced by barbiturates, however, is not identical pentobarbital was used for this purpose and the with normal sleep. Normal sleep consists of alter- dose was gradually decreased until no drug was nating phases of slow-wave sleep (SWS)—when given. More recently, phenobarbital or the benzodi- the electroencephalogram (EEG) shows a high- azepines—CHLORDIAZEPOXIDE and diazepam— voltage and low-frequency pattern—and rapid- have been used for their greater margin of safety. eye-movement (REM) sleep. In the REM sleep The reason that the benzodiazepines sometimes phase, the EEG shows an arousal pattern and skel- work is because the general central nervous system etal muscles relax, eyes move rapidly and fre- depressants—barbiturates, alcohol, and benzodi- quently, and dreaming is thought to take place. azepines—develop cross-dependence to one an- Barbiturates decrease REM (or dreaming) sleep other. Thus a patient’s barbiturate or alcohol with- and thereby disturb the balance between SWS and drawal signs are reduced or even eliminated by REM sleep. diazepam. As is true for most drugs that act on the CNS, the effects of these drugs are also influenced markedly by the user’s previous drug experience, the circum- (SEE ALSO: Addiction: Concepts and Definitions; stances in which the drug is taken, and the route of Withdrawal ) administration of the drug. For example, a dose taken at bedtime may produce sleep, whereas the BIBLIOGRAPHY same dose taken during the daytime may produce a CSA´ KY, T. Z. (1979). Cutting’s handbook of pharmacol- feeling of euphoria, incoordination, and emotional ogy: The actions and uses of drugs, 6th ed. New York: response. This, in many ways, is what happens with Appleton-Century Crofts. alcohol intoxication. In fact, the behavioral effects HENNINGFIELD, J. E., & ATOR, N. A. (1986). Barbitu- of this class of drugs is very similar to those ob- rates: Sleeping potion or intoxicant? In The encyclo- served after drinking ALCOHOL, and the user may pedia of psychoactive drugs. New York: Chelsea experience impairment of skills and judgment not House. unlike that experienced with alcohol. It is therefore MENDELSON, J. H., & MELLO, N. K. (1992). Medical di- not surprising that the effects of barbiturates are agnosis and treatment of alcoholism. New York: enhanced when taken in combination with alcohol, McGraw-Hill. antianxiety drugs (BENZODIAZEPINES), and other CNS depressants such as opioids, antihistamines, RALL, T. W. (1990). Hypnotics and sedatives: Ethanol. In A. G. Gilman et al. (Eds.), Goodman and Gilman’s and OVER-THE-COUNTER cough and cold medica- tions containing these drugs. Barbiturates, how- the pharmacological basis of therapeutics, 8th ed. ever, differ from some other SEDATIVE-HYPNOTIC New York: Pergamon. drugs in that they do not elevate the PAIN threshold. WINGER, G., HOFFMAN,F.G.,&WOODS, J. H. (1992). A In fact, patients experiencing severe pain may be- handbook of drugs and alcohol abuse: the biomedical come agitated and delirious if they are given barbi- aspects, 3rd ed. New York: Oxford University Press. turates without also receiving ANALGESICS. SCOTT E. LUKAS Barbiturates are generally classified as being long, intermediate, short, and ultra-short acting on the basis of their duration of effect. The long-acting BARBITURATES: COMPLICATIONS barbiturates, such as phenobarbital, which were at Barbiturates are central nervous system (CNS) DE- one time mainly employed as daytime sedatives for 164 BEERS AND BREWS the treatment of anxiety, produce sedation that rebound). The intensity of the withdrawal symp- lasts from twelve to twenty-four hours. Phenobar- toms varies with the degree of abuse and may range bital is still one of the drugs used for the treatment from sleeplessness and tremor in mild cases to de- of grand mal epilepsy. The short- and intermedi- lirium and convulsions in severe cases. Fatalities ate-acting drugs such as pentobarbital and seco- have occurred as a result of barbiturate WITH- barbital, which were once mainly employed as hyp- DRAWAL, usually from withdrawal of short-acting notics, produce CNS depression that ranges from barbiturates. three to twelve hours, depending on the compound In some individuals, barbiturates may produce used. The ultrashort-acting barbiturates (e.g., CNS excitement rather than CNS depression. This thiopental) are used for the induction of anesthesia, type of idiosyncratic reaction occurs most fre- because of the ease and rapidity with which they quently in elderly people. Among the side effects induce sleep when given intravenously. The effects sometimes seen, there may be rashes and muscle of barbiturates on judgment and other mental as and body aches. well as motor skills, however, may persist much longer than the duration of the hypnotic effect. For (SEE ALSO: Expectancies; Sleep, Dreaming, and this and other reasons, for the treatment of anxiety Drugs) or insomnia, barbiturates have largely been re- placed by the generally safer group of drugs called BIBLIOGRAPHY benzodiazepines. The respiratory system is significantly depressed GOODMAN, L. S., & GILMAN, A. G. (1975). The pharma- by the administration of barbiturate doses that are cological basis of therapeutics, 5th ed. New York: larger than those usually prescribed. Furthermore, Macmillan. there is a synergistic effect when barbiturates are KALANT, H., & ROSCHLAU, W. H. E. (1989). Principles of combined with alcohol and other central nervous medical pharmacology,5thed.Toronto:B.C. system depressants—often with a fatal outcome. Decker. Barbiturates are frequently used for suicides. For JAT M. KHANNA this reason, too, the barbiturates have been dis- placed by the less toxic benzodiazepines. The symptoms of acute barbiturate toxicity resemble BEERS AND BREWS Beers and brews are the effects observed after excessive alcohol inges- beverages produced by yeast-induced fermentation tion. Although repeated administration of barbitu- of malted cereal grains, usually barley malt, to rates results in CNS tolerance, thus producing less which hops and water have been added. They gen- intoxication, tolerance does not appear to develop erally contain 2 to 9 percent ethyl ALCOHOL, al- to the same extent in regard to the respiratory de- though some may contain as much as 15 percent. pressant and lethal effects of the barbiturates; the Various types and flavors are created by adding person addicted to barbiturates may therefore be at different combinations of malts and cereals and a greater risk of respiratory toxicity because of less allowing the process to continue for varying lengths pronounced CNS euphoric effects with higher of time. doses. Tolerance to barbiturates also affects metab- olism; the administration of these drugs speeds up BREWING HISTORY not only their own metabolism (i.e., shortens their effectiveness) but also the metabolism of a large The origin of beer is unknown, but it was an number of other drugs. This property has been of important food to the people of the Near East, use in some special cases (as in jaundice of the probably from Neolithic times, some 10,000 years newborn), but it can be hazardous in others when it ago. The making of beer and of bread developed at decreases the effectiveness of another drug (e.g., an the same time. In Mesopotamia (the ancient land anticoagulant used to treat thrombosis). between the rivers as the Greeks called it), an early Long-term users experience withdrawal symp- record from about 5,000 years ago describing the toms when the barbiturate is stopped abruptly. recipe of the ‘‘wine of the grain’’ was found written Abrupt cessation also leads to an increase in the in Sumerian cuneiform on a clay tablet. In ancient amount and intensity of REM sleep (REM Egypt, at about the same time, barley beer was BEERS AND BREWS 165 brewed and consumed as a regular part of the diet. bottom or are digested by enzymes. The carbona- It was known as hek and tasted like a sweet ale, tion (fizz) that occurred during fermentation is since there were no hops in Egypt. Egyptians con- then drawn off and forced back in during the tinued to drink it for centuries, although the name bottling process. was changed to hemki. More than 3,200 years ago, the Chinese made a beer called kiu that was most BEER TYPES likely made from two parts millet and one part rice. With water added, the concoction was heated in There are two major types of beers: top-ferment- clay pots; flour and various plants were added to ing and bottom-fermenting. Top fermentation oc- Њ Њ Њ Њ provide the yeast and flavors, respectively. curs at room temperature 59 to 68 F (15 –20 C) The ancient Greeks, however, preferred wine and is so named because the yeast rises to the top of and considered beer to be a drink of barbarians. the vessel during fermentation. This older process Beer was drunk on special occasions in ancient produces beers that have a natural fruitiness and Rome; Plutarch wrote of a feast in which Julius include the wheat beers, true ales, stouts, and por- Caesar served his officers beer as a special reward ters. Their flavor is most completely expressed after they had crossed the Rubicon river. Once the when served at moderate (i.e., room) temperatures. art of brewing reached England, beers and ales The development of yeasts that sank during this became the preferred drink of the rich and poor process resulted in brews that were more stable alike. King Henry VIII of England was said to between different batches. Most of the major consume large quantities during breakfast. It was brewers have switched to the bottom yeasts and soon discovered that sailors who drank beer cold storage (lagering). The significance of using avoided scurvy, a disease caused by a lack of ade- yeast that sinks during fermentation is that air- quate amounts of vitamin C. Thus, beer was added borne yeasts cannot mix with the special yeast and to each ship’s provisions and was even carried on contaminate the process. the Mayflower during the crossing of the Atlantic The most popular type of beer in the United Ocean in 1620. American colonists quickly learned States is lager, a pale, medium-hop-flavored beer. Њ Њ to make their beer with Indian corn (maize), and It is mellowed several months at 33 F (0.5 C) to much U.S. beer is still made with corn, although produce its distinctive flavor. Lager beers average rice and wheat are also used in the mix with barley 3.3 to 3.4 percent ethyl alcohol by weight and are malt. usually heavily carbonated. Pilsner is a European lager (that originated in medieval Pilsen, now the Czech city of Plzen) that is stored longer than other MAKING BEER lagers and has a higher alcohol content and a rich The first step in making beer is to allow barley to taste of hops. Dark beers are popular in Europe but sprout (germinate) in water, a process that releases are not generally produced in the United States. an important enzyme, amylase. Germinated barley The dark color is achieved by roasting the malt; seeds are called malt. Once the malt is crushed and dark beer has a heavier and richer taste than lager suspended in water, the amylase breaks down the beer. British beers are many and varied, both pale complex starch into more basic sugars. The reac- and dark; some have a number of unique additives, tion is stopped by boiling, and the concoction is including powdered eggshell, crab claws or oyster filtered. This clear solution is mixed with hops (to shells, tartar salts, wormwood seeds, and provide the bitter flavor) and a starter culture of horehound juice. Porter, popular in England, is yeast (to begin the alcoholic fermentation process). another dark beer—originally called porter’s beer, Carbon dioxide gas (the fizz or bubbles) is pro- it was a mixture of ale and beer. The porters of duced, along with ethyl alcohol (ethanol or drink- today are a sweet malty brew and contain 6 to 7 ing alcohol). The malt and hops are then removed percent alcohol. Malt liquors are beers that are (and generally sold for cattle feed) while the yeast is made using a higher percentage of fermentable skimmed off as fermentation proceeds. After the sugars, resulting in a beverage with 5 to 9 percent desired effect is achieved, the beer is filtered and alcohol content; the mild fruity flavor has a spicy bottled, or it is stored in kegs for aging. During the taste and lacks the bitterness of hops. Low-calorie aging process (2 to 24 weeks) proteins settle to the (sometimes called ‘‘light’’ or ‘‘lite’’) beers are pro- 166 BEERS AND BREWS

Figure 1 Figure 3 SOURCE: Impact Databank, M. Shanken Communications, Inc., New York, N.Y. duced by decreasing the amount of grain used in the initial brew (using more water per unit of vol- WORLDWIDE CONSUMPTION OF ume) or by adding an enzyme that reduces the BEERS AND BREWS amount of starch in the beer. These light beers About 128.6 billion liters of beer were commer- contain only about 2.5 to 2.7 percent alcohol. cially produced in the world in 1997 according to Brewing is subject to national laws concerning the World Drink Trends, 1999 Edition (cited in allowable ingredients in commercial products. Al- Alcoweb). The United States led the world in beer though chemical additives are allowed by some production, producing 23.6 billion liters of beer in countries (e.g., the United States), German and 1997. China followed with 17.0 billion liters, and Czech purity laws consider beers and brews a natu- Germany rounded out the top three in beer pro- ral historical resource and disallow anything that duction volume with 11.5 billion liters. For the same year, World Drink Trends reports that the was not part of the original (medieval) brewing Czech Republic drank the most beer, consuming tradition. Individuals sensitive to U.S. or Canadian 161.4 liters per person. Other countries leading in beers are often able to drink pure beers. beer consumption were the Republic of Ireland (152.0 liters per person) and Germany (131.2 liters per person). A 1999 study conducted by Euromonitor cited in Prepared Foods reported that the United States led the world in beer con- sumption, consuming over 17 billion liters. Bever- age World International cites another Euro- monitor study that lists the top three brewers for 1997 as Anheuser-Busch, Heineken, and Miller Brewing. Figures 1–3 show the relative distribu- tion of the top drinking and brewing nations, as well as the top brewing companies.

(SEE ALSO: Alcohol: Historyof Drinking )

BIBLIOGRAPHY

ABLE, B. (1976). The book of beer. Chicago: Henry Figure 2 Regnery. BEHAVIORAL ECONOMICS 167

ALCOWEB (1996a). Beer production by country (1995– Several concepts from behavioral economics are 1997). Alcohol, Health: Beer production (Cited relevant to this important issue. A central concept 22 August, 2000). Available from http:// is the demand law which stipulates that total con- www.alcoweb.com. sumption decreases as price increases, all else being ALCOWEB (1996b). Consumption of beer by country be- equal (Allison, 1979). Price can be considered any- tween 1995 and 1998. Alcohol, Health: Evolution of thing (e.g., response requirement, monetary price, beer consumption (Cited 22 August, 2000). Available delay, changes in the amount of the commodity from http://www.alcoweb.com. while holding the monetary or work price constant) BEVERAGE WORLD INTERNATIONAL (1999). First annual that decreases availability of a commodity. Indeed, top 10 global brewers report. May–June, 24. drug self-administration studies that vary price (re- JACKSON, M. (1988). The New World guide to beer. Phila- sponse requirement) report results consistent with delphia: Running Press. the demand law; that is, drug consumption de- PREPARED FOODS (1999). Beer-bellied yanks. (Beer con- creases as the response requirement decreases sumption increases in the U.S., Spain, UK, and Ger- (Griffiths, Bigelow, & Henningfield, 1980; Young many.) Aug, 37. & Herling, 1986). However, behavioral economics does more than simply restate this observation with SCOTT E. LUKAS a different terminology; it adds by quantitatively REVISED BY NANCY FAERBER characterizing the relation between price and con- sumption via the economic measure of own-price elasticity (Bickel & DeGrandpre, 1996; Hursh & BEHAVIORAL ECONOMICS Con- Bauman, 1987; Samuelson & Nordhaus, 1985). temporary conceptualizations view drug depen- Own-price elasticity measures the proportional dence as a ‘‘syndrome in which the use of a drug is change in consumption across price conditions. If given a much higher priority than other behaviors consumption of a particular reinforcer decreases that once had higher value’’ (Jaffe, 1990). Thus, in proportionally to a large extent as price increases, order to understand drug dependence, the complex then the consumption is referred to as elastic. If interactions among reinforcers must be under- consumption decreases proportionally to a limited stood. Consider, for example, the frequently ob- extent as price increases, then the consumption is served case of polydrug abuse. On some occasions, referred to as inelastic. Elastic and inelastic con- the drugs may be used simultaneously (e.g., co- sumption are quantified by elasticity coefficients caine and heroin), whereas on other occasions one greater than 1.0 and less than 1.0, respectively drug may be used in lieu of another (e.g., benzodi- (Hursh, 1980). When examined across a broad azepines and opioids). Understanding reinforcer range of prices, elasticity of demand for many rein- interactions is also vital to developing effective forcers is often mixed: inelastic at low prices and treatment because treatments, be they pharmaco- elastic at higher prices. logical (e.g., methadone, nicotine gum) or non- With this method, then, qualitatively different pharmacological (e.g., AA meetings, alternative be- reinforcers can be compared and distinguished in haviors), often try to supplant drug reinforcers with drug-dependent populations. For example, in a re- other more acceptable reinforcers. Although under- cent study money and cigarettes were compared standing reinforcer interactions is important for among cigarette-deprived subjects on progressive understanding drug abuse, no method currently ex- ratio schedules (Bickel & Madden, 1999). Response ists to quantify or even categorize these different requirements were increased across sessions and types of reinforcer interactions. the same response requirement was imposed sepa- Behavioral economics provides a means to un- rately for both commodities. At the lowest response derstand the interactions among qualitatively dif- requirements, money was self-administered to a ferent reinforcers. The value of behavioral econom- greater extent than cigarettes (a greater intensity of ics derives from its unique ability to quantify the demand). As response requirement increased, effects of qualitatively different reinforcers and money was shown to be more sensitive to price than their interactions (Bickel et al., 1992; Bickel, De- cigarettes. The own-price elasticities of money and Grandpre, & Higgins, 1995; Bickel & Vuchinich, cigarettes were 2.1 and 0.9, respectively, with 2000; Hursh, 1980, 1991). money being 2.3-fold more sensitive to price. Such 168 BEHAVIORAL ECONOMICS efforts can be meaningfully extended to clinical nomic measure of cross-price elasticity. In that re- settings via simulation technology (Petry & Bickel, view, price was defined as responses required per 1998; Jacobs & Bickel, 1999). Jacobs and Bickel milligram of drug per ingestion (i.e., unit price) used questionnaires to assess the reported con- (Hursh et al., 1988; Bickel et al., 1990). A wide sumption of cigarettes and heroin singly and con- variety of reinforcers (e.g., cocaine, food, heroin, currently across a range of prices ($0.01 to $1,120) and cigarettes) across several species (e.g., rats, in opioid-dependent smokers undergoing treat- humans, baboons, and rhesus monkeys) were ex- ment for heroin addiction. Across conditions in amined. Overall, the results of reanalysis demon- which cigarettes and heroin were available alone, strated that each of the studies demonstrated one of or concurrently, demand for heroin was less elastic the three types of interactions specified by econom- than for cigarettes. For example, heroin consump- ics. Extensions can also be made to clinical settings tion was defended to a greater extent across in- again by simulations. For example, the Petry and creases in price than cigarettes. Taken together, Bickel (1998) study described earlier found that these studies indicate that individuals with drug heroin prices affected other drug purchases. The dependence value the primary drug of dependence cross-price elasticity measure showed that as the more than other commodities. price of heroin rose and heroin purchases de- Own-price elasticity, like other behavioral ef- creased, valium and cocaine purchases increased. fects, is not an inherent ‘‘property’’ of a drug, but is However, increases in the price of valium did not determined by several variables including the con- affect heroin purchases. This suggests an asymmet- text in which it is measured (Hughes, Higgins, & rical relationship between heroin and valium pur- Bickel, 1988). Indeed, the presence of other rein- chases when the price of one drug increases while forcers can alter own-price elasticity (Hursh, 1984; the price of the other remains constant. Bickel et al., 1995). Within an economic frame- Collectively, these studies suggest that the avail- work, reinforcer interactions lie on a continuum ability of a concurrent reinforcer can significantly that can be quantified with a measure termed modulate drug intake. Sometimes, reinforcers in- cross-price elasticity (i.e., proportional change in teract as substitutes, whereas at other times they consumption of reinforcer A as a function of the function as complements. Introducing a substitute price of reinforcer B) (Hursh & Bauman, 1987). At tends to decrease drug consumption, while intro- one end of the continuum, reinforcers are substitu- ducing a complement may increase drug consump- table reinforcers; that is, as the price of one rein- tion. Unfortunately, few of these studies has pro- forcer increases (e.g., price of attending a movie spectively examined these interactions. Additional theater), consumption of a second reinforcer (i.e., research that systematically and parametrically ex- the substitute) will increase (e.g., video rentals). At amines reinforcer interactions may facilitate a the other end of the continuum, reinforcers can be greater understanding of the ways in which the complementary; that is, as the cost of one reinforcer availability of alternative reinforcers increases or increases (e.g., soup), the consumption of a second decreases drug consumption. reinforcer (i.e., the complement) also decreases This approach to studying interactions of any (e.g., soup crackers). Between these two extremes reinforcers may have several important implica- are independent reinforcers; as the cost of one rein- tions. First, this research may have implications for forcer increases (e.g., movie attendance), the con- understanding behavioral vulnerability. For exam- sumption of a second reinforcer (e.g., soup crack- ple, one issue in drug dependence is why only a few ers) will remain unchanged. The quantification of people exposed to a drug of abuse go on to become substitutes, compliments, and independent rein- dependent. Perhaps, vulnerable individuals have forcers is measured by cross-price elasticity values limited availability to alternative nondrug substi- greater than zero, less than zero, and equal to zero, tutes and easy access to complements for drug respectively (Hursh & Bauman, 1987). taking (e.g., Carroll, Lac, & Nygaard, 1989). Sec- A review and reanalysis of self-administration ond, this research may provide a useful way to studies support this continuum (Bickel et al., characterize the various types of polydrug abuse 1995). Specifically, the results of sixteen drug self- (e.g., Petry & Bickel, 1998). Third, such research administration studies that employed concurrently may provide an empirical basis for developing available reinforcers were reanalyzed using the eco- treatment strategies; that is, in treatment it may be BEHAVIORAL ECONOMICS 169

worthwhile to decrease the response cost of obtain- BICKEL, W. K., ET AL. (1992). Behavioral economics of ing other substitutable nondrug reinforcers. With drug self-administration. IV. The effects of response regard to complements, this research suggests that requirement on consumption of and interaction be- drug-abuse treatment may be more successful if tween concurrently available coffee and cigarettes. consumption of complements is also decreased. For Psychopharmacology, 107, 211–216. example, Higgins and colleagues (1993) examined BICKEL, W. K., & MADDEN, G. J. (1999). A comparison of the effects of disulfiram (antabuse) therapy among measures of relative reinforcing efficacy and behav- patients abusing cocaine and alcohol. Disulfiram is ioral economics: Cigarettes and money in smokers. a medication that is used to deter alcohol use by Behavioural Pharmacology, 10, 627–637. inducing nausea and vomiting when alcohol is con- BICKEL, W. K., & VUCHINICH, R. E. (2000). Reframing sumed. This study found that supervised disulfiram health behavior change with behavioral economics. therapy was associated with significant decreases in Hillsdale, NJ. Lawrence Erlbaum. alcohol and cocaine use as measured by breath and CARROLL, M. E., LAC, S. T., & NYGAARD, S. L. (1989). A urine samples. More recently, Carroll and col- concurrently available reinforcer prevents the acqui- leagues (1998) examined the effects of three stan- sition or decreases the maintenance of cocaine-rein- dardized psychotherapy treatments alone and with forced behavior. Psychopharmacology, 64, 1–7. disulfiram treatment among a large, diverse sample CARROLL, K. M., ET AL. (1998). Treatment of cocaine of individuals who abuse cocaine and alcohol. and alcohol dependence with psychotherapy and di- Their results indicated that disulfiram treatment sulfiram. Addiction, 93, 713–727. was associated with significantly better retention in GRIFFITHS, R. R., BIGELOW, G. E., & HENNINGFIELD,J.E. treatment and longer duration of abstinence from (1980). Similarities in animal and human drug taking alcohol and cocaine use. Fourth, behavioral eco- behavior. In N. K. Mello (Ed.), Advances in substance nomic analyses of research may predict conditions abuse, Vol. 1. Greenwich, CT: JAI Press, pp. 1–90. in which relapse is likely. Relapse may occur when HIGGINS, S. T., ET AL. (1993). Disulfiram therapy in pa- substitutable reinforcer interactions become un- tients abusing cocaine and alcohol. American Journal available and complements become available of Psychiatry, 150, 675–676. (Vuchinch & Tucker, 1988, 1996). Thus, the study HUGHES, J. R., HIGGINS, S. T., & BICKEL, W. K. (1988). of reinforcer interactions may increase our under- Real estate in behavioral analysis: Reinforcing ‘‘prop- standing of the etiology, maintenance, and treat- erties’’ of stimuli. PharmacologyBiochemistryand ment of drug dependence as well as relapse. Behavior, 29, 657. HURSH, S. R. (1980). Economic concepts for the analysis of behavior. Journal of the Experimental and Clinical BIBLIOGRAPHY Psychopharmacology, 34, 219–238. ALLISON, J. (1979). Demand economics and experimen- HURSH, S. R. (1984). Behavioral economics. Journal of tal psychology. Behavioral Sciences, 24, 403–415. the Experimental Analysis of Behavior, 42, 435–452. BICKEL, W. K., & DEGRANDPRE, R. J. (1996). Psychologi- HURSH, S. R. (1991). Behavioral economics of drug self- cal science speaks to drug policy: The clinical rele- administration and drug abuse policy. Journal of the vance and policy implications of basic behavioral Experimental and Clinical Psychopharmacology, 56, principles. In W. K. Bickel & R. J. DeGrandpre (Eds.), 377–393. Drug policyand human nature: Psychologicalper- HURSH, S. R., & BAUMAN, R. A. (1987). The behavior spectives on the control, prevention and treatment of analysis of demand. In L. Green & J. H. Kagel (Eds.), illicit drug use. New York: Plenum, pp. 31–52. Advances in behavioral economics, Vol. 1. Norwood, BICKEL, W. K., DEGRANDPRE, R. J., & HIGGINS,S.T. NJ: Ablex, pp. 117–165. (1995). The behavioral economics of concurrent drug HURSH, S. R., ET AL. (1988). A cost-benefit analysis of reinforcers: A review and reanalysis of drug self-ad- demand for food. Journal of the Experimental Analy- ministration research. Psychopharmacology, 118, sis of Behavior, 50, 419–440. 250–259. JACOBS, E. A., & BICKEL, W. K. (1999). Modeling drug BICKEL, W. K., ET AL. (1990). Behavioral economics of consumption in the clinic via simulation procedures: drug self-administration. I. Functional equivalence of Demand for heroin and cigarettes in opioid-depen- response requirement and drug dose. Life Science, 47, dent outpatients. Journal of Experimental and Clini- 1501–1510. cal Psychopharmacology, 7, 412–426. 170 BEHAVIORAL MODIFICATION AS A TREATMENT

JAFFE, J. H. (1990). Drug addiction and drug abuse. In administrations) to a drug, it may take more of the A. G. Goodman, T. W. Rall, A. S. Niles & P. Taylor drug to get the same effect as originally produced. (Eds.), The pharmacological basis of therapeutics, The expression behavioral tolerance often is eighth edition. New York: Pergamon Press, pp. 522– used simply to refer to a drug’s decreased potency 573. in affecting a specified behavior after repeated or PETRY, N. M., & BICKEL, W. K. (1998). Polydrug abuse continuous exposure to the drug. In other contexts, in heroin addicts: A behavioral economic analysis. however, the expression has taken on a more re- Addiction, 93, 321–335. stricted and special meaning; it is employed only SAMUELSON, P. A., & NORDHAUS, W. D. (1985). Econom- when behavioral factors have been shown experi- ics. New York: McGraw-Hill. mentally to have contributed to the development of VUCHINCH, R. E., & TUCKER, J. A. (1988). Behavioral tolerance. theories of choice as a framework for studying drink- This special meaning is applied when either of ing behavior. Journal of Abnormal Psychology, 92, two sets of circumstances are encountered. In the 408–416. first, drug tolerance is shown to be specific to the VUCHINCH, R. E., & TUCKER, J. A. (1996). Alcohol re- context in which the drug is administered; in the lapse, life events, and behavioral theories of choice: A second, drug tolerance is shown to occur only if prospective analysis. Journal of the Experimental and drug administration precedes particular behavioral Clinical Psychopharmacology, 4, 19–28. circumstances. Examples of each may help clarify YOUNG, A. M., & HERLING, S. (1986). Drugs as reinforc- the distinctions between them and between ‘‘sim- ers: Studies in laboratory animals. In S. R Goldberg ple’’ tolerance and behavioral tolerance. and I. P. Stolerman (Eds.), Behavioral analysis of Context-specific tolerance has been researched drug dependence. Orlando, FL: Academic Press, pp. extensively by Siegel and his colleagues (see Siegel, 9–67. 1989, for an overview). In a typical experiment two groups of subjects are compared; subjects in both WARREN K. BICKEL groups receive the same number of repeated expo- LOUIS A. GIORDANO sures to the drug (e.g., morphine) and then are tested for their response to the drug (e.g., alle- viation of pain). For one group, the test occurs in BEHAVIORAL MODIFICATION AS A the environment where drugging took place; for the TREATMENT See Treatment Types: Ap- other the test occurs in a novel environment. Typi- proaches Based on Behavioral Principles cally, only those from the group tested in the famil- iar environment show tolerance. Siegel’s theory is that subjects develop, via the principles of Pavlov- BEHAVIORAL TOLERANCE In everyday ian conditioning, a conditioned compensatory re- language, TOLERANCE implies the ability to with- sponse that is elicited by the drug-administration stand something. In pharmacology, the term toler- context—and that this response counteracts the ance is close to this meaning. To understand the effect of the drug (see Baker & Tiffany, 1985, for a technical meaning of the word, however, requires different view). The phenomenon of context-spe- an understanding of the concept of the potency of a cific tolerance helps explain why many overdoses of drug. A drug’s potency is expressed in terms of the abused drugs occur when the drug is taken in a amount (the dose) of the drug needed to produce a novel situation—the new context does not elicit certain effect. To illustrate, drugs may be com- compensatory responses that counteract the effects pared with respect to potency. For example, relief of the drug. from headache may be achieved with 650 milli- The importance of the temporal relationship be- grams of aspirin or with 325 milligrams of tween drug administration and behavior is illus- ibuprofen; in this case ibuprofen is said to be more trated by the phenomenon of ‘‘contingent’’ toler- potent, because less drug is needed to produce a ance. The basic technique for identifying particular effect (relief of headache). Tolerance is contingent tolerance was pioneered by Chen said to occur when a drug becomes less potent as a (1968), and a clear example is provided by Carlton result of prior exposure to that drug. That is, fol- and Wolgin (1971). Three groups of rats had the lowing exposure (usually repeated or continuous opportunity to drink milk for 30 minutes each day. BENZODIAZEPINES 171

For each group, injections of a drug or just a saline dence; Wikler’s Pharmacologic Theoryof Drug Ad- vehicle were made twice each day: For Group 1, diction) each session was preceded by an injection of 2 milligrams per kilogram of AMPHETAMINE, followed BIBLIOGRAPHY by an injection of just the saline vehicle; for Group 2, the order of injections was reversed: saline before BAKER, T. B., & TIFFANY, S. T. (1985). Morphine toler- drinking, amphetamine after; Group 3 (the control ance as habituation. Psychology Review, 92, 78–108. group) received saline both before and after each CARLTON, P. L., & WOLGIN, D. L. (1971). Contingent session. tolerance to the anorexigenic effects of amphetamine. For Group 1 the drug initially decreased drink- Physiology of Behavior, 7, 221–223. CHEN, C. S. (1968). A study of the alcohol-tolerance ing, but during the course of several administra- effect and an introduction of a new behavioral tech- tions, drinking recovered to control levels (i.e., tol- nique. Psychopharmacologia, 12, 433–440. erance developed). For Group 2, no effect on CORFIELD-SUMNER,P.K.,&STOLERMAN, I. P. (1978). drinking was observed as a function of receiving Behavioral tolerance. In D. E. Blackman & D. J. the drug after sessions, so after several days (by Sanger (Eds.), Contemporaryresearch in behavioral which time subjects in Group 1 were tolerant) these pharmacology. New York: Plenum. subjects were given amphetamine before (rather GENOVESE, R. F., ELSMORE, T. R., & WITKIN,J.M. than after) and saline after sessions (i.e., the condi- (1988). Environmental influences on the develop- tions for Group 1 were implemented). Even though ment of tolerance to the effects of physostigmine on these subjects had received amphetamine just as schedule-controlled behavior. Psychopharmacology, frequently as the subjects in Group 1, when it was 96, 462–467. given before the session, drinking was suppressed GOUDIE, A. J., & DEMELLWEEK, C. (1986). Conditioning just as much as it had been for Group 1 initially. factors in drug tolerance. In S. R. Goldberg & I. P. Following repeated precession exposure to amphet- Stolerman (Eds.), Behavioral analysis of drug depen- amine the subjects in Group 2 became tolerant. dence. New York: Academic. These findings and many others like them show SCHUSTER, C. R., DOCKENS, W. S., & WOODS,J.H. that, in many cases, for tolerance to develop to a (1966). Behavioral variables affecting the develop- drug’s behavioral effects, mere repeated exposure ment of amphetamine tolerance. Psycho- to the drug is not enough. In addition, the drug pharmacologia, 9, 170–182. must be active while the behavior of interest is SIEGEL, S. (1989). Pharmacological conditioning and occurring. (See Goudie & Demellweek, 1986, and drug effects. In A. J. Goudie & M. W. Emmett- Wolgin, 1989, for reviews.) Oglesby (Eds.), Psychoactive drugs: Tolerance and Contingent tolerance is sometimes called sensitization. Clifton, NJ: Humana. learned tolerance because it appears that it is a WOLGIN, D. L. (1989). The role of instrumental learning manifestation of learning to behave accurately in behavioral tolerance to drugs. In A. J. Goudie & while under the influence of a drug. An influential M. W. Emmett-Oglesby (Eds.), Psychoactive drugs: theory about the origin of contingent tolerance is Tolerance and sensitization. Clifton, NJ: Humana. the ‘‘reinforcement loss’’ theory of Schuster, MARC N. BRANCH Dockens and Woods (1966; for a review see Corfield-Sumner & Stolerman, 1978). Loosely stated, the theory is that contingent tolerance will emerge in situations where the initial effect of the BENZEDRINE/BENZEDRINE INHAL- drug is to produce a loss of reinforcement (e.g., ERS See Amphetamine Epidemics result in a failure to meet the demands of the task). Although there are limits to the generality of the theory (Genovese, Elsmore, & Witkin, 1988), it has BENZENE See Inhalants an excellent predictive record.

(SEE ALSO: Addiction: Concepts and Definitions; BENZODIAZEPINES The benzodiazepines Reinforcement; Tolerance and Physical Depen- were introduced into clinical practice in the 1960s 172 BENZODIAZEPINES for the treatment of anxiety and sleep disorders. Members of this class of drug were classified ini- tially as minor tranquilizers although this term has fallen into disfavor. These agents have proven to be safe and effective alternatives to older SEDATIVE- HYPNOTIC agents such as BARBITURATES,CHLORAL HYDRATE, glutethimide, and carbamates. Benzodi- azepines are widely prescribed drugs, with 8.3 per- cent of the U.S. population reporting medical use of these agents in 1990.

BASIC PHARMACOLOGY All benzodiazepines produce similar pharmaco- logic effects, although the potency for each effect may vary with individual agents. They decrease or Figure 1 abolish ANXIETY, produce sedation, induce and Outline of the basic structure of the maintain sleep, control certain types of seizures, benzodiazepines. R denotes substituent groups and relax skeletal muscles. The basic chemical such –H, –O, –OH, –NO , and –Cl that are structure is shown in Figure 1. 2 attached to the core benzodiazepine structure. Dissimilarity in the effects of different benzodi- These groups determine the precise azepines tend to be more quantitative than qualita- physiochemical and pharmacologic properties of tive in nature. Many of these differences are attrib- each benzodiazepine. utable to how benzodiazepines are absorbed, SOURCE: Adapted from Rall, T.W. (1990). Hypnotics distributed, and metabolized in the body. A few and sedatives: Ethanol. Figure created by Rebecca benzodiazepines—clorazepate for example—are Bulotsky. pro-drugs; that is, they become active only after undergoing chemical transformation in the body. diazepine receptors exist as part of a larger receptor The extent to which a benzodiazepine is soluble in complex (Figure 2). The interaction of the NEURO- fatlike substances—that is, the degree to which it is TRANSMITTER gamma-amino butyric acid (GABA) lipophilic—determines the rate at which it crosses with this complex leads to the enhanced flow of the tissue barriers that protect the brain. Drugs that chloride ions into neurons (Kardos, 1993). This are highly lipophilic such as DIAZEPAM (Valium) complex is referred to as the GABA receptor-chlo- rapidly enter and then leave the brain. Benzodiaze- A ride ion channel complex. Much of the available pines are metabolized in the body in a number of evidence indicates that the action of benzodiaze- ways (see Table 1). Many benzodiazepines are pines involves a facilitation of the effects of GABA transformed in the liver into compounds that pos- and similarly acting substances on the GABA re- sess pharmacologic activity similar to that of the A originally administered drug. Diazepam, ceptor complex, thus leading to an increased move- prazepam, and halazepam are all converted to the ment of chloride ions into nerve cells. Entry of active metabolite desmethyldiazepam, which is chloride ions into neurons tends to diminish their eliminated from the plasma at a very slow rate. responsiveness to stimulation by other nerve cells, Oxazepam (Serax) and lorazepam (Ativan), in con- and consequently substances that produce an in- trast, are conjugated with glucuronide, a substance crease in chloride flow into cells depress the activity formed in the liver, to form inactive metabolites of the central nervous system. This depressant ef- that are readily excreted into the urine. fect becomes manifested as either sedation or sleep. Most of the effects that result from the adminis- Agents that increase chloride ion inflow include not tration of benzodiazepines are a consequence of the only the benzodiazepines but also other central direct action of these agents on the central nervous nervous system depressant agents such as ETHANOL system. Benzodiazepines interact directly with pro- (alcohol) and the barbiturates. Benzodiazepines teins that form the benzodiazepine receptor. Benzo- differ from barbiturates in that they require the BENZODIAZEPINES 173

TABLE 1 Benzodiazepines Available in the United States

Anxiolytics Usual Dose Half-life Trans/ormation Metabolites Generic Name Trade Name (mg/day) (hours) Pathway (half-life, hours)

Alprazolam Xanax 0.75-4 8-15 Oxidation Alphahydroxyalprazolam Benzophenone Bromazepam 20-30 Oxidation Chlordiazepoxide Librium 15-100 5-30 Desmethylchlordiazepoxide Demoxepam Desmethyldiazepam (36-96) Clonazepam Klonopin 1.5-20 18-50 Nitroreduction Inactive 7-amino or 7-acetyl amino derivatives Clobazam Frisium 20-30 18 Oxidation Desmethylclobazam (up to 77) Clorazepate Tranxene 15-60 30-100 Oxidation Desmethyldiazepam (36-96) Diazepam Valium 4-40 20-70 Oxidation Desmethyldiazepam (36-96) Halazepam Paxipam 60-160 14 Oxidation Desmethyldiazepam (36-96) 3-hydroxyhalazepam Lorazepam Ativan 2-4 10-120 Conjugation Inactive glucuronide conjugate Oxazolam Oxidation Desmethyldiazepam (36-96) Oxazepam' Serax 30-120 5-15 Conjugation Inactive glucuronide conjugate Prazepam Centrax 20-60 30-100 Oxidation Desmethyldiazepam (36-96)

Hypnotics

Usual Dose Half-life Trans/ormation Metabolites Generic Name TradeName (mg/day) (hours) Pathway (half-life, hours)

Brotizolam 4-7 Oxidation Estazolam Pro Som 1-2 8-24 Oxidation Flunitrazepam 10-40 Oxidation nitro- Desmethylflunitrazepam reduction Flurazepam Dalmane 15-30 .5-3.0 Oxidation Desalkylflurazepam (36-120) Hydroxyethyl flurazepam (I- 4) Flurazepam aldehyde (2-8) Lormetazepam 8-20 Conjugation Nitrazepam Mogadon 2.5-10 20-30 Nitroreduction Quazepam Doral 7.5-15 20-40 Oxidation Oxoquazepam (25-35) Desalkylflurazepam (36-120) Temazepam Restoril 15-30 8-20 Conjugation Triazolam Halcion .125-.5 2-6 Oxidation

Perioperative Hypnotic

Usual Dose Half-life Transformation Metabolites Generic Name Trade Name (mg/day) (hours) Pathway (half-life, hours)

Midazolam Versed 1-2.5 1-4 Oxidation Hydroxymethylmidazolam mg/ml

NOTE: The half-life of a compound is the amount of time that must pass for the level of that agent in the plasma to be rcduecd by half. ·'Oxazepam is also a metabolite of diazepam, clorazepate, prazepam, halazepam, and temazepam. SOllHCE:i: Dmg Facts and Comparisons. (1994). St. Louis, MO: Facts and Comparisons. Greenblatt, D. J. (1991). Benzodiaze­ pine hypnotics: Sorting the pharmacokinetic facts. Journal of Clinical Psychiatry, 52 (Suppl. 9), 4-10. Greenblatt, D. J., & Shader, R. I. (1987). Pharmacokinetics of antianxiety drugs. In H. Y. Meltzer (Ed.), Psychopharmacology: The Third Gener­ ation of Progress. NY: Raven Press. 174 BENZODIAZEPINES

of higher doses of benzodiazepines. These drugs are classified as partial AGONISTS. The drug abecarnil, which belongs to the beta-carboline class of com- pounds, is an example of such an agent that has been used experimentally to treat anxiety. Flumazenil is a benzodiazepine derivative that has no activity of its own but acts to antagonize the actions of benzodiazepines at the benzodiazepine receptor. It is used to reverse the effects of these drugs during anesthesia or in benzodiazepine over- doses. Other compounds, including some of the beta-carbolines such as methyl-beta-carboline-3- carboxylate, act on the benzodiazepine receptor to Figure 2 produce effects that are opposite to those of benzo- Schematic of one possible form of the GABA A diazepines (Kardos, 1993; Zorumski & Isenberg, receptor-chloride ion channel complex. Chloride 1991). Administration of these inverse agonists can ions enter through the center channel formed by lead to the appearance of anxiety and convulsions. alpha (␣), beta (␤), and gamma (␥) subunits. GABA receptors on ␤ subunits regulate the flow of chloride ions through the channel. The THERAPEUTIC USE activityof GABA receptors can be modulated by Benzodiazepines are used for a variety of thera- benzodiazepine receptors located on the ␥ peutic purposes. Anxiety is the experience of fear subunit. that occurs in a situation where no clear threat SOURCE: Figure created by Rebecca Bulotsky. exists. Numerous studies have demonstrated that anxiety disorders, including generalized anxiety release of GABA to affect the movement of chloride, disorder and many phobias, can be treated effec- whereas at higher doses barbiturates, through their tively with benzodiazepines. Panic disorder is a own direct effects, can act to increase chloride in- psychiatric illness in which patients experience in- flow into cells. tense sporadic attacks of anxiety often accompa- The GABAA receptor complex is composed of nied by the avoidance of open spaces and other alpha, beta, and gamma subunits (Zorumski & places or objects that are associated with panic. Isenberg, 1991). Each subunit consists of a chain of High-potency benzodiazepines such as alprazolam twenty to thirty amino acids. Multiple subtypes of (Xanax) or clonazepam (Klonopin) can prevent the the alpha, beta, and gamma subunits have been occurrence of panic attacks in patients suffering shown to exist, and the types of subunits that form from panic disorder. Flurazepam (Dalmane), tri- a single receptor complex appear to vary in differ- azolam (Halcion), and the other benzodiazepines ent areas of the central nervous system. Some re- listed in Table 1 are used in the treatment of insom- searchers have proposed that different drugs selec- nia and other sleep disorders. All rapidly acting tively interact with benzodiazepine receptors benzodiazepines marketed in the United States composed of a particular kind of ␣ subunit, thereby have hypnotic effects. Classification of a benzodi- leading to differences in drug effects. Although azepine as a hypnotic is often more a marketing there is little evidence to support this hypothesis, strategy than it is a decision based on pharmaco- future research should clarify the issue. logic differences among the class of drugs. New compounds, such as the imidazopyridines, Status epilepticus is a seizure or a series of sei- have been developed that act at the benzodiazepine zures that occurs over an extended period of time. receptor but are chemically distinct from the ben- This condition can lead to irreversible brain dam- zodiazepines. Zolpidem is an imidazopyridine used age and is often successfully managed by the intra- in clinical practice as a hypnotic agent. Other new venous infusion of diazepam. Clonazepam is used drugs have been synthesized that can stimulate the either alone or in combination with other anticon- benzodiazepine receptor but do not produce the vulsant medications to treat absence seizure and maximal effects that result from the administration other types of seizure disorders. Clorazepate is used BENZODIAZEPINES 175 to control some types of partial seizures—that is, diazepines (Rall, 1990). These may include low- seizures that occur in a limited area of the brain. level anxiety, restlessness, depression, paranoia, The increase in central nervous system excitability, hostility, and rage. Sleep patterns may be disrupted seizures, and anxiety that may appear during alco- by benzodiazepine administration, and nightmares hol withdrawal can be treated with any benzodi- may increase in frequency. Benzodiazepines sup- azepine. Midazolam (Versed) is a benzodiazepine press two stages of the sleep cycle—the stage of that is rapidly metabolized in the body and is used deepest sleep, stage IV, and the rapid eye move- to help induce anesthesia during surgical proce- ment (REM) stage in which dreaming occurs. dures. The skeletal-relaxant properties of benzodi- azepines make them useful for the treatment of TOLERANCE AND back pain due to muscle spasms. PHYSICAL DEPENDENCE

TOLERANCE to a drug involves either a decrease ADVERSE EFFECTS in the effect of a given dose of a drug during the Benzodiazepines have proven to be exceptionally course of repeated administration of the agent or safe agents. The dose at which these agents are the need to increase the dose of a drug to produce a lethal tends to be exceedingly high. Fatalities are given effect when it is administered repeatedly. more apt to occur when these drugs are taken in Chronic treatment of animals with benzodiazepines combination with other central nervous system de- leads to a reduction in potency of these agents as pressant agents such as ethanol. Sedation is a com- enhancers of chloride ion uptake. These effects at mon adverse effect associated with benzodiazepine the cellular level are paralleled by the appearance use. Light-headedness, confusion, and loss of mo- of tolerance to the sedative effects of benzodiaze- tor coordination may all result following the ad- pines. Tolerance also develops to the impairment of ministration of benzodiazepines. MEMORY impair- motor coordination that is produced by these ment may be detected in individuals treated with drugs. Limited evidence suggests that the an- benzodiazepines, and this effect may prove to be tianxiety effects of benzodiazepines may not dimin- particularly troublesome to ELDERLY patients who ish with time, or at the very least that benzodiaze- are experiencing memory-related problems. pines retain their effectiveness as antianxiety PSYCHOMOTOR impairment can be hazardous to in- agents for several months. dividuals when they are driving. This problem can PHYSICAL DEPENDENCE results from adaptive be exacerbated in individuals who consume ethanol changes in the nervous system that may be related while they are being treated with benzodiazepines. to the development of tolerance. Dependence of this Hypnotic agents that are converted into active me- sort can be detected by the appearance of a charac- tabolites that are slowly eliminated from the body, teristic abstinence or WITHDRAWAL syndrome when such as flurazepam, may produce residual daytime chronic administration of a drug is either abruptly effects that can impair tasks such as driving. The discontinued or after the administration of an an- adverse effects of benzodiazepines on performance tagonist to the drug that has been taken for a tend to be more of a problem in elderly people than prolonged period of time (Ciraulo & Greenblatt, in in younger individuals. Patients with cirrhosis, a press). Individuals who are treated chronically with liver degenerative disease, are also more likely to benzodiazepines may exhibit signs and symptoms experience benzodiazepine toxicity than are those of withdrawal when the administration of these with normal liver function. The appearance of the drugs is discontinued. Minor symptoms of with- adverse effects associated with benzodiazepine ad- drawal include ANXIETY, insomnia, and night- ministration in both elderly people and in cirrhotic mares. Less common and more serious symptoms patients can be minimized by treating them with include psychosis, death, and generalized seizures. agents such as oxazepam and lorazepam, which Signs of withdrawal may become evident twenty- tend not to accumulate in the blood because they four hours after the discontinuation of a benzodi- are excreted rapidly into the urine as glucuronide azepine that is rapidly eliminated from the blood. conjugates. Peak abstinence symptoms may not appear until A small number of patients may exhibit para- two weeks after discontinuation of a benzodiaze- doxical reactions when they are treated with benzo- pine that is removed from the body slowly. Some of 176 BENZODIAZEPINES the symptoms that appear after benzodiazepine involve the use of drugs for recreational purposes— treatment is discontinued may be due to the recur- that is, drugs are administered to experience their rence of the anxiety disorder for which the drug had mood-elevating (euphoric) effects. For some indi- been originally prescribed. viduals, self-administration of drugs for these pur- In animals, the severity of withdrawal can be poses may lead to compulsive drug-seeking behav- directly related to the dose and length of time of ior and other extreme forms of drug-controlled administration of a benzodiazepine. This kind of behavior. These behavior patterns may become relationship has been harder to demonstrate in further reinforced by the effects of withdrawal clinical studies. Many patients who are treated with symptoms that dependent individuals attempt to benzodiazepines for prolonged periods of time may reduce by the administration of the abused agent. experience at least some symptoms of withdrawal, The APA specifies that individuals can be classified but most of these individuals should not be viewed as being drug dependent if they exhibit signs of as benzodiazepine ‘‘addicts’’ because they have re- drug tolerance, symptoms of withdrawal, cannot lied on their medications for medical reasons, have control their drug use, feel compelled to use a drug, taken the medications as directed by their physi- and/or continue to use a substance even if the con- cians, and will not continue to compulsively seek sequences of this use may prove harmful to them out benzodiazepines once their prescribed course of (American Psychiatric Association, 1994). treatment with these medications has been discon- Abuse of drugs may sometimes represent self- tinued. The intensity of abstinence symptoms that medication. COCAINE and AMPHETAMINE users may be seen in patients who are physically depen- sometimes rely on benzodiazepines to relieve the dent on benzodiazepines can be markedly reduced jitteriness that may result from the administration if patients are allowed to gradually taper off their of PSYCHOMOTOR STIMULANTS. Some abusers of medications. There may be a risk of physical with- benzodiazepines may be medicating themselves drawal from benzodiazepines in some patients who with these agents to treat preexisting conditions of abruptly stop the medication following as few as anxiety and DEPRESSION. four weeks after treatment. Patients who discon- The ABUSE LIABILITY of benzodiazepines—that tinue taking rapidly metabolized hypnotic drugs is, the likelihood that they will be misused—has such as triazolam may be at risk for experiencing been assessed in studies of the tendency of either rebound insomnia, even if they have been under human beings or animals to administer these treatment for a few days to one week. Serious prob- agents to themselves and studies of the subjective lems associated with benzodiazepine withdrawal effects that result from the administration of differ- are more likely to be a problem for patients who ent benzodiazepines. When provided access to co- have been treated with high doses of these medica- caine and other psychomotor stimulants, animals tions for four or more months. will consistently self-administer these agents at high rates over time. Primates will intravenously self-administer benzodiazepines at moderate rates ABUSE AND DEPENDENCE that are below those observed for the administra- Although no consensus exists as to the definition tion of BARBITURATES or COCAINE. This finding and of drug addiction, diagnostic criteria for drug abuse the results of a number of additional animal studies and dependence have been developed by both the indicate that the benzodiazepines have a lower American Psychiatric Association and the World abuse liability than do the barbiturates or the psy- Health Organization. Drug abuse can be viewed as chomotor stimulants (Ciraulo & Greenblatt, in the use of a pharmacological substance in a manner press). that is not consistent with existing medical, social, Individuals with a history of sedative-hypnotic or legal standards and practice. Alternatively, drug abuse will self-administer triazolam and diazepam abuse has been defined in the DIAGNOSTIC AND STA- (Roache & Griffiths, 1989). In contrast, normal TISTICAL MANUAL of Mental Disorders of the APA as volunteers do not prefer diazepam to placebo. Sub- involving a ‘‘maladaptive pattern of substance use jective responses to drugs can be assessed through manifested by recurrent and significant adverse the use of instruments such as the Addiction Re- consequences related to repeated use’’ (American search Center Inventory-Morphine Benzedrine Psychiatric Association, 1994). Abuse of drugs may Group Scale and the Profile of Moods States that BENZODIAZEPINES 177 help to standardize the reports of subjects concern- vey a complete picture of how benzodiazepines are ing their drug-induced experiences. Investigations misused at the nationwide level (Cole & Chiarello, in which subjective responses of normal subjects to 1990). benzodiazepine administration have been assessed Benzodiazepines are frequently used by individ- indicate that these agents tend not to produce mood uals who abuse other drugs, but they are rarely elevations in normal populations. On the other used as either initial or primary drugs of abuse. hand, individuals with a history of either alcohol- Benzodiazepine abusers often take these drugs in ism or sedative-hypnotic abuse are more likely to combination with other agents. In Scotland, drug experience euphoria after the administration of a abusers have often injected temazepam in combi- single dose of either diazepam or other benzodiaze- nation with the OPIOID drug BUPRENORPHINE pines. Adult children of alcoholics experience mood (Ruben & Morrison, 1992). Large percentages of elevation after the ingestion of either alprazolam or methadone-clinic patients have urine tests that are diazepam, thus suggesting that these individuals positive for benzodiazepines. METHADONE- may have a predisposition to benzodiazepine MAINTENANCE patients have indicated that abuse. diazepam, lorazepam, and alprazolam can produce Studies suggest that benzodiazepines are less desirable pleasurable effects (Sellers et al., 1993). likely to be abused than the barbiturates, opiates, Whether methadone patients use benzodiazepines or psychomotor stimulants, but that they carry to increase the effects of methadone or as self- more risk for abuse than do medications such as the medication for anxiety is not clear. antianxiety agent buspirone or drugs that have The percentage of alcoholics admitted for treat- sedating effects such as the antihistamine ment who also concurrently use benzodiazepines diphenhydramine (Preston et al., 1992). There also ranges between 12 to 23 percent. High rates of may be differences among the benzodiazepines benzodiazepine abuse have been found in alcohol- themselves. Some authorities believe that diazepam ics who have experienced failure in treatment pro- has greater abuse liability than halazepam, grams for alcohol abuse. Clinical experience sug- oxazepam, chlordiazepoxide, or clorazepate, al- gests that benzodiazepine abuse occurs with the though others believe that there is little difference greatest frequency in alcoholics with severe depen- among them. Diazepam, lorazepam, alprazolam, dence and in alcoholics who abuse multiple types of and triazolam all produce mood effects that are drugs. similar to those of known drugs of abuse. The rate Individuals with a history of either alcohol abuse at which these drugs reach the brain after adminis- or alcohol dependence often have anxiety disorders. tration may be a major determining factor in the The issue of treating alcoholics with benzodiaze- onset of euphoria or pleasant effects associated pines is complex because some of these patients can with abuse. Inferences about abuse potential are take the medications without abusing them or re- made on the basis of subjective effects and self- lapsing to alcohol use whereas others take them in administration in drug abusers and alcoholics. higher than prescribed doses and find that their Many experts question the applicability of these desire to drink alcohol is increased. findings to the general population. Studies that accurately reflect the extent of ben- SUMMARY zodiazepine abuse in the United States are not available. A survey of American households pro- A large number of benzodiazepines are available duced by the National Institute on Drug Abuse sug- for clinical use. These agents all share a set of gested that the nonmedical use of tranquilizers was pharmacologic properties that result from en- not a major health problem (Ciraulo & Greenblatt, hanced chloride flux at the GABAA-receptor com- in press). Only 2.4 percent of individuals between plex, which in turn results in the inhibition of neu- the ages of 18 and 24 and 1.3 percent of survey ronal activity in many regions of the central respondents who were older than 26 reported using nervous system. Differences in activity among the tranquilizers for nonmedical purposes. This type of benzodiazepines appear to be related primarily to survey does not take into account benzodiazepine differences in rates of absorption and metabolism, usage among groups such as homeless people, pris- although recent research has suggested that intrin- oners, and migrant workers, and so it cannot con- sic activity at benzodiazepine receptor subtypes 178 BENZODIAZEPINES: COMPLICATIONS

also may influence drug effects. These drugs have ZORUMSKI, C. F., & ISENBERG, K. E. (1991). Insights into been used extensively to treat anxiety, insomnia, the structure and function of GABA-Benzodiazepine seizures, and other disorders. They are safe and receptors: Ion channels and psychiatry. American effective and their use has rarely been associated Journal of Psychiatry, 148, 162–173. with irreversible adverse effects. Both physical and DOMENIC A. CIRAULO psychological dependence may be problematic for CLIFFORD KNAPP some individuals who are treated on a long-term basis with these agents or who have abused alcohol or other drugs. BENZODIAZEPINES: COMPLICA- TIONS As medicines, BENZODIAZEPINES have (SEE ALSO: Addiction: Concepts and Definitions; been widely used—as tranquilizers, to allay anxi- Benzodiazepines: Complications; Sleep, Dreaming, ety. Until the 1990s, they were believed to be both and Drugs) effective and extremely safe; however, beginning in the early 1980s, problems with these drugs started to become evident. Currently, the medical profes- BIBLIOGRAPHY sion in many countries is trying to inculcate a AMERICAN PSYCHIATRIC ASSOCIATION. (1994). Diagnostic cautious attitude toward their prescription and use. and statistical manual of mental disorders, 4th ed. Lay people and the media have also become in- Washington, DC: Author. creasingly critical of the widespread use of these CIRAULO, D. A., & GREENBLATT, D. J. (in press). Seda- medicines for apparently trivial indications. To un- tive-, hypnotic-, or anxiolytic-related disorders. Balti- derstand these problems, some aspects of the dif- more: Williams & Wilkins. ferent types and effects of these medicines will be COLE,J.O.,&CHIARELLO, R. J. (1990). The benzodiaze- outlined. pines as drugs of abuse. Journal of Psychiatric Re- search, 24 (Suppl. 2), 135–144. WHAT ARE BENZODIAZEPINES? KARDOS, J. (1993). The GABA-A receptor channel medi- ated chloride ion translocation through the plasma These medicines are used to lessen a patient’s membrane: New insights from 36 Cl-ion flux mea- anxiety; they include such drugs as surements. Synapse, 13, 74–93. CHLORDIAZEPOXIDE (Librium), diazepam (Val- PRESTON, K. L., ET AL. (1992). Subjective and behavioral ium), lorazepam (Ativan) and oxazepam (Serenid; effects of diphenhydramine, lorazepam and Serox). The term benzodiazepine describes a basic methocarbamol: Evaluation of abuse liability. Journal chemical structure. Some, like diazepam, are long acting and can be taken once daily; others, like of Pharmacologyand Experimental Therapeutics, lorazepam and alprazolam (Xanax), need to be 262(2), 707–720. taken more often. Most sleeping tablets (hypnotics) RALL, T. W. (1990). Hypnotics and sedatives: Ethanol. are benzodiazepines, and these include short-act- In A. G. Gilman et al. (Eds.), Goodman and Gilman’s ing drugs such as triazolam (Halcion), medium- the pharmacological basis of therapeutics, 8th ed. acting drugs such as temazepam (Restoril), and New York: Pergamon. long-acting drugs such as flurazepam (Dalmane) ROACHE,J.D.,&GRIFFITHS, R. R. (1989). Diazepam and and nitrazepam (Mogadon). triazolam self-administration in sedative abusers: Other medicines are used in psychiatry, such as Concordance of subject ratings, performance and ANTIDEPRESSANTS,ANTIPSYCHOTICS, and lithium. drug self-administration. Psychopharmacology, 99, These have effects that differ from the benzodiaze- 309–315. pines, effects both therapeutic and unwanted. RUBEN, S. M., & MORRISON, C. L. (1992). Temazepam misuse in a group of injecting drug users. British Journal of Addiction, 87, 1387–1392. WHAT DO BENZODIAZEPINES DO? SELLERS, E. M., ET AL. (1993). Alprazolam and benzodi- Tranquilizers promote calming, soothing, and azepine dependence. Journal of Clinical Psychiatry, pacifying—without sedating or depressant effects. 54(Suppl. 10), 64–75. They are effective in lessening ANXIETY whatever BENZODIAZEPINES: COMPLICATIONS 179 its context. Thus, they are useful in treating gener- izers but that a large group of long-term users is alized anxiety, which is often quite severe and accumulating. People starting tranquilizers have at comes on without apparent cause. Tranquilizers least a 10 percent chance of going on to long-term can also be used to deaden the upset of normal use, that is for more than 6 months. Some of these anxiety, the anxiety felt by people under stress, chronic users have chronic medical or social prob- feeling threatened by life’s problems. In these in- lems, and the tranquilizer blunts the unpleasant stances, the reasons for feeling anxious are clear, feelings of tension, anxiety, insomnia and, to a the degree of anxiety seems in line with the stress lesser extent, depression. experienced—but despite this, help is sought for the symptoms. Unfortunately, the borderline be- UNWANTED (SIDE) EFFECTS tween the medical disorder of clinical generalized anxiety and the normal response to stress is not Side effects are reactions to drugs that are not always clear. The professional consulted will usu- therapeutic or helpful, and they are therefore un- ally try to make the distinction and avoid using wanted. The most common side effects from taking tranquilizers to treat people upset by adverse cir- benzodiazepine are drowsiness and tiredness, and cumstances—thereby ‘‘medicalizing’’ everyday so- they are most marked within the first few hours cial and personal problems. after large doses. Other complaints of this type Similar considerations apply to the use of benzo- include dizziness, headache, blurred vision, and diazepines as sleeping tablets. Short-term use of feelings of unsteadiness. The elderly are particu- these drugs—for example, for disturbed sleep with larly sensitive to tranquilizers and may become jet travel across time zones, severe stress, or shift unsteady on their feet or even mentally confused. work—is generally accepted. Long-term use in the The feelings of drowsiness are, of course, what is chronically poor sleeper is not usually encouraged, wanted with a sleeping tablet. With the longer- however. acting benzodiazepines and with higher doses of Benzodiazepines can also be used as sedatives medium-duration or with short-acting drugs, before surgical operations, as light anesthetics dur- drowsiness can still be present the morning after ing operations, and to lessen muscle spasms, such taking a sleeping tablet; the drowsiness may even as occur with sports injuries. Some benzodiazepines persist into the afternoon. The elderly are more can be used to treat some forms of epilepsy. Benzo- likely to experience such residual, or ‘‘hang-over,’’ diazepines are prescribed mainly by general family effects. practitioners, although they vary greatly in how As well as these feelings of sedation, special test- often they use these medicines. Some still prescribe ing in a psychology laboratory indicates that alert- them widely, some hardly at all. Other doctors who ness, coordination, performance at skilled work, use benzodiazepines include psychiatrists, orthope- mental activities, and memory can all be impaired. dic specialists, and gynecologists. Patients should be warned about this, and advised not to drive or operate machinery, at least initially HOW MUCH ARE THEY USED? until the effects of the benzodiazepine can be as- An international survey at the beginning of the sessed and the dosage adjusted if necessary. If driv- 1980s showed that tranquilizers and sedatives of ing is essential—that is, to the patient’s liveli- any type had been used at some time during the hood—small doses of the benzodiazepines should previous year by 12.9 percent of U.S. adults, 11.2 be taken at first and the amount built up gradually percent in the United Kingdom (U.K.), 7.4 percent under medical supervision. Judgment and memory in the Netherlands, and 15.9 percent in France. are often impaired early in treatment, so important Persistent long-term users comprised 1.8 percent of decisions should be deferred. all U.S. adults, 3.1 percent in the U.K., 1.7 percent As with many drugs affecting the brain, benzo- in the Netherlands and 5.0 percent in France. The diazepines can interact with other drugs, especially proportion of repeat prescriptions for tranquilizers ALCOHOL. People taking tranquilizers or hypnotics has increased steadily since about 1970 in many should not also drink alcoholic beverages. Other countries, the U.K. in particular. This suggests that drugs whose effects may be enhanced include anti- fewer people are being newly started on tranquil- histamines (such as for hay fever), painkillers, and 180 BENZODIAZEPINES: COMPLICATIONS antidepressants. Cigarette smoking may lessen the and actually prevent the bereaved individual from effect of some benzodiazepines. coming to terms with loss. Patients taking benzodiazepines may show so-called paradoxical responses—that is to say, the LONG-TERM EFFECTS effects produced are the opposite of those intended. OF BENZODIAZEPINES Feelings of anxiety may heighten rather than lessen, insomnia may intensify, or, more disturb- It is not clear whether benzodiazepines and hyp- ing, patients may feel hostile and aggressive. They notics continue to be effective after months or years may engage in uncharacteristic criminal activities, of daily use. Undoubtedly, many patients believe sexual improprieties or offenses such as impor- that they continue to benefit in being less anxious, tuning or self-exposure, or show excessive emo- or in sleeping better. The effect of the drug may be more to stop the anxiety or insomnia that follows tional responses such as uncontrollable bouts of withdrawal, however, than to combat any continu- weeping or giggling. All these are signs of the re- ing, original anxiety. Most of the side effects lessen lease of inhibitions, and they are also characteristic over time, a process known as tolerance. Some of alcohol effects in some people. Although these impairments, however, such as memory distur- paradoxical effects may not last long, it is better to bances, may persist indefinitely, but patients usu- stop the benzodiazepine. ally come to terms with this—for example, by re- Benzodiazepines can affect breathing in individ- sorting to written reminders. uals who already have breathing problems, such as with bronchitis. Other side effects that may be occasionally encountered include excessive weight REBOUND gain, rash, impairment of sexual functioning, and Rebound occurs when stopping the drug makes irregularities of menstruation. Benzodiazepines the underlying condition worse. Most is known should be avoided during pregnancy whenever pos- about rebound in insomnia. Sleeping tablets may sible, as there may be a risk to the fetus. Given improve sleep by inducing it more rapidly, making during childbirth, benzodiazepines pass into the it sounder, and prolonging it. When the sleeping unborn infant and may depress the baby’s breath- tablet is stopped, rebound may occur on the follow- ing after birth. They also pass into the mother’s ing night or two, with the insomnia being worse milk and may sedate the suckling baby too much. than ever. Eventually, the rebound insomnia sub- Many people have taken an overdose of a tranquil- sides, but the patient may have been so distressed izer as a suicidal attempt or gesture. Fortunately, as to resume medication, thereby running the risk these drugs are usually quite safe and the person of indefinite use. The risk of rebound is greatest wakes up unharmed after a few hours’ sleep. with short-acting benzodiazepines, especially in higher dose. SIDE EFFECTS VERSUS A similar problem follows stopping a daytime MAIN EFFECTS tranquilizer, particularly lorazepam. Anxiety and tension rebound to levels higher than those experi- There are more subtle side effects of benzodiaze- enced on treatment and often higher than the initial pines, effects that interfere in various ways with the complaints. Tapering off the tranquilizer over a treatment of the anxiety or sleep disorder. The ben- week or two lessens or avoids this complication. zodiazepine lessens the symptom but does not alter Rebound may even be seen in the daytime between the underlying problem—say, an unhappy mar- doses of tranquilizer. The patient, increasingly anx- riage or a precarious job. Indeed, by lessening the ious as the effect of the earlier dose wears off, symptoms, the individual may lose his or her moti- watches the clock until his or her next dose is due. vation to identify, confront, and tackle the basic Rebound may also occur later in the day after tak- problems. Giving benzodiazepine medicalizes the ing a short-acting sleeping tablet the night before. problem by making the nervous or sad person into a patient, implying that there is something physi- WITHDRAWAL cally wrong. Finally, some events like bereavement need ‘‘working through’’—typically by grieving— In withdrawal, symptoms occur which the pa- but benzodiazepines can stop this normal process tient has not previously experienced. They come on BENZODIAZEPINES: COMPLICATIONS 181 a day or two after stopping alprazolam or loraze- may return at any time, depending on external pam, after a week or so on stopping diazepam or stresses. chlordiazepoxide. The symptoms rise to a cre- scendo and then usually subside over two to four HOW TO WITHDRAW weeks. In an unfortunate few, the symptoms seem to persist for months on end—sometimes called the Essentially, the patient must be prepared for post-withdrawal syndrome. The existence of this withdrawal by being told what to expect; he or she condition is disputed by some doctors, who ascribe should be taught other ways of combatting anxiety; the symptoms to return of the original anxiety for and withdrawal should be by graded tapering off which the drug was given. the dose over six to twelve weeks, occasionally Patients commonly experience bodily symptoms longer. Many people experience little or no upset, a few undergo much distress. Sometimes substituting of anxiety such as tremor, palpitations, dry mouth, diazepam in the lorazepam or alprazolam user or hot and cold feelings. Insomnia is usually helps. Antidepressants may be needed if the patient marked. Some complain of unpleasant feelings of becomes very depressed, but by and large, other being out of touch with reality or with their own drugs are unhelpful. bodies. Severe headaches and muscle aches and Family and social support is essential. Usually pains can occur, sleep is greatly disturbed, appetite the family doctor can supervise the withdrawal is lost as is several pounds of weight. Disturbances quite safely, but occasionally specialist advice is of perception are characteristic of benzodiazepine sought. A self-help group may provide useful con- withdrawal and include intolerance to loud noises tinued advice and support. or bright lights, numbness or pins and needles, It is important that tranquilizers are never unsteadiness, a feeling of being in motion (as on a stopped abruptly. There is a greatly increased risk ship at sea), and a sensing of strange smells and of severe complications such as seizures or tastes. Some people become quite depressed; rarely, convulsions. some experience epileptic fits or a paranoid psycho- sis (with feelings of persecution and loss of contact with reality). ABUSE OF TRANQUILIZERS Only a few patients prescribed benzodiazepines HOW BIG IS THE PROBLEM? push the dose up above recommended levels. If this happens, the user may become intoxicated, with The withdrawal symptoms are evidence of phys- slurred speech and incoordination. Some people ical dependence—that is, the body has become so with alcohol problems also abuse benzodiazepines. used to the effects of the benzodiazepine that it Intravenous (IV) injection of benzodiazepines and cannot manage without. About a third of long-term hypnotics has become an increasing problem and (over a year) steady users show withdrawal, even has led to controls on these drugs concerning man- when the tranquilizer or hypnotic is tapered off. ufacture and prescription in various countries, in- Some users have tried to stop and have encountered cluding the United States and the U.K. Some ad- problems. Many others have never tried to stop and dicts abuse benzodiazepines alone; others combine so are unaware whether they are dependent. Be- it with heroin-type drugs. Injection of benzodiaze- cause these people continued to take the doses pre- pines can result in clotting of the veins. It also scribed by their doctors, the medical profession was carries the risk of getting infectious diseases from reluctant for a long time to admit the scale of the sharing dirty syringes, such as hepatitis and the problem—perhaps 500,000 people dependent on human immunodeficiency virus (HIV or the AIDS tranquilizers in the U.K. alone. In addition, the virus). similarity between some withdrawal symptoms and features of the original anxiety has led to confusion ALTERNATIVES TO in the mind of both the patient and the doctor. True THE TRANQUILIZERS withdrawal symptoms, however, arise at a predict- able time after stopping the benzodiazepine and are Dissatisfaction with the benzodiazepine tran- new experiences for the patient; the old anxiety and quilizers and hypnotics has led to numerous initia- insomnia symptoms are familiar to the patient and tives to find better alternatives. Some drugs have 182 BENZOYLECOGNINE

been developed that are better benzodiazepines, in WOODS, J. H., KATZ, J. L., & WINGER, G. (1987). Abuse that they are less sedative and perhaps less likely to liability of benzodiazepines. Pharmacological Re- induce dependence. Others are chemically not ben- views, 39(4), 251–419. zodiazepines but share many of their properties, MALCOLM H. LADER both therapeutic and unwanted. Other compounds seem to act in a totally different way in the brain and are less sedative and probably much less likely BENZOYLECOGNINE Cocaine is metabo- to induce dependence. One such compound— lized by plasma and liver enzymes (cholinesterases) buspirone (Buspar)—has been available for a few to water-soluble metabolites that are excreted in years, but many others are in the process of devel- the urine. The two major metabolites are ben- opment. Finally, interest has been rekindled in the zoylecognine and ecognine methyl ester, with only use of other types of older drugs to treat anxiety; benzoylecognine reported to have behavioral activ- examples include the antihistamines and the beta ity. Since COCAINE has a relatively short half-life blockers. and may only be present in the urine for twenty- Problems with the benzodiazepines has led to a four to thirty-six hours, benzoylecognine levels in reevaluation of the whole role of prescribed medi- urine are useful markers of cocaine use, because it cines in the management of anxiety, insomnia, and stress-related disorders. Numerous nondrug meth- ods have been developed and improved, among them relaxation training; cognitive therapy, in which patients learn to think less anxious thoughts; behavior therapy, in which the patient learns to confront stressful situations; and sleep counseling. Alternative medicine, like ACUPUNCTURE, is en- joying a vogue and helps some anxious people. Figure 1 Benzoylecognine CONCLUSIONS is present for a longer time in urine, two to four Hailed as wonder drugs, prescribed widely and days, depending on the quantity of cocaine in- for long periods of time, the benzodiazepines have gested. Assays for this metabolite are frequently now been shown to be problematic medicines with employed in treatment programs, to evaluate com- undoubted benefits but definite risks. For short- pliance with the program, and in workplace drug term treatment in the severely anxious and testing to indicate cocaine use. Under these condi- sleepless, they are still useful—although other tions, it is important to keep in mind that ben- drugs are beginning to supplement and even sup- zoylecognine in the urine is an indication of prior plant them. For the bulk of anxious people, though, cocaine use, but reflects neither current use nor nondrug treatments are increasingly popular. impairment.

(SEE ALSO: Addiction: Concepts and Definitions; (SEE ALSO: Cocaethylene; Drug Testing and Analy- Complications; Iatrogenic Addiction; Sleep, sis) Dreaming, and Drugs; Tolerance and Physical De- MARIAN W. FISCHMAN pendence; Withdrawal )

BIBLIOGRAPHY BETEL NUT Betel nut, the seed of the betel AMERICAN PSYCHIATRIC ASSOCIATION. (1900). Task force palm (Areca catechu), is one of the most widely report: Benzodiazepine dependence, toxicity, and used substances in areas of the western Pacific and abuse. Washington, DC: Author. parts of Africa and Asia. It is prepared with other CURRAN,H.V.,&GOLOMBOK, S. G. (1985). Pill popping: substances as a mixture for chewing and is used as How to get clear. Boston: Faber & Faber. a mild stimulant by more than 200 million people. BETEL NUT 183

References to betel nut appear in ancient Greek, Sanskrit, and Chinese texts from more than a cen- tury B.C. Ancient historic documents of Ceylon refer to its use, and its prevalence in Persia by 600 A.D.is documented by Persian historians. Its use in differ- ent parts of the Arab world by the eighth and ninth centuries is also well documented, and it had be- come an important aspect of the economy and so- cial life in India, Malaysia, the Philippines, and New Guinea. Betel was probably brought to Europe by Marco Polo, around 1300; it soon proved to be an important commodity in the western Pacific and a source of tax revenue for the Dutch in the mid-1600s. Figure 1 Betel Palm and Betel Nut PATTERNS OF USE the use of KAVA, or of the consumption of ALCO- The mottled brown-and-gray betel seeds are HOL in Western countries. In some areas of the gathered before they ripen during the period be- world, such as Papua New Guinea, betel-nut mix- tween August and November. They are boiled in tures are often offered as a before-dinner ‘‘appe- water, cut into slices and dried in the sun, becoming tizer’’ or as an after-dinner treat. Like kava, in dark brown or reddish in color. This betel seed, or many places, sharing betel-nut mixture is impor- nut, becomes the primary ingredient in the betel tant in courtship and marriage customs and in es- nut chewing mixture (‘‘quid’’), which is made up of tablishing friendships. several ingredients. While the component sub- stances differ in different parts of the world, all the ACTIVE INGREDIENTS preparations contain fresh chunks or dried pow- dered forms of the betel nut. Mixtures prepared for The major active ingredient of betel nut is children frequently contain only the husk of the arecoline, present in a concentration estimated to nut, while the full strength form for adults always be 0.25 percent. The mixture also contains small has the nut itself. amounts of pilocarpine and muscarine. These three The second ingredient of the quid is usually a ingredients are all natural plant products that act form of peppermint or mustard, or the leaf, bean in the body in a manner similar to the normal brain and/or bark of the shrub-like or climbing pepper NEUROTRANSMITTER acetylcholine. In the presence plant vine (Piper betel ). The third component is of calcium hydroxide, arecoline is also converted to slaked lime, which is usually produced from lime- another psychoactive substance, aredaidine. stone or by burning sea shells or coral stones in the Chewing betel nut produces immediate effects presence of water. This process produces calcium that in some ways resemble those of NICOTINE, but hydroxide, usually used as a white powder. While which are likely to continue for hours. These in- all betel-nut quids contain some of the three main clude euphoria and feelings of general arousal and components, other ingredients, such as spices, dyes, activation, perceived by the user as a decrease in and aromatics are frequently added. In India, to- tiredness and a blunting of feelings of irritability. bacco is mixed with the quid. The combination of Other prominent effects are also related to the nut, mustard or vine, lime, and other ingredients acetylcholine-like actions. These include sweating, create an alkaline, bitter-tasting mixture that is increased production of saliva, and an increase in chewed, forming a red paste which stains the teeth, breathing rate and lacrimation (tearing of the mouth, gums, and lips, and generating large eyes). Effects on the digestive tract include a de- amounts of saliva. Like tobacco chewers, betel-nut crease in appetite and, especially if the drug is chewers spit out the excess juices. taken on an empty stomach, diarrhea. All these Some habitue´s chew betel nut all day long. effects can be blocked by atropine, a type of anti- Others use it as part of social custom, not unlike acetylcholine drug. 184 BETEL NUT

Some of the active ingredients in betel nut are seen in at least mild form in up to 50 percent of used in modern pharmacological treatment in the chronic betel-nut chewers. This condition usually Western world. Betel-nut preparations have been has a very slow onset, and if use continues it is used in Western society as a purgative and in veter- irreversible, untreatable, and likely to become pro- inary medicine as an agent for treating worm infes- gressively more severe. The major finding involves tation in animals. Probably the most interesting use a loss of elasticity of the tissue lining the mouth, appears around 1842, when betel nut was included which causes stiffness that can become so severe as in toothpastes in England. It was touted as an to interfere with eating. Associated problems are a important way to prevent decay, a claim that may burning sensation in the mouth, ulcers or blisters or may not be accurate, although much larger doses on the lining of the mouth, decreased sense of taste, than those found in toothpastes would be required and dryness of the mouth lining. to really be clinically effective. It was also said that There is little doubt that betel-nut substance can this ingredient would help strengthen the tooth produce fairly intense psychological dependence. enamel and remove tartar, claims of questionable Individuals can develop a pattern of constant use, value. In view of the fact that betel, as it is com- feeling unhappy and incomplete if they cannot get monly used, stains the teeth dark red to black, is their betel nut. They are also likely to feel they thought to cause tooth decay, and can cause serious cannot work properly without it, and may spend a lesions of the mouth and throat, it is curious that it great deal of money and time obtaining and using should have appeared in Western society in prepa- betel-nut mixtures. It is not clear, however, that rations for dental care. there is a prominent and identifiable form of physi- cal withdrawal associated with cessation of use. SOME DANGERS Betel-nut consumption can be viewed as a pub- The acetylcholine-type drugs, especially musca- lic-health hazard in parts of the world where its use rine, can be deadly when taken in high doses. In is prevalent, because, at least theoretically, the fact, muscarine is the active ingredient causing habit of spitting the juice on the street can increase some forms of lethal mushroom poisoning, but it is the spread of diseases such as tuberculosis. unlikely that the mixture of any of the plant prod- ucts in betel-nut preparations are potent enough to (SEE ALSO: Plants, Drugs from) cause lethal overdose. Regular ‘‘recreational’’ use of betel nut is, however, responsible for a number of BIBLIOGRAPHY adverse health consequences that can contribute to the risk for early death. BEECHER, D., ET AL. (1985). Betel nut chewing in the The most prominent dangers associated with be- United States, Journal of the Indiana Dental Associa- tel-nut chewing are probably the result of a com- tion, 64, 42–44. bined effect of the active ingredients and the lime FORD, C. S. (1967). Ethnographical aspects of kava. In on the gums. The first and most frequently ob- D. H. Efron, B. Holmstedt, & N. S. Kline, (Eds.), served physical changes are white plaques appear- Ethnopharmacologic search for psychoactive drugs. ing on the mucosal lining of the mouth or on the PHS Publ. No. 1645. Washington, DC: U.S. Depart- tongue. These are precancerous lesions (leu- ment of Health, Education, and Welfare. koplakia) that often lead to the development of LEWIN, L. (1964). Phantastica: Narcotic and stimulating very aggressive and serious tumors (squamous cell drugs. New York: Dutton. carcinoma), which can subsequently invade mus- SCHUCKIT, M. A. (1992). Betel Nut: A widespread drug of cles and bone tissue. The prevalence of this cancer abuse. Drug Abuse & Alcoholism Newsletter, 21(1). among regular betel-nut users is estimated to be as San Diego: Vista Hill Foundation. high as 7 percent. Potentially lethal cancers may SCHULLIAN, D. M. (1984). Toothpastes containing betel also develop in the esophagus. Chronic use may nut from England of the 19th century. Journal of also cause oral submucous fibrosis—a form of fiber Historyof Medicine, 39 , 65–68. formation (fibrosis) that usually starts just beneath TALONU, N. T. (1989). Observations of betel nut use, the gums and may involve the back of the throat habituation, addiction and carcinogenesis. Papua and the pharynx. The problem is estimated to be New Guinea Medical Journal, 32, 195–197. BLOOD ALCOHOL CONCENTRATION, MEASURES OF 185

TAUFA, T. (1988). Betel nut chewing and pregnancy. S-shaped glass capillaries that contained a thin film Papua New Guinea Medical Journal, 31, 229–233. of potassium oxalate and sodium fluoride on the MARC A. SCHUCKIT walls of the tube. In Widmark’s day, the small JEROME H. JAFFE amounts (aliquots) of blood needed for each analy- sis could be measured more accurately by weight than by volume, since constriction pipettes were not yet available. Widmark therefore weighed the BETTY FORD CENTER See Treatment amount of blood required to the nearest milligram Programs/Centers/Organizations: An Historical (0.001 g) with the aid of a torsion balance. The Perspective results of ethanol determinations were then re- ported in terms of mass per mass units, actually milligram of ethanol per gram of whole blood (mg/ BHANG This is one of the many names given g), sometimes referred to as per mille (meaning, to the HEMP plant, Cannabis sativa, and its prod- parts per thousand). This way of reporting BAC ucts. Bhang is of Hindi origin (from bha˜g, which survives today in Scandinavian countries where came into English about 1563) and refers to the Widmark’s method became widely used for legal leaves and flowering tops of uncultivated hemp purposes. plants. In 1895, the Indian Hemp Commission took Widmark’s micromethod of blood-ethanol anal- the position that bhang was not a major health ysis involved the following four steps: hazard. Bhang is taken in a beverage in India called (1) separation of ethanol from blood by diffusion in thandaii, may be served in sweetmeats, or is used in specially blown glassware; (2) oxidation of ethanol making ice cream. It is often served at weddings or with a mixture of potassium dichromate and sulfu- religious festivals and is freely available from side- ric acid; (3) addition of potassium iodide to the walk stands in the major cities. Generally, in India, reaction mixture after oxidation of ethanol; and the use of bhang and other cannabis products has (4) back titration of liberated iodine with standard been considered lower class. Probably as a result of sodium thiosulfate and a starch indicator to detect continuing British-based influence, the upper-class an endpoint. drugs are alcohol and opium. Many later modifications to this basic procedure appeared, such as using a different endpoint indi- (SEE ALSO: Cannabis Sativa; Marijuana; Plants, cator for the titration (e.g., methyl orange), or an- Drugs from) other kind of oxidizing agent (e.g., ferrous salts), or separation of ethanol from the biological matrix in LEO E. HOLLISTER a different way. It became common practice to refer to these modified methods with the name of the scientist who first published the report—including BLOOD ALCOHOL CONCENTRATION, Harger, Kozelka-Hine, Smith, Southgate-Carter, MEASURES OF The first analytical methods and Cavette, to name just a few. for measuring ALCOHOL (ethanol) in blood and Later developments in methods of ethanol anal- other body fluids were developed in the nineteenth ysis (such as gas chromatography) plus the avail- century. Although by modern standards these pio- ability of modern clinical laboratory equipment neer efforts were fairly crude, they were sufficiently made it more convenient to dispense the aliquots of reliable to establish a quantitative relationship be- blood needed for analysis by volume rather than by tween blood-alcohol concentration (BAC) and the weight. Micropipettes and more recently diluter- various signs and symptoms of inebriation. A sig- dispenser devices are now widely used for dilution nificant advance in methodology came in 1922 of blood prior to the analysis. The term ‘‘concentra- when Erik M. P. Widmark published his micro- tion’’ has little meaning when used alone, because method for analyzing ethanol in specimens of capil- it can be expressed in many different ways. The lary blood. choice of units for reporting BAC differs among Blood was drawn by pricking a fingertip or countries: for example, milligrams per hundred earlobe. The specimen for analysis, 100–150 milli- milliliters (mg/100 ml) in Great Britain (unfortu- grams, was collected with specially prepared nately often appearing as the ambiguous mg%); 186 BLOOD ALCOHOL CONCENTRATION, MEASURES OF

gram percent weight per volume (g% w/v) in the by the legislature when the statute was drafted. United States; and milligrams per milliliter (mg/ Table 1 gives examples of concentration units com- ml) in many European countries. Other ways of monly used to report BAC for legal purposes. Note reporting BAC in clinical medicine are milligrams that if ethanol were determined in plasma or se- per deciliter (mg/dl), grams per liter (g/liter), or rum, the concentration would be about 10 to 15 micrograms per liter (␮g/liter). When countries percent higher than for the same volume of whole outside Scandinavia enacted legal limits of ethanol blood, because there is more water in the sample in the blood of motorists, the concentrations were after the erythrocytes (red blood cells) are re- defined in units of mass of ethanol per unit volume; moved. whether it was grams, milligrams, or micrograms of In clinical chemistry laboratories, the Syste`me ethanol in a volume of milliliters, deciliters, or liters International d’Unite´s (SI) has gained worldwide seems chosen arbitrarily. acceptance. According to the SI system, the amount Because the specific gravity of whole blood is of substance implies ‘‘mole’’ rather than mass. The greater than water (on average, 1 ml of whole blood mole or a submultiple thereof replaces mass units weighs 1.055 g), BAC expressed in terms of mass such as grams or milligrams. Accordingly, the con- per mass (w/w) is not the same as mass per volume centration of a substance of known molecular (w/v). In fact, a concentration of 0.10% w/v equals weight might appear as mole/liter or millimole per 0.095% w/v. This difference of about 5.5 percent liter (mmol/l) or micromole per liter (␮mol/liter). could mean punishment or acquittal in borderline Note that liter is the preferred unit of volume when cases of driving while under the influence of alco- reporting concentrations of a substance in solution hol. With the current trend toward ‘‘per se’’ ethanol in the SI system. The molecular weight of ethanol is limits in many U.S. states, great care is needed to 46.06, and therefore a concentration of 1.0 mol/l ascertain whether w/v or w/w units were intended corresponds to 46.06 g of ethanol in 1 liter of BLOOD ALCOHOL CONCENTRATION, MEASURES OF 187

solution. Likewise 1.0 mmol/l contains 46.06 mg; BrAC when evidential breath-ethanol analyzers 1.0 ␮mol/l contains 46.06 ␮g, and so on. Publica- were introduced in these countries. Similarly, in tions in the field of biomedical alcohol research some U.S. states, a legal limit of 0.1 g/210 liters in often report BAC in this way. It follows that 0.1 g% breath is considered equivalent to 0.1 g% w/v in w/v or 100 mg/dl is the same as 21.7 mmol/l. blood for law-enforcement purposes. Table 2 gives Statutory limits of BAC existed in several coun- the statutory limits of breath-ethanol concentra- tries before methods of analyzing the breath were tions in several countries. developed. It therefore became a standard practice Both the prescribed BAC or BrAC limits for mo- to convert the concentration of ethanol measured in torists and the units of concentration used to differ the breath (BrAC) into the presumed concentration among countries and even within regions of the in the blood. For this purpose, a conversion factor, same country. The notion of reaching an interna- usually 2,100:1 was used. Presumably, it was less tional agreement about one common BAC or BrAC troublesome to make this conversion than to re- limit for motorists is an attractive one but hardly write the statute to include both BAC and BrAC as attainable. evidence of impairment. Accordingly, breath-etha- nol analyzers were calibrated in such a way that the (SEE ALSO: Blood Alcohol Content; Breathalyzer; readout was obtained directly in terms of the pre- Driving Under the Influence; Drug Testing and sumed BAC. This conversion of breath to blood Analysis) ethanol created the dilemma of a constant blood breath ratio existing for all subjects under all con- BIBLIOGRAPHY ditions of testing. In the United States and else- where, a blood/breath factor of 2,100:1 was ap- JONES, A. W. (1989). Measurement of alcohol in blood proved for legal purposes with the understanding and breath for legal purposes. In K. E. Crow & R. D. that this gives a margin of safety (about 10%) to Batt (Eds.), Human metabolism of alcohol, vol. I. the accused. Indeed, more recent research suggests Boca Raton, FL: CRC Press. that the blood/breath factor should be 2,300:1 for WIDMARK, E. M., P. (1922). Eine Mikromethode zur closer agreement between direct BAC and the result Bestimmung von A¨ thylalkohol im Blut. Biochemical derived from BrAC. In the Netherlands and Great Zeitschrift, 131, 473. Britain, 2,300:1 was chosen to set the legal limit of A. W. JONES 188 BLOOD ALCOHOL CONTENT

BLOOD ALCOHOL CONTENT The tage; 25 percent are Aymara Indians, 30 percent consumption of alcoholic beverages results in the are Quechua Indians, and 30 percent are mestizos absorption into the bloodstream of ALCOHOL (etha- (of mixed Indian and European ancestry). Al- nol, also called ethyl alcohol) from the stomach and though Bolivia is rich in mineral resources— small intestine. The amount of alcohol distributed petroleum, natural gas, tin, lead, zinc, copper, and in the blood is termed blood alcohol concentration gold—it is an economically depressed country, (BAC) and is proportional to the quantity of etha- with 66 percent of the population living below the nol consumed. It is expressed as the weight of alco- poverty line. Most of the population works in agri- hol in a fixed volume of blood, for example, grams culture, which is generally low paying, while a per liter (g/l) or milligrams per deciliter (mg/dl). small number work in the mines. In 1998, Bolivia The measurement of blood alcohol concentrations had a national debt of some 4.1 billion in U.S. has both clinical and legal applications. dollars and an annual gross domestic product Consuming food with alcohol generally de- (GDP) of 23.4 billion dollars. creases the amount of alcohol that can be quickly Much of the Bolivian population lives on the absorbed into the bloodstream. Consuming more bleak, treeless, windswept Altiplano (high plain), a than one drink per hour causes the BAC to increase plateau more than 13,000 feet above sea level. The rapidly, because it is exceeding the rate at which Altiplano is an arid expanse of red earth, of about the body can metabolize alcohol. The percentage of 40,000 square miles, with widely scattered Ilamas, body fat that contributes to a person’s total weight sheep, cattle, and homesteads. However, the also affects BAC. A larger proportion of fat pro- Altiplano is considered to be the most livable part vides less body water into which the alcohol can of the country, with 70 percent of the population distribute, thus increasing BAC. For this reason, residing along its western quarter. Much of the rest women generally have a higher BAC for a given of the people live in the Yungas, the Chapare, and number of drinks when compared to men. the Beni—the tropical jungles of northeastern and central Bolivia, where Erythroxylum coca thrives. (SEE ALSO: Blood Alcohol Concentration, Measures Erythroxylum coca, or simple ‘‘coca,’’ is the shrub of ) from which COCAINE is derived (Inciardi, 1992).

BIBLIOGRAPHY COCA PRODUCTION

FISHER, H., SIMPSON, R., & KAPUR, B. (1987). Calcula- Historically, the chewing of coca leaves was a tion of blood alcohol concentration (BAC) by sex, cultural practice among the Indian peasant la- weight, number of drinks and time. Canadian Jour- borers of the Andes. The mild stimulation received nal of Public Health, 78, 300–304. from the low cocaine-content leaves enabled work- ers to endure the burdens of their 12- to 14-hour MYROSLAVA ROMACH days in the mines and in the fields, so both Bolivian KAREN PARKER and Peruvian laws have permitted controlled pro- duction of coca for domestic consumption—about 12,000 kilograms (kg) in Bolivia (which also in- BNDD See U.S. Government Agencies: Bu- cludes production for international pharmaceutical reau of Narcotics and Dangerous Drugs use). A part of the Bolivian economy has therefore always depended on the cultivation, transport, and sale of coca leaves. BOLIVIA, DRUG USE IN Bolivia is a land The growers of illegal coca in Bolivia are the of gaunt mountains, cold desolate plains, and semi- thousands of farm families who have shifted away tropical lowlands situated in the central part of from the cultivation and harvest of more traditional South America. Straddling the Andes mountains, crops. In the early 1990s, coca accounted for as Bolivia’s 424,165 square miles occupy an area much as 40 percent of Bolivia’s agricultural pro- about the size of Texas and California combined. It duction, about 50 percent of its gross domestic is a big country, but with a population of only 7.9 product, and about 67 percent of its export earn- million. About 15 percent are of European heri- ings. However, the Bolivian government, with the BOLIVIA, DRUG USE IN 189

nor the ingestion of either powder-cocaine or CRACK-cocaine, but rather, the smoking of COCA PASTE—an intermediate product in the transfor- mation of the coca leaf into pure cocaine. In jungle refineries, coca leaves are treated with a wide vari- ety of chemicals, including alcohol, benzol (a petro- leum derivative used in the manufacture of motor fuels and insecticides), sulfuric acid, leaded gaso- line, sodium carbonate, and kerosene. The process yields crude cocaine (coca paste). Whereas the co- caine content of leaves is relatively low, 0.5 percent to 1 percent by weight, paste has a cocaine concen- tration ranging up to 90% (Inciardi, 1992). Known to most South Americans as basuco, susuko, pasta basica de cocaina, or just simply pasta, coca paste is typically smoked straight or in cigarettes mixed with either TOBACCO or MARI- JUANA. The smoking of coca paste became popular in Bolivia and other parts of South America begin- ning in the early 1970s (Jeri, 1984). Readily avail- able and inexpensive, it had a high cocaine content and was absorbed quickly. As the phenomenon was studied, however, it was quickly realized that paste smoking was far more serious than any other form of cocaine use. In addition to cocaine, paste con- tains traces of all the chemicals used to process the coca leaves initially, the oxidized products of these In the Bolivian jungle, a soldier helps to destroy solvents, plus any number of other alkaloids pres- an illegal chemical lab that was used for ent in the coca leaf. processing coca into cocaine paste for shipment When the smoking of paste was first noted in to Colombia. (᭧ Bill Gentile/CORBIS) South America, the practice seemed to be restricted to the coca-processing regions of Bolivia, Colombia, assistance of the United States, began to take steps Ecuador, and Peru, appealing primarily to low- in the 1990s to eradicate illegal coca cultivation. income groups—it was a cheaper price than refined Bolivia is now the third-largest cultivator of coca, cocaine. By the early 1980s, however, it had spread after Peru and Columbia. Voluntary and forced to other South American nations and to the various eradication programs have dramatically reduced segments of the social strata; throughout that dec- coca production, with a 55 percent reduction since ade, paste smoking further expanded to become a 1995. The Bolivian government has encouraged major drug problem for much of South America. farmers to grow legal crops and has set a goal of Although there have been no systematic studies of total elimination of illegal coca production by coca paste use in Bolivia, most observers report that 2002. it is concentrated among the impoverished youths of the country’s many rural and urban shantytowns COCA PASTE USE (Farah, 1989; Germani, 1988; Noya, 1989), where it contributes to other health-compromising condi- Not surprisingly, drug use in Bolivia is related to tions such as poor nutrition, sniffing of gasoline or the production of coca and cocaine. Many people in other INHALANT drugs, and excessive use of alco- Bolivia have tried coca products in one form or holic beverages. New population surveys being another. However, in Bolivia abuse of cocaine gen- completed in Bolivia should help people in that erally involves neither the chewing of coca leaves country understand the nature and magnitude of 190 BOOZE their coca-related problems and help them devise meet its objectives. However, by the late 1990s, preventive strategies. Congress had moved toward a border policy that was supported by increased funding and a stronger (SEE ALSO: Coca Plant; Colombia As Drug Source) management system. In 1977, a U.S. government interagency team BIBLIOGRAPHY led by the Office of Drug Abuse Policy (ODAP) conducted a comprehensive review of border con- BURKE, M. (1991). Bolivia: The politics of cocaine. Cur- trol and recommended consolidation of the princi- rent History, 90, 65–68, 90. pal border-control functions into a single border- FARAH, D. (1989). Bolivia’s cocaine trade is consuming management agency. Executive departments failed its children. Washington Post, September 18. to agree on distribution of resources and organiza- GERMANI, C. (1988). Coca addiction hits home among tional placement of the new agency. The border- rural children of drug-producing Bolivia. Christian management agency never materialized. Science Monitor, September 29. Border control in the United States was de- HEALY, K. (1988). Bolivia and cocaine: A developing scribed in the review as an extremely complex country’s dilemmas. British Journal of Addiction, 83, problem involving vast distances, many modes of 19–23. transportation, millions of arrivals and departures, INCIARDI, J. A. (1992). The war on drugs II: The continu- and millions of tons of cargo. Laws to be enforced ing epic of heroin, cocaine, crack, crime, AIDS, and involved illegal drugs and other contraband, terror- public policy. Mountain View, CA: Mayfield. ists, public-health threats, agricultural pests and JERI, F. R. (1984). Coca-paste smoking in some Latin diseases, endangered species, entry visas, duties, American countries: A severe and unabated form of and so forth. Nine federal agencies shared border- addiction. Bulletin on Narcotics, 15–31. control responsibilities, contributing to overlap, NOYA, N. (1989). Cocaine crisis in Bolivia. Paper pre- duplication of effort, and duplicated management sented at What works: An international perspective on systems. drug abuse, treatment, and prevention research, Oc- The ODAPreport recommended consolidating tober 22–25, New York. the inspection and patrolling functions, including WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- operational and administrative support. The po- ICY. (2000). National Drug Control Strategy: 2000 tential for improved effectiveness in a consolidated Annual Report. Washington, D.C. border-management agency was widely recog- JAMES A. INCIARDI nized. A similar report by the U.S. Congress’s Gen- REVISED BY FREDERICK K. GRITTNER eral Accounting Office (GAO) also recommended single-agency management and responsibility for border control. Controversy over which activities to include and which executive department should BOOZE See Distilled spirits; slang and jargon control the new agency was, however, effective in blocking further action. Major change came when Congress passed the BORDER MANAGEMENT The effective Illegal Immigration Reform and Immigrant Re- management of U.S. borders has become a priority sponsibility Act of 1996 (IIRIRA). The IIRIRA is a for the U.S. government, as it attempts both to tough, enforcement-oriented law that seeks to re- control illegal immigration and to prevent the im- strict the passage of undocumented aliens across portation of illegal narcotics. Though most of the the U.S. borders. The IIRIRA mandated increasing focus has been placed on the U.S.-Mexico border, the number of Border Patrol agents by 5000. The increasing drug traffic and illegal immigration from law also mandated that the additional Border Pa- Canada has led to more surveillance of the northern trol agents be deployed in sectors along the border border as well. The effectiveness of border manage- in proportion to the numbers of illegal crossings at ment has historically been very difficult, as many such sectors. The legislation, however, requires that federal agencies had some jurisdiction in this area. the Attorney General coordinate with and act in The failure to coordinate and consolidate border conjunction with state and local law enforcement operations limited the ability of the government to agencies to ensure that deployment of resources to BRAIN STRUCTURES AND DRUGS 191

the border does not degrade or compromise the BIBLIOGRAPHY capabilities of interior Border Patrol stations. HAVEMANN, J. (1978). Carter’s reorganization plans— Even before the passage of the IIRIRA, the Bor- scrambling for turf. National Journal, 10, (20), 788– der Patrol had begun to implement new enforce- 794. ment strategies. A 1998 Government Accounting OSUNA,JUAN P. (1999). Update On Selected Enforcement Officer report noted that the Immigration and Nat- Provisions of The Illegal Immigration Reform And uralization Service (INS) had has made progress in Immigrant Responsibility Act Of 1996. 99-01 Im- implementing some, but not all, aspects of the migr. Briefings 1. necessary strategy to curtail illegal entry in the ANDREAS,PETER. (April 2000). U.S.-Mexico Drug Con- southwest. The strategy, begun in 1994, called for trol in the Age of Free Trade.Borderlines. the Border Patrol to (1) allocate additional Border RICHARD L. WILLIAMS Patrol resources in a four-phased approach starting REVISED BY FREDERICK K. GRITTNER with the areas of highest-known illegal activity; (2) make maximum use of physical barriers; (3) increase the proportion of time Border Patrol BRAIN STRUCTURES AND DRUGS agents spend on border enforcement activities; and Psychoactive or behaviorally active drugs are sub- (4) identify the appropriate mix of technology, stances that alter internal and external behavioral equipment, and personnel needed for the Border processes including activity levels, moods and feel- Patrol. At ports of entry along the southwest bor- ings. As a result of these changes, while some of der, the strategy called for the inspections program these substances can lead to compulsive drug use to increase inspector staff and use additional tech- and drug addiction, others are used to manage neu- nology to increase the deterrence and detection of ropsychological disorders. In both cases these drugs illegal entry and to improve management of legal do not produce unique behavioral or neurological traffic and commerce. effects. Their behavioral activity results from modi- In addition to the increases in personnel, the fying existing neuronal systems. To understand the IIRIRA required the construction of new barriers actions of abused drugs on the brain, one must have along the border and authorizes the purchase of an understanding of the functions that brain cells new equipment. The law directed the Attorney serve in the expression of behavior in general. This article focuses on information that will assist read- General to install additional barriers to deter illegal ers in understanding the biological basis of drug crossings, especially in areas of high numbers of actions on the brain, and particularly the actions of illegal entries. The legislation mandated the con- commonly abused drugs. First, the general classifi- struction of fencing and road improvements in the cation of brain cells will be discussed, followed by a 14-mile border area near San Diego, starting at the discussion of brain structure as it relates to function Pacific Ocean and extending eastward. In particu- and drug action. The classification of brain cells lar, the law mandated the construction of second based on the chemical nature of communication and third fences, in addition to the existing rein- between cells will then be discussed as it relates to forced fence, as well as roads between the fences. the actions of abused drugs. As for policing illegal narcotic shipments, the U.S. Customs Service has employed technology to CLASSIFICATION OF BRAIN CELLS assist its agents. For example, giant x-ray machines The brain is a complex structure that has many have been installed at ports of entry. Trucks and different types of cells. Brain cells are subdivided their cargo are examined in this non-intrusive way into groups based on a number of criteria that to detect cocaine vapors. Other high-tech equip- include whether they serve as (1) structural support ment, such as night-vision goggles, motion sensors cells (glia) or (2) cells that receive and transmit and low-light TV cameras are now being used on information (called neurons or nerve cells). If cells the border. are the latter, then additional criteria are: (a) shape or size; (b) their connections; (c) the distance over (SEE ALSO: Drug Interdiction; Operation Intercept) which they transmit information; and (d) which 192 BRAIN STRUCTURES AND DRUGS chemicals are released to transmit information to other cells. Most of the effects that drugs produce, which are related to abuse potential, are situated on brain cells that process or transmit information. For that reason, the discussions to follow will consider only actions on interneurons (nerve cells that con- nect to other nerve cells). The actions of drugs on the brain are complex and seldom involve only one type of brain cell. Nerve cells have a high level of connec- tivity between one another. Cells in one brain region send inputs to and receive outputs from other re- gions. These factors make the identification of cells in the brain responsible for a given drug effect difficult to distinguish. This is true of even the most simple behaviors, which involve complex interac- Figure 1 tions between millions of cells. For these reasons, the The Lobes of the Brain. understanding of the processes underlying addic- The brain consists of several major sections or tion is incomplete; however, significant progress has lobes. These include the frontal, parietal, been made during the past 20 years. For example, it occipital, temporal, and cerebellum. is generally believed that there are brain systems that are dedicated to the processes underlying eu- the sensory cortex in the most frontal portion of the phoria and feelings of well-being that are stimulated brain, the frontal cortex, is involved in cognitive by abused drugs. functions and thinking. It is the evolution of this region that is believed to be responsible for superior ORGANIZATION OF THE BRAIN: cognitive functioning in humans. BRAIN REGIONS The Thalamus. Information processing in- cludes sensory information that comes in from The Cerebral Cortex. A number of experi- sense organs (for example, eyes, ears, tongue) to mental approaches have developed to study the the brain through the spinal cord or directly basis of behavior in the brain. One of these has been through cranial nerves (nerve cells connected di- to study the role of brain regions in behavior. The rectly to the brain). This in-coming information brain is composed of distinct substructures. The from sense organs goes to a central relay station most general categorization scheme separates the called the thalamus. The thalamus is specialized, brain into five segments called lobes (Figure 1). much like the cerebral cortex, in that defined areas From front to back these include the frontal, parietal receive input that is specific to a sensory modality. and occipital lobes and the cerebellum. The tempo- For example, input from the eyes through the optic ral lobe is on the lateral surface of the brain. The nerve goes to a region of the thalamus called the outermost surface of the brain is called the cortex; dorsal lateral geniculate nucleus. This area of the this part of the brain has expanded in size the most in higher animals and is thought to be responsible for thalamus, in turn, sends the information transmit- the high level of intelligence in nonhuman and hu- ted from sense organs to the appropriate area of the man primates. Areas of the cortex are specialized so cortex. For example, the lateral geniculate sends that specific physiological functions are mediated by visual information to the area of the cortex special- cells in defined cortical regions. For example, visual ized for vision, which is located in the occipital processes occur in cells located on the surface of the lobe. Similarly, the cerebral cortex sends com- back of the brain in the occipital lobe. In front of this mands to the effector systems (usually muscles) region, on the border between the parietal and that act on the environment through the same relay frontal lobes, is the area that controls movement, system. As one can easily see, the thalamus is a very which is called the motor cortex. The area of the important structure for the coordination of inputs brain that controls sensation, the sensory cortex, is and outputs from the brain. Thus, degenerative just in front of the motor cortex. The area in front of diseases of this structure are very debilitating, as BRAIN STRUCTURES AND DRUGS 193 would be drugs that specifically altered the func- The Motor System. Motor function (move- tion of this structure. ment) involves a number of brain structures that The Brain Stem. Other areas of the brain are include the caudate nucleus-putamen, which sits responsible for life processes of which we are not above and in front of the thalamus, the premotor usually aware. These processes are generally con- cortex, and the motor cortex as previously de- trolled by the part of the brain called the brain scribed. Drugs that increase (stimulants) or de- stem, which is located between the spinal cord and crease (depressants such as alcohol) activity levels the cerebral hemispheres of the brain. The brain may do so by affecting the activity of these struc- stem contains the cell bodies for centers that main- tures. Although the basic mechanisms may differ tain heart rate, blood pressure, breathing, and for drugs of different classes, the overall effect may other involuntary or unconscious life-sustaining be the same. processes. A number of psychoactive agents have actions on NEURONS located in the brain stem. For NEUROTRANSMITTER SUBSTANCES example, OPIATES such as morphine or heroin have Besides categorizing the parts of the brain by a direct inhibitory effect on the brain stem respira- structure, the brain can also be separated into sys- tion (breathing) centers. This is why heroin OVER- tems based on the distribution of the chemicals that DOSES are often fatal—since the breathing centers nerve cells use to communicate with one another. stop working. Drugs that do not affect neurons in Thus, cell bodies for some important nerve cells are this area, such as marijuana, are seldom life-threat- localized in specific brain nuclei (collection of nerve ening. A significant part of the reticular formation cell bodies). Some drugs of abuse have specific is also located in the brain stem. This system sends actions on subsets of cells that use or release a outputs into the brain and down the spinal cord. It specific chemical to communicate with other cells. regulates arousal by increasing or decreasing the For example, ALCOHOL (ethanol) is believed to act brain’s responses to environmental events. Thus, on at least three systems in the brain–the ones morphine decreases pain by altering the sensitivity containing the nerve cells that release SEROTONIN, of brain cells involved in pain perception. The GLUTAMATE,andGAMMAAMINOBUTYRIC ACID brain stem is important in the control of pain and (GABA). The cell bodies of serotonin-releasing nerve also contains the cell bodies for some important cells are localized in the brain-stem region called nerve cells involved in the euphoric and depressant the raphe’ nuclei, while glutamate-releasing and actions of drugs. GABA-releasing cells are distributed widely throughout the brain (see figure 2). BRAIN SYSTEMS What about the different actions of drugs of abuse, where do they act in the brain? As stated The Limbic System. Another important ana- previously, it is still not fully understood how the tomical brain system through which abused drugs actions of drugs on the brain eventually affect be- act is the LIMBIC SYSTEM. This system is a collection havior. Our knowledge at this time (2000), how- of structures that lie between the brain stem and ever, indicates some specific actions on some de- the cerebral cortex. It includes the olfactory bulb, fined sites and cell systems. The so-called stimulant frontal and cingulate cortices, NUCLEUS ACCUM- drugs (e.g., AMPHETAMINE,COCAINE,METH- BENS, amygdala, hypothalamus, hippocampus and AMPHETAMINE) produce overall effects on the brain septum, all of which have direct connections with resulting in increased activity, faster speech and one another. The limbic system is involved in the thought patterns, and euphoria. This overall effect control of motivated behaviors such as eating, results from changes in a number of specific behav- drinking and sexual behaviors and in the expres- ioral patterns and represents a complex action of sion of emotional behaviors including anxiety and these drugs on several important neuronal systems aggression. Tumors or lesions of these structures in the brain. Neurochemical studies of the brain often lead to abnormal emotional expression. Drugs have shown that these stimulant drugs enhance that directly affect this system can produce changes and/or prolong the action of the neurotransmitters in goal-directed behaviors, mood (euphoria- DOPAMINE,NOREPINEPHRINE, and SEROTONIN that dysphoria) and emotions. are released by cells that produce these chemicals to 194 BRAIN STRUCTURES AND DRUGS

Figure 2 Figure 3 Serotonin Pathways. Dopamine Pathways. The serotonergic neurons originate mainly from Dopamine is not only a precursor of the raphe´ nuclei in the brain stem and project to noradrenaline but also a transmitter of its own. the forebrain, the cerebellum, and the spinal Dopamine represents more than 50 percent of cord. Very high concentrations of serotonin are the total catecholamine content of the central also found in the pineal gland. Serotonin- nervous system. The highest levels of dopamine containing neurons are involved in such are found in the neostriatum, nucleus functions as pain, temperature regulation, accumbens, and tuberculum olfactorium. There sensory perception, and sleep. are four main dopaminergic systems in the brain: the nigrostriatal, the mesolimbic nad communicate with other brain cells. The dopamine mesocortical, and the tuberoinfundibular cells send inputs to only a few structures in the systems. The nigrostriatal system appears to be involved in motor function, while the the forebrain. These include the caudate nucleus that is tuberoinfundibular dopamine neurons are involved in motor functions and areas of the limbic involved in hypothalamic-pituitary control. The system that are involved in emotional behaviors functions of the mesolimbic and mesocortical and euphoria. The areas of this system to which systems are less well known, although it is dopamine cells send inputs include the amygdala, conceivable that they play a role in psychotic the nucleus accumbens, the olfactory tubercle, and disease and in reinforcing effects of drugs. the frontal and cingulate cortices (see Figure 3). Norepinephrine and serotonin cells send inputs more widely to most all forebrain regions, even though their cell bodies are localized in specific BIOLOGICAL BASIS OF ADDICTION brain-stem nuclei. These drugs stimulate motor Activation of Brain Reinforcement or activity by increasing the function of the dopamine system, which sends inputs to the caudate nucleus. Hedonic Systems. One common effect of abused Stimulants produce feelings of well-being and eu- drugs is that they produce feelings of euphoria and phoria by enhancing dopaminergic activity in pleasantness or they decrease unpleasantness. limbic areas. Serotonin is also involved in the ef- Abused drugs produce these reinforcing effects by fects of stimulant use and withdrawal, but just how activating brain-cell systems that are naturally in- is not yet clear. volved in the reinforcing effects of non-drug rein- BRAIN STRUCTURES AND DRUGS 195 forcers such as eating desirable foods, listening to pleasing music, sex, leaving unpleasant circum- stances, and so on. Chemical stimulation by drugs can, however, produce activation of these systems far beyond that produced by these other natural reinforcers. The activation of the mesocor- ticolimbic dopaminergic system is believed to be critically involved in the neuronal processes that regulate the reinforcing effects of all environmental events. The major components of this system (see Figure 4) include the ventral tegmental area, nu- cleus accumbens, frontal cortex and ventral cau- Figure 4 date-putamen. In addition, the nucleus accumbens Neuronal circuits involved in the reinforcing is regulated by cells originating in the limbic system effects of stimulant drugs. including the amygdala, frontal cortex, hippocam- The major components of this system include the pus, and thalamus. The nucleus accumbens alters dopamine pathways from the ventral tegmental activity in motor systems by the activation of cells area to the nucleus accumbens caudate-putamen in the ventral pallidum and ventral tegmental area and frontal cortex. The limbic system inputs to (Koob1992; Feldman et al., 1997). Many research- the accumbens from the amygdala, frontal ers believe that the ability to modulate these sys- cortex, hippocampus and thalamus and the tems by chemical agents is the factor that leads to outputs from the nucleus accumbens to the abuse. Such euphoric effects appear to pose a par- ventral pallidum and substantia nigra. (Adapted ticular problem for those adolescents who have from Koob, 1972, and Feldman et al., 1977) underdeveloped inhibitory systems, have limited experience with socially accepted forms of personal gratification, and have higher than average levels of aggression. Even without such characteristics, ado- havioral effects that are not the same in everybody lescence is one of the most confusing and stressful and can even change in the same individual. For periods of human development. Ready access to example, alcohol can produce feelings of euphoria simple chemical means of activating reward sys- in a social situation or depression when one is tems under these conditions can easily lead to alone. Another example is cocaine, a very potent abuse. stimulant of brain systems involved in euphoria Drugs Do Not Have Intrinsic Hedonic Prop- and feelings of well-being. However, when animals erties. The euphoria that occurs after chemical are given simultaneous infusions of cocaine without activation of these systems is not only the result of control of delivery, cocaine becomes a stressor that the direct actions of the drug on neurons but is also will lead to the animal’s death much faster than influenced by the expectations of the individual and animals controlling and self-administering the the environment in which the drug is taken. Studies drug. in laboratory animals have shown large differences Dopamine Hypothesis of Drug Abuse. It is in the effects of a drug on the brain depending on widely accepted since the mid-1990s that the whether the drug is self-administered or adminis- abuse potential of a wide variety of drugs, at least tered to the animal passively (not under its con- in part, is directly related to the direct actions of trol). It has become clear that the act of drug taking these chemical agents on brain mesocorticolimbic and control over when the drug is taken are per- dopamine cells (see Figure 3 and 4). The dopa- haps the two most important factors in the pleasant mine cells in this system send inputs to the limbic feelings that follow drug intake. The drug itself has system, including the limbic cortical regions. The no consistent intrinsic hedonic properties. Why is it dopamine hypothesis states that drugs that are important for an individual to control the onset of abused directly activate these dopamine-releasing drug action through self-administration? It sug- nerve cells, resulting in the production of rein- gests that the activation of these brain systems is forcement and/or feelings of euphoria and well- also under behavioral influences. Drugs have be- being. This may be correct for PSYCHOMOTOR 196 BRAIN STRUCTURES AND DRUGS

STIMULANTS like amphetamine and cocaine, which that appear to be involved in the euphoric proper- have direct actions upon dopamine releasing nerve ties of drugs include acetylcholine, glutamate, opi- cells, but convincing evidence for dopamine being oid, and serotonin-releasing cells. As of the very primarily responsible for the abuse of alcohol (eth- beginning of the 21st century, there is significantly anol) opiates, and particularly for BENZODIAZE- less research data supporting the involvement of PINES is lacking. Dopamine-releasing nerve cells these cells; however, it is clear that the brain’s clearly have an important function in the behav- opioid receptors are necessary for the reinforcing ioral process and in the euphoria produced by psy- effects of opiates and that dopamine may not be the chomotor stimulants. To ascribe a universal role exclusive mediator of the euphoric effects of opi- for these cells in all euphorogenic processes is, however, likely to be an oversimplification. Scien- ates. Serotonin and glutamate may have important tists initially focused on dopamine nerve cells often roles in the euphoric properties of alcohol, while at the expense of exploring the involvement of acetylcholine-releasing neurons may have a role in other brain neurochemicals. However, more recent the general processes underlying euphoria. studies have demonstrated the involvement of ad- Studies in laboratory animals have suggested ditional neurochemicals and neuronal inputs. This that specific brain circuits are involved in the pro- research has increased knowledge that complex cesses related to drug reinforcement. These include brain neuronal networks regulate behavioral ef- areas of the cortex, the midbrain, and the brain fects that are called euphoria. It is likely that out- stem and involve acetylcholine, dopamine, gluta- puts of the cerebral cortex have a significant role mate, gammaaminobutyric acid, norepinephrine, in these processes. The roles of these neuronal sys- opioid, and serotonin-releasing neurons. The fron- tems have not been explored. tal and cingulate cortices (nucleus accumbens, lat- A drug may be subject to abuse if it directly eral hypothalamus, and amygdala) that are in- activates the neuronal networks that are responsi- cluded in the limbic system are part of these ble for feelings of well-being and euphoria (positive circuits, as are the ventral pallidum and thalamus. reinforcement) or if it decreases the unpleasant or aversive nature of the environment in which the Brain-stem dopamine, norepinephrine, and seroto- individual exists (negative REINFORCEMENT). Most nin nerve-cell nuclei send projections to these fore- scientific studies of the biological basis of addiction brain regions involved in such processes. In turn, have focused upon the positive reinforcing effects these regions send output nerve cells to structures of drugs, a focus which has led some to emphasize that utilize acetylcholine and glutamate primarily. the role of dopamine in addiction. However, drug Some of these forebrain structures are in turn con- self-administration in humans and in laboratory nected to the brain-stem cell nuclei for dopamine, animal models likely involves both positive and norepinephrine, and serotonin releasing nerve cells negative reinforcement. The act of taking the drug by GABA-releasing nerve cells. itself may result in circumstances that produce strain and pressures upon one’s normal patterns of living. In addition, the drug itself may activate CONCLUSION body and brain systems that are involved in stress, This is a simplified description of complex neu- thus directly producing unpleasant circumstances. ronal networks that are believed to play a major For these reasons, the research with animals that role in the production of euphoric effects or rein- has implicated dopamine in the positive reinforcing forcement in the brain. It is likely that this com- effects of stimulant drugs is likely more the result of plexity will increase as research continues to define both positive and negative reinforcement. It could and elucidate the basic biology of brain-behavior be that decreases in the unpleasant nature of one’s existence may involve increases in the activity of relationships. Investigations of drug self-adminis- dopamine-releasing nerve cells. It should also be tration continue to add significantly to this field of noted that stressful situations can activate some of study in the early 2000s. This ongoing research will these same regions. help us to understand the basic biology of drug Neuronal Network Hypothesis of Drug abuse so that more efficient and effective forms of Abuse. In addition to dopamine, the nerve cells treatment and prevention can be developed. BREATHALYZER 197

ACKNOWLEDGMENTS The production of this discourse was funded in part by USPHS Grants.

BIBLIOGRAPHY

KOOB, C. F. (1992). Drugs of abuse: Anatomy. pharma- cology and function of reward pathways. Trends in Pharmacological Sciences, 13, 177-184. KOOB,G.E,&BLOOM, F. E. (1988). Cellular and molec- ular mechanisms of drug dependence. Science, 242, 715-723. FELDMAN, R. S., MEYER, J. S., & QUENZER, L. F. (1997) Principals of Neuropsychopharmacology. High school students MaryHerz and Mitch Sunderland, MA: Sinauer. Sutherland take a mandatoryBreathalyzertest from principal George Yerger before entering the JAMES E. SMITH prom in Grant, Nebraska, May3, 1997. STEVEN I. DWORKIN (APPhoto/George Hipple)

BREATHALYZER Breath-analysis nose, or balancing on one foot, in order to corrobo- LCOHOL present machines detect and measure the A rate the officer’s conclusion of intoxication of the in deep lung air and convert this to an estimate of motorist based on objective findings. If the officer BLOOD ALCOHOL CONCENTRATION (BAC). The basis concludes that the motorist has failed one or more for this calculation is the relatively constant though of these tests, the officer requests that the motorist small proportion of alcohol that the body excretes submit to a Breathalyzer test. The results of the test through the lungs. BAC is approximately 2,300 either bolster and corroborate police opinion testi- times breath alcohol concentration, although there mony of intoxication or, in those states that set is some variation among individuals. Breath analy- presumptive blood alcohol intoxication levels, to sis machines use methods such as thermal conduc- demonstrate that the motorist’s blood alcohol level tivity and infrared absorption to detect alcohol in exceeded the permissible level. lung air. Because breath alcohol analysis is quick If a motorist refuses to take a breathalyzer test, and non-invasive, it is a useful tool in a variety of situations. The breathalyzer has traditionally been the police cannot compel the person to take the test. associated with law enforcement agencies for moni- However, states have enacted implied consent laws toring drinking and driving. However, it is increas- that are civil, rather than criminal, in nature. Un- ingly being used in clinical sellings. A number of der these laws, if a motorist refuses to take the models—both portable and fixed ones—are avail- breathalyzer test, the motorist’s driver’s license is able. automatically suspended for a set period of time. The Breathalyzer breath test machine is the Thus, motorists who are confronted with the alter- tradename of the model manufactured by Smith natives must balance the criminal sanctions that and Wesson, but the name has become synonymous follow a high alcohol reading from the breathalyzer with breath test machines. It has emerged as a against the immediate suspension of their driving powerful tool for law enforcement officers in polic- privileges. However, in the late 1990s, some states, ing motorists who are operating motor vehicles including New York and California, enacted laws while under the influence of illegal levels of alcohol. that made refusing a breathalyzer test a crime. In Officers routinely conduct field sobriety tests on these and several other states, legislators concluded motorists they suspect of driving while intoxicated. that a license suspension was not a severe enough An officer first requests that the motorist suspected penalty for drunk drivers. of intoxication perform certain physical tests, such Because breathalyzer test results serve as power- as walking a straight line, putting a finger to the ful incriminating evidence, defendants and their 198 BRITAIN, DRUG USE IN lawyers often seek to challenge the reliability of the tional use. The differentiation between medical and tests. This has produced a group of experts that nonmedical usage was not clearly drawn then. Con- routinely testify as to the way the test was adminis- cepts such as addiction were not then widely ac- tered and the reliability of the breathalyzer ma- cepted. The story of drug use in Britain since the chine itself. The breathalyzer must be calibrated late nineteenth century is the story of how and why periodically. Calibration is a procedure performed drugs became defined as a social problem and by laboratory personnel to ensure the accuracy and which factors brought the establishment of certain reliability of the instrument. Routine maintenance forms of drug-control policy. These were, in fact, is also performed to ensure the continued accuracy issues that often bore little relationship to the and proper function of the breathalyzer. Once cali- objective dangers of the drugs concerned. brated, a certificate of calibration is completed by In the early twentieth century, there was limited the laboratory and a certified copy provided to the involvement either by doctors or by the state in the law enforcement agency using that breathalyzer. control of drug use and addiction. The supply of Failure to follow maintenance schedules can raise a opiates and other drugs was controlled by the phar- reasonable doubt about the machine’s results and maceutical chemist. As dispensers and sellers of lead to an acquittal. Apart from the alleged techni- drugs over the counter, they were the de facto cal defects of a breathalyzer, experts often testify agents of control. A rudimentary medical system of that the officer failed to follow the proper protocol treatment operated via the Inebriates Acts (codified for operating the machine or that the defendant’s in 1890), whereby some inebriates could be com- blood alcohol level was incorrectly inflated due to mitted to a form of compulsory institutional treat- biological factors. ment. Legislation covered only liquids that were Breathalyzers are also being used as preventive drunk (e.g., LAUDANUM) not injectables. Users of devices. Courts are now ordering persons convicted hypodermic morphine or cocaine were therefore of repeat driving while intoxicated violations to in- not included under this system. stall a breathalyzer interlock on their cars. The Drug addiction was not perceived as a pressing social problem in early twentieth-century Britain, driver must breathe into the machine before start- nor, indeed, was it one. Numbers of addicts de- ing the car. If the alcohol level is too high, the car creased as overall consumption declined. No spe- will not start. After the car has started, the driver cific figures are available for that period, but vari- must periodically breathe into the device for a re- ous indicators, such as poisoning mortality test. If the driver fails the test, the car honks its statistics, indicate this conclusion. The twentieth horn and flashes its lights. century nevertheless brought increased controls and the classification of opiates and other drugs as (SEE ALSO: Driving Under the Influence; Drunk dangerous. Dangerous drugs were regulated Driving) through a penal system of control rather than through the mechanisms of health policy. BIBLIOGRAPHY Two factors brought regulation. The first was Britain’s involvement in an international system of GILES, H. G., ET AL. (1990). Alcohol and the identifica- tion of alcoholics. Lexington and Toronto: D. C. drug control; the second was the impact of World Heath. War I (1914–1918) and its aftermath. U.S. pres- sure on the international scene pushed an initially MYROSLAVA ROMACH unwilling Britain into a system of control that rap- KAREN PARKER idly extended from the 1909 Asian regulation dis- REVISED BY FREDERICK K. GRITTNER cussed at Shanghai to the worldwide system envis- aged in the 1912 Hague Convention. Prior to World War I, however, only the United BRITAIN, DRUG USE IN The legal use of States, by way of the HARRISON NARCOTICS ACT of what we now term illicit drugs was widespread in 1914, had put this system of drug control into nineteenth-century Britain. Opiates in various operation. Britain favored a simple extension of the forms were used by all levels of society, both for existing Pharmacy Acts. The influence of emer- self-medication and for what we now call recrea- gency wartime conditions, however, brought a dif- BRITAIN, DRUG USE IN 199 ferently located and more stringent form of control. sumers. The average age of new addicts also The fear of a cocaine epidemic among British sol- dropped sharply. Initial government reaction, in diers patronizing prostitutes in the West End of the report of the first Brain Committee (1961), was London—a fear which on later investigation muted; however, the second report (1965), pro- proved to have been largely illusory—allowed the duced when the committee was hastily reconvened, passage of drug regulation in 1916 under the De- had an air of urgency. Controls were introduced on fence of the Realm Act. International drug control amphetamines in 1964. The report’s proposals in its turn became part of the postwar peace settle- (implemented in the Dangerous Drugs Act of 1967) ment at Versailles. The 1920 Dangerous Drugs Act took the prescribing of heroin and cocaine out of therefore enshrined a primarily penal approach; the hands of general practitioners and placed it in control was located in the Home Office rather than those of specialist hospital doctors working in drug- in the newly established (1919) Ministry of Health. dependence units. A formal system was established British drug policy was henceforward marked by that notified the Home Office about addicts. a tension between rival conceptualizations of the The clinic system established in 1968 did not drug-addiction issue; drugs as a penal issue versus operate as originally intended. In the 1970s, as the drugs as a health matter. The 1920s saw this con- rise in numbers of addicts appeared to stabilize, flict at its height. Britain seemed likely to follow a clinic doctors moved toward a more active concept penal course similar to that of the United States, on of treatment, substituting orally administered whose 1914 act the British legislation was con- METHADONE for injected heroin and often insisting sciously modeled, but British doctors soon re- on short-term treatment contracts rather than on asserted their professional control. By 1926, Brit- maintenance prescribing. These clinic policies ain’s ROLLESTON REPORT legitimated a medical aided the emergence of a drug black market in approach that could entail medical ‘‘maintenance Britain in the late 1970s. An influx of Iranian prescribing’’ of opiates to a patient who would refugees from the Islamic revolution of 1979, otherwise be unable to function. The Rolleston Re- bringing financial assets in the form of heroin, also port established what became known as the BRIT- stimulated the market. ISH SYSTEM of drug control—a liberal, medically The British elections of 1979 returned a Conser- based system—albeit one that operated within vative government with a renewed emphasis on a Home Office control. penal response to illicit drugs. Britain participated This system remained in operation for nearly 40 enthusiastically in the U.S.-led international ‘‘war years, until the rapid changes of the 1960s. The on drugs,’’ but there were also strong forces inside 1920s, 1930s, and 1940s were decades when the Britain arguing for a more health-focused ap- numbers of addicts were small and there were few proach. In 1985, the discovery of acquired immu- nonmedical users (less than 500). It is generally nodeficiency syndrome (AIDS) among injecting recognized that the British System of medical con- drug users in Edinburgh, Scotland, was the trigger trol operated because of this situation rather than for policies that emphasized the reduction of harm as the cause of it. This equilibrium began to break from drug use rather than a prohibitionist stance. down after World War II (1939–1945), when more Nevertheless, in the early 1990s, the tension be- extensive recreational, or nonmedical, use of drugs tween penal and health concepts and the interde- (such as HEROIN and COCAINE) began to spread for pendence of the two approaches to policy still re- a variety of reasons. These included the spread of mained unresolved. cannabis (MARIJUANA)—from the new immigrant The use of drugs within British society continued to the white population, overprescribing of heroin to expand in the 1990s. Amphetamines are still by a number of London doctors, thefts from phar- second only to cannabis as the most widely used macies, and the arrival of Canadian heroin addicts. drugs in the United Kingdom, but few users are in Other drugs—in particular, AMPHETAMINES—also contact with drug treatment services or seek any became recreationally popular. medical help. Services are oriented towards opiate The official numbers of heroin addicts rose rap- users and black market amphetamine is not expen- idly, from 94 persons in 1960 to 175 in 1962; and sive, so there is a lower likelihood that financial cocaine users increased from 30 in 1959 to 211 in problems will force users into treatment. Heroin 1964. Nearly all of these were nonmedical con- use has also continued to grow. During the 1980s 200 BRITISH JOURNAL OF ADDICTIONS this emerged in a large number of communities the National Health Service: new treatment pro- round the country and in a pattern different from grams and a through-care service for drug using that of the 1960s. This new pattern of use mainly prisoners will be set up. Mandatory urine testing in involved adolescents and young adults, and the prisons has proved controversial. Some policy ana- heroin was taken by a new method called ‘‘chasing lysts have argued that U.K. policy is moving to a the dragon’’—heating heroin on tin foil, with va- harsher stance, in effect to compulsory treatment pors inhaled through a tube. But there was great and to a greater emphasis on criminal justice initia- regional variation, with injecting still popular in tives, and to coercion. The government’s unwilling- some areas. Heroin use has continued to grow; the ness to accept the conclusions of an independent number of known addicts has grown from about inquiry into drug policy, which recommended lib- 5000 in 1980 to approximately 50,000 by the late eralization of the law on cannabis, has been cited as 1990s, with figures still growing at about 20 per- evidence of this. However, there is also official in- cent a year. Cocaine use has also risen, but the terest, following a House of Lords report, in the speed and penetration of crack cocaine into the medical uses of cannabis and a National Treatment country has been nowhere near as rapid or as sub- Agency is to be set up, emphasizing the health stantial as U.S. commentators had predicted. Sur- aspects of drug use. The duality of policy continues. veys suggest that snorting cocaine is more popular than crack or heroin and is on the increase in clubs. (SEE ALSO: Anslinger, HarryJ., and U.S. Drug Pol- Ecstasy (MDMA) use has also received wide media icy; British System of Drug-Addiction Treatment; publicity, but surveys suggest it is used less fre- Opioids and Opioid Control: History) quently than other ‘‘dance drugs,’’ LSD and am- phetamine. BIBLIOGRAPHY British governments, conservative for most of the 90s and governed by the Labour party since BERRIDGE, V. (1993). AIDS and British drug policy: Con- 1997, have continued to publish national strategies tinuity or change? In V. Berridge & P. Strong (Eds.), on drugs, the first of which appeared in the 80s. In AIDS and contemporaryhistory . Cambridge: Cam- 1995, Tackling Drugs Together: a strategyfor En- bridge University Press. gland, 1995-1998, was published and strategies BERRIDGE, V. (1999). Opium and the people. Opiate use for Scotland and Wales followed. The strategy and drug control policyin nineteenth and earlytwen- committed the government to take effective action tieth centuryEngland . London: Free Association through law enforcement, accessible treatment and Books. a new emphasis on education and prevention to ROYAL COLLEGE OF PSYCHIATRISTS AND ROYAL COLLEGE increase community safety from drug related OF PHYSICIANS. (2000). Drugs: Dilemmas and choices. crime; reduce young people’s drug use and reduce London: Gaskell. health risks and damage associated with drug use. VIRGINIA BERRIDGE In 1998, the new Labour government published Tackling Drugs Together to Build a Better Britain: the Government’s Ten Year Strategyfor Tackling Drug Misuse, which reiterated these main themes. BRITISH JOURNAL OF ADDICTIONS Former Chief Constable, Keith Hellawell, was See Addiction appointed ‘‘Drug Czar,’’ or national coordinator; his deputy had a background in rehabilitation ser- vices. BRITISH SYSTEM OF DRUG-ADDIC- The relationship between penal and health re- TION TREATMENT To many observers from sponses in drug policy has remained central. Arrest outside the United Kingdom (U.K.), the British referral schemes are common and the government System is synonymous with heroin maintenance, is now to expand pilot treatment and testing orders, with doctors supplying drugs on demand to ad- which will give an alternative to custody to drug dicts. To some it has been viewed as an approach of using offenders who agree to undergo treatment. extreme folly; to others it is an effective policy of Treatment services in prisons have expanded since supreme pragmatism. To those who know and the incorporation of the prison health service into work within it, the British System is somewhat BRITISH SYSTEM OF DRUG-ADDICTION TREATMENT 201 more complex. Indeed, the extent to which a clearly important in the rapid development of new ser- defined system can be identified has been the focus vices, including injecting-equipment exchange of debate. Here, we will demonstrate that a particu- schemes in the 1980s as a public-health mea- lar set of factors have combined in the U.K. to sure to reduce the spread of HIV. create an evolving system of care for drug takers, 2. Control and Monitoring of Drug Takers and which has been responsive both to the changing Their Physicians. The extent to which the Brit- drug scene and to the individual needs of the drug ish System has aimed to exercise control over taker. This review will identify the key characteris- drug takers has been variable. However, part of tics of the British System. Important historical the purpose of prescribing drugs in the context milestones in the development of the system will be of addiction treatment (see below) has been to identified. Finally the effectiveness of the system attract drug takers to have contact with statu- will be discussed. tory services. An index of drug takers (mainly of HEROIN and COCAINE) known to physicians has been maintained by the Home Office since WHAT IS THE BRITISH SYSTEM? 1968. This has allowed some indication of the Since a key characteristic of the system has been scale of the problem to be known as well as its evolution during the twentieth century, ob- preventing individuals from attending more servers at different stages in this process have had than one clinic. At the same time, in response to different views as to its nature and purpose. This concerns over irresponsible prescribing by cer- late twentieth-century view proposes the following tain physicians, only those physicians in posses- five characteristics of the British System: sion of a special license issued by the Home Office were entitled to prescribe heroin and co- 1. An Evolving System of Health and Social Care caine to drug takers. Although the recent (early for Drug Takers. Since the 1920s, the British 1990s) policy has been to encourage the in- policy toward addiction has been principally in creased involvement of general practitioners in the form of treatment conducted by medical prescribing METHADONE, the prescribing behav- practitioners. This differed from most other ju- ior of all doctors in relation to addictive drugs risdictions, particularly the United States, remains closely monitored. where addiction was deemed a deviant and 3. Drug Prescribing. The overall contribution of criminal activity under the HARRISON NARCOT- drug prescribing as a component of the British ICS ACT (1914) through and until the revisions System has been important, but overestimated of the late 1960s and early 1970s. While the by some. Certainly, the right of physicians to burden of care for drug takers has expanded prescribe, and drug takers to receive, addictive over time from the general practitioner to spe- drugs in the context of treatment has been a key cialist psychiatrist and then back to the gener- part of the British System since its inception. At alist (often the general practitioner), the British various times, opiates (including injectable her- System has to a large extent been located in the oin and methadone), cocaine, AMPHETAMINES, public-health sector, latterly in the National and BARBITURATES have been prescribed in this Health Service. Specialist drug-dependence cli- context. The aims of such prescribing, as well as nics were established throughout the U.K. from the prescribing practices, have varied over time. the 1960s onward. The principal aim throughout has been to pro- Two important consequences of the emphasis vide a method of detoxification that is as com- on health rather than correctional services have fortable and medically safe as possible. It has been (1) the attention to the health and social also been accepted at a policy level, however, needs of the drug taker—particularly crucial in that some individuals who are either unable or the wake of the recent human immunodefi- unwilling to stop drugs may require long-term ciency virus (HIV) epidemic in injecting drug prescribing, with a view to stabilization or takers, and (2) the opportunity to influence the maintenance treatment—in some instances development of public-health strategies on a na- with injectable drugs. Since the 1970s, oral tional scale through the existing system of methadone (in the form of tablets or linctus—a health-care services. This second point has been syrup) has been the opiate prescription of choice 202 BRITISH SYSTEM OF DRUG-ADDICTION TREATMENT

in view of its greater safety and lower resale levels. At the system level, experiments in the value on the black market. The prescription of provision of a range of services have been possi- other drugs had largely ceased in this context by ble, including a wide range of drug prescribing- the mid-1980s. Heroin prescribing and the pre- and-injecting equipment exchange schemes. At scribing of injectable methadone still have a few the individual level, treatments may be tailored proponents, despite a lack of controlled scien- to individual needs rather than having the im- tific evidence to support their effectiveness (see position of tightly restricted, prescriptive, and below). Although there is international interest blanket approaches. in the right of British doctors to prescribe in- jectable heroin, fewer than 200 patients receive such treatment (in the early 1990s). Of more MILESTONES IN THE HISTORY OF interest is the prescribing of injectable metha- THE BRITISH SYSTEM done as a potential intermediate step in convert- 1920 ing the heroin injector to oral methadone. Introduction of the Dangerous Drugs Drug prescribing within the British System Act following the International has been characterized by a greater permissive- Opium Convention at the Hague ness and flexibility than is the case in most other (1912). This restricts the dis- jurisdictions, alongside a continued overall con- servative approach by most medical practition- pensing of several drugs to phy- ers to prescribing agonist drugs to the drug sicians, including opiates and abuser. cocaine. 4. Competition with the Black Market. A promi- 1926 nent aim at various times in the history of the The Rolleston Committee publishes British System has been that of attracting the its report (see ROLLESTON RE- drug taker away from the black market and into PORT), which establishes the treatment. The putative benefits of such a right of medical practitioners to scheme would be to remove demand for illicit prescribe drugs in the context of drugs, leading to elimination of the black mar- the treatment of addiction. ket; improve health benefits to the drug user for 1920s–1960s taking pharmaceutical rather than illicit drugs; Small numbers (approx. 400–500) and reduce criminality associated with purchas- of mainly ‘‘therapeutic addicts’’ ing illicit drugs. While there were relatively few and addicted physicians receive heroin takers in Britain until the 1960s, the opiate prescriptions as treat- continued nonexistence of an imported black ment for addiction. market meant that prescribed heroin was the 1961 main source of supply, but it actually contrib- The first Brain Committee publishes uted to a growth in the number of drug takers. its report. In reviewing the pe- Since no convincing evidence has emerged to riod since the Rolleston Com- support the value of this approach, the prescrib- ing of drugs has become based more on individ- mittee’s report it reaffirms the ual medical indications than on economic medical practitioner’s role and policy. recommends no change in the 5. Flexibility. Perhaps the most striking feature of system. the British System has been its capacity to 1960s evolve in response to the changing drug prob- A small number of physicians, lem. Whether this has been the result of deliber- mainly in London, are prescrib- ate policy or benign laissez faireism is open to ing large quantities of heroin debate. The result has allowed a flexible re- leading to a rapid increase in the sponse without overt government intervention number of heroin injectors (in- in medical practice (beyond the constraints de- creasing to 2,000 in number) scribed). Flexibility has been possible at two and growing public alarm. BRITISH SYSTEM OF DRUG-ADDICTION TREATMENT 203

1965 emerges that drug takers repre- The Brain Committee is reconvened sent a heterogeneous group, to consider the increasing prob- many of whom do not require lem and publishes its second re- specialist treatment. The report port. It recommends several re- recommends (1) an expanded strictions including (1) the role for the generalist, (2) the establishment of specialized development of nonmedically treatment clinics, (2) the licens- based treatment approaches, ing of medical practitioners for and (3) a requirement for prescribing, and (3) the Home health authorities to monitor the Office Addicts Index. scale of heroin problems in each 1967 community. This results in more The Dangerous Drugs Act imple- restrictive opiate prescribing ments the recommendations of and a broadening of the range of the Brain Committee and pro- hibits physicians from prescrib- treatment options. ing heroin or cocaine to drug 1984 takers (except for the purpose of Guidelines for Good Clinical Practice relieving pain caused by organic in the Treatment of Drug Misuse illness or injury) unless specially are published. This is the first licensed by the Home Office. central guidance to physicians This practically restricts pre- since the inception of the sys- scribing to the newly established tem, which indicates the flexi- specialist clinics. bility of practice that physicians 1980s had been accorded. An epidemic of heroin taking occurs 1988/1989 on a scale not previously en- The ACMD publishes two reports on countered in the U.K.—mainly AIDS and Drug Misuse. This as a result of new illicit trade major policy review is prompted routes opening up from the by the epidemic in HIV infec- Golden Crescent (Iran, Paki- tion in injecting drug takers. stan, Afghanistan, etc.) to sup- The reports recommend greater plement the Far East’s GOLDEN emphasis on attracting and re- TRIANGLE trade. The epidemic taining in treatment drug takers is mainly among young Cauca- unable or unwilling to change sian males in inner city areas their behavior. This results in throughout the U.K. and leads less restrictive opiate prescrib- to a rapid increase in crime (to ing practices, the introduction support the habit). The esti- of low threshold and user mated number of heroin takers increases from around 20,000 friendly services, and the fur- in the early 1980s to as many as ther expansion of injecting- approximately 150,000 by the equipment exchange schemes end of the 1980s. through the late 1980s and 1982 early 1990s. The Advisory Council on the Misuse 1991 of Drugs (ACMD) publishes its New Guidelines for Good Clinical Treatment and Rehabilitation Practice is published. These are report. The specialist clinics are written by physicians for physi- overwhelmed by the upsurge in cians and aimed at the demand; a new recognition generalist. 204 BRITISH SYSTEM OF DRUG-ADDICTION TREATMENT

1992 Further, the U.K. experience with barbiturate and Targets for reductions in drug in- amphetamine prescribing was wholly negative and jecting are introduced as part resulted in its complete discontinuation. of the British Government’s At an individual level, remarkably little con- Health of the Nation white pa- trolled research has been carried out to evaluate per—and also formed a part of different prescribing or other treatment ap- the AIDS response. proaches, given the opportunity available to do so 1993 in the British System. One controlled trial with The ACMD’s third report on AIDS ninety-six heroin takers involved the random as- and drug misuse is published. signment to either injectable heroin or oral metha- The constituency of concern is done maintenance. The results suggested advan- broadened from opiate injectors tages and disadvantages in both treatments. At one to those who inject amphet- year follow-up, more in the methadone group were amines and BENZODIAZEPINES. abstinent than in the heroin group, but more had Recommendations include a fo- also returned to illicit drug use in the methadone cus on the impact of hidden group. drug-taking populations, With the increasing emphasis on treatment in through outreach, and the intro- the primary care setting in the 1980s, specialist duction of oral methadone pro- Community Drug Teams were established with the grams (along North American brief of encouraging the increased involvement of and Australasian lines). general practitioners. The main advantage of such an approach is, in theory at least, that this should HAS THE BRITISH SYSTEM allow greater availability of services than could be BEEN EFFECTIVE? provided by specialist clinics alone. During the 1990s, there has been an important but modest Clearly, the question of effectiveness is difficult increase in the extent of general practitioner in- to answer in the context of a national problem volvement, but this still falls short of the goal of subject to many external and internal influences, universal availability of treatment for drug takers. within a system that has evolved over many years. Overall, it can be said that the principal benefits Further, it is difficult to compare the effects of of the British System have been (1) to ensure the policies toward drug problems in various countries: humanitarian handling of drug takers, through Drug problems are often culturally specific, and treatment services, and (2) to allow the evolution of attempted solutions that may be acceptable in one a system of care responsive to changing needs— setting may be unwelcome or unhelpful in another. which also has been relatively free from unneces- On one level, it is clear that the U.K. has not been sary governmental constraints. spared the epidemic rise in heroin taking experi- enced by other Western industrialized countries; (SEE ALSO: Britain, Drug Use in; Injecting Drug nor has it avoided the spread of HIV in intravenous Users and HIV; Needle and Syringe Exchanges and drug takers—however, the epidemic of HIV has HIV/AIDS) been far less severe than in several other European countries and in the United States. Regional varia- BIBLIOGRAPHY tion in the pattern of the HIV epidemic in the U.K. suggests that the areas where prescribing and spe- CONNELL, P. H. (1968). Drug dependence in Great Brit- cialist clinics were limited, such as in Edinburgh, ain: A challenge to the practice of medicine. In H. Scotland, experienced a much more rapid spread— Steinberg (Ed.), Scientific basis of drug dependence. although closer examination reveals this to be in- London: Churchill. sufficient as the sole explanation. DORN,N.,&SOUTH,N.(EDS.). (1987). A land fit for At times, there have been disadvantages to the heroin?: Drug policies, prevention and practice. Ba- British System. In particular, a situation where singstoke: Macmillan. addictive drugs were overenthusiastically pre- JUDSON, H. F. (1974). Heroin addiction in Britain. New scribed contributed to a worsening of the problem. York: Harcourt Brace Jovanovic. BULIMIA NERVOSA 205

MACGREGOR,S.(ED.). (1989). Drugs and British society: in industrialized countries. The etiology of bulimia Responses to a social problem in the 1980s. London: is unknown, although psychological, sociocultural, Routledge. and biological theories have been proposed. Many MINISTRY OF HEALTH (1926). Report of the Departmental consider Western societies’ increasing emphasis on Committee on Morphine and Heroin Addiction thinness, especially among women, to be a contrib- (Rolleston Report). London: HMSO. uting influence. STIMSON, G. V., & OPPENHEIMER, E. (1982). Heroin ad- Parallels between bulimia nervosa and sub- diction: Treatment and control in Britain. London: stance abuse have been drawn based on an ADDIC- Tavistock. TION model, a self-psychology model, and a psycho- STRANG, J. (1989). ‘The British System’: Past, present, biological model. According to the addiction model, and future. International Review of Psychiatry, 1, food is the ‘‘substance’’ that is abused in bulimia 109–120. nervosa. Although there are superficial similarities STRANG, J., & GOSSOP, M. (1993). Responding to drug in phenomenology between binge eating and sub- abuse: The ‘British System’. Oxford: Oxford Univer- stance abuse, these similarities are selective and sity Press. rely on a loose definition of addiction. The self- STRANG, J., & STIMSON,G.V.(EDS.). (1990). AIDS and psychology perspective is that both bulimia nervosa drug misuse: Understanding and responding to the and substance abuse arise from a common deficit in drug taker in the wake of HIV. London: Routledge. psychological functioning. Difficulties regulating TREBACH, A. S. (1982). The heroin solution. New Haven: affect and tension generate a need for the external Yale University Press. distraction provided by food or psychoactive sub- stances, respectively. This model may have some D. COLIN DRUMMOND heuristic value but it has not, as of the mid-1990s, JOHN STRANG received empirical validation. The psychobiologi- cal view regards eating and drinking as consumma- tory behaviors with the potential for dysregulation. BULIMIA NERVOSA Since 1980, bulimia One possibility is a shared disturbance in the brain nervosa has been recognized by the American Psy- neurochemical functioning that regulates drives of chiatric Association as an autonomous eating disor- appetite. There is some evidence that brain der. The term bulimia means ‘‘an extreme hunger,’’ SEROTONIN function may be disrupted in both bu- but the word is most commonly understood to refer limia nervosa and ALCOHOL abuse; however, re- to BULIMIA NERVOSA. It is characterized by recur- search in this area has just begun and the validity of rent episodes of binge eating followed by such regu- this model is unknown as of the mid-1990s. lar activities as self-induced vomiting, excessive use Among women receiving treatment for sub- of laxatives and/or diuretics, fasting or dieting, and stance abuse, estimates of the prevalence of bulimia vigorous exercise—all of which are directed at nervosa range from 8 to 17 percent, and estimates weight control. A characteristic feature in the bu- of the prevalence of some eating disorder range limic patient is a persistent concern with weight from 26 to 47 percent. Similarly, estimates of alco- and body shape. Other psychiatric disorders can hol abuse among women seeking treatment for bu- accompany bulimia, particularly major depression. limia nervosa range from 27 to 49 percent. Thus, The full syndrome affects 1 to 3 percent of the substance abuse and bulimia nervosa occur to- adolescent and young adult female population, but gether in young women much more frequently than many more experience subclinical variants of the would be expected for independent disorders. One disorder. Bulimia nervosa does occur in males, but potential source of this comorbidity lies in genetic such incidence is rare. risk. Several studies have indicated an overrepre- This disturbance in eating affects mostly young sentation of alcohol abuse in the families of women women—usually women of normal weight—and is with eating disorders. Another possibility is that often preceded by ANOREXIA nervosa (restricted certain psychological factors place certain women eating). The bulimic symptoms may continue for at risk for the development of either bulimia many years with exacerbations and remissions. nervosa or substance abuse. There is some limited From the mid-1970s to the mid-1990s, the preva- evidence for an underlying ADDICTIVE PERSONAL- lence of eating disorders appeared to be increasing ITY in both disorders. As well, women with both 206 BUPRENORPHINE disorders seem to have more difficulties, generally, BUPRENORPHINE Buprenorphine is a with impulsive behaviors. semisynthetic OPIATE which is produced from The treatment of bulimia nervosa depends on its thebaine, a naturally occurring ALKALOID present severity. Many cases of the eating disturbance re- in the ripe pods of the opium poppy (Papaner solve on their own. Specific interventions that may somniferum). Buprenorphine has an ANALGESIC po- be tried include psychodynamic (individual, fam- tency twenty-five to fifty times greater than MOR- ily, group) therapies as well as cognitive and be- PHINE on a weight basis. However, the analgesic haviorally oriented therapies and pharmacological actions of buprenorphine are quite similar to those of morphine and the other opiates after taking into treatments. Modest improvements have been re- consideration its greater potency. It is assumed that ported with the use of ANTIDEPRESSANT medica- these effects are dependent upon its ability to act at tion. Studies conducted in the late 1990s have mu (morphine) receptors in the brain. Once bound shown that ondansetron (a drug commonly used to the receptor, however, buprenorphine only pro- for patients with vomiting associated with chemo- duces a limited effect, and thus it is termed a partial theraphy) could be an effective treatment for those AGONIST. This ability to produce only a partial with bulimia; this drug was not shown to treat the response may explain why buprenorphine lowers psychological aspects of the disorder though (Kiss, breathing (respiratory depression) less than drugs 2000). such as morphine. Because it is a partial agonist, buprenorphine administration to morphine-depen- dent patients does not elicit significant withdrawal BIBLIOGRAPHY symptoms and can therefore be used as a metha- FAIRBURN, Christopher G., ET AL. (2000). The natural done-like opiate substitute in treatment programs. course of bulimia nervosa and binge eating disorders Another reason for the use of the agent in this in young women. Archives of General Psychiatry, 57, respect is its particularly long duration of action. 659. Single doses of buprenorphine can attenuate or GOLDBLOOM, D. S. (1993). Alcohol abuse and eating dis- prevent many of the actions of morphine for up to orders: Aspects of an association. Alcohol and Alco- thirty hours. Thus, buprenorphine maintenance holism. programs have been proposed to treat opiate KISS,ALEXANDER (2000). Treatment of chronic bulimic addiction. symptoms: new answers, more questions. The Lancet, The interactions of buprenorphine with ANTAGONISTS are interesting. Buprenorphine ac- 355, 769. tions can be readily prevented by antagonists such MITCHELL, J. E. (1990). Bulimia nervosa. Minneapolis: as NALOXONE, when the antagonist is administered University of Minnesota Press. prior to buprenorphine. However, antagonists PEVELER, R., & FAIRBURN, C. (1990). Eating disorders in given after buprenorphine do not readily reverse women who abuse alcohol. British Journal of Addic- the opioid actions. This unique pharmacology dis- tion, 85, 1633–1638. tinguishes it from traditional opiates such as mor- VANDEREYCKEN, W. (1990). The addiction model in eat- ing disorders: some critical remarks and a selected bibliography. International Journal of Eating Disor- ders, 9, 95–101. WILSON, G. T. (1991). The addiction model of eating disorders: a critical analysis. Advances in Behaviour Research and Therapy, 12, 27–72. MARION OLMSTED DAVID GOLDBLOOM MIROSLAVA ROMACH KAREN PARKER Figure 1 REVISED BY REBECCA MARLOW-FERGUSON Buprenorphine BUPRENORPHINE 207 phine. Many believe that this observation is due to whether buprenorphine can be useful in the treat- the prolonged occupation of the receptor by ment of cocaine abusers. buprenorphine. Once it is bound, other drugs can no longer get to the receptor. (SEE ALSO: Heroin; Treatment/Treatment Types) In the early 1990s, it was proposed that buprenorphine might also prove effective in lower- BIBLIOGRAPHY ing COCAINE use. Some studies in primates showed that buprenorphine lowered the amounts of cocaine JAFFE, J. H., & MARTIN, W. R. (1990). Opioid analgesics taken. Although some small clinical studies in peo- and antagonists. In A. G. Gilman et al. (Eds.), Good- ple also suggested a similar effect, more controlled man and Gilman’s the pharmacological basis of ther- studies did not show a special effect on cocaine use. apeutics, 8th ed. New York: Pergamon. More extensive work will be needed to determine GAVRIL W. PASTERNAK C

CAFFEINE Caffeine is the world’s most self-administer dietary doses of caffeine, even when widely used behaviorally active drug. More than 80 they are not informed that caffeine is the drug percent of adults in North America consume caf- under study; and some evidence indicates that daily feine regularly. Average per capita caffeine intakes use of caffeine produces tolerance to caffeine’s be- in the United States, Canada, Sweden, and the havioral and physiological effects. United Kingdom have been estimated at 211 milli- grams, 238 milligrams, 425 milligrams, and 444 CLASS AND CHEMICAL STRUCTURE milligrams per day, respectively; the world’s per capita caffeine consumption is about 70 milligrams Caffeine is an ALKALOID that is often classified as per day. These dose levels are well within the range a central nervous system stimulant. Caffeine is of caffeine doses that can alter human behavior: As structurally related to xanthine, a purine molecule little as 32 milligrams of caffeine, less than the with two oxygen atoms (see Figure 1). Several im- amount of caffeine in most 12-ounce cola soft portant compounds, including caffeine, consist of drinks, can improve vigilance performance and re- the xanthine molecule with methyl groups at- action time; and doses as low as 10 milligrams, less tached. A methyl group consists of a carbon atom than the amount of caffeine in some chocolate bars, and three hydrogen atoms. These methylated xan- can alter self-reports of mood. These data suggest thines, called methylxanthines, are differentiated that a large number of people are daily consuming by the number and location of methyl groups at- behaviorally active doses of caffeine. Caffeine-containing foods and beverages are ubiquitously available in and widely accepted by most contemporary societies—yet dietary doses of caffeine can produce behavioral effects that share characteristics with prototypic drugs of abuse: physical dependence, self-administration, and TOLERANCE. Chronic administration of only 100 milligrams of caffeine per day, the amount of caf- feine in a cup of coffee, can produce PHYSICAL DEPENDENCE, as evidenced by severe and pro- nounced withdrawal symptoms that can occur upon abrupt termination of daily caffeine. Under Figure 1 some circumstances, research volunteers reliably The Caffeine Molecule

209 210 CAFFEINE tached to the xanthine molecule. Caffeine is a 1, 3, performance of complex tasks, increase physical 7-trimethylxanthine. The ‘‘tri’’ refers to the fact endurance, work output, hand tremor, and reports that caffeine has three methyl groups. The ‘‘1, 3, 7’’ of nervousness, jitteriness, restlessness, and refers to the position of the methyl groups on the anxiousness. purine molecule. Other important methylxanthines include theophylline, theobromine, and DISCOVERY paraxanthine. All these methylxanthines are me- tabolites of caffeine. In addition, theophylline and Caffeine, derived from natural caffeine-contain- theobromine are ingested directly in some foods ing plants, has been consumed for centuries by and medications. various cultures. Consumption of tea was first doc- umented in China in 350 A.D., although there is some evidence that the Chinese first consumed tea SALIENT FEATURES as early as the third century B.C. Coffee cultivation Sources. Coffee and TEA are the world’s pri- began around 600 A.D., probably in what is now mary dietary sources of caffeine. Other sources in- Ethiopia. clude soft drinks, cocoa products, and medications. Caffeine was first chemically isolated from cof- Caffeine is found in more than sixty species of fee beans in 1820 in Germany. By 1865, caffeine plants. COFFEE is derived from the beans (seeds) of had been identified in tea, mate´ (a drink made from several species of Coffea plants, and the leaves of the leaves of a South American holly), and kola Camellia sinensis plants are used in caffeine- nuts (the chestnut-sized seed of an African tree). containing teas. CHOCOLATE comes from the seeds or beans of the caffeine-containing cocoa pods of THERAPEUTIC USES Theobroma cacao trees. In developed countries, soft drinks, particularly COLAS, provide another Caffeine is incorporated in a variety of over-the- common source of dietary caffeine. Only a portion counter preparations marketed as analgesic, stimu- of the caffeine in soft drinks comes from the kola lant, cold, decongestant, menstrual-pain, or appe- nut (Cola nitida); most of the caffeine is added tite-suppression medications. As an ingredient in during manufacturing. Since the 1960s, a marked ANALGESICS (painkillers), caffeine is used widely in decrease in coffee consumption in the United States the treatment of ordinary types of headaches, al- has been accompanied by a substantial increase in though evidence for caffeine’s analgesic effects is the consumption of soft drinks. Mate´ leaves (Ilex limited: Caffeine may only diminish headaches that paraguayensis), guarana seeds, and yoco bark are result from caffeine withdrawal, but it is also com- other sources of caffeine for a variety of cultures. bined with an ergot ALKALOID in the treatment of Table 1 shows the amounts of caffeine found in migraine. Caffeine may have some therapeutic ef- common dietary and medicinal sources. As can be fectiveness in its ability to constrict cerebral blood seen in the range of values for each source in this vessels. The use of caffeine as a central nervous table, the caffeine content can vary widely depend- system (CNS) stimulant does have an empirical ing on method of preparation or commercial brand. basis, but there is little evidence that caffeine has Effects on Mood and Performance. It has appetite-suppressant effects. long been believed that caffeine stimulates mood Because of various effects of caffeine on the res- and behavior, decreasing fatigue and increasing piratory system, caffeine is used to treat asthma, energy, alertness, and activity. Although caffeine’s chronic obstructive pulmonary disease, and neo- effects in experimental studies have sometimes natal apnea (transient cessation of breathing in been subtle and variable, dietary doses of caffeine newborns)—although other agents, including have a variety of effects on mood and performance. theophylline, are usually preferred for the treat- Doses below 200 milligrams have been shown to ment of asthma and chronic obstructive pulmonary improve vigilance and reaction time, increase tap- disease. ping speed, postpone sleep, and produce reports of Historically, caffeine has been used medically to increased alertness, energy, motivation to work, de- treat overdoses with opioids and central depres- sire to talk to people, self-confidence, and well- sants, but this use has decreased considerably with being. Higher doses can both improve or disrupt the development of alternative treatments. CAFFEINE 211

ABUSE sules or in coffee, and even when they are not informed that caffeine is the drug under study. For Case reports have described individuals who example, heavy coffee drinkers given repeated consume large amounts of caffeine—exceeding one choices between capsules containing 100 milli- gram per day (1,000 milligrams). This excessive grams caffeine or placebo under double-blind con- intake, observed particularly among psychiatric ditions showed clear preference for the caffeine patients, drug and alcohol abusers, and anorectic capsules and, on average, consumed between 500 patients, can produce a range of symptoms— and 1,300 milligrams of caffeine per day. Experi- muscle twitching, ANXIETY, restlessness, nervous- mental studies with low to moderate caffeine con- ness, insomnia, rambling speech, tachycardia sumers have found that between 30 and 60 percent (rapid heartbeat), cardiac arrhythmia (irregular of those subjects reliably choose caffeine over heartbeat), psychomotor agitation, and sensory placebo in blind-choice tests. Subjects tend to show disturbances including ringing in the ears and less caffeine preference as the caffeine dose in- flashes of light. creases from 100 to 600 milligrams, and some The disorder characterized by excessive caffeine subjects reliably avoid caffeine doses of 400 to 600 intake has been referred to as caffeinism. There is milligrams. some suggestion that excessive caffeine consump- tion can be linked to psychoses and anxiety disor- ders. Substantial amounts of caffeine are also used TOLERANCE by a small percentage of competitive athletes, de- Chronic caffeine exposure can produce a de- spite specific sanctions against such use. creased responsiveness to many of caffeine’s effects Abused drugs are reliably self-administered un- (i.e., tolerance). This has been observed in both der a range of environmental circumstances by nonhumans and humans. Research with humans and most are also self-administered by nonhumans has clearly demonstrated that chronic laboratory animals. Caffeine has been self-injected caffeine administration can produce partial toler- by laboratory nonhuman primates and self-admin- ance to various effects of caffeine and can produce istered orally and intravenously by rats, but there complete tolerance to caffeine’s stimulating effect has been considerable variability across subjects on locomotor activity in rats. A number of studies and across studies. also suggest that tolerance to caffeine develops in Human self-administration of caffeine has been humans: Daily doses of 250 milligrams of caffeine variable, as well; however it is clear that human can increase systolic and diastolic blood pressure, subjects will self-administer caffeine, either in cap- however tolerance quickly develops to these effects 212 CAFFEINE within four days. The stimulating effects of caffeine equal to one strong cup of coffee, two strong cups of on urinary and salivary output also diminish with tea, or three soft drinks. Caffeine withdrawal ef- chronic caffeine exposure. Although tolerance ap- fects can vary within an individual in that a given pears to develop to some of the central nervous individual may not experience caffeine withdrawal system effects of caffeine, this aspect of caffeine during every period of caffeine abstinence. The tolerance has not been well explored. Comparisons severity of the withdrawal symptoms usually ap- of the effects of caffeine between heavy and light pears to be an increasing function of the mainte- caffeine consumers provide indirect evidence that nance dose of caffeine. Caffeine suppresses caffeine repeated (regular) caffeine use diminishes the withdrawal symptoms in a dose-dependent man- sleep-disturbing effects and alters the profile of ner, so that the magnitude of suppression increases self-reported mood effects. For example, 300 milli- as a function of the administered caffeine dose. grams of caffeine may produce self-reports of jit- The data described above indicate that the large teriness in people who normally abstain from caf- majority of the adult population in the United feine but not in regular caffeine consumers. High States is at risk for periodically experiencing signif- chronic caffeine doses (900 mg per day) can elimi- icant disruption of mood and behavior when there nate the self-reported mood effects (tension, anxi- are interruptions of daily caffeine consumption. ety, nervousness and jitteriness) of 300 milligrams The nature and time course of effects of termi- of caffeine given twice a day. nating daily caffeine consumption is illustrated in Figure 2, a recent experiment involving seven adult PHYSICAL DEPENDENCE subjects. The subjects followed a caffeine-free diet throughout the study and received identically ap- Evidence of physical dependence on caffeine is pearing capsules daily. Prior to the study, subjects provided by the appearance of a withdrawal syn- had received 100 milligrams of caffeine daily for drome following abrupt termination of daily caf- more than 100 days. Placebo capsules were substi- feine. Although there have been relatively few dem- tuted for caffeine without the subjects’ knowledge, onstrations of caffeine withdrawal in nonhumans, and subjects continued to receive placebo capsules abrupt termination of chronic daily caffeine has for twelve days, after which caffeine administration been shown to clearly decrease locomotor behavior was resumed. The top panel of the figure shows that in rats. Considerably more is known about caffeine substitution of placebo for caffeine produced statis- withdrawal in humans. Caffeine withdrawal is well tically significant increases (asterisks) in the aver- documented in anecdotal case reports dating back age ratings of headache during the first two days of to the 1800s and in experimental and survey stud- placebo substitution. Headache ratings gradually ies from the 1930s to the present. Caffeine with- decreased over the next twelve days and continued drawal is typically characterized by reports of at low levels during the final caffeine condition. headache, fatigue (e.g., reports of mental depres- The bottom panel of the figure shows that substitu- sion, weakness, lethargy, sleepiness, drowsiness, tion of placebo for caffeine produced similar time- and decreased alertness), and possibly anxiousness. limited increases in subjects’ ratings of lethargy/ Descriptions of the withdrawal headache suggest fatigue/tired/sluggish. that it develops gradually and can be throbbing and severe. ORGAN SYSTEMS When caffeine withdrawal occurs, its intensity can vary from mild to severe. Anecdotal descrip- Caffeine affects the cardiovascular, respiratory, tions of severe withdrawal suggest that it can be gastrointestinal and central nervous systems. Most incompatible with normal functioning and include notably, caffeine stimulates cardiac muscles, re- flulike symptoms, fatigue, severe headache, nau- laxes smooth muscles, produces diuresis by acting sea, and vomiting. In general, caffeine withdrawal on the kidney, and stimulates the central nervous begins twelve to twenty-four hours after terminat- system. The potential of dietary doses of caffeine to ing caffeine, peaks at twenty to forty-eight hours, stimulate the central nervous system is primarily and lasts from two to seven days. Caffeine with- inferred from caffeine’s behavioral effects. Low to drawal can occur following termination of caffeine moderate caffeine doses can produce changes in doses as low as 100 milligrams per day, an amount mood (e.g., increased alertness) and performance CAFFEINE 213

High caffeine doses can produce a rapid heartbeat (tachycardia) and in rare cases irregularities in heartbeat (cardiac arrhythmia). Caffeine’s effects on peripheral blood flow and vascular resistance are variable. In contrast, caffeine appears to in- crease cerebrovascular resistance and decrease ce- rebral blood flow. Moderate doses of caffeine can increase respira- tory rate in caffeine-abstinent adults. Caffeine also relaxes the smooth muscles of the bronchi. Because of caffeine effects on respiration, it has been used to treat asthma, chronic obstructive pulmonary dis- ease, and neonatal apnea (transient cessation of respiration in newborns). Moderate doses of caffeine can act on the kidney to produce diuretic effects that diminish after chronic dosing. Caffeine has a variety of effects on the gastrointestinal system, particularly the stimu- lation of acid secretion. These effects can contrib- ute to digestive upset and to ulcers of the gastroin- testinal system. Caffeine increases the concentration of free fatty acids in plasma and increases the basal metabolic rate.

TOXICITY High doses of caffeine, typically doses above 300 milligrams, can produce restlessness, anxiousness, nervousness, excitement, flushed face, diuresis, Figure 2 gastrointestinal problems, and headache. Doses The Termination Effects of Daily Caffeine above 1,000 milligrams can produce rambling Consumption speech, muscle twitching, irregular heartbeat, SOURCE: Griffiths et al. (1990). Low-dose caffeine rapid heartbeat, sleeping difficulties, ringing in the physical dependence in humans. ears, motor disturbances, anxiety, vomiting, and convulsions. Adverse effects of high doses of caf- (e.g., improvements in vigilance and reaction feine have been referred to as caffeine intoxication, time). Higher doses produce reports of nervousness a condition recognized by the American Psychiatric and anxiousness, measurable disturbances in sleep, Association. Extremely high doses of caffeine— and increases in tremor. Very high doses can pro- between 5,000 and 10,000 mg—can produce con- duce convulsions. vulsions and death. Caffeine’s cardiovascular effects are variable Extremely high doses of caffeine, well above di- and depend on dose, route of administration, rate etary amounts, have been shown to produce of administration, and history of caffeine consump- teratogenic effects (birth defects) in mammals. Al- tion. Caffeine doses between 250 and 350 milli- though there is some evidence to the contrary, di- grams can produce small increases in blood pres- etary doses of caffeine do not appear to affect the sure in caffeine-abstinent adults. Daily caffeine incidence of malformations or of low-birth-weight administration, however, produces tolerance to offspring. Although there has been some suggestion these cardiovascular effects within several days; that caffeine consumption increases the incidence thus comparable caffeine doses do not reliably af- of benign fibrocystic disease and cancer of the pan- fect blood pressure of regular caffeine consumers. creas, kidney, lower urinary tract, and breast, asso- 214 CAFFEINE ciations have not been clearly established between nate caffeine at markedly slower rates, requiring caffeine intake and any of these conditions. Simi- over 10 days to eliminate about 95 percent of a larly, dietary caffeine has been associated with lit- dose of caffeine. By 1 year of age, caffeine elimina- tle, if any, increase in the incidence of heart disease. tion rates increase substantially, exceeding those of Controversies continue over the medical risks of adults; school-aged children eliminated caffeine caffeine. Although research has not definitively re- twice as fast as adults. solved all the controversies, health-care profes- sionals must make recommendations regarding MECHANISMS OF ACTION safe and appropriate use of caffeine. In a recent survey of physician specialists, more than 65 per- Three mechanisms by which caffeine might ex- cent recommended reductions in caffeine in pa- ert its behavioral and physiological effects have tients with arrhythmias, palpitations, tachycardia, been proposed: (1) blockade of receptors for aden- esophagitis/hiatal hernia, fibrocystic disease, or ul- osine; (2) inhibition of phosphodiesterase activity cers, as well as in patients who are pregnant. resulting in accumulation of cyclic nucleotides; and (3) translocation of intracellular calcium. Only one PHARMACOKINETICS of these, however, the blockade of adenosine recep- tors, occurs at caffeine concentrations in plasma Absorption and Distribution. Caffeine can produced by dietary consumption of caffeine. be effectively administered orally, rectally, in- Adenosine (an autacoid—or cell-activity modifier), tramuscularly, or intravenously; however, it is usu- found throughout the body, has a variety of effects ally administered orally. Orally consumed caffeine that are often opposite to caffeine’s effects— is rapidly and completely absorbed into the blood- although caffeine is structurally very similar to stream through the gastrointestinal tract, produc- adenosine. As a result, caffeine can bind to the ing effects in as little as fifteen minutes and reach- receptor sites normally occupied by adenosine, ing peak plasma levels within an hour. Food thereby blocking adenosine binding, and prevent- reduces the rate of absorption. Caffeine readily ing adenosine’s normal activity. Thus, caffeine’s moves through all cells and tissue, largely by simple ability to stimulate the central nervous system, and diffusion, and thus is distributed to all body organs, quickly reaching equilibrium between blood and all increase urine output and gastric secretions, may tissues, including brain. Caffeine crosses the pla- be due to the blockade of adenosine’s normal ten- centa, and it passes into breast milk. dency to depress the central nervous system and Metabolism and Excretion. The bloodstream decrease urine output and gastric secretions. The delivers caffeine to the liver, where it is converted to methylxanthine metabolites of caffeine (including a variety of metabolites. Most of an ingested dose of paraxanthine, theophylline, and theobromine) are caffeine is converted to paraxanthine and then to also structurally similar to adenosine and block several other metabolites. A smaller proportion of adenosine binding. caffeine is converted to theophylline and theobro- mine; both of those compounds are also further (SEE ALSO: Addiction:Concepts and Definitions; metabolized. Some of these metabolites may con- Tolerance and Physical Dependence) tribute to caffeine’s physiologic and behavioral effects. BIBLIOGRAPHY The amount of time required for the body of an adult to remove half of an ingested dose of caffeine DEWS,P.B.(ED.) (1984). Caffeine. New York: Springer- (i.e., the half-life) is 3 to 7 hours. On average, Verlag. about 95 percent of a dose of caffeine is excreted GRAHAM, D. M. (1978). Caffeine—Its identity, dietary within 15 to 35 hours. Cigarette smoking produces sources, intake and biological effects. Nutrition Re- a twofold increase in the rate at which caffeine is views, 36, 97–102. eliminated from the body. There is a twofold de- GRIFFITHS, R. R., & WOODSON, P. P. (1988). Caffeine crease in the caffeine elimination rate in women physical dependence: A review of human and labora- using oral contraceptive steroids and during the tory animal studies. Psychopharmacology, 94, 437– later stages of pregnancy. Newborn infants elimi- 51. CALCIUM CARBIMIDE 215

GRIFFITHS, R. R., ET AL. (1990). Low-dose caffeine phys- Alcohol (ethanol) is normally metabolized first ical dependence in humans. Journal of Pharmacologi- to acetaldehyde, which is then quickly metabolized cal and Experimental Therapy, 255, 1123–1132. further so that levels of acetaldehyde are ordinarily HUGHES, J. R., AMORI,G.,&HATSUKAMI, K. D. (1988). A quite low in the body (acetaldehyde is toxic). survey of physician advice about caffeine. Journal of Carbimide produces competitive inhibition of he- Substance Abuse, 1, 67–70. patic (liver) aldehyde-NAD oxidoreductase dehy- RALL, T. W. (1990). Drugs used in the treatment of drogenase (ALDH), the enzyme from the liver re- asthma. In A. G. Gilman et al. (Eds.), Goodman and sponsible for oxidation of acetaldehyde into acetate Gilman’s the pharmacological basis of therapeutics, and water. Within two hours of taking carbimide 8th ed. New York: Pergamon. by mouth, ALDH inhibition occurs. If alcohol is SPILLER,G.A.(ED.) (1984). The methylxanthine bever- then ingested, blood acetaldehyde levels are in- ages and foods:Chemistry, consumption, and health creased; also mild facial flushing, rapid heartbeat, effects. New York: Alan R. Liss. shortness of breath, and nausea occur with just one WEISS, B., & LATIES, V. G. (1962). Enhancement of hu- drink. As more is drunk, the severity of the reaction man performance by caffeine and the amphetamines. increases, with rising discomfort and apprehension. Pharmacological Review, 14, 1–36. Severe reactions can pose a serious medical risk that requires immediate attention. KENNETH SILVERMAN ROLAND R. GRIFFITHS DOSAGE AND ADMINISTRATION In Canada, Temposil is available as round, white CALCIUM CARBIMIDE Citrated calcium 50-mg tablets engraved with the letters ‘‘LL’’ and carbimide is a mixture of two parts citric acid to ‘‘U13.’’ The usual dosage is 50 or 100 mg every one part calcium carbimide; it slows the metabo- twelve hours. The drug should never be given to an lism of ALCOHOL (ethanol) from acetaldehyde to intoxicated patient and preferably no sooner than acetate, so it is used in the treatment of ALCOHOL- 36 hours after the last drink. ISM. It is also known as calcium cyanamide. As an Calcium carbimide should be used with caution antidipsotropic—an antialcohol or alcohol-sensi- in patients with asthma, coronary artery disease, or tizing medication, it has been used for treatment in myocardial disease. Canada, the United Kingdom, and Europe since its In the event of an overdose, the patient should be introduction for clinical use in 1956. Its only thera- given pure (100%) oxygen by mask or antihista- peutic use is for the treatment of alcoholism. In mines administered intravenously. Canada it is sold under the brand name Temposil. As of 2000, however, calcium carbimide is still not SIDE EFFECTS approved for use in the United States. Unlike disulfiram, carbimide does not have the potential side effect of liver damage. Carbimide, PHARMACOLOGY however, exerts antithyroid activity, which can be clinically significant in patients with preexisting The PHARMACOKINETIC data on the absorption hypothyroid disease. According to a 1999 Cana- metabolism and elimination of carbimide in hu- dian monograph, other side effects of calcium mans are incomplete. Since nausea, headache, and carbimide include fatigue, skin rashes, ringing in vomiting occur because of the rapid absorption of the ears, mild depression, a need to urinate fre- carbimide, for treatment purposes it is formulated quently, and impotence. The clinical significance of as a slow-release tablet. Peak plasma concentra- transient white blood cell increases remains un- tions of carbimide following oral administration in clear. experimental animals occur at 60 minutes; the drug is then metabolized at a relatively rapid rate so that USE IN TREATMENT half disappears about every 90 minutes (i.e., an apparent elimination half-life of 92.4 minutes). In The rationale for use of carbimide in alcoholism humans, an alcohol challenge reaction will occur on treatment is similar to that of disulfiram. The an average of 12 to 24 hours after drinking. threat of an unpleasant reaction, which one may 216 CALIFORNIA CIVIL COMMITMENT PROGRAM expect following drinking, is sufficient to deter 660), that a state could establish a program of drinking. For alcoholics in treatment who take a compulsory treatment for narcotic addiction and drink, the ensuing reaction is unpleasant enough to that such treatment could involve periods of invol- strengthen their overall conditioned aversion to al- untary confinement, with penal sanctions for fail- cohol. Their reduction of alcohol consumption dur- ure to comply with compulsory treatment proce- ing carbimide treatment is expected to result in dures. In 1966, Congress passed the Narcotic general bodily improvement. A second approach Addict Rehabilitation Act (28 U.S.C. sections involves the use of carbimide as part of a RELAPSE- 2901-2903) that permitted federal judges and PREVENTION treatment, whereby an individual prison officials to refer narcotic-addicted proba- might take it in anticipation of a high-risk situa- tioners and inmates to the Lexington and Fort tion. As of 2000, scientific evidence supporting the Worth facilities as an alternative to traditional in- efficacy of carbimide in alcoholism treatment is carceration. This Act established statutory author- inconclusive because of a lack of well-controlled ity for involuntary inpatient and outpatient treat- clinical trials. No multicenter clinical trials have yet ment and treatment in lieu of prosecution. The been performed. Comprehensive Drug Abuse Prevention and Con- trol Act of 1970, more commonly known as the (SEE ALSO: Causes of Substance Abuse:Learning; Controlled Substances Act, authorized the diver- Disulfiram; Treatment Types:Aversion Therapy ) sion of drug-involved offenders from the criminal justice system into drug abuse treatment programs. The California Civil Addict Program (CAP) was BIBLIOGRAPHY the first true civil commitment program implemen- MEDICAL ECONOMICS COMPANY. (1999). Physicians’ Desk ted in the United States. In 1961, following a rec- Reference, (PDR), 53rd edition. Montvale, NJ: Au- ommendation by the Study Commission on Narcot- thor. ics, it was placed under the direction of the PEACHEY, J. E., & ANNIS, H. (1985). New strategies for Department of Corrections and equipped with clear using the alcohol-sensitizing drugs. In C. A. Naranjo standards for commitment procedures. Addicts & E. M. Sellers (Eds.). Research advances in new psy- convicted of a felony or misdemeanor could be chopharmacological treatments for alcholism (pp. committed to CAP for seven years and then re- 199–218). New York: Excerpta Medica. turned to court for disposition of the original PEACHEY,J.E.ET AL. (1989a). Calcium carbimide in charge, or time served in CAP was credited toward alcoholism treatment. Part 1: A placebo-controlled, the sentence. Addiction was determined by two double-blind clinical trial of short-term efficacy. Brit- court-appointed physicians and patients under- ish Journal of Addiction, 84, 877–887. went a sixty-day evaluation period (McGlothlin, PEACHEY,J.E.ET AL. (1989b). Calcium carbimide in Anglin, and Wilson 1977). alcoholism treatment. Part 2: Medical findings of a The program provided both inpatient and out- short-term, placebo-controlled, double-blind clinical patient treatment phases and was viewed as a mod- trial. British Journal of Addiction, 84, 1359–1366. ified therapeutic community. During the initial eight years of CAP (1961-1969), this outpatient JOHN E. PEACHEY program was very stringent adhering to the re- REVISED BY REBECCA J. FREY quirement, ‘‘You use, you lose.’’ During the 1970s the program might tolerate infrequent drug use if one’s overall behavioral pattern was deemed ac- CALIFORNIA CIVIL COMMITMENT ceptable (Anglin 1988). Participants in CAP exhib- PROGRAM Coercive treatment approaches for ited sustained reductions in drug use, fewer multi- drug addiction have been utilized consistently ple relapses and relapses that were of shorter throughout the twentieth century, beginning with duration and separated by longer periods of non the morphine maintenance clinics of the 1920s. addiction (Anglin 1988). CAP has an important Federal narcotics treatment facilities were estab- place in the history of compulsory substance abuse lished in Fort Worth, Texas and Lexington, Ken- treatment, but the program has been dramatically tucky in the 1930s. In 1962, the U.S. Supreme altered since the late 1970s. As of 1990, the length Court held, in Robinson v. California (370 U.S. of the commitment period has been reduced from CANADA, DRUG AND ALCOHOL USE IN 217 seven years to an average of three years. The com- Incarceration of drug-using offenders costs from munity phase is often disorganized, ancillary ser- $25,000 to $50,000 per year. In contrast, the most vices have been dramatically cut, and there is no comprehensive Drug Court System costs an average treatment service available beyond the minimal of $3,000 annually for each offender. The Califor- 120-hour Civil Commitment Education Program nia Drug and Treatment Assessment (CALDATA) (Wexler 1990). estimated a cost of less than $8 per day for outpa- In 1972, the Treatment to Alternatives Street tient treatment that compares with estimates of Crime (TASC) program was created by President $50 to $70 per day associated with jail time. The Nixon’s Special Action Office for Drug Abuse Pre- recent CALDATA study showed a significant re- vention. TASC, a national program designed to duction in criminal activity during and after treat- divert drug-involved offenders into appropriate ment, in drug sales and the use of a weapon or community-based treatment programs, was funded physical force. by the National Institute of Mental Health (NIMH) TASC will continue to expand into the 21rst and the Law Enforcement Assistance Administra- Century, primarily because it has been recognized tion (LEAA). Federal funding for TASC began to by the National Institute on Drug Abuse, the Office wane beginning in the 1980s until funding was of National Drug Control Policy and the Office of completely withdrawn in 1982. The Judicial Assis- Treatment Improvement as an effective program tance Act of 1984 revived federal endorsement and for reducing drug use and related crime (Inciardi fiscal support for TASC. This legislation authorized and McBride 1992). The courts and their treatment a criminal justice block grant program designed to providers provide an early opportunity for treat- address drug-related crime and the drug-involved ment and a cost-effective alternative to traditional offender. In the more than 100 jurisdictions where criminal case processing. TASC currently operates, it serves as a court diver- sion mechanism or a condition to probation super- vision. After referral to community-based treat- BIBLIOGRAPHY ment, TASC monitors the client’s progress and ANGLIN, D. (1988). The efficacy of civil commitment in compliance and reports back treatment results to treating narcotic addiction. Compulsory treatment of the referring justice system agency. Clients who vi- drug abuse: Research and clinical practice. (NIDA olate the conditions of their referral are generally Research Monograph 86, Rockville, MD: U.S. Depart- returned to the justice system for continued pro- ment of Health and Human Services. cessing or sanctions (Inciardi and McBride 1992). INCIARDI, J. A., & MCBRIDE, D. C. (1992). Reviewing the TASC served as the precursor for the system of ‘TASC’ (Treatment Alternatives to Street Crime) Ex- ‘Drug Courts’ currently operating in California and perience. Journal of Crime and Justice XV (i):45-61. in many other states. A Drug Court is a special MCGLOTHLIN, W. H., ANGLIN,M.D.,&WILSON,B.D. court given the responsibility of select felony and (1977). An evaluation of the California Civil Addict misdemeanor cases involving nonviolent drug-us- Program Services Research Monograph Series. Rock- ing offenders. The program includes random drug ville, MD: U.S. Department of Health, Education, and testing, judicial supervision, counseling, educa- Welfare. tional and vocational opportunities and the imposi- WEXLER, H. K. (1990). Summary of findings and recom- tion of sanctions for failure. There are 600 Drug mendations of the second invited review of California Courts in the nation with about 92 in California. Department of Corrections substance abuse treatment Each is set up utilizing the guidelines of the Federal efforts. Unpublished manuscript, Narcotics and Drug Office of Drug Court Policy. Clients are responsible Research, Inc., New York. for their development and participation in the treatment process. Regular status hearings are held HARRY K. WEXLER with the judge and the drug court team. After the REVISED BY TERRENCE P. MURPHY, J.D. successful completion of the criminal drug court program, a minimum of 12 months, the drug charge is dismissed. California Drug Courts operate CANADA, DRUG AND ALCOHOL USE on Federal and State grant money and matching IN Alcohol, tobacco, and cannabis are the most funds from the county where the court is located. prevalent drugs of abuse in Canada. A 1996 na- 218 CANADA, DRUG AND ALCOHOL USE IN tional survey found that 76.8 percent of Canadian CONSEQUENCES adults aged 15 and over were current drinkers A 1993 survey found that 5.1 percent of current (who had consumed ALCOHOL at least once in the drinkers had had a physical health problem due to past year); an additional 13.5 percent said they their drinking at some point. About 2 percent said were former drinkers, while only 9.7 percent said it had interfered with their friendships or social life, they never drank. Per-adult consumption was and 2.1 percent said it had affected their home lives about 450 drinks per year (7.64 l) of absolute alco- or marriages. Finally, 4.7 percent said it affected hol (ethanol). Overall alcohol consumption has de- their financial positions. creased in Canada since the 1980s. In 1996, about 8 percent of current drinkers In 1996, 29 percent of adults were current reported drinking and driving. Of fatally injured smokers and another 29 percent were former drivers who had been tested, 45 percent had posi- smokers. Overall, the percentage of the population tive BLOOD ALCOHOL CONCENTRATIONS (BAC), who smoke has been dropping since the 1970s. with 28 percent exceeding 150 milligrams. (The Practically all TOBACCO is consumed as cigarettes, legal level in Canada for impairment is 80 milli- with daily consumption per smoker estimated at grams.) 20.6 (more than one pack) in 1996. In 1996, there were 95,877 federal drunk driv- The 1994 national survey found that 23.1 per- ing offenses, although the number has been declin- cent of adults had used MARIJUANA or HASHISH at ing for several years. Most offenses are for impaired some point, while 7.4 percent had used it the past operation of motor vehicles, but about 8 percent year. Less than one percent were current COCAINE are for refusal or failure to provide a breath sample. or CRACK users, and 3.8 percent had used it at some There were 16,239 people jailed for drunk driving time. Also, 1.1 percent of adults had used LYSERGIC offenses in 1996, about 20 percent of all jailed ACID DIETHYLAMIDE (LSD), AMPHETAMINES people. (speed), or HEROIN in the past year, and 5.9 percent In 1996, there were 194,916 provincial liquor had used them at some point. act offenses, and 14,329 juvenile offenders were High school students and ‘‘street’’ kids reported convicted in liquor act offenses. However, only the use of numerous illegal drugs, such as LSD, 1,201 people were jailed for liquor act offenses, as HALLUCINOGENS, speed, heroin, glue and other IN- most are dealt with by fines, suspended sentences, HALANTS, or made nonprescription use of stimu- or attendance at detoxification centers. lants, BARBITURATES, and tranquilizers. Most In 1996, there were 65,106 illicit drug offenses indigenous youth smoke and have rates of alcohol of all types with most (47,002) being for cannabis; problems and illicit drug use several times higher there were 11,188 offenses for cocaine and 1,233 than the national average. Almost all street youth for heroin. Almost all convictions were under the in Toronto used alcohol and one or more illicit Alcoholic Control Act. Offenses under the Food and drugs. Drug Act, which covers LSD, stimulants, and non- The 1996 survey found that 4.5 percent of narcotic drugs were 1,306. adults used sleeping pills, 4.3 percent used tran- In 1996, 8,684 people were sent to federal or provincial prisons for drug offenses, the majority of quilizers such as Valium, .9 percent used diet pills which were for cannabis and cocaine related of- or stimulants, 3 percent used antidepressants, and fenses; they constituted about 16 percent of all 13 percent used narcotic painkillers such as De- federal jail prisoners and 7 percent of provincial jail merol, morphine, or codeine. (In Canada, codeine prisoners. of less than 8 milligrams per tablet is an over-the- counter drug.) Alcohol, tobacco, and illegal drug use is gener- TREATMENT ally higher among Canadian men than women, but In 1996 about 400,000 Canadians were alcohol prescription psychoactive-drug use is greater in dependent (2.7% of all adults). The total number women. For all types of licit and illicit drugs except treated for alcohol dependence is unknown but tranquilizers and barbiturates, male Canadian stu- probably no more than half have been treated. In dents are heavier users than are females. 1996, 81,000 cases were treated in hospitals for the CANCER, DRUGS, AND ALCOHOL 219 consequences of alcohol problems, such as car acci- CARCINOGENESIS dents, drownings, falls, liver problems, strokes, The likelihood of a substance to cause cancer is gastrointestinal problems, and many other causes. called carcinogenicity; this is determined in several There were over 7,000 cases treated in hospitals ways. The first is to see if cells grown in vitro (in a because of illicit drugs. This included drug psy- test tube) with the potential carcinogen develop choses, poisonings, dependency, and various types cell-structure abnormalities in the new-grown cells. of accidents. The second is to see if the substance will result in cancers in animals. The third is to look at the DEATHS clinical course of a disease in a human patient. In 1995, there were 6,701 deaths directly due to Finally, the outcomes in a group of people exposed alcohol diagnoses. The larger proportions were due to the substance will be compared to outcomes in to motor vehicle accidents (1,444 persons), suicide those not exposed—either by following the natural (955 persons), liver disease (1,037 persons), alco- course of history in a population through time in hol dependence (590 persons), and accidental falls cohort studies or in case-control. (452 persons). Other causes include various can- In spite of these methods, however, identifying cers, circulatory problems, and accidents. There carcinogens is complex and difficult. One reason is were only 804 deaths attributed to illicit drug use in the long time delay between use of a carcinogenic 1995. The majority were due to suicide (329 per- chemical and the appearance of cancer symptoms; sons), opiate poisoning (160 persons), and AIDS intervals of 20–30 years are not unusual. As a (83 persons). result, carcinogenic effects are rarely detected in early studies of new medications. Secondly, carci- BIBLIOGRAPHY nogenesis appears to be a multistep process involv- ing environmental, nutritional, and genetic factors ADRIAN, M., JULL, P., & WILLIAMS R. T. (B.) (1989). as well as use of a carcinogenic drug. Statistics on alcohol and drug use in Canada and Carcinogens are classified as genotoxic or other countries:Data available by 1988 . Toronto: epigenetic. Genotoxic carcinogens act directly on Addiction Research Foundation. the DNA in human cells, in effect producing abnor- SINGLE, E., WILLIAMS, B., & MCKENZIE, D. (1994). Ca- mal cells. Almost all identified drug carcinogens, nadian profile:Alcohol, tobacco and other drugs however, fall into the second category, the 1994. Ottawa and Toronto: The Canadian Centre on epigenetic carcinogens. These substances encour- Substance Abuse and the Addiction Research Foun- age the proliferation of latent tumor cells in a tissue dation of Ontario. or organ. SINGLE, E., ET AL. (1999). Canadian profile:Alcohol, tobacco and other drugs. Ottawa and Toronto: Centre for Addiction and Mental Health and the Canadian DRUGS OF ABUSE AND CANCER Centre on Substance Abuse. Alcohol. Animal data do not show that admin- STATISTICS CANADA. (1998). National Population Health istering ALCOHOL alone causes cancer although Survey, 1996-1997, Ottawa. there is sufficient evidence for the carcinogenicity MANUELLA ADRIAN of acetaldehyde (the major metabolite of alcohol). REVISED BY REGINALD G. SMART When alcohol was administered to animals who were also exposed to known carcinogens, the ani- mals who were given the alcohol had a higher rate CANCER, DRUGS, AND ALCOHOL The of tumors of pituitary and adrenal glands, pancre- relationship between cancer and drugs, including atic islet cells, esophagus, and lungs. They also had alcohol, has several aspects. One is the question of higher levels of liver-cell (hepatocellular) carcino- carcinogenesis; that is, whether alcohol and other mas, liver angiosarcomas, and neoplastic nodules abused substances cause cancer. Another is the of the liver, as well as benign tumors of the nasal relationship between prescription medications and cavity and trachea. cancer. A third is the complications of cancer treat- Cancers of the Digestive Tract. Epidemiological ment in patients with a history of substance abuse. studies in humans have shown a causal relationship 220 CANCER, DRUGS, AND ALCOHOL between alcohol consumption and cancer of the PRESCRIPTION DRUGS AND CANCER digestive tract, primarily cancer of the oral cavity, Very few drugs that are suspected of causing the pharynx (nasopharynx excluded), and the lar- cancer in humans are used in contemporary medi- ynx—all two to five times more likely in alcoholics; the esophagus—two to four times more likely; and cal practice. Those that are, however, fall into two the liver—liver cancer was increased 50 percent, significant categories: alkylating agents that are with primary liver cancer increasing twofold to used to treat cancer; and birth control pills and threefold. These findings persisted, even after ad- other hormone preparations. justing for the effects of smoking, with the relative Alkylating agents. These antineoplastic drugs risk for cancer increasing with the amount of alco- include busulfan (Myleran), used to treat leukemia hol consumed. that has not responded to other drugs; cyclophos- There may be a possible causal link between phamide (Cytoxan), an immunosuppressant used alcohol, especially beer, and cancer of the large to treat ovarian cancer and malignant lymphoma; bowel. The risk for colon cancer was increased melphalan (Alkeran); ifosfamide (Ifex), used to between 15 percent and threefold depending on the treat testicular cancer and Ewing’s sarcoma; study; that for rectal cancer was increased up to cisplatin (Platinol), a drug derived from platinum; twofold. Unfortunately, these studies did not con- and chlorambucil (Leukeran), used in the treat- trol for differences in diet. ment of leukemia and Hodgkin’s disease. All of The mechanism of carcinogenic action appears these drugs have serious side effects ranging from to be that alcohol acts as a local irritant to the upper liver toxicity to fibrosis of the lungs, as well as gastrointestinal tract, whereas chronic excessive carcinogenic potential. Cyclophosphamide in par- drinking affects the liver, because of the accumula- ticular increases a patient’s risk of secondary can- tion of the alcohol metabolite acetaldehyde. cers for several years after it has been discontinued. Breast Cancer. A strong association exists between Synthetic Hormones and Steroid Prepara- alcohol and breast cancer, and there appears to be a tions. The natural and synthetic estrogens used dose-response relationship with an apparent rela- for contraception and for postmenopausal hormone tive risk of 1.5 to 2. This relationship holds even replacement have been associated with an in- after controlling for a number of other factors creased risk of uterine cancer. As of the late 1990s, known to affect breast cancer. As the full etiology these estrogens are usually combined with pro- (cause) of breast cancer is not yet known, an gestins, which appear to lower this risk. Diethylstil- as-yet-unrecognized factor may account for some bestrol (DES), which is used to treat menopausal of these findings. Overall, it has been estimated that as many as 10 percent of all cancer deaths are due symptoms and advanced cancers of the breast, may to alcohol. cause vaginal or cervical cancer in women whose Tobacco and Illicit Drugs. The role of TO- mothers took DES during pregnancy. BACCO as a carcinogen is well established and is Oxymetholone (Anadrol), a steroid related to tes- discussed elsewhere. The role of other drugs as a tosterone, is reported to increase the risk of liver cause of cancer is still unclear. Some drugs may cancer. have a role in cancer development because of mode of administration or degree of carcinogenicity. In SUBSTANCE ABUSE AND vitro studies have shown mutagenic properties in a CANCER TREATMENT number of drugs—LYSERGIC ACID DIETHYLAMIDE (LSD), OPIUM and its derivatives such as MOR- On the one hand, NARCOTIC and psychoactive PHINE, synthetic narcotics such as METHADONE, drugs have an important role in cancer treatment. and some compounds found in MARIJUANA. There Cancer patients have used Cannabis sativa (mari- have been clinical reports of cancers in the respira- juana) to reduce the nausea associated with chemo- tory tract, primarily the lungs, in heavy marijuana therapy. LSD has been used in treating psychologi- users, of the nasal passages in cocaine users, and in cal disturbances associated with cancer. Although a number of organs in LSD users. Higher rates of it was once feared that cancer patients would be- esophageal cancer have been reported in opium come addicted to opioids given for pain control, a smokers. recent study showed that of 11,882 cancer patients CANNABIS SATIVA 221 with no prior substance abuse history, only four CANNABIS SATIVA This is the botanical became addicts after treatment with opioids. name for the HEMP plant that originated in Asia. It On the other hand, preexisting abuse of these is the basis of the hemp industry as well as the same substances complicates cancer treatment. A source of the widely used intoxicant history of substance abuse may shorten a cancer TETRAHYDROCANNABINOL (THC), the active agent patient’s life expectancy and undermine the effec- in MARIJUANA,HASHISH,GANJA, and BHANG. tiveness of palliative care. Ongoing substance abuse disrupts the patient’s relationships with physicians HISTORY and other caregivers. As of 2000, the National Can- cer Institute has issued guidelines for the clinical The use of Cannabis sativa has been recorded management of cancer patients with substance for thousands of years, beginning in Asia. It was abuse histories. These guidelines include evalu- known to the ancient Greeks and later to the Arabs, who, during their spread of Islam from the seventh ation and treatment of comorbid psychiatric disor- to the fifteenth centuries, also spread its use across ders, evaluation of the patient’s tolerance of drugs, the Levant and North Africa. Some 200–300 mil- and monitoring of hospital inpatients. lion people are estimated to use Cannabis in some form worldwide. Thus, it is not only one of the (SEE ALSO: Complications:Immunologic ) oldest known but also one of the most widely used mind-altering drugs. BIBLIOGRAPHY Since the 1960s, the rise in its use in the United

BEERS, M. H., & BERKOW, R. (Eds.) (1999). The Merck States has been enormous and associated with the Manual of Diagnosis and Therapy, 17th ed. youth movement and countercultural revolution. Whitehouse Station, NJ: Merck Research Laborato- Although the drug was in use before that time, it ries. was popular only in some ethnic and specialized BRESLOW, N. E., & DAY, N. E. (1980/1987). Statistical groups (e.g., jazz musicians). By the 1990s, some methods in cancer research, vol. 1, The analysis of 30–40 million Americans are estimated to have case-control studies; vol. 2, The design and analysis used it and a substantial number use it regularly— of cohort studies. Lyon, France: World Health Orga- although since 1979 the number of youngsters ini- nization (IARC Scientific publications no. 32 and 82). tiated into its use has been declining after a steep HANKS, G. W., & JUSTINS, D. M. (1992). Cancer pain: rise with an increasingly lower age of first use. Management. Lancet, 339(8800), 1031–1036. HARDMAN,J.G.,&LIMBIRD, L. E. (Eds.) (1996). Good- BOTANY man and Gilman’s The Pharmacological Basis of Cannabis sativa grows in the tropical, subtropi- Therapeutics, 9th ed. New York: McGraw-Hill. cal, and temperate regions. It is generally consid- MEDICAL ECONOMICS COMPANY. (1999). Physicians’ Desk ered a single species of the mulberry family Reference, (PDR), 53rd edition. Montvale, NJ: Au- (Moraceae) with multiple morphological variants thor. (e.g., C. indica or C. americana). It is an herb of NATIONAL CANCER INSTITUTE. (2000). Substance Abuse varying size; some are quite bushy and attain a Disorder and Supportive Care. Bethesda, MD: Office height of 10 to 15 feet (3 to 4.6 m). Due to genetic of Cancer Communications. differences, some plants produce strong fibers (but WILSON, B. A., SHANNON, M. T., & STANG, C. L. (Eds.) little THC) and others produce a substantial quan- (1995). Nurses Drug Guide, 3rd ed. Norwalk, CT: tity of THC but weak fibers. The fiber-producer is Appleton & Lange. grown commercially for cloth, rope, roofing materi- WORLD HEALTH ORGANIZATION. (1988). Alcohol drink- als, and floor coverings; this was cultivated as a ing—IARC monographs on the evaluation of carcino- cash crop in colonial America for such purposes genic risks to humans. Lyon, France: World Health (Hart, 1980). During World War II, when it ap- Organization International Agency for Research on peared that the United States might be cut off from Cancer, vol. 44. Southeast Asian hemp, necessary to the war effort, MANUELLA ADRIAN the plants were cultivated in the mid-western REVISED BY REBECCA J. FREY states. Some of them continue to grow wild today, 222 CASUAL DRUG USE

Figure 1 Biosynthetic Pathway of Cannabinoids Figure 1 Biosynthetic Pathway of but since they are of the fiber-producing variety, duced by smoking or eating some of the whole plant Cannabinoids they contain little drug content. can be attained by using THC alone. The drug-producing variety is widely cultivated in societies where its use is condoned. Illegal crops USE AS A SOCIAL DRUG are also planted, some in the United States. The choice parts are the fresh top leaves and flowers of Cannabis grows so easily that it is called a weed. the female plant. The leaves have a characteristic In the United States, where it remains illegal, it is configuration of five deeply cut serrated lobes. possible for those who wish to use it as a social drug When they are harvested, they often resemble lawn to grow their own supply. The ease of cultivation cuttings—which accounts for the slang term keeps the price of imported illicit marijuana down, ‘‘grass.’’ which helps account for some of its widespread use. Such cultivation is, however, as illegal as possession CHEMISTRY of the drug obtained from illicit ‘‘street’’ sources. The collective name given to the terpenes found in Cannabis is cannabinoids. Most of the naturally (SEE ALSO: Anslinger, Harry J., and U.S. Drug Pol- occurring cannabinoids have now been identified, icy; High School Senior Survey) and three are the most abundant—cannabidiol (CBD), tetrahydrocannabinol (THC), and canna- BIBLIOGRAPHY binol (CBN). The steps from CBD to THC to CBN represent the biosynthetic pathway in the plant. HART, R. H. (1980). Bitter grass:The cruel truth about THC is an optically active resinous material that is marihuana. Shawnee Mission, KS: Psychoneurologia very lipid-soluble but water-insoluble; these physi- Press. cal properties make pharmacological investigations RAZDAN, R. K. (1986). Structure-activity relationships in difficult, since various nonpolar solvents must be cannabinoids. Pharmacology Review, 38, 75–148. used. Although many other materials have been LEO E. HOLLISTER found in this plant, the cannabinoids are unique to it and THC is the only one with appreciable mental affects. THC is believed to be largely, if not solely, responsible for the effects desired by those who use CASUAL DRUG USE See Addiction: Con- Cannabis socially. Virtually all the effects pro- cepts and Definitions CAUSES OF SUBSTANCE ABUSE: Drug Effects and Biological Responses 223

CATECHOLAMINES The catecholamines ing the initiation-consolidation phase, behaviors are a series of structurally similar amines (e.g., DO- that lead to the taking of a drug are gradually PAMINE, epinephrine, NOREPINEPHRINE that func- strengthened through operant and classical condi- tion as hormones, as NEUROTRANSMITTERS, or both. tioning processes and by biochemical changes in Catecholamines are produced by the enzymatic the brain. The drug effects include a cascade of conversion of tyrosine, sharing the chemical root of discriminative or internally appreciated drug cues 3,4-dihydroxyphenylethanolamine. The three (i.e., subjective effects). The presence of these cues major catecholamines (mentioned above) derive often leads to associated autonomic responses and from sequential enzymatic reactions-tyrosine is reports of urges in humans. These responses and converted to dihydroxyphenylacetic acid (dopa); urges may result in an unfolding of a sequence of dopa, which is not an end product but a common behavioral and physiological events leading to con- intermediate (and the medication of choice for Par- tinued drug consumption. kinson’s disease), is converted to dopamine; dopa- After a pattern of chronic drug use is estab- mine is converted to noradrenaline (also called nor- lished, individuals may become tolerant to certain epinephrine); and noradrenaline is converted to effects of a drug. In addition, they may experience adrenaline (also called epinephrine). These sub- withdrawal effects when they stop taking a drug. stances are the neurotransmitters for the sympa- Withdrawal effects are often opposite to the drug- thetic neurons (nerve cells) of the autonomic ner- induced state and usually involve some form of vous system, as well as for three separate broad sets dysphoria—a state of illness and distress. Over of brain neuropathways. time, withdrawal effects become associated with FLOYD BLOOM stimuli in the environment, as was the case for the euphoric and other direct effects of the drug. Be- cause of operant and classical conditioning pro- cesses, these associated stimuli can then produce CATHINONE See Khat conditioned effects that are often characterized as urges or cravings, and that may trigger relapse. The underlying NEUROTRANSMITTER systems CAUSES OF SUBSTANCE ABUSE This within the brain, subserving these behavioral fea- section contains articles on some of the many fac- tures of drug effects, are just beginning to be under- ESEARCH on the neural substrates of tors thought to contribute to substance use, abuse, stood. Early R reward in general used electrical brain stimulation and dependence. It includes discussions of Drug as the reward. For example, Olds (1977) found Effects and Biological Responses, Genetics Learn- that rats would press a lever to receive a brief elec- ing, and an article on the Psychological (Psychoan- trical pulse to the hypothalamus; rats would press alytic) Perspective. Sociocultural causes and Vul- this lever to such an extent that they did not engage nerability, are discussed in several articles in consummatory reward activities such as eating throughout the Encyclopedia, for example, Eth- and drinking. Subsequent research indicated that nicity and Drugs, Families and Drug Use, Poverty activation of certain systems in the brain, namely and Drugs. See also the article Disease Concept of the mesolimbic and nigrostriatal dopaminergic sys- Alcoholism and Drug Addiction and the section on tems, were most sensitive to brain stimulation rein- Vulnerability. forcement. Several theories have been suggested to explain the importance of the brain reward system for the survival of species (Conrad, 1950; Glick- Drug Effects and Biological Responses man & Schiff, 1967; O’Donahue & Hagmen, 1967; Although many indirect factors lead to an individ- Roberts & Carey, 1965). ual abusing drugs, a person’s response to the effects Further research demonstrated that most drugs of the drugs themselves contribute both to their use of abuse lower the threshold for this brain stimula- and abuse. These drug effects should be considered tion reward, thus suggesting that such drugs may in relation to four phases of drug use: (1) initiation- activate the same, or similar, reward pathways (see consolidation, (2) maintenance, (3) repeated with- Koob & Bloom, 1988). As will be seen, further- drawal and relapse, and (4) postwithdrawal. Dur- more, the reinforcing effects of the drugs them- 224 CAUSES OF SUBSTANCE ABUSE: Drug Effects and Biological Responses selves—that is, effects that lead individuals to take anxiety. Over the first few hours, drug craving is the drugs—are directly mediated by these REWARD replaced by an intense desire for sleep. During this systems. The fact that many drugs induce activa- time, the individual may use ALCOHOL, tion of these systems may indicate a mechanism BENZODIAZEPINES,orOPIATES to induce sleep. Fol- underlying the addiction-related effects of drugs of lowing the crash, hypersomnolence (excessive abuse. sleep) and hyperphagia (excessive appetite) de- velop. Following the first few days of hypersomno- COCAINE AND OTHER STIMULANTS lence and hyperhagia, other symptoms emerge that are the opposite of the effects of cocaine— COCAINE is an indirect catecholamine agonist withdrawal symptoms. During this withdrawal pe- that acts by blocking the reuptake of monoamines, riod, which lasts three to ten days, individuals ex- including DOPAMINE (DA), NOREPINEPHRINE (NE), perience decreased energy, limited interest in their and serotonin (5-HT). During the process of reup- environment, and anhedonia. They are also take, the previously released neurotransmitter is strongly susceptible to RELAPSE and starting an- actively transported back from the synaptic cleft other binge cycle (Gawin & Ellinwood, 1988; into the presynaptic terminal of the neuron where Gawin & Kleber, 1986; Jaffe, 1985). This phase is the neurotransmitter was produced and released followed in time by the extinction phase, in which (Pitts & Marwah, 1987). In contrast to cocaine, relapse to cocaine use is prevented. During the AMPHETAMINE acts not only by inhibiting uptake, extinction phase, brief periods of drug CRAVING but also by releasing catecholamines from newly also occur. These episodes of craving are thought to synthesized storage pools from the presynaptic ter- be triggered by conditioned stimuli that were previ- minal of the neuron (e.g., Carlsson & Waldeck, ously associated with the drug. If the individual 1966). experiences these cues without the associated drug Amphetamine and cocaine are both potent PSY- effects—that is, resists relapse—then the ability of CHOMOTOR stimulants. They produce increased these cues to elicit drug cravings should diminish alertness and energy and lower ANXIETY and social over time, which in turn should lessen the probabil- inhibitions. The acute reinforcing actions of the ity of relapse (Gawin & Ellinwood, 1988). stimulants are primarily determined by their aug- As already noted, acute administration of co- mentation of DA systems. With prolonged con- caine produces profound inhibition of dopamin- sumption: (1) acute TOLERANCE becomes substan- ergic uptake (Fuxe, Hamberger, & Malmfors, tial, and (2) the individual starts to regularly 1967). The relation between cocaine dose and DA consume higher and many more doses if the re- levels is linear; therefore, larger amounts of cocaine sources are available. Over time, in high-dose regi- result in higher extracellular DA levels. These levels mens, the behavioral pattern of use becomes stereo- of DA are thought to underlie the reinforcing effects typed and restricted. In settings of low availability, of cocaine (Gawin & Ellinwood, 1988). Because the individual focuses on the acquisition and con- both cocaine and amphetamine result in enhanced sumption of the drug. These effects of stimulants dopaminergic neurotransmission, thereby produc- occur within weeks or months of continued use. ing elevated extracellular levels of catecholamines, The individual may also start ‘‘bingeing’’ during these elevated neurotransmitter levels would pre- this period. A binge is characterized by the read- sumably have local time-dependent inhibitory ef- ministration of the drug approximately every ten to fects on the enzyme tyrosine hydroxylase, which is twenty minutes, resulting in frequent mood swings responsible for controlling their rate of synthesis. (i.e., alternations of highs and lows). Cocaine Therefore, this substrate-inhibitory mechanism binges typically last twelve hours, but may last as might compensate for the increased catecholamine long as seven days. levels and activity by decreasing their synthesis. It has been proposed that cocaine abstinence Galloway (1990) found that cocaine, in a way that consists of a three-phase pattern: crash, WITH- was consistent with this proposition, decreased DA DRAWAL, and extinction (Gawin & Kleber, 1986; synthesis in a dose-dependent manner in various Gawin & Ellinwood, 1988). The crash phase im- brain regions. mediately follows the cessation of a binge and is Chronic, intermittent stimulant use (e.g., 1–2 characterized by initial depression, agitation, and injections per 24 hrs) produces other behavioral CAUSES OF SUBSTANCE ABUSE: Drug Effects and Biological Responses 225 effects besides euphoria and increased energy: White, 1989). However, seven days after termina- (1) stimulant psychosis, which is characterized by tion of daily cocaine injections, when cocaine-in- paranoia, anxiety, stereotyped compulsive behav- duced sensitization is still fully present, somatoden- iors, and HALLUCINATIONS, and (2) sensitization or dritic autoreceptors are no longer reduced in ‘‘reverse tolerance.’’ Sensitization refers to the fact sensitivity (Zhang, Lee, & Ellinwood, 1992). Evi- that the effects of cocaine are progressively en- dence regarding changes in terminal autoreceptor hanced. Although sensitization has been demon- sensitivity is mixed. Dwoskin et al. (1988) found strated in animal studies, it is not clear whether it that terminal autoreceptors were supersensitive, occurs in humans. There are nevertheless several not subsensitive, to a DA agonist twenty-four hours possible explanations for sensitization. First, be- following chronic cocaine use. Henry et al. (1989) cause cocaine blocks dopaminergic, uptake, chron- also found that terminal autoreceptors were super- ic cocaine use could somehow harm the functioning sensitive to DA following chronic daily cocaine in- of the dopamine uptake mechanism; the evidence jections. Although autoreceptor supersensitivity regarding this possibility is equivocal (Zahniser et cannot explain sensitization, it is a possible mecha- al., 1988b). Second, sensitization could also be the nism underlying the previously described an- result of enhanced dopaminergic release, similar to hedonia and anergy experienced by cocaine abusers that found to be chronic after amphetamine admin- during the withdrawal phase. Fourth and last, istration (Castaneda. Becker, & Robinson, 1988). there could be an increase in the number or sensi- Akimoto, Hammamura, & Otsuki (1989) found tivity of postsynaptic DA receptors. The evidence enhanced DA release in the striatum one week fol- regarding this hypothesis is also mixed (Zahniser et lowing chronic cocaine administration. Similar al., 1988a). For example, Peris et al. (1990) found data has been obtained by others (Kalivas et al., an increased number of postsynaptic D2 receptors 1988; King et al., 1993; Pettit el al., 1990). Co- in the NUCLEUS ACCUMBENS one day following ces- caine levels in blood and cerebrospinal fluid have sation of chronic cocaine administration; however, also been reported to be elevated in chronically after one week the number of receptors had re- treated subjects (Reith, Benuck, & Lajtha, 1987); turned to normal levels. In contrast, there is some however, these increases cannot account for most of evidence that postsynaptic DA receptors are de- the change in DA release (Pettit et al., 1990). Fur- creased following chronic cocaine use. Volkow et thermore, some researchers report no consistent al. (1990) found lower uptake values for [18 effects in this regard. Third, there could be changes F]n-methylspiroperidol in human cocaine users in autoreceptor sensitivity following chronic co- who had been abstinent for one week, as compared caine administration. Autoreceptors for particular with normal subjects. Uptake values were similar, neurotransmitters are those receptors that reside on however, for normal subjects and cocaine users thesameNEURON that releases the who had been abstinent for one month. NEUROTRANSMITTER. The autoreceptors on the so- In contrast with these results, Yi and Johnson matodendritic area of neurons regulate impulse (1990) have reported that chronic intermittent co- flow along the neuron, whereas autoreceptors on caine use impairs the regulation of synaptosomal the terminal regions of the neuron regulate the 3[H]-DA release by DA autoreceptors, thus sug- amount of neurotransmitter released per impulse gesting a subsensitivity or down-regulation of re- and neurotransmitter synthesis (Cooper, Bloom, & lease-modulating DA autoreceptors seven days af- Roth, 1986). Sensitization could, therefore, be the ter chronic cocaine administration. The differences result of decreased autoreceptor sensitivity. Such in the results of the Yi and Johnson (1990) and the subsensitivity would result in either increased im- Dwoskin et al. (1988) studies may be due to differ- pulse flow, if somatodendritic autoreceptors were ences in the administration schedules or in the pro- altered, or increased neurotransmission/synthesis, cedures used to measure autoreceptor sensitivity. if terminal autoreceptors were altered. The net ef- In contrast with the changes induced by inter- fect, in either case, would be an increase in dopa- mittent but chronic drug administration, a regimen minergic neurotransmission. There is some evi- that involves the chronic administration of steady- dence of decreased somatodendritic autoreceptor state levels of drug results in decreased DA overflow sensitivity twenty-four hours after the cessation of when striatal brain slices are perfused with cocaine. chronic cocaine administration (Henry, Greene, & This result may be due to the development of su- 226 CAUSES OF SUBSTANCE ABUSE: Drug Effects and Biological Responses

persensitive autoreceptors. Autoreceptor supersen- with the inconclusive results on cocaine, research sitivity would result in decreased dopaminergic ac- involving amphetamine is much clearer. First, tivity. There is some support for this hypothesis chronic METHAMPHETAMINE administration re- from research involving the chronic administration duces the number of DA uptake sites (Ricaurte, of amphetamine. Lee and colleagues (Lee, Ellin- Schuster, & Seiden, 1980; Ricaurte, Seiden, & wood, & Nishita, 1988; Lee & Ellinwood, 1989) Schuster, 1984). Second, DA and tyrosine-betahy- found that twenty-four hours after withdrawal droxylase levels are reduced for extended periods from a week of continuous administration of am- following chronic amphetamine administration phetamine, all indicators of autoreceptor activity (Ricaurte et al., 1980, 1984). Third, there is evi- demonstrated a pronounced subsensitivity. Similar dence of neuronal degeneration, chromatolysis, results have been found following the continuous and decreased catecholamine histofluorescence infusion of cocaine (Zhang et al., 1992). However, (Duarte-Escalante & Ellinwood, 1970). by the seventh day of withdrawal (a period associ- As with cocaine’s effects on DA reuptake, co- ated with anergia, irritability, and ‘‘urges’’ in hu- caine also blocks 5-HT reuptake. Since activation man stimulant abusers), nigrostriatal somatoden- of 5-HT postsynaptic receptors affects neurotrans- dritic autoreceptors progress from an initial mission in neurons that release DA, this blockade subsensitivity to a supersensitive state, whereas ter- prolongs the inhibitory effects of 5-HT on dopa- minal autoreceptors are normosensitive. The minergic neurotransmission (Taylor & Ho, 1978). changes in sensitivity of receptors clearly depend However, cocaine also inhibits the firing rates of on the way the drug is administered and which dorsal raphe 5-HT neurons (Cunningham & receptors are evaluated. The evidence, moreover, is Lakoski, 1988, 1990). Thus, acutely the net effect not always consistent. of cocaine on 5-HT neurotransmission in the nu- There is also evidence that chronic cocaine ad- cleus accumbens will depend on the relative contri- ministration produces neurotoxicity—i.e., actual butions of uptake inhibition, which would increase destruction of neural tissue—although there are synaptic 5-HT, and inhibition of neuronal firing, conflicting results and the relationship of this neu- which would decrease synaptic 5-HT. Broderick rotoxicity to the addiction process is unclear. For (1991) reported that acute, subcutaneous injec- example, Trulson and colleagues (1986) demon- tions of cocaine resulted in a dose-dependent in- strated decreased tyrosine hydroxylase activity crease in DA levels, as measured by dialysis of the sixty days after chronic cocaine treatment (see also nucleus accumbens. This suggests a decrease in Trulson & Ulissey, 1987), thereby indicating de- 5-HT levels that may result from activation of creased DA synthesis. (Tyrosine hydroxylase is the somatodendritic 5-HT autoreceptors located in the rate-limiting step in the biosynthesis of DA; Cooper dorsal raphe nucleus. Acute cocaine administration el al., 1986.) Similarly, Taylor and Ho (1978) has indeed been reported to almost completely in- found that chronic administration of cocaine de- hibit the basal firing rate of dorsal raphe serotoner- creased tyrosine hydroxylase activity in the cau- gic neurons. date, but Seiden and Kleven (1988) were unable to As with the effects of chronic amphetamine ad- replicate the findings of Trulson. As contrasted ministration on the functioning of DA systems, CAUSES OF SUBSTANCE ABUSE: Drug Effects and Biological Responses 227 chronic methamphetamine administration has violent and aggressive behavior. After extensively been shown to induce pronounced long-term reviewing the literature, Brown and Linnoila changes in tryptophan hydroxylase activity, as well (1990) concluded that low levels of CSF 5-HIAA as in 5-HT content and number of uptake sites are related to disinhibition of aggressive/impulsive (Ricaurte et al., 1980). The effects of chronic co- behavior and not to antisocial acts in and of them- caine on serotonergic functioning are less well es- selves. The transition to high-dose cocaine use tablished. For example, Ho et al. (1977) found might be considered impulsive behavior because decreased levels of 5-HT following chronic cocaine the individual is focusing on the immediate, short- administration. Seiden and Kleven (1988). how- term advantages of drug consumption while ignor- ever, failed to find any effects of chronic cocaine on ing the long-term advantages of drug abstinence. the biosynthesis of serotonin. Hence, the 5-HT receptor supersensitivity, and re- Some of these discrepancies can be reconciled by sulting inhibition of 5-HT neurotransmission, may the fact that different chronic dosing regimens pro- be a contributing factor to the development of the duce different changes in 5-HT systems. For exam- high-dose, bingelike pattern of cocaine abuse. ple, Cunningham and colleagues found that daily injections of cocaine resulted in an increased sensi- tivity of dorsal raphe somadendritic 5-HT autore- OPIATES ceptors to cocaine’s inhibitory effects as measured The OPIATES are derived from the POPPY plant by electrophysiological techniques (Cunningham & and have been used for centuries. A number of Lakoski, 1988, 1990). These results are consistent types of endogenous opiate RECEPTORS have been with the behavioral data of King and colleagues identified and their locations mapped. There are (1993a), who found that daily cocaine injections high concentrations of opiate receptors in the cau- produced an enhanced inhibitory effect of NAN- date nucleus, nucleus accumbens, periventricular 190 on cocaine-induced locomotion and an en- gray region, and the nucleus arcuatus of medobasal hanced excitatory effect of 8-OH-DPAT on loco- hypothalamus (Pert, Kuhar, & Snyder, 1975, motion. In contrast with these results, the continu- 1976). These areas may be differently involved in ous infusion of cocaine via an osmotic minipump the reinforcing, aversive, and dependence-produc- results in a decreased sensitivity of dorsal raphe ing effects of the opiates. Furthermore, different somadendritic 5HT autoreceptors and a decreased receptor subtypes may mediate the different effects excitatory effect of 8-OH-DPAT on locomotion of the opiates. (King, Joyner, & Ellinwood, 1993b; King et al., The opiates produce ANALGESIA, changes in 1993b). mood (e.g., euphoria and tranquility), drowsiness, Interestingly, the depletion of 5-HT or reduction respiratory depression, and nausea (Jaffe & Martin, of 5-HT neurotransmission is associated with im- 1990). These drugs also reduce motivated behav- pulsive behavior. For example, Linnoila et al. (1983) found that violent offenders with a diagno- ior; there is a decrease in appetite, sexual drive, and aggression. Intravenous administration of opioids sis of PERSONALITY DISORDER associated with im- pulsivity had lower levels of 5-hydroxyindoleacetic results in initial effects of flushing of the skin and acid (5-HIAA, the metabolite of 5-HT) than other sensations in the abdominal regions that have been offenders. Bouilliouc et al. (1978, 1980) reported likened to a sexual orgasm (Jaffe, 1990). suppressed 5-HIAA levels in the cerebrospinal fluid With continuous use of opioids, marked toler- (CSF) of XXY-chromosome (aggressive) institu- ance develops to some, but not all, of the effects of tionalized criminals. Lithium has been successfully these drugs. Tolerance to opioids is generally char- used to treat violent offenders (Sheard, 1971, acterized by a shorter duration of effect and atten- 1975; Sheard et al., 1976; Tupin et al., 1973). uated analgesia, euphoria, and other CNS- Lithium treatment produces increases in CSF depressant effects; however, there is less tolerance 5-HIAA in humans (Fyro et al., 1975; Sheard & to the lethal effects of opiates. Therefore, if an Aghajanian, 1970), and central nervous system individual administers ever larger doses to obtain (CNS) 5-HT in nonhumans (Sheard & Aghajanian, the same effect (e.g., the rush or high), this may 1970; Mandell & Knapp, 1977); this indicates that increase the probability of a lethal overdose (Jaffe, increases in 5-HT are associated with decreases in 1990). 228 CAUSES OF SUBSTANCE ABUSE: Drug Effects and Biological Responses

Although the course and severity of withdrawal nucleus accumbens (Di Chiara & Imperato, 1988). symptoms following opiate abstinence depend on Second, although opiates generally produce seda- which opiate was used, the dose and pattern of tion, low doses of systemic morphine increase loco- consumption, the duration of use, and the interdose motor activity (Domino, Vasko, & Wilson, 1976). interval, the opiate withdrawal syndrome follows Third, injections of morphine into the ventral teg- the same general progression. Approximately eight mental area produce circling behavior (Holmes, to twelve hours after the last dose, individuals ex- Bozarth, & Wise, 1983); injections of opiates into perience yawning, lacrimation, and rhinorrhea; the ventral tegmental area produce increased loco- twelve to fourteen hours after the final dose, they motion, as with systemic injections of opiates, may fall into a fitful, restless sleep and awaken thereby suggesting increased dopaminergic trans- feeling worse than when they went to sleep. With mission (Blaesig & Herz, 1980). Fourth, selective the continuation of opiate withdrawal, they experi- lesions of the dopaminergic system decrease opiate ence increasing dysphoria, anorexia, gooseflesh, ir- self-administration, although not to the extent of ritability, agitation, and tremors. At the peak inten- affecting cocaine self-administration (Bozarth & sity of the withdrawal symptoms, they may Wise, 1985). Fifth, rats learn to self-administer experience exacerbated irritability, insomnia, in- opiates directly into the ventral tegmental area tense anorexia, weakness, and profound depres- (Bozarth & Wise, 1981), rats also inject opiates sion. Common symptoms include alternating cold- into the nucleus accumbens and the lateral hypo- ness and intense skin flushing and sweating, thalamus (Goeders, Lane, & Smith, 1984). Sixth, vomiting and diarrhea (Jaffe, 1990). This pattern administration of the D1 antagonist SCH 23390, of symptoms indicates that during the initial with- but not the D2 antagonists sulpiride and spiperone, drawal phase there is a generalized CNS hyper- block the reinforcing effects of morphine. excitability. Thus, the addicted opiate abuser con- Ettenberg et al. (1982) found no effect of alpha tinues to recycle opiate use to both avoid or termi- flupenthixol, primarily a D2 antagonist, on heroin nate the wtihdrawal symptoms, and to reexperience self-administration, although the same doses de- the euphoric effects. This powerful combination of creased cocaine self-administration. Similar results euphoria, tolerance, and withdrawal can lead to have been reported by others using other dopamin- profound levels of addiction. ergic antagonists (De Wit & Wise, 1977). Thus, Studies have found that rats and monkeys will both place preference and self-administration pro- self-administer opioids, thus indicating that these cedures indicate that opiates are not reinforcing drugs serve as reinforcers (Koob & Bloom, 1988). through D2 receptors, which are vital to stimulant Chronic opioid administration results in physical reinforcement. These results indicate that opiate dependence, as demonstrated by the presence of a reinforcement is at least partially independent of withdrawal syndrome following drug cessation. the D2 stimulant type of reinforcement, yet they do Most clinicians hold the classic position that PHYSI- act through a dopaminergic mechanism to induce a CAL DEPENDENCE (i.e., avoidance of withdrawal significant part of their effects. symptoms) is a major motivating factor in opiate Chronic administration of opiates produces sev- self-administration, but evidence indicates that re- eral behavioral and neurochemical effects that may inforcement and withdrawal are separate pro- be related to their reinforcing effects. First, chronic cesses. Bozarth and Wise (1984) demonstrated that administration of MORPHINE results in the augmen- rats will self-administer morphine into the ventral tation of the behavioral effects of low doses of mor- tegmental area without the presence or develop- phine. In other words, subjects undergoing chronic ment of any apparent withdrawal symptoms. opiate administration become sensitized to the be- Chronic administration of morphine into the peri- havioral effects of morphine (Ahtee, 1973, 1974). aqueductal gray area, however, produces signs of a Second, chronic morphine administration results in strong withdrawal syndrome. decreased DA turnover in the striatum and limbic Several lines of evidence indicate that dopamin- system during withdrawal (Ahtee & Attila, 1980, ergic neurotransmission may partially mediate the 1987). Third, in mice withdrawn from morphine, reinforcing effects of opiate administration. First, the synthesis and release of DA are attenuated injection of met-enkephalin into the ventral teg- (Ahtee et al., 1987); similar results have been ob- mental area results in increases in DA release in the tained with human heroin addicts in which CSF CAUSES OF SUBSTANCE ABUSE: Drug Effects and Biological Responses 229 homovanillic acid concentrations were decreased during chronic administration, there is functional (Bowers, Kleber, & Davis, 1971). down-regulation of both the dopaminergic and se- These results indicate that during chronic mor- rotonergic systems. Upon withdrawal from opiates, phine administration there is a down-regulation of there is a subsequent supersensitivity of the dopa- the dopaminergic system and a neuroadaptation to minergic system. This dopaminergic supersensitiv- this depletion. During withdrawal from opiate ad- ity may be involved in opiate craving and general ministration there is an augmentation of dopamin- irritability during withdrawal. ergic mechanisms. Indeed, during withdrawal rats are sensitized to the behavioral effects of apomor- (SEE ALSO: Addiction:Concepts and Definitions; phine (Ahtee & Atilla, 1987), and small doses of Brain Structures and Drugs; Opioids:Complica- morphine increase striatal homovanillic acid levels tions and Withdrawal; Research:Animal Model; more in withdrawn than in control rats, thereby Tolerance and Physical Dependence; Wikler’s indicating that the dopaminergic system is sensi- Pharmacologic Theory of Drug Addiction) tized at this point (Ahtee, 1973, 1974). Thus, some of the withdrawal symptoms (e.g., irritability and BIBLIOGRAPHY dysphoria) may be mediated by changes in dopa- minergic functioning. AHTEE, L. (1980). Chronic morphine administration de- Acute administration of opiates increases the creases 5-hydroxytryptamine and 5-hydroxyindole- synthesis of 5-HT and the formation of 5-HIAA, acetic acid content in the brain of rats. Med Bio, 58, and these effects are eliminated by the administra- 38–44. tion of opiate antagonists (Ahtee & Carlsson, AHTEE, L. (1974). Catalepsy and stereotypes in rats 1979), thus suggesting that opiate administration treated with methadone: Relation to striatal dopa- results in increased serotonergic functioning. In- mine. Euro J. Pharmacol, 27, 221–230. deed, acute administration of dynorphin-(1–13), AHTEE, L. (1973). Catalepsy and stereotyped behaviour while it decreases striatal dopamine, actually in- in rats treated chronically with methadone: Relation creases striatal serotonin (Broderick, 1987). This to brain homovanillic acid content. J Pharm Pharma- increased serotonergic functioning may contribute col, 25, 649–651. to the ‘‘post-consummatory calm’’ produced by AHTEE,L.&ATILLA, L. M. J. (1987). Cerebral mono- opiate drugs: Increasing serotonergic functioning amine neurotransmitters in opioid withdrawal and would tend to inhibit incentive-motivated behav- dependence. Med Bio, 65, 113–119. iors and produce a calm, tranquil state. Indeed, the AHTEE,L.&ATILLA, L. M. J. (1980). Opioid mecha- atypical anxiolytic drug buspirone exerts its anxi- nisms in regulation of cerebral monoamines in vivo. In ety-reducing effects via serotonergic activation. O. Eraenkoe, S. Soinila, & H. Paevaerinta (Eds.), During withdrawal from chronic opioid admin- Histochemistry and Cell Biology of Autonomic Neu- istration, 5-HIAA levels are decreased (Ahtee, rons, SIF Cells, and Paraneurons. Advances in Bio- 1980; Ahtee et al., 1987). This pattern of seroto- chemical Psychopharmacology, 25, 361–365. New nin results could well cause increased impulsivity York: Raven Press. and a higher probability of relapse, similar to that AHTEE, L., & CARLSSON, A. (1979). Dual action of meth- described earlier in relation to the psychomotor adone on 5-HT synthesis and metabolism. Naunyn- stimulants. Schmiedeberg’s Arch Pharmacol, 307, 51–56. In summary, like cocaine, the opiates are con- AHTEE, L., ET AL. (1987). The fall of homovanillic acid sumed because of their reinforcing properties. and 5-hydroxyindoleacetic acid concentrations in These reinforcing properties are the result of acti- brain of mice withdrawn from repeated morphine vation of endogenous opiate receptors; further- treatment and their restoration by acute morphine more, activation of the dopaminergic system modu- administration. J Neutral Trans, 68, 63–78. lates the reinforcing effects of opiates. During AKIMOTO, K., HAMMAMURA, T., & OTSUKI, S. 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release by D2 autoreceptors. Pharmacol Biochem Be- may also influence an individual’s response to drug hav, 36, 457–461. ingestion by either heightening pleasant sensations ZAHNISER, N. R., ET AL. (1988a). Repeated cocaine ad- or suppressing unpleasant ones, such as the ‘‘flush- ministration results in supersensitive nigrostriatral ing’’ reaction to alcohol (which can include ele- D-2 dopamine autoreceptors. In P. M. Beart, G. vated skin temperature, increased pulse rate, head- Woodruff, & D. M. Jackson (Eds.), Pharmacology ache, and nausea) and the queasiness caused by and Functional Regulation of Dopaminergic Neurons, opioids. An individual’s response to drugs may also London: Macmillan. be determined by genetically influenced differences ZAHNISER, N. R., ET AL. (1988b). Sensitization to cocaine in the receptor proteins on which the drugs act, in the nigrostriatal dopamine system. In D. Clouet, K. differences in the enzymes that metabolize these Asghar, & R. Brown (Eds.), National Institute on drugs, or differences in the proteins that remove Drug Abuse Research Monograph, Washington, DC: these drugs from their sites of action. U.S. Government Printing Office. ZHANG, H., LEE, T. H., & ELLINWOOD,E.H.JR. (1992). GENETIC PREDISPOSITION The progressive changes of neuronal activities of the nigral dopaminergic neuron upon withdrawal from Researchers suspect that a tendency to alcohol- continuous infusion of cocaine. Brain Research, 594, ism can be inherited, and studies of twins, adopted 315–318. children of alcoholics, and half siblings of alcoholic EVERETT H. ELLINWOOD parents have confirmed these suspicions, although G. R. KING a direct genetic link has yet to be found. Studies have shown that the first-degree relatives of alco- holics are fourteen times more likely to be addicts themselves. Even when the children of alcoholic Genetic Factors Why do some people be- parents are adopted into new families, their risk of come alcoholics or drug addicts, while others who becoming alcoholics is still far higher if one of their try the same substances, even to excess, avoid the biological parents was an alcoholic. All of these snare of dependence? Could there be a genetic basis for such behavior? Given the strong familial pat- statistics are especially significant for males, who terns of substance abuse that often occur, the an- seem more than twice as likely as females to inherit swer may be yes—in some cases. Evidence points drug and alcohol dependence. Animal studies indicate that an inherited differ- toward at least one inheritable form of ALCOHOL- ence in nerve cell membranes may be a factor in ISM; a genetic vulnerability to drug abuse has not been confirmed by research, although it may exist. alcoholism. Alcohol lowers the viscosity of the Researchers know that many environmental and nerve-cell membrane, which may interrupt neural psychological factors are implicated in addictions, excitation or interfere with the membrane proteins including a dysfunctional family, poor academic involved with neurotransmission. Studies per- performance, delinquent behavior, and perhaps formed on two genetically different strains of mice most importantly, easy access to drugs. The showed that alcohol-sensitive mice had nerve-cell abuser’s personality is also a factor, and alcoholics, membranes that were more susceptible to the vis- in particular, often exhibit similar traits: an inabil- cosity-lowering effects of alcohol than mice that ity to handle frustration, extreme sensitivity, poor were less susceptible to alcohol (Goldstein, 1982). self-image, and isolation. While some of these qual- Another genetic factor may be the alteration of ities may be inherited, they do not prove a direct membrane-bound neuronal enzymes, such as so- genetic link to alcohol or drug abuse—they simply dium-potassium ATPase, an ion pump that is re- act as a petri dish in which self-destructive behav- sponsible for the movement of sodium-potassium ior can develop. ions through the cell membrane. Alcohol inhibits Physiology, on the other hand, is determined the sodium-potassium ATPase, leading to specula- directly by genetic inheritance, and it is in this tion that there may be a genetic predisposition to arena that scientists have begun to discover what alcoholism in people who show an atypical resis- may be an inborn predispostion to some forms of tance to the alcohol-induced inhibition of this en- substance abuse-particularly alcoholism. Heredity zyme. CAUSES OF SUBSTANCE ABUSE: Genetic Factors 233

Alcohol also affects the proteins that make up Asians, alcohol dehydrogenase is more active than RECEPTORS, including the NMDA receptor, which in Caucasians; it rapidly converts alcohol to acetal- mediates neuronal excitation following release of dehyde. In these same Asian populations, there is a the NEUROTRANSMITTER glutamate and is the major genetic deficiency in acetaldehyde dehydrogenase, excitatory pathway in the brain, and the GABA so that acetaldehyde accumulates and produces the receptor, the major inhibitory pathway in the cen- unpleasant flushing reaction described above. This tral nervous system. Changes in either of these same rapid and unpleasant accumulation of acetal- receptor proteins could predispose an individual to dehyde is what alcoholic patients risk when they alcoholism by altering their response to the drug. take the drug DISULFIRAM (Antabuse) to deter them The A1 allele. Alcohol interferes with the re- from drinking. The acetaldehyde dehydrogenase lease of the neurotransmitters NOREPINEPHRINE and deficiency may actually deter many Asians from DOPAMINE. One promising area of research indi- abusing alcohol. Asians that do become alcoholics cates that some severe forms of alcoholism (and do not exhibit the acetaldehyde dehydrogenase de- possibly drug abuse) may occur in subjects who ficiency common in the general Asian population. have up to 30 percent fewer DOPAMINE receptors in their brains than usual; this deficiency is caused by PSYCHIATRIC DISORDERS a variant gene for the dopamine D2 receptor, called the A1 allele. In addition to a physiology that changes their People with this trait may be far less able than metabolization of and reaction to drugs and alco- most to find enjoyment in everyday activities and hol, certain psychiatric diagnoses are regularly have much greater difficulty coping with the overrepresented among alcoholics and drug depen- stresses of life. One researcher, in fact, has tied the dents. These include depression, anxiety disorders, presence of the A1 allele to a condition he calls the and ANTISOCIAL PERSONALITY, all of which may be ‘‘reward-deficit syndrome’’ (Blum et al.). Posses- inherited. When these complications are factored sion of the A1 allele is identified with a range of in, it becomes difficult to distinguish genetically impulsive behaviors, possibly caused by a brain based substance abuse from risky, self-destructive chemistry that spurs people to substance abuse and behavior caused by mental illness. other self-destructive behaviors in the search for neurochemical satisfaction. SAMPLE AND CONTROL VARIABLES Because alcohol and many other drugs release a flood of dopamine into the brain, addicts may turn Many factors affect a person’s susceptibility to to alcohol and drugs to get the feelings they crave. drug abuse, which makes studying the genetic A smaller-than-usual number of dopamine recep- bases for addiction difficult, particularly where tors may also diminish or suppress the unpleasant drug addiction is concerned. Studies must match sensations many people feel when they become in- control and drug-abusing populations adequately, toxicated and heighten the inebriation, which in- and the sample size must be large enough to detect creases the likelihood that the substance will be small genotype changes from background influ- used again and in greater quantities. ences. Individual variables (such as severity of de- Predisposition against substance abuse. pendence) need to be consistent between research Genetic predisposition may also inhibit the devel- groups. It’s also difficult to determine whether an opment of alcoholism because heredity may deter- individual currently in the control group will ex- mine the way people metabolize alcohol. The major press addictive behavior in the future. For these chemical pathway for the metabolism of alcohol and other reasons, scientists have been unable to requires two enzymes: alcohol dehydrogenase, prove a definitive link between an individual’s ge- which converts alcohol to acetaldehyde; and acetal- netic makeup and a tendency to substance abuse, dehyde dehydrogenase, which converts acetalde- although they strongly suspect its existence, espe- hyde to acetic acid. Acetic acid is then converted by cially in the more severe forms of alcoholism and a series of enzymes to carbon dioxide and water. drug dependence. Recent studies indicate that there is a genetic difference in the enzymes involved in the alcohol (SEE ALSO: Conduct Disorder; Complications:Men- metabolism of Asians. In a significant proportion of tal Disorders; Epidemiology of Drug Abuse; Women 234 CAUSES OF SUBSTANCE ABUSE: Learning

and Substance Abuse; Vulnerability As Cause of WITHDRAWAL syndrome from absence of a drug). Substance Abuse) As a result of this signaling relationship, the CS produces conditioned responses (CRs), related to BIBLIOGRAPHY the US in use. In the area of drug use, a number of investigators have suggested that environmental BLUM, K., CULL, J. G., BRAVERMAN, E. R., & COMINGS, events that signal upcoming withdrawal or drug D. E. Reward Deficiency Syndrome. American Scien- use in humans elicit CRs—which motivate further tist. http://www.sigmaxi.org/amsci/Articles/ drug taking (Baker, Morse, & Sherman, 1987). 96Articles/Blum-full.html. Operant conditioning involves learning about GOLDSTEIN, D., CHIN, J., & LYON, R. (1982). Ethanol contingencies between behaviors and their out- disordering of spin-labeled mouse brain membranes: comes. A typical operant conditioning situation sets Correlation with genetically determined ethanol sen- up contingencies between three different events—a sitivity in mice. Proceedings of the National Academy response; the outcome of that response (the reward of Sciences, U.S.A., 79, 4231–4233. or reinforcer); and the stimulus situation in which HESSELBROCK, M. M., & KEENER, J. (1985). Psychopa- that response—outcome relationship is established thology in hospitalized alcoholics. Archives of General (the discriminative stimulus). Drugs of abuse func- Psychiatry, 42, 1050–1055. tion as potent reinforcers for human addicts, since ROUNSAVILLE, B., WEISSMAN, M., KLEBER, H., & WILBER, a variety of behaviors are directed solely toward C. (1982). Heterogeniety of psychiatric diagnosis in their attainment and use. Consequently, under- treated opiate addicts. Archives of General Psychia- standing the rules governing the acquisition of op- try, 39, 161–166. erant behaviors directed toward drug reinforcers UHL, G. R., PERSICO, A. M., & SMITH, S. S. (1992). Cur- may be critical to understanding addiction. rent excitement with D2 receptor gene alleles in sub- Classical and operant conditioning processes stance abuse. Archives of General Psychiatry. may be activated simultaneously during drug seek- GEORGE R. UHL ing and self-administration. Events that have con- REVISED BY AMY LOERCH STRUMOLO sistently signaled drug use may eventually come to evoke CRs in the form of craving—urges to use the drug. In this way, signals of drug use may act as discriminative stimuli motivating the drug user to Learning The role played by learning factors begin drug-seeking behavior. For example, walk- in drug and alcohol abuse has recently received ing past a known dealer might act as a CS for a much attention. Two basic learning mechanisms heroin addict, evoking the CR of craving for HER- are thought to be activated when an organism re- OIN. This craving response might then increase the peatedly self-administers a psychoactive substance. likelihood of behaviors that are rewarded by the First, classical conditioning processes are engaged desired drug effects—buying and preparing when environmental stimuli signal the upcoming heroin. effects of the drug. Second, operant conditioning occurs as an organism learns that particular behav- iors lead either to a drug reward or to punishment. OPERANT CONDITIONING WITH The effects of these two processes presumably in- DRUG REINFORCERS teract, and they are thought to influence repeated A large body of data shows that virtually all drug use and/or relapse to drug use following a drugs of dependence in human beings act as rein- period of abstinence. forcers for animals in operant-conditioning situa- Classical conditioning occurs when an organism tions. Typical studies on the reinforcing properties learns about a contingency between two events in of drugs involve rats or monkeys fitted with venous the external environment. The most common situa- catheters, through which a drug can be adminis- tion involves learning that a biologically neutral tered directly. Responses directed toward an object, event (the conditioned stimulus, CS, such as a light such as a lever, result in infusions of the drug. or a tone) signals the upcoming occurrence of a The basic finding of such studies has been that a biologically relevant event (the unconditioned wide variety of abused drugs—including COCAINE, stimulus, US, such as the effects of a drug or the MORPHINE, heroin, d-AMPHETAMINE, pentobarbi- CAUSES OF SUBSTANCE ABUSE: Learning 235

tal, and ALCOHOL—all serve to establish and main- preference for one response is taken to indicate a tain operant behaviors in animals. Other drugs preference for the drug associated with that re- with a lesser abuse potential in humans—such as sponse. A finding of particular interest from such aspirin, tricyclic antidepressants, hallucinogens, studies has been that cocaine appears to be pre- and opioid mixed agonist/antagonists—fail to sup- ferred not only to a number of other drugs but also port responding. to nondrug rewards such as food and social contact The degree to which a given drug of abuse rein- (Johanson, 1984)—but it is important to vary the forces behavior appears to depend more on the other reinforcers as well. Animals will choose less schedule of reinforcement of the drug than on its cocaine when the amount of food provided is intrinsic properties. A schedule of REINFORCEMENT greater or tastier. refers to the pattern of access provided to the rein- Far fewer systematic data on the reinforcing forcing event. For example, ratio schedules require properties of drugs have been collected with human an animal to make some predetermined number of subjects. A number of experiments have shown that responses before a reinforcer is given. Yet interval human subjects will work for tokens exchangeable schedules are set up so that responses are effective for OPIOIDS, alcohol, pentobarbital, DIAZEPAM at producing a reinforcer only after a delay follow- (Valium), and d-amphetamine. In addition, drug- ing the previous one. Reinforcers in ratio schedules abusing individuals will reliably produce arbitrary depend solely on the number of responses made; responses in a laboratory for immediate access to therefore, these schedules typically result in higher their drugs of choice. For example, heroin addicts response rates than interval schedules in which re- will repeatedly push a button to receive heroin in- sponses made too early are ineffective. Because re- jections and cocaine users will choose to perform inforcement schedules largely determine the rate of responses leading to cocaine injections over re- responding in a given situation, the abuse potential sponses that yield injections of saline (Henning- of the various drugs cannot be reliably assessed by field, Lukas, & Bigelow, 1986). comparing how quickly animals respond for each In sum, a body of both animal and human data substance. now exists that documents the way drugs of abuse Other techniques for making such comparisons can act as potent reinforcing events. The pattern of are available, however, and one technique for com- drug use exhibited by an individual user, however, paring the reinforcing properties of various sub- appears to depend as much on the schedule of drug stances involves calculating for each a so-called availability as on the particular properties of the breaking point under a fixed ratio schedule of rein- chosen drug. Therefore, predicting patterns of drug forcement. A fixed ratio schedule requires that an taking by humans will require a better understand- animal make a fixed number of responses (the ra- ing of the parameters of drug availability that exist tio) for each reinforcement received. For a given in the real world. drug dose, the breaking point is reached when a ratio too high to support responding is required. CLASSICAL CONDITIONING OF The breaking point achieved with the highest toler- DRUG-RELATED CUES able dose of a drug is often taken to be an index of that drug’s reinforcing properties. Drugs with the Conditioned Withdrawal Model. A number highest breaking point are considered to be the of investigators have advanced the idea that stimuli most reinforcing and hence to have the highest that reliably signal drug use elicit CRs that moti- abuse potential. Of drugs studied with such a pro- vate further drug use. For example, Wikler (1980) cedure, cocaine appears to have the highest break- noted that drug-free heroin addicts participating in ing point. For example, in some experiments, ani- discussions of drug use appeared to go through mals have been willing to press a lever up to 12,000 episodes of withdrawal as a result. Withdrawal re- times for a single dose of cocaine. fers to the unpleasant symptoms experienced by Choice experiments provide a second means for drug abusers following the abrupt cessation of drug comparing the reinforcing properties of two differ- use. Since the individuals discussed by Wikler had ent drugs. Animals in such designs are typically not used heroin for a long time, their withdrawal given a choice between two responses, each of symptoms could not have been the result of recent which leads to infusions of a different drug. A termination of the drug. Wikler proposed instead 236 CAUSES OF SUBSTANCE ABUSE: Learning that events that reliably signal the onset of natu- ing effect). Thus drug-related events cause drug rally occurring drug withdrawal become CSs capa- use by prompting the user to anticipate the pleasur- ble of evoking withdrawal symptoms on their own. able consequences. Like the models of Siegel and On future occasions, the mere presence of drug- Wikler, this theory proposes that events signaling related stimuli evoke conditioned withdrawal states drug use become conditioned stimuli that encour- that compel the person to counter these unpleasant age the drug user to initiate drug-seeking behav- feelings with drug use. iors. The models differ only in their characteriza- A second model that also invokes conditioning tion of the CR elicited by the drug-related events. was put forth by Siegel (1979), who proposed that Some evidence for this model lies in the observa- stimuli paired with drug use come to evoke condi- tion that many animals show drug-like responses to tioned compensatory responses, which oppose the stimuli paired with drug use, particularly when direct effects of the drug. As these drug-opposite stimulant drugs such as cocaine or d-amphetamine responses grow in size, over repeated conditioning are used. Furthermore, many researchers have experiences, they increasingly oppose the effects of found that animals that have stopped responding the drug. Therefore, addicts should find that, over for a drug reinforcer may resume responding fol- time, higher doses of the drug should be necessary lowing a small unearned dose of the drug (a prim- to achieve a given effect. This pattern is indeed ing dose). Environmental signals for drug use may observed, and it is known as drug tolerance. Ac- act in the same way as these priming doses. Some cording to Siegel’s model, drug-related cues en- research suggests that the stimuli associated with countered in the absence of drug taking produce rewards can elicit release of the neurotransmitter drug-opposite responses, which are not canceled by dopamine in the reward center of the brain, an the direct effects of the drug. These drug-opposite event that is produced by the effects of most re- responses are then thought to represent what the warding drugs. user experiences as withdrawal symptoms. Human Data. Since the 1970s, investigators According to Siegel’s model, conditioning can have collected data from a number of sources to motivate drug use in two ways. First, the with- document that stimuli associated with drug use in drawal symptoms generated by drug-related stim- humans acquire conditioned properties. Evidence uli following a period of abstinence can lead to drug for this statement has come from three primary use aimed at relieving these unpleasant effects. sources: Second, tolerance to the effects of a drug may moti- ● self-reports by addicts about the conditions vate a user to increase his or her level of use in an under which they experience craving and attempt to maintain a fixed level of drug effect. withdrawal Siegel’s model has not gone unchallenged. The ● attempts to establish drug conditioning in the primary problem appears to be that signals for laboratory drug use do not always produce drug-opposite re- ● assessments of responding to cues thought to sponses. Instead, such signals sometimes produce have become drug CSs in the natural responses that resemble the direct effects of the environment drug. The conditions determining whether CRs produced by drug-related stimuli are drug-like or Self-reports of Conditioned Effects. Many drug- drug-opposite have not been fully worked out. Yet abuse patients report drug craving and withdrawal drug-like responses (e.g., drug-induced euphoria) when faced with drug-related stimuli in their home to environmental stimuli may act to motivate drug environment. Wikler (1980) reported that drug- use as well. Some researchers have asserted that it free heroin addicts who returned to their home is the memory of drug-induced euphoria that is the (addiction) environment following a period of major factor contributing to continual drug use and treatment experienced symptoms of heroin with- relapse. drawal. O’Brien (1976) took a more systematic ap- Conditioned Incentive Model. Stewart, proach, interviewing heroin addicts and construct- deWit, and Eikelboom (1984) have proposed that ing a hierarchy of real-world events that result in conditioned drug stimuli provide the impetus for withdrawal feelings and craving for drug use. Such further drug use by producing mild drug-like ef- reports encouraged the idea that events that signal fects, which whet the appetite of the user (the prim- drug self-administration in the home environment CAUSES OF SUBSTANCE ABUSE: Learning 237 come to evoke conditioned responses, which moti- ments of withdrawal. Opiate-related stimuli, then, vate further drug use. Consequently, investigations appear to evoke both subjective and physiological have attempted to study this phenomenon under responses related to drug use; it appears likely that controlled laboratory conditions. such responses have a basis in prior conditioning. Laboratory Conditioning Studies. O’Brien and his Studies with alcoholics have yielded similar re- colleagues (1986) found that neutral stimuli paired sults. In a typical experiment, the reactions of alco- either with opiate administration or with opiate holics to the sight and smell of an alcoholic bever- withdrawal appeared to elicit conditioned with- age are compared with responses evoked by a drawal reactions. A number of later studies using nonalcohol (placebo) drink. The results show alcohol as the unconditioned stimulus have also greater craving/urges to drink induced by the alco- tended to find drug-opposite responses elicited by hol cue than by the control stimulus. Such data the experimental CS, although drug-like effects suggest that alcohol-related cues acquire the ability have been observed as well. to evoke conditioned responses. Studies of conditioning in the laboratory permit Classical/Operant Conditioning Interaction. the conclusion that such conditioning can occur as As mentioned earlier, much of the work on drug a consequence of drug-taking behavior by addicts. conditioning contains the implicit notion that clas- However, the contingency between potential CSs sical and operant learning effects combine to moti- and drug effects in the natural environment is un- vate drug use (or craving, even if no drug use doubtedly less precise than that programmed in the actually occurs). The most common idea is that laboratory. Therefore, affirming the role of drug- drug CSs evoke craving and withdrawal states, related stimuli in drug use requires a direct assess- which motivate the performance of drug-seeking ment of the effects of such events. behaviors. These behaviors are reinforced, in turn, Cue-Assessment Studies. To determine whether by the effects of the drug. Although much evidence events associated with drug use in the natural envi- suggests that psychoactive drugs of abuse have ronment acquire conditioned properties, many powerful reinforcing properties—and that signals studies have recreated typical drug-related stimuli of those drugs elicit conditioned responses—the in the laboratory. In such studies, subjects are ex- question remains as to whether these classically posed to audiotapes, videotapes, slides, and para- conditioned responses actually motivate drug-seek- phernalia with drug-related content, while physio- ing behaviors. logical and self-report responses are obtained. One technique used in a study to examine this Responses to such drug-related stimuli are then issue involved asking opiate abusers to describe the usually compared with the responses subjects make conditions under which they had relapsed to drug when they are exposed to comparable stimuli lack- use. After some probing, many patients were able ing a drug-specific content. So far, the majority of to describe specific events or stimuli that triggered cue-assessment studies have been carried out with craving and withdrawal leading to use. Such re- either opiate-abusing subjects or alcoholics, al- ports, however, suffer from the difficulty that retro- though there have also been some studies of cocaine spective self-reports from individuals reluctant to abusers. analyze their own behavior may be inaccurate. For opiate users, exposure to visual stimuli and Because of the ethical limitations imposed on paraphernalia typically associated with opioid use providing drugs to drug abusers, little laboratory have been found to produce subjective reports of work has been done to examine whether drug- craving for opiates and withdrawal, as well as other related cues increase drug self-administration. physiological changes associated with withdrawal, Some data have been collected by Ludwig, Wikler, including drops in skin temperature and skin resis- and Stark (1974), however, who found that alco- tance and increases in heart rate. Other studies holics in a barlike environment worked harder at have shown that opiate users given a medication an alcohol-rewarded task than did subjects in a that blocks the effects of the opiates (an opiate AN- laboratory setting. This result supports the idea TAGONIST) initially report pleasurable sensations that alcohol-related stimuli impact directly on the after only injection—even of placebo (saline solu- motivation to drink alcohol. Yet, no nonalcoholic tion). After several repetitions of the placebo, the subjects were studied, preventing the conclusion injections begin to become aversive, including ele- that alcoholics are uniquely susceptible to alcohol- 238 CAUSES OF SUBSTANCE ABUSE: Learning related events. Because the assumption that re- ing subjects to avoid drug-related situations or to sponses to drug-related stimuli motivate actual make alternative responses in the presence of drug- drug use is central to learning models, more studies related stimuli. These new responses are designed using drug taking as a dependent measure are to compete with the drug-seeking behaviors usually clearly needed. elicited by drug-related cues. Rather than try to Treatment Implications of Learning and eliminate craving produced by drug cues, this Conditioning Theories. If classical and operant treatment attempts to give the patient ways to conditioning motivate drug use, then substance- avoid cues plus alternatives to drug use. Behavioral abuse treatments should aim at reducing the im- alternatives to drug use range from simple time-out pact of these learning effects. The most commonly periods, to forming images inconsistent with drug discussed interventions include aversion training, use, to acting in ways that reduce the chances of use extinction, and behavioral alternatives. or cue exposure (e.g., going out to eat). These ap- AVERSION THERAPY or training involves teaching proaches are now commonly designated as COGNI- subjects that stimuli and responses that once termi- TIVE THERAPIES or RELAPSE-PREVENTION ap- nated in drug effects will lead to unpleasant out- proaches. The advantage of these procedures over comes. The most common technique has been to aversion therapy and extinction lies in the greater pair self-administrations of a drug with electric potential for patients to use their training in the shock or with chemically induced sickness (e.g., clinic to deal with high-risk situations in the real Antabuse). Although there are some anecdotal re- world. ports of successful treatment using such therapy, Whether these particular conditioning interven- systematic data are not abundant. In addition, such tions provide lasting help to substance abusers re- aversion training suffers from the disadvantage mains to be seen—but data exist to suggest that in that patients are unlikely to continue to administer alcoholics, opiate addicts, and cocaine users, these punishments to themselves once outside treatment. cognitive therapies and relapse-prevention tech- Since the treatment setting is clearly different from the home environment, subjects may simply learn niques do have value. They reduce the probability that drug-taking behavior is reinforced at home but of relapse. punished in the clinic. Extinction training consists of exposing subjects (SEE ALSO: Addiction:Concepts and Definitions; repeatedly to drug-related stimuli and responses, to Conditioned Tolerance; Naltrexone in Treatment break the association between these events and the of Drug Dependence; Wikler’s Pharmacologic The- effects of drug use. Operant extinction procedures ory of Drug Addiction) require subjects to perform repeatedly drug-use behaviors in the absence of a drug reinforcer. This BIBLIOGRAPHY can be accomplished by having subjects administer their drug of abuse in the usual way—while they BAKER, T. B., MORSE, E., & SHERMAN, J. E. (1987). The are maintained on medication blocking the drug’s motivation to use drugs: A psychobiological analysis effects. In this way, drug responses go unrein- of urges. In C. Rivers (Ed.), The Nebraska symposium forced, because the drug effects are missing. Ex- on motivation:Alcohol use and abuse . Lincoln: Uni- tinction of classically conditioned stimuli typically versity of Nebraska Press. requires subjects to view repeatedly drug-related CHILDRESS, A. R., MCLELLAN, A. T., & O’BRIEN,C.P. scenes and handle paraphernalia without using the (1985). Behavioral therapies for substance abuse. In- abused substance. Such training has the advantage ternational Journal of Addiction, 20, 947–969. of not requiring subjects to accept punishment. DRUMMOND, D. C., COOPER, T., & GLAUTIER,S.P. Nevertheless, subjects might show extinction in the (1990). Conditioned learning in alcohol dependence: context of the clinic but continue to experience Implications for cue exposure treatment. British Jour- conditioned effects that lead to drug use in the nal of Addiction, 85, 725–743. unaffected home environment. GOUDIE, A. J., & DEMELLWEEK, C. (1986). Conditioning Behavioral alternatives training represents a factors in drug tolerance. In S. R. Goldberg & I. P. third approach to reducing the impact of condition- Stolerman (Eds.), Behavioral analysis of drug depen- ing on drug abuse. This technique involves teach- dence. Orlando, FL: Academic Press. CAUSES OF SUBSTANCE ABUSE: Psychological (Psychoanalytic) Perspective 239

HENNINGFIELD, J. E., LUKAS, S. E., & BIGELOW,G.E. acute (short-term) and the chronic (long-term) use (1986). Human studies of drugs as reinforcers. In of drugs and ALCOHOL cause individuals to seem S. R. Goldberg & I. P. Stolerman (Eds.), Behavioral pleasure oriented, self-centered, and/or destructive analysis of drug dependence. Orlando, FL: Academic to self and others, thus making them difficult to Press. approach, understand, or treat. In other respects, JOHANSON, C. E. (1984). Assessment of the dependence the controversy or lack of understanding derives potential of cocaine in animals. National Institute on from competing ideas or schools of thought that Drug Abuse Research Monograph, No. 50, 54–71. debate (if not hotly contend) whether substance Rockville, MD. abuse is a disease or a symptom, whether biological JOHANSON, C. E., & FISCHMAN, M. W. (1989). The phar- and genetic factors are more important than envi- macology of cocaine related to its abuse. Pharmaco- ronmental or psychological ones, and/or whether logical Review, 41, 3–52. substance abuse causes or is the result of human LUDWIG, A. M., WIKLER, A., & STARK, L. H. (1974). The psychological suffering. Furthermore, in recent first drink: Psychobiological aspects of craving. Ar- years psychological factors were minimized, be- chives of General Psychiatry, 30, 539–547. cause we entered the era of biological psychiatry/ O’BRIEN, C. P. (1976). Experimental analysis of condi- psychology, in which empirical interest in brain tioning factors in human narcotic addiction. Pharmo- structure and function (down to the microscopic cological Review, 27, 533–543. and molecular level) has predominated over inter- O’BRIEN, C. P., EHRMAN, R. N., & TERNES, J. W. (1986). est in the person, the person’s mind, and subjective Classical conditioning in human opioid dependence. aspects of human psychological life that govern our In S. R. Goldberg & I. P. Stolerman (Eds.), Behav- emotions and behavior. Although one cannot ig- ioral analysis of drug dependence. Orlando, FL: Aca- nore that substances of abuse are PSYCHOACTIVE— demic Press. powerful chemicals that act on the brain—there is SHERMAN, J. E., JORENBY, M. S., & BAKER, T. B. (1988). a tendency to lose sight of the total person whose Classical conditioning with alcohol: Acquired prefer- ways of thinking, feeling, and behaving (including ences and aversions, tolerance and urges/craving. In subjective feelings about self and others) are D. A. Wilkinson & D. Chaudron (Eds.). Theories of equally and profoundly affected both by that alcoholism. Toronto: Addiction Research Foundation. chemistry and by the subjective effects produced by SIEGEL, S. (1979). The role of conditioning in drug toler- those psychoactive substances. ance and addiction. In J. D. Keehn (Ed.), Psychopa- Clearly, biological, genetic (i.e., hereditary), and thology in animals:Research and treatment implica- sociological factors are important in the develop- tions. New York: Academic Press. ment of drug abuse and dependence. Such factors are best studied by empirical methods, and modern STEWART, J., DEWIT, H., & EIKELBOOM, R. (1984). The role of unconditioned and conditioned drug effects in technology—including the computer—has yielded the self-administration of opiates and stimulants. new and valuable data since the late 1960s to Psychological Review, 91, 251–268. explain aspects of addictive behavior. It is also noteworthy that during this period (a time when YOUNG, A. M., & HERLING, S. (1986). Drugs as reinforc- ers: Studies in laboratory animals. In S. R. Goldberg substance abuse has been most prevalent, studied, & I. P. Stolerman (Eds.), Behavioral analysis of drug and treated), clinical work with substance abusers has yielded data and findings of equal importance dependence. Orlando, FL: Academic Press. and validity, and this work has focused on some of WIKLER, A. (1980). Opioid dependence: Mechanisms the important subjective psychological factors that and treatment. New York: Plenum. also explain aspects of addictive behavior—some STEVEN J. ROBBINS which empirical methods alone do not adequately fathom or explain. I will present here a psychological understand- Psychological (Psychoanalytic) Per- ing of drug abuse and dependence based on the spective The psychological study and under- perspective gained from clinical work with alco- standing of substance abusers has tended to be holic and drug-dependent individuals. In psychol- difficult, controversial, and complicated. Part of ogy and clinical psychiatry, it is referred to as the this derives from the nature of addictive illness; the case method of study of human psychological prob- 240 CAUSES OF SUBSTANCE ABUSE: Psychological (Psychoanalytic) Perspective lems. Guided by psychodynamic principles (the as- individuals as they are for the many other patients sumptions of which will be explained), this article who benefit from this perspective. will review what three decades of clinical work and The psychological study and understanding of case study with substance abusers has yielded on addictive illness necessarily requires the condition some of the main psychological influences that of abstinence (being free of drug/alcohol use). make likely or compelling the dependence on, and Again, there is considerable debate about the dura- continued use and relapse to, drugs and alcohol. tion of abstinence required before meaningful or valid psychological inferences can be made about ASSUMPTIONS individuals with addictive disorders. In my experi- ence, however, the confounding effects of acute and A psychodynamic perspective of human psycho- chronic drug/alcohol use are variable, and it is logical life problems rests on the principle that we often surprising that within days or weeks—but are all more or less susceptible to various forms of certainly within several months of abstinence— human psychological vulnerabilities—at the same how much can be learned about a person’s makeup time, we are also more or less endowed with human and psychology that predisposed him or her to use psychological strengths or capacities to protect and become dependent on substances. This point against these vulnerabilities. Without ignoring he- about the requirement for a period of abstinence reditary factors, especially those that affect temper- from drugs and alcohol is important to emphasize, ament, a psychological, and in this case psychody- otherwise it can be and is rightfully argued that namic perspective attempts to understand what appear to be the psychological causes of de- psychological forces at work (for example, drives pendence on psychoactive substances are actually and feelings) that operate within the individual at the result of such a dependence. Fortunately, in the same time that there is a corresponding interest recent years, the combination of modern detoxifi- in the psychological structures and functions that cation approaches, psychoeducational/rehabilita- observably (and just as often, less obviously) oper- tion/RELAPSE PREVENTION programs, TWELVE- ate to regulate or control our drives, feelings, and STEP groups, and individual and group psychother- behavior. apeutic approaches, have been increasingly suc- A psychodynamic approach to human psychol- cessful in establishing and maintaining abstinence. ogy greatly depends on a developmental perspec- This, in turn, has made psychological treatments tive or an appreciation of the psychological forces, and understanding increasingly possible. structures, and functions as they develop and change over one’s lifetime. Psychodynamic clini- PSYCHOLOGICAL SUFFERING cians are especially interested in the way individu- AND SELF-CONTROL als are influenced in the earliest phases of develop- ment by parents (and other caregivers), and then in A clinical-psychodynamic perspective suggests the development of relationships with other chil- that human psychological suffering and problems dren and peers, and later in the life cycle in rela- with self-control are at the heart of addictive dis- tionships with adults and small and large groups— orders. In fact, it is probably safe to say that to all of which shape our life views and experiences, as understand the psychology of addictive behavior is well as our attitudes, values, and characteristic to understand a great deal about human psycho- ways of reacting and behaving. logical problems of suffering and control in gen- Based on these assumptions, clinicians have the eral. The suffering that influences addictive be- opportunity, most usually in the context of treating havior occurs at many levels, but it principally patients, to study and understand how the degree evolves out of susceptibilities involving people’s of developmental impairments (or strengths) has self-esteem, relationships, emotions, and capaci- predisposed toward (or protected against) psycho- ties to take care of themselves. Individuals who logical and psychiatric dysfunction, including ad- find various or particular drugs appealing (includ- dictive vulnerability. In my experience, and that of ing alcohol) or who become dependent on them, my associates, we believe that modern psychody- discover that, short-term, the drug action or effect namic-clinical approaches are as relevant and use- relieves or controls their distress—that is, such ful for studying and treating substance-dependent drugs are used to self-medicate distress. Although CAUSES OF SUBSTANCE ABUSE: Psychological (Psychoanalytic) Perspective 241 problems with self-esteem and relationships are are used to change or control their emotions or important parts in the equation of addictive be- suffering. In the first instance the operative motive havior, it is mainly the problems with how sub- is the relief of suffering; in the second, it is the stance-dependent individuals experience, tolerate, control of suffering. and express their feelings and their problems with The self-medication hypothesis rests on the ob- self-care that makes addictive behavior so malig- servation that patients, if asked, will indicate that nantly likely and compelling. they prefer or discover that one class of drugs has Problems with emotions and self-care painfully more appeal than another. Still, the drugs preferred and repetitiously become involved with attempts to by an individual are not the ones that are always control suffering and behavior. This process in- used. Drugs that are actually used are just as often cludes such self-defeating coping patterns as ac- the result of other factors, such as cost and avail- tion, activity, psychological defensiveness (e.g., de- ability. nial, boastful or arrogant postures, attitudes of The three main classes of drugs that have been invulnerability and toughness), and, ultimately, studied are the OPIOID analgesics (pain relievers), the use of drugs and alcohol. What originally was a depressants or SEDATIVE-HYPNOTICS (soothing, re- ‘‘solution’’ for suffering and self-regulation— laxing, or sleep-inducing drugs), and STIMULANTS where substances were used for relief or control— (activating or energizing drugs). The main appeal turns into a problem where there is a progressive of opioids (e.g., HEROIN,MORPHINE, oxycodone) is loss of control of one’s self, the drugs or alcohol that they are powerful subduing or calming agents. employed to combat one’s difficulties, and possibly Besides calming or subduing physical pain for life itself. which they were originally intended, opioids are also very effective in reducing or alleviating dis- THE SELF-MEDICATION HYPOTHESIS tressing or disruptive emotions. Beyond its calming influence on physical and emotional pain in gen- The self-medication hypothesis specifically re- eral, however, I have found that the main and fers to some individuals who, by dint of tempera- specific action of opioids, namely as an anti-rage or ment or developmental factors, experience and anti-aggression drug, makes them especially ap- find that certain painful feelings (or affects) are pealing and compelling for those who struggle intense and unbearable and that the specific ac- within, and with others, with feelings of intense tion or effect of one of the various classes of anger, AGGRESSION, and hostility. Such a state of abused drugs (e.g., analgesics, depressants, or affairs is not uncommon for people who, in their stimulants) relieves their psychological pain and early life development or in later life experiences, suffering. The self-medication hypothesis also im- have suffered major trauma, neglect, or abuse. plies that the particular drug or class of drugs Such individuals, when they first use opioids, dis- preferred is not random. Rather, it is determined cover the extraordinary calming and soothing ef- by how that class of drugs with its specific actions fects of these drugs on their intense anger and interact with emotional states or particular pain- rage—and thus they become powerfully drawn or ful feelings unique to the individuals who use or attached to them. select their ‘‘drug-of-choice.’’ Whereas opioid-dependent people have much This is only one aspect of addictive suffering— difficulty controlling their feelings, especially anger namely that emotions are experienced in the ex- and rage, those who prefer or who are dependent on treme and that addictive-prone individuals feel too depressants generally have the opposite problem— much pain, so resort to particular drugs to relieve namely they are too controlled or too ‘‘tightly their suffering. Another aspect of addictive suffer- wrapped’’ around their feelings. As is the case with ing, to be covered subsequently, is that emotions other substance abusers, developmental life experi- are just as often absent, nameless, and confusing ences, in this case often involving distrust and trau- and that such individuals experience pain of a dif- matic disappointment, have had a special influence ferent type; they consciously feel too little of their on their experience of emotions. In the case of those distress and do not know when or why they are who prefer depressants, they are the ones who have bothered (e.g., feeling empty, void, or cut off from special difficulties experiencing emotions involving emotions), and drugs or alcohol in these instances loving or caring feelings, interpersonal depen- 242 CAUSES OF SUBSTANCE ABUSE: Psychological (Psychoanalytic) Perspective dency, and closeness; in psychological terms, they early perspective is now outdated, counterem- are defensive and repressed around these emotions pathic, and does disservice to understanding the and have difficulty in experiencing or expressing motives of addicted and alcoholic individuals. them. Depressants (e.g., alcohol, Seconal, Xanax) In contrast, the self-medication hypothesis has have appeal for these people, because such drugs evolved from contemporary psychodynamic the- help them to relax their defenses and release them ory, which has placed the centrality of feelings (or from their repressions. Mainly, such drugs briefly affects) ahead of drives or instincts and has empha- (the short- or quick-acting depressants) produce a sized the importance of self-regulation, involving sense of safety and an inner sense of warmth, affec- self-development or self-esteem (i.e., self-psychol- tion, or closeness that otherwise these people can- ogy), relationship with others (i.e., object-relations not experience or allow. theory), and self-care (i.e., ego or structural psy- Finally, stimulants (i.e., AMPHETAMINES and chology/theory). These contemporary psychody- COCAINE are the most popular and widely used) namic findings have evolved since the 1950s, based have appeal for those who suffer with overt and/or on the works of investigators such as Weider and subtle states of depression, mania, and hyperactiv- Kaplan, Milkman and Frosch, Wurmser, Krystal, ity—in which problems with activation, activity, Woody and associates, Blatt and associates, Wilson, and energy are common. For example, ambitious Dodes, and Khantzian. driven types—for whom performance, prowess, Although the self-medication hypothesis has and achievement are essential—find such drugs es- gained wide acceptance as an explanation for drug/ pecially appealing on two counts: (1) stimulants alcohol dependency, it is not without its critics and are uplifting when they become depressed if their it fails to deal with at least two fundamental prob- goals and ambitions, often unrealistic, fail them; lems or observations that it does not explain or (2) stimulants are facilitating and make action and address. First, many individuals suffer with the activity easier when such people are on the up- painful feelings and emotions that substance abus- swing, making it easier for them to be the way they ers experience, but they do not become addicted or like to be when they are performing at their best. alcoholic. Secondly, the self-medication hypothesis Stimulants cast a wide net of appeal because, in fails to take into account that addicted and alco- addition, they counter feelings of low energy, low holic individuals suffer as much if not more as a activity, and low self-esteem in those suffering with result of their drug/alcohol use, and this might overt or less overt (unrecognized or atypical) de- appear to contradict the hypothesis that substances pression. Finally, those individuals suffering with are used to relieve suffering. attention deficit-hyperactivity disorder (ADHD), Many of these criticisms, inconsistencies, and often subclinical or not recognized, are also drawn apparent contradictions are better understood or to and become dependent on stimulants, because of resolved when addictive problems are considered the paradoxically opposite calming effect that stim- more broadly—in terms of self-regulation vulner- ulants have for people with this disorder—much abilities or as a self-regulation disorder. For hu- like hyperactive children who respond well to the mans, life is the constant challenge of self- prescribed stimulant Ritalin. regulation, as opposed to the release, relief, or con- trol of instincts and drives as early theory sug- gested. What is in need of regulation involves feel- SELF-REGULATION ings, the sense of self (or self-esteem), VULNERABILITIES relationships with others, and behavior. Those To explain why people became addicted, early prone to addictive problems are predisposed to be psychodynamic theory placed great emphasis on so, because they suffer with a range of self- subconscious and unconscious factors, pleasure regulation vulnerabilities. Their sense of self, in- and aggressive instincts or drives, and the symbolic cluding self-regard, is often shaky or defective meaning of drugs. To some extent, the stereotype of from the outset of their lives. A basic sense of well- substance abusers as pleasure-seeking destructive being and a capacity for self-comfort and self- characters (to self and others), in part, still persists soothing is very often lacking or underdeveloped and derives from these early formulations. Albeit from the earliest phases of development. Subse- useful and innovative at the time, much of this quent development of self-esteem and self-love, if CAUSES OF SUBSTANCE ABUSE: Psychological (Psychoanalytic) Perspective 243 it develops at all, remains shaky and inconsistent, As I have indicated, substance abusers suffer in given the compromised sense of self from which the extreme with their emotions—they feel too self-regard evolves. Needless to say, a poor sense much or they feel too little. When there is too much, of self or low self-esteem (which usually originates we have described how drugs can relieve the in- in a compromised or deficient self-other parenting tense unbearable feelings that addicts and others relationship), ultimately affects subsequent self- experience. Where there is too little and people are other relationships and profoundly affects one’s (or seem to be) devoid of, cut off from, or confused capacity to trust or to be dependent upon or to by their feelings (e.g., alexithymia, disaffected, or become involved with others. affect deficits), addicts prefer to counter the help- It should not be surprising, then, that for some lessness and loss of control caused by their lack of the energizing and activating properties of stimu- feelings. Instead, they choose to use drugs to lants help self-doubting reticent individuals to change and control their feelings, even if it causes overcome their depressive slumps and withdrawal; them more distress. They exchange feelings that are or that the soothing, relaxing effects of depressants vague, confusing, and out-of-control, for drug-in- help individuals who are restricted and cut off from duced feelings that they recognize, understand, and others to break through their inhibitions and briefly control, even if such are painful and uncomfort- experience the warmth and comfort of human con- able. Therefore, the factors of relief and control tact that they otherwise do not allow or trust; or yet dominate people’s motives for depending on still, that those whose lives are racked by anger and drugs—even if these people have to endure the pain related agitation would find a drug like heroin (an that their dependence on drugs also entails. opioid analgesic) to be a powerful containing calm- Finally, deficits in self-care (again deriving from ing antidote to their intense and threatening emo- early-life developmental problems) make it likely tions, which disrupt them from within and threaten that certain individuals will become involved with most of their relationships with others. These ex- hazardous activities and relationships that lead to amples, and those previously covered in relation to drug experimentation, use, and dependence. Self- self-medication motives that govern drug use and care deficits refer to a major self-regulation prob- dependency, help demonstrate the how and why of lem, wherein individuals feel and think differently specific drug effects—which often become so com- around potential or actually dangerous situations pelling that they may consume the lives of some and activities, including those that involve drug/ users. alcohol experimentation and use. Where most of us In my experience, the regulation of feelings (or would be apprehensive or frightened or would an- affects) and self-care become the two most compel- ticipate some guilt and shame, addictive and alco- ling self-regulatory problems; they combine to holic-prone individuals show little or no such make dependence on substances more likely than worry. Studying these patients’ pre- and postaddic- any other self-regulation factors. Focus on these tive behavior patterns very often reveals similar two factors explains clearly why most people who unfeeling, unthinking, fearless behavior in con- suffer subjective painful emotions do not necessar- ducting other aspects of their lives—for example, ily become addicted as well as why so many sub- preventable accidents, health-care problems, and stance abusers persist in using debilitating sub- financial difficulties seem evident and common. Be- stances despite the great suffering that ensues from ing out of touch with, or not feeling, their feelings their abuse. (that is, their ‘‘affect deficits’’ or ‘‘dis-affected It should be noted that in this article I have state’’) contributes to their self-care problems and stressed psychological factors and have not pursued thus makes it more likely that they would engage in how the regular use of addictive drugs causes the dangerous pursuit of drug/alcohol abuse, where TOLERANCE AND PHYSICAL DEPENDENCE; the drugs, others with better self-care functions would not then, are used to remain ‘‘normal.’’ It is not insig- (even in those instances where the unbearable psy- nificant however, that the emotional pain involved chological suffering and states of distress are like in physical WITHDRAWAL just as often is an exag- those experienced by addicts). In this respect, pain- gerated form of the pain that the drug-of-choice ful or unbearable feelings, alone, are not sufficient originally relieved. This aspect of drug use and to cause substance abuse or dependence. Rather, it relapse are covered elsewhere in this encyclopedia. is when individuals lack adequate self-care capaci- 244 CENTER ON ADDICTION AND SUBSTANCE ABUSE (CASA) ties and experience intense suffering that condi- CENTER ON ADDICTION AND SUB- tions exist for addictive behavior to develop or be STANCE ABUSE (CASA) The Center on Ad- likely. diction and Substance Abuse at Columbia Univer- sity (633 Third Avenue, New York, NY 10017) was (SEE ALSO: Addiction:Concepts and Definitions; established in 1992 as a not-for-profit entity affili- Causes of Substance Abuse:Learning; Complica- ated with the university. It was founded by Joseph tions:Mental Disorders; Conduct Disorder and A. Califano, Jr., a former secretary of health, edu- Drug Use; Coping and Drug Use; Disease Concept cation, and welfare in the Carter administration, of Alcohol and Drug Abuse; Vulnerability:Psycho- and Herbert D. Kleber, M.D. CASA has been analytic) funded by major grants from the Robert Wood Johnson Foundation, as well as other foundations, BIBLIOGRAPHY private companies, and government agencies. Califano, who has had a long-term interest in sub- BLATT, S. J., ET AL., (1984). Psychological assessment of stance-abuse problems, was a vigorous advocate of psychotherapy in opiate addicts. Journal of Nervous smoking cessation programs when he was a mem- and Mental Disease, 172, 156–165. ber of the Carter cabinet. In organizing CASA, he DODES, L. M. (1990). Addiction, helplessness and narcis- assembled a board of directors that includes many sistic rage. Psychoanalytical Queries, 59, 398–419. prominent people in politics, industry, academia, KHANTZIAN, E. J. (1990). Self-regulation and self-medi- ADVERTISING, and the media. Kleber, a well-known cation factors in alcoholism and the addictions. In M. drug abuse researcher and former deputy director Galanter (Ed.), Recent developments in alcoholism, of the Office of National Drug Control Policy under vol. 8. New York: Plenum. William Bennett and President George Bush, is ex- KHANTZIAN, E. J. (1985). The self-medication hypothesis ecutive vice president and medical director. of addictive disorders. American Journal of Psychia- Califano is president and chairman of the board. try, 142, 1259–1264. The work of the center initially emphasized KHANTZIAN, E. J., & MACK, J. E. (1983). Self-preserva- analysis of available data on the social and ECO- tion and the care of the self-ego instincts reconsidered. NOMIC COSTS of substance abuse (ALCOHOL,TO- Psychoanalytical Study of Childhood, 38, 209–232. BACCO, and illicit drugs). The center then moved on KHANTZIAN, E. J., HALLIDAY, K. S., & MCAULIFFE,W.E. to creating national demonstration projects, major (1990). Addiction and the vulnerable self. New York: policy papers on key issues in the substance abuse Guilford Press. field, and research projects on treatment. KRYSTAL, H. (1982). Alexithymia and the effectiveness CASA has demonstration programs at thirty- of psychoanalytic treatment. International Journal of eight sites in twenty-five cities and sixteen states. Psychoanalysis and Psychotherapy, 9, 353–378. These demonstration programs include CASA MILKMAN, H., & FROSCH, W. A. (1973). On the preferen- START, a program to help thirteen- to eighteen- tial abuse of heroin and amphetamine. Journal of year-old children who are using alcohol, tobacco, Nervous and Mental Disease, 56, 242–248. or illicit drugs or who are at high risk of doing so. It WEIDER, H., & KAPLAN, E. (1969). Drug use in adoles- involves collaboration between schools, police de- cents. Psychoanalytical Study of Childhood, 24, 399– partments and community organizations, and is 431. aimed at preventing substance abuse, improving WILSON, A., ET AL. (1989). A hierarchical model of opiate school performance, and reducing delinquency addiction: Failures of self-regulation as a central as- among these children. CASA WORKS FOR FAMI- pect of substance abuse. Journal of Nervous and Men- LIES is the first comprehensive national demon- tal Disease, 177, 390–399. stration designed to help drug and alcohol addicted WOODY, G. E., ET AL. (1986). Psychotherapy for sub- mothers on welfare achieve self-sufficiency. It is a stance abuse. Psychiat. Clin. N. Am. 9, 547–562. sixteen million dollar, three-year demonstration WURMSER, L. (1974). Psychoanalytic considerations of that combines in a single course of treatment and the etiology of compulsive drug use. Journal of the training: drug and alcohol treatment, literacy and American Psychoanalytical Association, 22, 820– job training, parenting and social skills, violence 843. prevention, health care, family services, and a E. J. KHANTZIAN gradual move to work. The program is being tested CENTRE FOR ADDICTION AND MENTAL HEALTH 245 in eleven sites in nine states and will serve more CENTRE FOR ADDICTION AND than one thousand women and their children. More MENTAL HEALTH The Centre for Addiction sites are planned. and Mental Health is a clinical, research, and Reports put out by CASA include: Substance teaching facility that is associated with the Univer- Abuse and the American Adolescent; Substance sity of Toronto. The Centre is one of only four Abuse and the Mature Woman; Substance Abuse mental health and addictions facilities to receive and America’s Prison Population; Substance Abuse the Centre of Excellence designation by the World Health Organization (WHO). It was created in on the College Campus; Substance Abuse and Sex; 1998 through the merger of the Queen Street Men- Substance Abuse and Learning Disabilities; and tal Health Centre, the Donwood Institute, the Substance Abuse in Rural America. Other projects Clarke Institute of Psychiatry, and the Addiction include CASA’s National Commission on Sports Research Foundation. The Centre’s central re- and Substance Abuse, which will produce a com- search and clinical facilities are located in Toronto prehensive analysis of substance abuse and sports and 12 additional offices are found in communities in America; the National Evaluation of Substance throughout the province of Ontario. Abuse Treatment (NESAT), which follows two The Centre’s underlying goals are to advance the thousand individuals in close to two hundred treat- understanding of mental health and addiction and ment programs from intake up to one year or more to utilize that knowledge in their treatment pro- afterwards, to evaluate the effectiveness of drug grams. It aims to prevent problems, find more ef- and alcohol treatment programs; CATS, the Co- fective treatments for mental illness and addictions, caine Alternative Treatment Study, which looks at and improve the quality of life for persons who are the effectiveness of acupuncture as a treatment for afflicted with mental illness or struggling with ad- cocaine in over 500 patients at six university sites dictions. It is a patient-centered institution that provides services that are sensitive to gender, age, across the U.S.; and an analysis of drug courts and race, culture, religion, and sexual orientation. The their effectiveness. Centre is a unique entity that is recognized for its Through articles both in the popular press and ability to: scientific journals, press conferences, and testi- mony before congressional committees, CASA con- ● Integrate biological, clinical, and social re- ducts a continuing campaign to raise public aware- search; ● Translate research results into treatments and ness about the pervasiveness of and the SOCIAL tools for practical use; COSTS OF SUBSTANCE ABUSE. The priorities for the ● Blend treatments for alcohol and drug addic- organization are to explain to the American people tion and mental health disorders; the social and economic costs of substance abuse ● Conduct leading-edge research; and and its impact on their lives, to identify what can be ● Provide continuity of care in one location. done, which prevention and treatment programs work and for whom, and to encourage individual The Centre is involved with many programs to institutions to take responsibility to prevent and strengthen the capacity and quality of mental combat substance abuse. health and addiction services in Ontario. One pro- gram, the Assertive Community Treatment Team, uses a multi-disciplinary team to provide intensive (SEE ALSO: Economic Costs of Substance Abuse; treatment of chronic mental illness in diverse com- Social Costs of Substance Abuse) munities. Another program educates family physi- JEROME H. JAFFE cians, who have patients with addiction and mental REVISED BY HERB KLEBER health disorders, through a series of continuing ed- ucation seminars. The Centre aids the smaller, more distant Ontario communities by sending ‘‘fly- in’’ consultation teams or through video confer- CENTRAL NERVOUS SYSTEM See encing with patients or health care providers. In Brain Structures and Drugs; Limbic System; Neu- addition, the Ontario Tobacco Research Unit is rotransmission housed at the Centre and provides funds for sur- 246 CHAIN OF CUSTODY veillance, evaluation, and research into nicotine ad- CHAIN OF CUSTODY See Drug Testing diction. The Clarke Institute of Psychiatry is the primary research site of the Centre. Funding is provided by CHEMICAL DEPENDENCE See the Ontario Ministry of Health, research grants, Addiction: Concepts and Definitions and donations. Psychiatric research programs in- clude biochemistry, endocrinology, epidemiology, genetics, molecular biology, neurochemistry, neu- CHEWING TOBACCO See Tobacco: His- roimaging, positron emission tomography (PET), tory of; Treatment: Tobacco, an Overview and transgenics. Major areas of research include: ● Investigating the biological aspects of mental illness and addiction; CHILD ABUSE AND DRUGS In the ● Studying nicotine addiction; United States, on average, a child is abused every ● Investigating treatments for depression; 13 seconds. Because of social awareness, reported ● Investigating treatments for children with be- child abuse has increased dramatically since the havioral problems; 1980s. Some states have experienced a 20 percent ● Improving the treatment of schizophrenia; increase in reported child abuse between 1990 and ● Studying pathological gambling; and 1991. The American Public Health Association ● Studying the issues of mental health and the (APHA) estimates that 1.7 million children are homeless. abused or neglected annually in the United States. This means that by 1992 a total of about 63.5 The Centre publishes the Journal of Addiction million (2.8%) of children under 18 years of age and Mental Health, a magazine that provides in- were abused. formation and news items relevant to mental health Reported cases in the 1990 National Child professionals and other interested parties. The Abuse and Neglect Data System totaled about half readership includes professionals, patients, con- the APHA estimate, or only 893,856. This total sumers, and family members. Initially aimed at a comprised 227,057 victims of physical abuse; Canadian readership, the Centre hopes to expand 403,430 victims of neglect; 138,357 victims of sex- the Journal of Addiction and Mental Health to at- ual abuse; 59,974 victims of emotional maltreat- tract an international readership. Also published by ment; and 68,207 other. These figures represent the Centre is the Balanced Scorecard which pro- only the reported cases—the proverbial tip of the vides an overview of the performance of the Centre. iceberg. Research suggests that as many as 10 per- Key personnel at the Centre include: Dr. Paul cent of children may be sexually abused and even Garfinkel, president and chief executive officer; more children physically abused or neglected. In Jean Simpson, executive vice president and chief addition, each year a higher percentage of U.S. operating officer; Dr. Georgiana Beal, chief of children are being raised in poverty, often by over- nursing practice and professional services; Dr. stressed and drug-abusing parents. David Goldbloom, physician-in-chief; Dr. Patrick Smith, Vice president, addiction programs; Jean INCIDENCE AND PREVALENCE OF Trimnell, vice president; mental health programs; DRUG ABUSE Dr. Franco Vaccarino, vice president, research; Although the casual use of drugs is decreasing in Carolyn Nutter, vice president, community health the United States, reported drug abuse is increasing and education; and Mary Deacon, president and in women of child-bearing age. While it is believed executive director, CAMH foundation. that more children are being raised by alcohol-, The Centre for Addiction and Mental Health, is tobacco-, or other drug (ATOD)-abusing parents, located at 33 Russell Street, Toronto, Ontario, the scope of the problem is undetermined. Longitu- Canada M5S 2S1, (416) 535-8501, dinal studies of children of ATOD-abusing parents http://www.camh.net. are currently underway by the U.S. Centers for Dis- BELINDA ROWLAND ease Control (CDC), the NATIONAL INSTITUTE ON CHILD ABUSE AND DRUGS 247

DRUG ABUSE (NIDA), and the NATIONAL INSTITUTE such as poor parenting skills, family disorganiza- ON ALCOHOLISM AND ALCOHOL ABUSE (NIAAA). tion, involvement in criminal activity, and a dispro- The Children of Alcoholics Foundation estimates portionately high incidence of mental and physical that in the U.S. population about one in eight were illness. Several types of child abuse and neglect raised in homes with one alcoholic parent. Studies involving children of drug abusers are reviewed suggest that as many as 11 percent of newborns are below. drug-exposed in utero. About six million women of Prenatal Drug Exposure. A number of states childbearing age are marijuana users and 10,000 legally define in utero exposure to alcohol and other children per year are born to women using opiates. drugs as child abuse. States with excessively puni- Polydrug use and frequent use of alcohol and other tive laws requiring child removal are rapidly drugs by parents increases the difficulty of re- changing these laws. For example, in California, searching any causal relationships between a spe- the law mandating that infants be removed from cific drug and child abuse. detected drug-abusing mothers at birth has been The National Committee for the Prevention of modified; in San Francisco, a positive urine toxicol- Child Abuse (NCPCA) estimates that 10 million ogy alone cannot be the only reason for removal. In U.S. children are raised by ATOD-abusing parents many states, medical or social-services personnel or caretakers and at least 675,000 children every are mandated to report such cases to protective- year are seriously abused by ATOD caretakers. services workers; this can result in the avoidance of ATOD-abusing women have higher fertility rates prenatal care by ATOD-abusing pregnant women. and more multiple births than non-ATOD-abusing For this reason, social-services employees may hes- women. Reasons for these repeated pregnancies in itate to notify authorities. Additionally, notification drug-abusing women may include lack of sex edu- of authorities can appear to be (and may in some cation and birth control, irregular menstruation, cases be) racially biased and discriminatory if more carelessness when using drugs, peer pressure and poor women of color are referred. In one Florida cultural norms, the desire to replace lost children, study only one percent of white but ten percent of the need for increased welfare payments, the enjoy- African-American drug-abusing pregnant women ment of being pregnant (decreased depression), were reported to child-protective services. and having an infant to love them. These interest- Alcohol and other drugs can cause teratogenic ing findings should be studied further to determine effects—resulting in abnormalities in the fetus. Iso- their validity and related psychological, sociologi- lating the specific effects of individual drugs has cal, and biological causal mechanisms. been complicated by the large proportion of women who are polydrug abusers and by additional factors of poor nutrition, disease, stress, and lack of pre- RELATIONSHIP OF CHILD natal care. Alcohol and tobacco are the drugs most MALTREATMENT AND ATOD ABUSE commonly used by women during pregnancy; as Do addicted parents abuse their children more? many as 1 percent of births may be affected by FE- Do both addicted and nonaddicted parents abuse TAL ALCOHOL SYNDROME (FAS). Some researchers their children more when using alcohol or drugs? assert that FAS may be the major cause of mental Unfortunately, clear empirical research is lacking retardation. Characteristics of FAS include facial on the relationship of child abuse and alcohol abuse anomalies, retarded growth, and abnormalities of or child abuse and drug abuse. The validity of ex- the heart, kidneys, ears, and skeletal system. The isting research is threatened by problems, such as long-term effects of FAS are still being studied but unclear definitions of ATOD abuse, lack of control appear to include reduced intelligence, attention groups or longitudinal causal studies, and inappro- deficits, learning disorders, hyperactivity, impul- priate statistical and research design techniques for sivity, and more antisocial behaviors than the separating causation and coincidence (Bays, norm. 1990). Nevertheless, a relationship does exist be- The perinatal and long-term effects of other tween child abuse and ATOD abuse—and defi- drugs have been studied—such as COCAINE,METH- nitely between ATOD abuse and child neglect. Sim- AMPHETAMINE,MARIJUANA,OPIATES,and ilar risk factors for child abuse exist for both child- PHENCYCLIDINE (PCP). Although a number of im- abusing parents and substance-abusing parents, mediate problems are apparent, including drug 248 CHILD ABUSE AND DRUGS withdrawal and developmental delays, with good adult. In addition, infants can ingest alcohol, nic- postnatal environments many of these children can otine, and other drugs through breast milk. Passive overcome their in utero exposure if structural dam- inhalation of tobacco is recognized as a health haz- age is not severe. Some researchers have reported ard to children; however, passive inhalation of that even when cocaine-exposed infants were CRACK (freebase cocaine), PCP, marijuana, or reared in adoptive homes from birth, some showed hashish also has negative effects. Children living neurological deficits. Significant central nervous with parents who manufacture synthetic DESIGNER system (CNS) damage occurs with cocaine expo- DRUGS in their homes, such as methamphetamine, sure. The major effects at birth of most drugs, how- are exposed to hazardous toxic chemicals. Some ever, including alcohol and tobacco, are preterm ATOD-abusing parents allow their children to deliveries of low-birthweight infants, indicative of drink alcohol or use the drugs they find lying growth retardation that may affect both brain and around the house. Some parents deliberately give physical development. Sudden infant death syn- their children alcohol or other drugs (i.e., tincture drome (SIDS) is also two to twenty times higher in of opium) to reduce their crying, sedate them, or to infants exposed to cocaine and opiates. induce intoxication to amuse the parents. any rela- Few longitudinal studies have tracked the im- tively healthy child with unexplained neurological pact of drug exposure on children. The longest fol- symptoms, seizures, or death may have been ex- low-up study is of prenatal opiate-exposed children posed to drugs. evaluated at ten years of age, and it is very difficult Physical Abuse. Until recently, child-welfare to separate the impact of a poor postnatal environ- agencies did not routinely screen for alcohol and ment from prenatal drug exposure (unless the chil- drug abuse in caregivers of abused children. Be- dren are adopted). The few longitudinal studies cause only about 40 percent of public child-welfare conducted of prenatal drug-exposed infants have agencies and 71 percent of private child-welfare found almost no long-term developmental prob- agencies even inquire about caregiver substance lems directly related to their drug exposure. A few use, little is known about the incidence of substance cross-sectional studies of children of drug abusers abuse in child abuse cases. The Child Welfare have found clinically significant negative impacts League of America (CWLA) reported, after a 1990 on their emotional, academic, and behavioral survey of its 547 member agencies, that 37 percent status. These studies suggest that the greater the of the children served by state agencies and 57 degree of maternal drug abuse, the greater the percent of children served by private agencies were negative impact on the child’s mental and estimated to be affected by ATOD family problems. behavioral status as measured by standardized A review of the literature found five studies clinical measures. suggesting a strong overlap between physical abuse The quality of the infant’s postnatal environ- and parental alcoholism. Physical and sexual abuse ment as actively constructed by the mother or care- has been reported in 27 percent of alcoholic fami- giver appears to be the most significant factor in lies and 19 percent of opiate-addicted families. Se- determining the impact of drugs on the drug-ex- rious neglect was even more common (30.5%). posed or nondrug-exposed infant. Studies find that Overall, 41 percent of children of addicts were children born to drug-abusing mothers can look found to be physically abused or neglected. In normal or be resilient to their in utero exposure to 1987, 50 percent of all reported child abuse and drugs if they are provided a nurturing environment neglect cases in New York City were associated with that includes responsiveness to their needs, stimu- parental drug abuse and 64 percent of cases were lation, and early childhood education. associated with parental alcohol and drug abuse. Postnatal Exposure to Drugs. Children can Of all child fatalities, 25 percent had related to a be hurt by ingesting or inhaling alcohol, tobacco, positive child drug toxicology (an overdose, OD). and other drugs. In 1978, PCP was the second most ATOD abuse is frequently implicated when the common cause of poisoning in young children at courts remove a child from the home. A 1986 Illi- Los Angeles Children’s Hospital. Four major ways nois study indicated that 50 percent of all outplace- exist for children to become intoxicated: passive ments were from substance-abusing families and inhalation, accidental self-ingestion, being given 68 percent of these parents refused ATOD treat- drugs by a minor, and deliberate poisoning by an ment. Children growing up in abusive environ- CHILD ABUSE AND DRUGS 249 ments have increased, unfulfilled dependency or demands of others. The concept of refusing an- needs, low self-esteem, distrust of others, and prob- other person access to their bodies (and in later lems with aggression and anxiety. life, to their privacy, time, physical space, and Child Sexual Abuse. A high percentage of possessions) has not been incorporated into their drug abusers report that they were sexually abused sense of identity. This leaves the survivors vulner- as children. Child molesters are often intoxicated able to subsequent violations or coercive tactics when the abuse occurs. Alcohol’s influence on the throughout their lives. It could also lead adult sur- brain allows a disinhibition of socially proscribed vivors to become perpetrators who abuse their own behaviors, including incest and the sexual molesta- or other children because of their own boundary tion of children. A 1986 review of the research inadequacies. suggests that alcohol is involved in about 30 to 40 Risk Factors for Child Abuse by Substance percent of child sexual-abuse cases, particularly Abusers. Child-welfare authorities consider pa- when girls are abused. A 1988 study found 48 rental substance abuse to be a major risk factor for percent of fathers who had committed incest were child abuse. Under the influence of alcohol and alcoholic but 63 percent of fathers were drinking at other drugs, adults are less inhibited and have re- the time of the abuse. Because of the high heritabil- duced judgement and emotional control. Uppers ity rate of male-limited alcoholism (the most severe (stimulants such as cocaine, methamphetamine, type of alcoholism associated with early drinking PCP, and amphetamines) can cause anxiety, irrita- and antisocial behavior in males), sexually mo- bility, paranoia, and aggressiveness. Downers (de- lested children may be more genetically vulnerable pressants such as alcohol, opiates, sedatives, and to ATOD-abused antisocial behavior. Thus, the cy- barbiturates) have also been related to depression, cle of childhood sexual abuse is perpetuated over irritability, and loss of control while disciplining generations, because of the overlap between the children. It has been suggested that organic brain two types of abuse. damage, hypoglycemia, and sleep disturbances Childhood sexual abuse is a major risk factor for caused by alcohol exacerbates child abuse by alco- greater psychological distress, dissociative experi- holics. ATOD-abusing parents are often irritable ences, depression, eating disorders, relationship, and angry because of neurochemical imbalances trust, and intimacy difficulties, post-traumatic caused by persistent drug abuse. Some researchers stress response, psychotic disorder, and heavy drug attest that these neurochemical imbalances can last abuse. A very high percentage of drug abusers at for several years after detoxification. Furthermore, inpatient and residential treatment programs re- neurotransmitter imbalances, which can be either port being sexually abused as children. When direct biologically inherited or lifestyle-induced, may pre- questions were asked of the clients, men’s reports of cede parental drug abuse and lead to self-medica- childhood sexual abuse increased from four percent tion with drugs. For example, excessively aggres- to 16 percent for adult males, and to 42 percent for sive adolescent human and monkey males have adolescent males. Reports by women increased been found to have lower levels of serotonin. Alco- from 20 percent to 75 percent of adult women, and hol and carbohydrates increase brain levels of sero- to a high of 90 percent for adolescent women. Other tonin. Low levels of serotonin are associated with studies indicate that between 25 and 44 percent of depression and eating disorders. Doctors prescribe female drug abusers report childhood sexual abuse serotonin-uptake inhibitors, such as fluoxetine compared to 15 percent of nonaddicted women. (Prozac), to reduce mental disorder like depression Psychological conflicts arising from childhood and bulimia. sexual abuse are often a hidden factor contributing Psychosocial risk factors for child abuse include to drug abuse and relapse. Sexually molested chil- the following: dren are reported to experience boundary inade- quacy, resulting in difficulty establishing and en- 1. Modeling Physical and Sexual Abuse and Vio- forcing the personal, psychological, or social lence as seen in the child’s home as enacted by boundaries necessary to maintain a sense of the adults or the abuser’s friendship groups, or as self that is separate from other people. Hence, sur- portrayed in popular media (movies, television, vivors of childhood sexual assault often do not see radio). Drug abusers often belong to subcultures themselves as individuals separate from the desires where violence is common. Children raised in 250 CHILD ABUSE AND DRUGS

violent homes are more likely to become abusers and narcissism are less empathic toward their as adults, thus perpetuating the cycle of children’s suffering. It is harder to decenter violence. from their own perspective, needs, and emotions 2. Family Violence and Conflict. High levels of in order to consider the child’s feelings. Depres- family conflict found in drug-abusing families sion, bipolar disorder, and psychosis can cause can lead to family violence. Absence of empathy parents to become angry, irrational, and abu- and support among family members in the sive. Parents with personality disorders are less home environment increases the risk of child likely to internalize societal taboos against child abuse and family violence. Ironically, women abuse and sexual abuse. who are victimized by their spouses have preg- 6. Physical Illness and Handicaps. Physical illness nancy rates 2.3 times higher than national aver- and physical handicaps can reduce the patience ages. Children growing up in abusive homes parents need to handle the stress inherent in experience increased anxiety, powerlessness, dealing with children. Physical illness is more and self-deprecation, which may lead to ATOD common in ATOD-abusing families because of abuse and, in turn, to aggression, conflict, and their lifestyle and lack of preventive health care. physical/sexual abuse of others. Intravenous drug abusers and their children 3. Poor Parenting Skills. Drug-abusing parents or have higher rates of common infections, as well caretakers have been found to have less ade- as increased exposure to diseases transmitted quate parenting skills, spend less time with their through the blood (HIV/AIDS and hepatitis), children, have unrealistic developmental expec- sexually transmitted diseases (syphilis, gonor- tations that can lead to excessive punishment, rhea, and herpes), and tuberculosis. and lax, overly severe, or inconsistent discipline. 7. Criminal Involvement. Drug-abusing parents Verbal abuse in the form of threatening, chastis- are at high risk for criminal involvement by ing, belittling, and criticizing are common. nature of their use alone or by the need to obtain Studies have found that drug-abusing parents, considerable sums of money to support their whether in recovery or not, are able to increase habit. Prostitution, theft, and drug dealing are their parenting skills after participating in a reported in about half of all drug-abusing par- 14-week parent-training program (The ents. Arrest and incarceration may increase the Strengthening Families Program). stress on the family and can reduce inhibitions 4. Poverty and Stress. Many children of drug- to sexual abuse upon reunification of the family. abusing parents or caretakers are raised in pov- erty. Money that would normally be available Children of ATOD abusers frequently are more for food, clothing, transportation, medical and difficult to parent because of the increased preva- dental care, and to provide social and educa- lence of ATTENTION DEFICIT DISORDER (ADD), hy- tional opportunities for the children is often di- peractivity, CONDUCT DISORDERS, and learning dis- verted into purchases of tobacco, alcohol, and orders. Some of these difficult temperament drugs. Crack-addicted parents sometimes use characteristics are caused by in utero exposure to food stamps and welfare checks to purchase drugs, some by genetic inheritance, and others by crack. Lack of money to handle daily crises lack of nurturing and inconsistent parenting. Re- elevates the usual level of life stressors and in- gardless of the cause, children of ATOD-abusing creases parental anger and irritability. Unem- parents are frequently the most difficult to raise, ployment, which frequently results in low self- even if they are raised by unstressed, happy, esteem, can lead to increased child abuse. healthy, non-ATOD-abusing parents. 5. Mental Disorders. Approximately 90 percent of drug abusers have other mental disorders, such PROPOSED RESPONSES as depression, bipolar-affective disorder, narcis- sism, ANTISOCIAL PERSONALITY, organic brain Reasonable evidence exists to indicate that chil- disease, and psychosis. Mental disorders of this dren who are raised by ATOD-abusing parents are nature can have a severe impact on a person’s at increased risk of abuse and neglect, as well as of ability to parent and can lead to child abuse. subsequent addiction and delinquent behaviors. Parents suffering from antisocial personality Additional research is needed on the long-term ef- CHILDHOOD BEHAVIOR AND LATER DRUG USE 251

fects of reported physical or sexual abuse. Because BIBLIOGRAPHY of the high overlap between child abuse and drug ADAMS, E. H., GFROERER, J. C., & ROUSE, B. A. (1989). abuse, ATOD treatment agencies should routinely Epidemiology of substance abuse including alcohol ask their clients if they have been or are being and cigarette smoking. Annals of the New York Acad- physically or sexually abused. It is also important that child-welfare agencies routinely determine emy of Science, 562, 14. whether caregiver or family member ATOD abuse BURGESS,A.(ED.). (1985). Rape and sexual assault:A is contributing to the maltreatment of children. research handbook. New York: Garland. Because it is not possible to remove all children CWLA NORTH AMERICAN COMMISSION ON CHEMICAL from risky family environments, additional re- DEPENDENCY AND CHILD WELFARE. (1992). Children search is needed on ways to protect children. at the front:A different view of the war on alcohol and Caregivers and professionals can help maltreated drugs. Washington, DC: Child Welfare League of children to avoid abuse or become more psycho- America. logically resilient to future ATOD abuse. Some CONTE, J. R., & BERLINER, L. (1988). The impact of children are resilient to negative outcomes, even sexual abuse on children: Empirical findings. In though they were exposed to drugs in utero or L. E. A. Walker (Ed.), Handbook of sexual abuse of lived with drug-abusing parents. Some of these children. New York: Springer. children were really never exposed to the same FINKELHOR, D. (1984). Child sexual abuse:New theory degree of negative influences because they were and research. New York: Free Press. sheltered by a caring adult who addressed their FINKELHOR, D. (1986). A Sourcebook on child sexual needs. The emerging literature on resiliency pro- abuse. Beverly Hills: Sage. cesses and mechanisms should be reviewed and RUTTER, M. (1990). Psychosocial resilience and protec- used to inform resiliency research with children of tive mechanisms. In J. E. Rolf et al. (Eds.), Risk and drug abusers and to make prevention interven- protective factors in the development of psychopathol- tions more effective. ogy. New York: Cambridge University Press. Negative outcomes primarily appear to be re- KAROL L. KUMPFER lated to the physical and emotional abuse and ne- JAN BAYS glect typically endured by children of drug-abusing parents. Even children of drug-addicted mothers can be resilient to their high-risk environments if their mothers realize the negative impact of their CHILDHOOD BEHAVIOR AND LATER chaotic street lives on their infants and work to DRUG USE Social scientists can point with con- improve their parenting skills. This may include fidence to risk factors from childhood that predict finding external supports to learn parenting skills, drug use and deviance in adolescence. In general, such as parent-and-family-skills training pro- the findings indicate that certain childhood person- grams, locating good early-childhood education for ality traits, family experiences, and ecological fac- the child and outside child care, and possibly even tors strongly affect adolescent drug-using behavior. considering foster care or adoption. Research has A child who is irritable and easily distracted, shown more positive outcomes for drug-exposed in- who throws temper tantrums, fights often with sib- fants if the mothers were willing to use whatever lings, and engages in predelinquent behavior is external social supports were necessary to provide more likely than others to use drugs in adolescence. the best opportunities for learning and emotional Other investigators have also found childhood AG- growth for the child. Such mothers clearly were GRESSION to be a most powerful predictor of adoles- able to understand and empathize with their chil- cent drug use and deviance. dren’s needs and were willing to separate from their Poor childhood impulse control and a difficult infants for short or long periods, if necessary, for temperament have been related to adolescent mari- the welfare of their children. juana use. When problematic factors continue into adolescence, both the use of illicit drugs and the (SEE ALSO: Childhood Behavior and Later Drug psychopharmacological effects of some drugs may Use; Coping and Drug Use; Family Violence and then actually serve to exacerbate and enlarge the Substance Abuse; Poverty and Drug Use) adolescent’s feelings of irritability and aggressive- 252 CHINA ness—as evidenced by continuing temper tan- ment of a child at risk. Where needed or warranted, trums, aggression, and delinquent behavior. early intervention may facilitate the development In addition to childhood personality traits that of later drug-resistant personality traits—a posi- predict future drug use, family experiences can also tive parent-child bond and association with non- serve as predictors. In a longitudinal study dealing deviant peers—and, consequently, the result with the early childhood precursors of adolescent should be lower drug use in the adolescent. drug use, researchers found that greater mother As children grow up, there are also several later involvement with the child protected against later points and distinct psychological domains at which drug use. It has also been found that children who it is possible to ameliorate drug use. During adoles- became frequent drug users had mothers who were cence, for example, a decrease in the risk factors cold and who gave them little encouragement. The that relate to personality, family, or peers may also connection between peer factors during childhood result in less to no drug use. and later drug use has received little empirical study, although peer factors during adolescence are (SEE ALSO: Child Abuse and Drugs; Conduct Disor- of demonstrable importance and have long been ders; Coping and Drug Use; Families and Drug known to be so. Childhood ecological factors, such Use; Family Violence and Substance Abuse; Poverty as relatively low socioeconomic status, are related and Drug Use) to greater adolescent drug use. Factors from childhood do not directly affect BIBLIOGRAPHY adolescent drug use; rather, they are mediated by the factors of adolescence. More specifically, the BLOCK, J., BLOCK, J. H., & KEYES, S. (1988). Longitudi- risk factors of childhood are associated with the nally foretelling drug usage in adolescence: Early risk factors of adolescence—and these, in turn, childhood personality and environmental precursors. become related to drug use. Child Development, 59, 336–355. The risk factors of adolescence include aspects BROOK, J. S., WHITEMAN, M., & FINCH, S. (1992). Child- of unconventionality (such as rebelliousness); diffi- hood aggression, adolescent delinquency and drug culty in the parent-child mutual attachment rela- use: A longitudinal study. Journal of Genetic Psychol- tion (such as low parental affection and identifica- ogy, 153(4), 369–383. tion); and the adolescent’s associating with deviant BROOK, J. S., ET AL. (1992). African-American and peers. More specifically, findings indicate that non- Puerto Rican drug use: Personality, familial, and achieving aggressive children—those with diffi- other environmental risk factors. Genetic, Social, and culty in emotional control and those who have re- General Psychology Monographs, 118(4), 417–438. ceived little economic and psychosocial support— COHEN, P., COHEN, J., & BROOK, J. S. (1993). An epide- are most likely to be rebellious adolescents, to have miological study of disorders in late childhood and a conflictual, nonaffectionate relationship with adolescence—II. Persistence of disorders. Journal of their parents, and to be associated with deviant Child Psychology and Psychiatry, 34(6), 869–877. peers. Adolescent rebelliousness, difficulty in the LOEBER, R. T. (1991). Antisocial behavior: More endur- parent-child attachment, and associating with de- ing than changeable? Journal of the American Acad- viant peers are the factors related to greater drug emy of Child and Adolescent Psychiatry, 30, 393–397. use in adolescence. MCCORD, J. (1981). Alcoholism and criminality. Journal of Studies on Alcohol, 42, 739–748. PREVENTION AND TREATMENT SHEDLER, J., & BLOCK, J. (1990). Adolescent drug use and psychological health: A longitudinal inquiry. Because the risk factors of both childhood and American Psychologist, 45, 612–630. adolescence come from different domains, a multi- factorial approach to drug-use prevention and JUDITH S. BROOK treatment is essential. Moreover, since childhood PATRICIA COHEN drug-prone personality characteristics and adverse childhood experiences seem to determine adoles- cent risks for drug use, logic and social responsibil- CHINA See Asia, Drug Use In; Golden Trian- ity dictate that one intervene early in the develop- gle CHINESE AMERICANS, ALCOHOL AND DRUG USE AMONG 253

CHINESE AMERICANS, ALCOHOL AND into a new cultural setting, their alcohol use may be DRUG USE AMONG In 1980, the Chinese- influenced by the extent to which they adopt the American community, with a population of values of the surrounding culture. Sue (1987) 812,178, comprised the largest subpopulation of states that alcohol abuse is more congruent with Asian/Pacific Islanders in the United States. Dur- American than Chinese values, since Chinese val- ing the 1980s, the population of Chinese Ameri- ues are antithetical to alcohol abuse. This ‘‘accul- cans nearly doubled—1,618,973 according to the turation hypothesis’’ (Austin & Lee, 1989) has re- 1990 data from the U.S. Bureau of the Census ceived mixed support with respect to the experience (although the Filipino-American community had of Chinese Americans. This suggests that more in- by then become the largest Asian subgroup). The vestigation is necessary to help determine which largest numbers of Chinese Americans reported in influences result in the retention of cultural values the 1990 census are in the states of California and which result in adaptation to the new culture. (704,850), New York (284,144), Hawaii (68,804), Texas (63,232), New Jersey (59,084), OPIUM Massachusetts (53,792), and Illinois (49,936). The Chinese-American ethnic community actually OPIUM is thought to have been introduced to consists of people from many countries, and recent China by Arab traders during the ninth century. waves of immigration especially contribute to the Initially, it was taken internally as medicine heterogeneity of this ethnic group. Chinese immi- (Singer, 1974). Not until the mid-seventeenth cen- grants have come to the United States from British tury was the practice of smoking opium (usually in Hong Kong, the People’s Republic of China, the pipes) introduced by the Portuguese. Little of the Republic of China (Taiwan), and from various opium poppy (Papaver somniferum) was actually countries in Southeast Asia, Latin America, and grown or used in China before the sixteenth cen- the Caribbean. Approximately 63.3 percent of the tury. By the eighteenth century, however, opium Chinese-American respondents to the 1980 census had become a profitable cash cargo—from British had been foreign (non-U.S.) born. India to China’s ports, where foreigners were al- lowed only confined access to trade—for the Portu- guese, Dutch, and English—and then after 1810 ALCOHOL for the Americans (Goodie, 1963). Smoking opium In China, historically, alcohol was sanctioned for had become so widespread and so debilitating in religious ceremonies, especially ancestor worship. China that its sale was forbidden by imperial de- Today, in China and among Chinese immigrants, cree as early as 1729 and its importation was pro- alcohol is commonly served at celebrations and hibited in 1800. The emperor’s declarations were banquets, and some people consume alcohol at not universally honored, however, and much dis- meals—beer, wine, brandy, or whiskey. Drinking- agreement existed on how to deal with opium ad- centered institutions, however, are absent (Hsu, dictions, the drain of silver to foreigners, and the 1955; Singer, 1972; Wang, 1968). In Chinese tra- tribute system of then-developing foreign relations dition, moderate drinking is believed to have me- (Fairbank, Reischauer, & Craig, 1965). dicinal effects, but excessive use is believed to bring Meanwhile, an illicit opium trade continued to on ‘‘nine-fold harm’’ (Yu & Liu, 1986/87) and is grow—for example, from approximately 5,000 condemned in folk culture as one of the four vices. chests imported to Canton in 1821 by British Many hypothesize that cultural influences are im- traders to approximately 30,000 chests by the late portant in shaping drug-use patterns as well as 1830s (Fairbank, Reischauer, & Craig, 1965). Ef- beliefs about drug use. Some research ties cultural forts in an anti-opium campaign were stepped up, beliefs to differences in drinking patterns, despite and hostilities between China and Britain eventu- similarities in availability (Glassner & Berg, 1980; ally led to the Opium Wars. Britain had asserted Mizruchi & Perrucci, 1962). that it was not bound by the trade restrictions Chinese cultural beliefs regarding the religious imposed on Canton, and Britain won the wars. As a and medicinal benefits of moderate drinking and result, Hong Kong, a major port and center for all the harm associated with excessive use may control kinds of trade, was ceded to Britain in 1842. Illicit drinking patterns in China, but when people move opium remained an important export until 1911, at 254 CHINESE AMERICANS, ALCOHOL AND DRUG USE AMONG which time the British Parliament forbade its ship- CONCLUSION ment to China. By this time, however, cultivation of More rigorous surveys are still needed to obtain the opium poppy was flourishing in China, and an accurate picture of alcohol- and other drug-use markets for MORPHINE,HEROIN, and other narcotic patterns among Chinese Americans. Since this is a concentrates were growing. Although opium dens heterogeneous group, future studies should take provided an atmosphere and opportunity for drug into account whether people in the sample are U.S. use by individuals or as a social activity, in China or foreign born, their country of origin, their degree opium smoking remained one of the four vices. of acculturation, and other demographic character- Much of the research on ALCOHOL and other istics that will provide a better basis for comparison drug use has grouped all Asians and Pacific with other groups. Islanders together. Only two studies have compared Although it has long been asserted that re- Asian groups, and they have suggested significant sponses to drug problems should be sensitive to differences among them. In a 1981 study con- cultural diversity, until recently little research has ducted in Los Angeles, Kitano and Chi (1986– focused on drug use among people other than 1987) found differences in alcohol consumption blacks or whites in the United States. Such research patterns among respondents from four groups of would be useful for developing culturally appropri- Asians: Chinese, Japanese, Korean, and Filipino. ate interventions. Most of the respondents were from thirty to sixty- one years old. Except in the Japanese sample, the (SEE ALSO: Ethnic Issues and Cultural Relevance in majority were foreign born and most had an aver- Treatment; Ethnicity and Drugs; Papaver somni- ferum) age annual income of 20,000 to 30,000 dollars. Among these four groups, the following identified themselves as abstainers: 31.2 percent of Chinese BIBLIOGRAPHY males and 68.8 percent of females; 32.8 percent of AUSTIN,G.,&LEE, H. (1989). Substance abuse among Japanese males and 33.8 percent of females; 34.5 Asian-American youth (Prevention Research Update percent of Filipino males and 80.0 percent of fe- 5, Winter). Portland, OR: Western Center for Drug- males; and 45.8 percent of Korean males and 81.6 Free Schools and Communities. percent of females. CAHALAN,D.,&CISIN, I. H. (1976). Drinking behavior The lowest prevalence of heavy drinking was and drinking problems in the United States. In B. reported by Chinese Americans (14% male, 0% Kissin & H. Begleiter (Eds.), Social aspects of alco- female), followed by Koreans (25.8% male, 0.8% holism. New York: Plenum. female), Filipinos (29.0% male, 3.5% female), and CHI, I., KITANO,H.H.L.,&LUBBEN, J. E. (1988). Male Japanese (28.9% male, 11.7% female). Most of the Chinese drinking behavior in Los Angeles. Journal of male heavy drinkers were in the age category 26– Studies on Alcohol, 49(1), 21–25. FAIRBANK, J. K., REISCHAUER, E. O., & CRAIG,A.M. 35 among Chinese, in the age category 36–45 (1965). East Asia:The modern transformation . Bos- among Koreans, and evenly divided among age ton: Houghton Mifflin. categories for Japanese and Filipinos. GLASSNER, B., & BERG, B. (1980). How Jews avoid alco- Kitano and Chi found that among Chinese hol problems. American Sociological Review, 45, Americans in their Los Angeles sample those most 647–664. likely to drink at any level were men, under the age GOODRICH, L. C. (1963). A short history of the Chinese of forty-five, and of relatively high social and edu- people. New York: Harper & Row. cational background. They found that parental HSU, F. L. K. (1955). American and Chinese. London: drinking and going to or giving parties were the Cresset Press. most important variables distinguishing drinkers KITANO,H.H.L.,&CHI, I. (1986–1987). Asian-Ameri- from abstainers among their Chinese adult male cans and alcohol use. Alcohol Health and Research sample (Chi, Kitano, & Lubben, 1988). Going to World, 11(2), 42–47. bars and having friends who drank were also sig- MIZRUCHI, E. H., & PERRUCCI, R. (1962). Norm qualities nificant factors. and differential effects of deviant behavior: An ex- CHOCOLATE 255

ploratory analysis. American Sociological Review, 27, CHLORDIAZEPOXIDE Chlordiazepoxide 391–399. (brand name Librium) is a member of the SINGER, K. (1974). The choice of intoxicant among the BENZODIAZEPINE family of drugs currently used to Chinese. British Journal of Addiction, 69, 257–268. treat insomnia, anxiety, muscle spasms, and some SINGER, K. (1972). Drinking patterns and alcoholism in forms of epilepsy. It was the first benzodiazepine to the Chinese. British Journal of Addiction, 67, 3–14. be used in clinical practice in the 1960s, as an alternative to PHENOBARBITAL or MEPROBAMATE,in SUE, D. (1987). Use and abuse of alcohol by Asian Amer- treating psychoneuroses, anxiety, and tension. Its icans. Journal of Psychoactive Drugs, 19(1), 57–66. advantage over BARBITURATES and other central WANG, R. P. (1968). A study of alcoholism in Chinatown. nervous system depressants is that it is less toxic, International Journal of Social Psychiatry, 14, 260– especially after an overdose. 267. In addition to the previously mentioned uses, YU, E. S. H., & LIU, W. T. (1986/87). Alcohol use and chlordiazepoxide is frequently used to treat the sei- abuse among Chinese-Americans. Alcohol Health and zures or DELIRIUM TREMENS (DTs) that appear dur- Research World, 11(2), 14–17, 60. ing alcohol withdrawal. In the late 1990s, Dr. Mi- RICHARD F. CATALANO chael Mayo-Smith conducted a meta-analysis to TRACY W. HARACHI determine if benzodiazepines effectively prevent delirium in patients experiencing DTs. Although benzodiazepines were shown to be effective, this study was not conclusive since chlordiazepoxide CHLORAL HYDRATE Chloral hydrate is was the only benzodiazepine tested, and further one of the oldest sedative agents still in use. It was testing is needed on other benzodiazepines before made by the German chemist Liebig in 1832 and an overall claim can be made (Johnson et al., introduced into general use in 1869 as a substitute 1997). for LAUDANUM, an alcoholic solution of OPIUM. Chloral hydrate differs from the BARBITURATES in BIBLIOGRAPHY that it is a simple molecule composed of two carbon atoms, three hydrogen atoms, two oxygen atoms, JOHNSON, J. R., ET AL. (1997). Pharmacologic treatment and three chloride atoms. It is the famous (or infa- of alcohol withdrawal. JAMA, The Journal of the American Medical Association, 278, 1317–1319. mous) substance added to alcohol to make a CHLORDIAZEPOXIDE AND CLIDINIUM (2000). USP DI Vol- Mickey Finn, a drink known to cause those who ume II Advice for the Patient: Drug Information in drink it to become unconscious. Because it shares Lay Language, 93. many effects of other central nervous system de- SCOTT E. LUKAS pressants, it can be used to treat the alcohol with- REVISED BY REBECCA MARLOW-FERGUSON drawal syndrome. Chloral hydrate was a popular sedative for elderly patients because its effects oc- cur quickly, last only a short time, and leave no nagging hangover effect. However, it is inconve- CHOCOLATE An ingredient of many popu- lar treats—candies, sweets, baked goods, soft nient to use (up to 2 grams must be taken by drinks, hot drinks, ice cream, and other frozen mouth) and, after the introduction of the desserts. It is prepared, often as a paste, from the BENZODIAZEPINES, its use has decreased. roasted crushed seeds (called cocoa beans) of the small South American cacao tree called Theobroma BIBLIOGRAPHY cacao (this is not the shrub known as the COCA PLANT, which produces COCAINE, Erythroxylon HARVEY,STEWART C. (1980). Hypnotics and sedatives. coca). In A. G. Gilman, L. S. Goodman, & A. Gilman (Eds.), The cacao tree has small yellowish flowers, fol- Goodman and Gilman’s the pharmacological basis of lowed by fleshy yellow pods with many seeds. The therapeutics, 6th ed. New York: Macmillan. dried, partly fermented fatty seeds are used to SCOTT E. LUKAS make the paste, which is mixed with sugar to pro- 256 CHROMOSOME

CHROMOSOME Chromosomes are struc- tures in the nucleus of the cell that contain the DNA or hereditary material which form genes. Genes are the commonly known units of heredity, and some may contribute to a tendency toward addiction in ways that are not yet understood. Each chromo- some is an elongated structure that is clearly visible during cell division. Humans possess twenty-three pairs including the sex chromosomes. A male has an X and a Y sex chromosome, whereas a female has two X sex chromosomes. One of each pair comes from each parent. Figure 1 MICHAEL J. KUHAR Cacao Leaves and Pod duce the chocolate flavor loved throughout the CHRONIC PAIN Chronic or persistent pain world. Cocoa butter and cocoa powder are other is defined as pain that lasts for longer than six important extracts from the bean. Cocoa beans months. Chronic pain can stem from cancer, ill- were introduced to Europe by the Spanish, who ness, injury, or postsurgical changes. Often, per- brought them back from the New World in the sons with chronic pain suffer from syndromes that sixteenth century. They had first been used by the cannot be confirmed by laboratory tests. These civilizations of the New World—Mexicans, Aztecs, chronic pain syndromes include central pain syn- and Mayan royalty—in a ceremonial unsweetened dromes, fibromyalgia, headache, lower back pain, drink and as a spice in special festive foods, such as myofascial pain syndrome, neuropathic pain, and mole´. They were first used in Europe by the privi- phantom limb pain. Frequent locations of chronic leged classes to create a hot, sweet drink. By the pain include the back, head, joints, chest, abdo- seventeenth century, cocoa shops and COFFEE men, and extremities. Chronic pain is common and shops (cafe´s) became part of European life, serving its sufferers are more likely to have anxiety or de- free TOBACCO with drinks and thereby increasing pression, have poor perception of their health, de- trade with the New World colonies. creases in their quality of life, and experience a Chocolate produces a mild stimulating effect disruption of their livelihood than those who are caused by the THEOBROMINE and CAFFEINE it con- not in pain. tains. Both are ALKALOIDS of the chemical class In most cases, there is no cure for the chronic called xanthines. Theobromine in high doses has pain so treatment is aimed at pain control and many effects on the body, and it is possible to rehabilitation. Unfortunately, chronic pain is often become addicted to some xanthines, such as caf- ineffectively treated because physicians can be re- feine. Nevertheless, some people are so attracted to luctant to prescribe strong, potentially addictive the flavor that compulsive or obsessive use has re- medications. The ineffective pain treatment is com- sulted in the newly coined term chocoholic. Some pounded by commonly associated conditions such scientists are researching the phenylethylamine in as depression, insomnia, fatigue, and a decrease in chocolate as the factor that encourages compulsive general physical functioning. Therefore, treating chocolate ingestion. the pain alone is not sufficient. The optimal approach to the chronic pain suf- BIBLIOGRAPHY ferer is an interdisciplinary team that may be com- prised of a pain management physician, nurse spe- SERAFIN, W. E. (1996). Drugs used in the treatment of cialist, psychologist, physical therapist, asthma. In J. G. Hardman et al. (Eds.), The Pharma- pharmacist, and vocational counsellor. The physi- cological Basis of Therapeutics, 9th ed. (pp. 659– cian conducts a thorough assessment of the patient 682). New York: McGraw-Hill. and determines the appropriate medical interven- MICHAEL J. KUHAR tions. The psychologist conducts a thorough psy- CHRONIC PAIN 257 chological assessment, educates the patient on consciousness (e.g. drowsiness, sedation, confu- techniques to reduce pain, and tends to any associ- sion), nausea, vomiting, constipation, urinary re- ated mental health illnesses. The nurse specialist tention, and itching. acts as a case manager and educator. The physical Other medications used in the treatment of therapist ascertains the patient’s physical endur- chronic pain include antidepressants and anticon- ance, flexibility, and strength and conducts the vulsants. Nerve blocks, injection of anesthetics into physical rehabilitation process. The vocational trigger points, or injection of steroids into the epi- counsellor identifies and devises strategies to allow dural space of the spinal cord may also be utilized. the patient to return to work. In addition to dis- Implantable methods are utilized as treatments of pensing medications, the pharmacist will review last resort. These methods involve implanting drug past and present use of medicinal agents and edu- delivery systems or electrodes into specific areas of cate the patient on the proper use of medications. the spinal cord.

PHARMACOLOGICAL MANAGEMENT TOLERANCE, DEPENDENCE, OF CHRONIC PAIN AND ADDICTION In the treatment of chronic pain, drugs (analge- The continued use of opioids leads to tolerance, sics) are usually administered in a stepwise fashion in which increasingly higher doses of drug must be beginning with mild, relatively safe agents and used to obtain the original level of pain relief. Tol- progressing to stronger agents as necessary. In erance develops slowly, occurring over a period of 1986, the World Health Organization (WHO) pro- months to years. Cross-tolerance to other opioids posed a stepwise plan, frequently called the develops, although to a lesser extent. Tolerance can ANALGESIC LADDER, for the oral treatment of cancer be differentiated from physical dependence and ad- pain. This plan provides adequate pain relief for up diction. to 90 percent of cancer patients but may have Physical dependence is a characteristic of opioid limited success for other chronic pain patients. Step use because of the mode of action. It reflects a state one of the ladder is recommended for patients with of neurological adaptation to the drug. With physi- mild pain and consists of nonopioid analgesics, step cal dependency, discontinuation of opioid use leads two is for moderate pain and consists of mild opi- to withdrawal symptoms (e.g. sweating, tearing, oids, and step three is for severe pain and consists rapid heart rate, nasal discharge, abdominal of strong opioids. More than one analgesic may be cramps, nausea, and vomiting). To prevent with- used at a time for an added effect, a procedure drawal symptoms, patients on long term opioid use called adjuvant therapy. are gradually weaned off the medication. Physical Nonopioid analgesics consist of acetaminophen dependence on opioids does not lead to addiction, and nonsteroidal anti-inflammatory drugs although it may compel the patient to seek opioids (NSAIDs). Acetaminophen is an effective analgesic to relieve symptoms of withdrawal. that has a minimal side effect profile. Nonsteroidal For chronic pain patients taking opioids, toler- anti-inflammatory drugs have both analgesic and ance and physical dependence are not indicators of anti-inflammatory properties. Examples of non- addiction. Addiction is not a characteristic of opi- steroidal anti-inflammatory drugs are aspirin, oid use, rather, it is dependent upon the user. In ibuprofen, naproxen, meclofenamate, piroxicam, fact, the medical use of opioids is only very rarely and more recently celebrex and vioxx. Major side associated with addiction. The agonist-antagonist effects associated with the use of nonsteroidal anti- class of opioids (buprenorphine, butorphanol, inflammatory drugs include kidney toxicity, bleed- nalbuphine, pentazocine, and dezocine) has a low ing disorders, and stomach disorders. abuse potential. Opioid analgesics are available in different Any patient taking opioids to treat chronic pain strengths. Examples of opioid analgesics are mor- can meet the criteria for addiction set forth by the phine, fentanyl, methadone, and meperidine. The American Psychiatric Association in the Diagnostic side effects of opioids may be much more serious and statistical manual of mental disorders:DSM- than those seen with nonopioid analgesics. Side ef- IV. Therefore, it is very difficult to diagnose addic- fects include respiratory depression, alterations in tion in chronic pain patients who are taking opi- 258 CIGARETTE COMPANIES oids. Chronic pain patients who are being ineffec- an extended period of time for any treatment to be tively treated could display the drug-seeking meaningful. Civil commitment is a useful strategy behavior that is characteristic of addiction, a phe- for diverting into treatment those who ordinarily nomenon called pseudoaddiction. Alternatively, would not seek assistance voluntarily, and it has the patient receiving effective pain treatment may been shown to suppress daily narcotic use and take extreme measures to insure an adequate sup- criminal involvement (Leukefeld & Tims, 1988). ply of medication. This behavior is termed thera- peutic dependence. HISTORICAL CONTEXT Suggestive signs of addiction within the context of opioid therapy for chronic pain include: The concept of compulsory treatment for drug abusers in the United States was proposed shortly ● Loss of control over opioid use; after Congress passed the Harrison Act of 1914. By ● Preoccupation with the use of opioids despite 1919, the Narcotics Unit of the U.S. Treasury De- adequate pain control; and partment had convinced Congress to establish a ● Continued use of opioids even with their ad- chain of federal ‘‘narcotics farms,’’ where heroin verse consequences. users convicted of federal law violations could be incarcerated and treated for addiction (Inciardi, BIBLIOGRAPHY 1988). The first of such farms, established in 1935, was the U.S. Public Health Service Hospital in Lex- ASHBURN,M.A.&RICE, L. J. (1998). The Management ington, Kentucky. Three years later, a sister hospi- of Pain. New York, NY: Churchill Livingstone. tal was established in Fort Worth, Texas. The goal ASHBURN,M.A.&STAATS, P. S. (1999). Management of of the facilities was to use vocational and psychiat- chronic pain. Lancet, 353, 1865-1869. ric therapy to help free the addicts of their psycho- GALLAGHER,R.M.(ED.) (1999). The medical clinics of logical dependence on drugs, to treat withdrawal North America: Chronic pain. Philadelphia, PA: W. B. illness, and to correct mental and social problems. Saunders Company. Follow-up studies from Lexington in the 1940s in- BELINDA ROWLAND dicated that addicts treated under legal coercion with posthospital supervision had better outcomes than voluntary patients, primarily because volun- CIGARETTE COMPANIES See tary patients rarely completed the treatment pro- Advertising and Tobacco Use gram (Maddux, 1988). However, later studies failed to support these early positive findings. Dur- ing the 1950s, hospital staff members recom- CIGARETTES AND SMOKING See mended the enactment of a federal civil commit- Nicotine; Tobacco, History of; Treatment: To- ment law for narcotic addicts, but legal counsel in bacco, An Overview the Department of Health, Education, and Welfare considered such a law unconstitutional. Then in 1962, President John F. Kennedy convened a White House Conference on Narcotic CIRRHOSIS See Complications: Liver and Drug Abuse where nearly all members ap- proved the civil commitment of narcotic addicts. Civil commitment was advocated as protection for CIVIL COMMITMENT The term com- society and rehabilitation for the individual. A monly used for compulsory treatment is civil com- compulsory treatment program aimed at the fed- mitment. Typically, civil commitment serves as an eral offender was enacted by the NARCOTIC ADDICT alternative to incarceration (prison) by providing REHABILITATION ACT (NARA) of 1966. By that compulsory, court-ordered treatment for chronic time, about twenty-five states had laws permitting drug abusers, especially antisocial addicts respon- civil commitment, and a few major programs were sible for committing a large number of criminal enacted in response to public fears of growing acts. It is generally believed that narcotic addicts drug-related street crime (Inciardi, 1988). Califor- must be brought into a supervised environment for nia, in 1961, launched its Civil Addict Program CIVIL COMMITMENT 259

(CAP), the first large-scale civil commitment pro- daily heroin use as well as in property crime and gram to be implemented in the United States. Be- antisocial activities. Although many patients did cause of its relative success, in 1966, New York’s become readdicted at some point, their relapses Narcotic Addiction Control Commission (NACC) were typically of shorter duration and less frequent established the largest and costliest civil commit- than those not involved in treatment (Anglin, ment program in history—the NEW YORK STATE 1988). The general conclusion drawn from these CIVIL COMMITMENT PROGRAM. studies was that civil commitment, when ade- quately implemented, might be an effective means CIVIL COMMITMENT PROGRAMS of reducing narcotic addiction and of minimizing adverse, addiction-related behavior. Repeated in- The federal NARA and the California and New terventions are typically required, however, be- York compulsory treatment programs had a similar cause drug dependence is a chronic condition intent: They made it possible for the necessary marked by relapses (Leukefeld & Tims, 1988). legislation to be enacted and for commitment pro- cedures to be carried out. They served to control LIMITATIONS OF CIVIL COMMITMENT and rehabilitate the compulsive drug abuser by providing secure treatment environments as an al- Civil commitment helps get drug abusers into ternative to regular incarceration in correctional treatment and keeps the abusers in treatment for facilities (Leukefeld & Tims, 1988). Eligible ad- an extended length of time. Outcome studies have dicts convicted of a crime could be committed by generally shown that the success of treatment is the court or could choose commitment over incar- directly related to the amount of time spent in ceration. Addicts not involved in criminal proceed- treatment and that long-term supervision upon re- ings could commit themselves voluntarily or could turn to the community, with objective monitoring be involuntarily institutionalized upon the petition (DRUG TESTING), is an essential component of a of another individual (such as a peace officer) (Mc- successful program. Furthermore, civil commit- Glothlin, Anglin, & Wilson, 1977). Integral to each ment often makes treatment available before a of these programs was supervised aftercare with crime is committed, and it provides clear treatment antinarcotics testing. Length of commitment terms goals rather than only providing punishment ranged from three years in NARA to seven years in (Leukefeld & Tims, 1988). Still, such a program as CAP. civil commitment has serious limitations. It is costly Although nearly all of NARA’s civil commitment and can overwhelm facilities unless adequate fund- programs were generally considered unsuccessful, ing, facilities, and staff have been made available. the funding for community programs contained Many addicts are considered unwilling or unsuit- within the same legislation did provide seed money able for participation. External coercion can bring for the nationwide establishment of some of today’s drug users into treatment, but it cannot assure that basic drug-treatment programs in the community as patients they will participate in treatment. Even (Maddux, 1988). It was also believed that the New with the advent of intensive interventions designed York State Civil Commitment Program failed, and to engage the patients, some patients simply partic- the process of dismantling it began in 1971 (In- ipate passively (Maddux, 1988). Finally, the scope ciardi, 1988). The failure of this program is partly of civil commitment is restricted by constitutional attributable to the fact that it was administered by guarantees of individual liberty. The question re- the social welfare agency of New York State, which mains: Within a free society, to what extent should had little experience controlling addicts. In con- the government curtail the civil liberties of a com- trast, CAP, California’s program, was deemed at pulsive drug user? least moderately effective in modifying behavior, Today, there is an increasing tendency to see because it was implemented through the California civil commitment as control rather than treatment Department of Corrections, which had trained per- and it serves only a limited number of addicts who sonnel who were familiar with treating substance are sufficiently problematic in their behavior to abusers (Anglin, 1988). warrant commitment. The use of such measures as Follow-up studies of the California program civil commitment in a better coordinated and ex- found that participants exhibited reductions in panded fashion, however, could produce significant 260 CLINICAL TRIALS NETWORK individual and social benefits (Anglin, 1988). Civil ioral treatments in diverse patient populations. commitment may also gain more popular support Clinical trials have been used for diseases such as as a means for dealing with intravenous drug users cancer and AIDS as a fast, effective, and safe way to who are at risk for contracting or transmitting test new treatments. Also, as with other diseases, AIDS. there are a number of effective treatments for ad- diction. However, the efficacy of these new treat- (SEE ALSO: Coerced Treatment for Substance Of- ments has been demonstrated primarily in special- fenders; Treatment Alternatives to Street Crime ized treatment research settings, with somewhat [TASC]) restricted patient populations. As a consequence, few of these new drug-abuse treatments are being BIBLIOGRAPHY applied on a wide-scale basis in real-life practice settings ANGLIN, D. (1988). The efficacy of civil commitment in In response, NIDA has established the National treating narcotic addiction. Compulsory treatment of Drug Abuse Treatment Clinical Trials Network drug abuse:Research and clinical practice (NIDA Re- (CTN). The CTN is based on a model used success- search Monograph 86). Rockville, MD: U.S. Depart- fully by other NIH institutes, including the Na- ment of Health and Human Services. tional Cancer Institute, the National Heart Lung INCIARDI, J. A. (1988). Compulsory treatment in New and Blood Institute, and the National Institute of York: A brief narrative history of misjudgment, mis- Allergy and Infectious Diseases. The CTN provides management, and misrepresentation. The Journal of a research infrastructure to test whether new and Drug Issues, 18(4), 547–560. improved treatment components are effective in LEUKEFELD,C.G.,&TIMS, F. M. (1988). An introduc- real-life settings with diverse patient populations. tion to compulsory treatment for drug abuse: Clinical practice and research. Compulsory treatment of drug abuse:Research and clinical practice (NIDA Re- THE CTN STRUCTURE search Monograph 86). Rockville, MD: U.S. Depart- NIDA has established the first six nodes of the ment of Health and Human Services. CTN in various regions of the country. Each node LEUKEFELD,C.G.,&TIMS, F. M. (1988). Compulsory or functional unit of the CTN is affiliated with a treatment: A review of findings. Compulsory treat- research-based organization and a number of drug- ment of drug abuse:Research and clinical practice abuse treatment programs in the community. The (NIDA Research Monograph 86). Rockville, MD: U.S. CTN brings together researchers and practitioners Department of Health and Human Services. as partners to conduct full-scale testing of promis- MADDUX, J. F. (1988). Clinical experience with civil com- ing new medications and behavioral treatments in a mitment. Compulsory treatment of drug abuse:Re- wide range of community drug-abuse treatment search and clinical practice (NIDA Research Mono- settings with patients from a variety of ethnic and graph 86). Rockville, MD: U.S. Department of Health social back-grounds. (The nodes to date include and Human Services. nodes in New England, the Delaware Valley, the MCGLOTHLIN, W. H., ANGLIN,M.D.,&WILSON,B.D. Mid-Atlantic, the Northwest, the Pacific region, (1977). An evaluation of the California Civil Addict Program (Services Research Monograph Series). and New York.) Each of these centers is linked with Rockville, MD: U.S. Department of Health, Educa- at least five community treatment programs in its tion, and Welfare. region. CTN research is carried out in the commu- nity-based treatment setting. Each node works HARRY K. WEXLER with the other nodes and with NIDA to conduct multisite and cross-regional clinical trials research.

CLINICAL TRIALS NETWORK In an ef- THE MISSION OF THE CTN fort to find the most effective treatments for drug addiction, the National Institute on Drug Abuse The overall goal of the CTN is to improve the (NIDA) has established a clinical trials research quality of drug-abuse and addiction treatment network to test new pharmacological and behav- throughout the nation using science as the vehicle. CLONIDINE 261

Toward this end, the mission of the CTN is three- For more information about NIDA’s National fold: Drug Abuse Treatment Clinical Trials Network, visit the NIDA website at www.drugabuse.gov. (1) Conduct studies of behavioral, pharmacologi- ALAN I. LESHNER cal, and integrated behavioral and pharmaco- logical treatment interventions in multisite clinical trials to determine effectiveness across a broad range of community-based treatment settings and diversified patient populations. CLANDESTINE LABORATORIES See (2) Transfer the research results to physicians, Amphetamine Epidemics; Colombia as Drug providers, and their patients to improve the Source quality of drug abuse treatment throughout the country using science as the vehicle. (3) Provide advice on changing policies to ensure the delivery of effective therapies in commu- CLASSIFICATION OF DRUG TYPES nity-based treatment programs. See Drug Types

CURRENT AND FUTURE DIRECTIONS

Three science-based treatment research proto- CLONE, CLONING A clone is a group of cols will start in 2000, including two behavioral organisms that derive from a single ancestor and therapies developed to enhance treatment out- are genetically identical. A clone can be a group of comes, and one that will test a new medication for mammals such as sheep, or a group of cells in use in opiate detoxification. Several other protocols culture. are currently being developed. All treatment com- Cloning cells is a powerful tool in biology and ponents to be tested have been shown to be effective medicine, since growing large quantities of identi- in controlled research environments. cal cells allows for a large harvest of the various When complete, it is expected that the network identical and useful components of these cells. It is will consist of twenty to thirty nodes consisting of possible to construct genetic components in the regional research treatment centers linked to ten to laboratory, place them in cells, and then have the fifteen community-based treatment programs that cells grow and multiply to produce large quantities represent the variety of settings and patient popu- of the components. lations prevalent in that particular region of the Cloning is an essential technique in modern mo- country. The CTN will help ensure that treatment lecular biology; it is used widely in studying genetic research in drug abuse and addiction meets the effects in the drug-abuse field. Cloning much larger needs of the wider community, including minori- organisms such as cows and sheep is expected to ties, women, children, adolescents, and un- have a major impact in that production of the best derserved populations. The CTN will also be useful of any species can theoretically be accomplished by to other aspects of NIDA’s research portfolio. For cloning. This is an important goal in agriculture example, multi-site clinical trials with diverse pa- today. tient populations will provide a valuable resource MICHAEL J. KUHAR to researchers interested in elucidating genetic and environmental determinants of vulnerability. Ulti- mately, increased understanding of the roles played by genetics, environment, and their interaction in CLONIDINE While not itself life-threaten- shaping an individual’s susceptibility to drug ad- ing, the opioid WITHDRAWAL syndrome is ex- diction will lead to a variety of more targeted drug tremely unpleasant and contributes to further opi- abuse prevention and treatment approaches. For oid use and relapse. HEROIN addicts report that the more information, visit NIDA’s website at acute withdrawal syndrome begins in approxi- www.nida.nih.gov. mately eight hours after their last injection and 262 CLONIDINE includes the following: craving for the drug, anxi- Research and clinical experiences since the origi- ety, perspiration, perspiration with hot and cold nal discoveries have (1) supported the notion of LC flashes, tearing of the eyes and nose, restlessness, hyperactivity as one of the neural substrates for the problems sleeping, problems falling asleep, goose opioid withdrawal syndrome; (2) supported the ef- bumps, aching bones and muscles, loss of appetite, ficacy of clonidine—establishing clonidine detoxi- nausea, vomiting, diarrhea, abdominal cramps, fication as one of the standard treatments for adult spontaneous yawning, and a group of symptoms opioid addicts—and extended it to neonates (new- called flu-like. borns) and to alcohol, nicotine, and other drug During the later years of the nineteenth century withdrawals that share a preponderance of behav- and early years of the twentieth, some cures for this iours with opioid withdrawal; (3) demonstrated opioid withdrawal syndrome have been far worse that abstinence could be maintained by some opi- than the withdrawal itself—with some actually oid addicts and that others could benefit from an- causing death. Soon after it became available in the tagonist therapy with NALTREXONE, thanks to clo- mid-nineteenth century, injectable MORPHINE was nidine or accelerated clonidine-naltrexone proposed as a treatment for opium eating; then detoxification; (4) led to considerable progress in heroin or COCAINE were, in the late nineteenth cen- the understanding of the critical cellular event tury, proposed as cures for morphine addiction. causing LC hyperactivity in opioid withdrawal and From the mid-twentieth century until the 1970s, hypoactivity in the presence of clonidine or opioid most medical treatment of the opioid withdrawal agonists; and (5) led to the rapidly expanding clini- syndrome involved either gradual reduction of the cal armamentarium available to treat addicts on dose of opioid or the substitution of METHADONE, the basis of rodent and primate studies. followed by its gradual reduction. In 1978, Gold and coworkers proposed that the nonopiate antihy- CLONIDINE SHORTENS pertensive clonidine could be an effective nonopiate DETOXIFICATION treatment for opiate withdrawal distress. The sci- entific basis for the proposition that clonidine Detoxification of opioid addicts with clonidine would be useful was based on the hypothesis that has been used to facilitate the transition from the opiate withdrawal syndrome was caused by hy- chronic opioid administration to naltrexone (a peractivity or hyperexcitability of a specific brain long-acting opioid ANTAGONIST) or to drug-free nucleus composed of noradrenergic neurons, called status. Naltrexone possesses opioid-blocking action the locus coeruleus (LC). There was considerable at all opioid-receptor sites in the body and brain, neuroscientific research to support this withdrawal rather than having an affinity for a specific type of hypothesis and the rationale for the efficacy of opioid receptor. It is a useful medication for those clonidine. patients willing to take it to prevent relapse. When Since 1977/78, clonidine has been tried in nu- recovering addicts take naltrexone, they make opi- merous inpatient and outpatient opioid addict pop- oid effects unavailable to themselves. The affinity ulations worldwide and studied by researchers in of naltrexone for the receptors is such that they are numerous well-controlled studies. In virtually all unable to feel the effects of heroin, methadone, or studies, clonidine has been shown to be a safe and other exogenous opioids. While the original cloni- effective nonopioid treatment that could control dine treatment protocol of Gold and his colleagues several aspects of opioid withdrawal. Clonidine, (1978a, b) facilitated the initiation of naltrexone while having opiate-like effects in reversing several by avoiding the extra ten-day wait required after aspects of opiate withdrawal, is not an opiate and is the last methadone, an accelerated detoxification therefore not subject to the burdensome regulatory protocol has been developed using naltrexone and CONTROLS that have been placed on the use of clonidine simultaneously. Since clonidine reduces opioids. Clonidine has its most demonstrable ef- precipitated withdrawal as well as the withdrawal fects on autonomic elements of opioid withdrawal: that results from simply discontinuing chronic opi- sweating, gastrointestinal complaints (cramps, di- oid administration, total withdrawal and naltrex- arrhea, nausea), and elevated blood pressure. It one induction time has been shortened to six days does not have substantial capacity to alleviate mus- with little loss in success rate (Charney, Heninger, cle aches, insomnia, or craving for opioids. & Kleber, 1986). CLUB DRUGS 263

OTHER NEW USES JAFFE J. H. (1990). Drug addiction and drug abuse. In A. G. Gilman, et al. (Eds.), Goodman and Gilman’s Clonidine has been tried with varying success in the pharmacological basis of therapeutics, 8th ed. a number of medical problems where the behav- New York: Pergamon. iors, signs, and/or symptoms resemble those seen in MARK S. GOLD opiate withdrawal or following LC electrical or chemical stimulation to a certain degree. Clonidine has also been tried in humans on the basis of nor- CLUBDRUGS Club drugs is a term that adrenergic hyperactivity in generalized and panic encompasses those drugs commonly abused within ANXIETY; obsessive-compulsive symptomatology; the context of the club and rave scenes which have Gilles de La Tourette’s syndrome; mania; ATTEN- developed over the past decade in the United States TION DEFICIT DISORDER; narcolepsy; neuroleptic- and Europe. Club drugs are a diverse group in induced akathisia; ALCOHOL withdrawal and NIC- terms of pharmacology, psychological effect, and OTINE withdrawal; and phaeochromocytoma. Clo- toxicity. They form a unified grouping because of nidine’s ANALGESIC effects have been rediscovered the context in which they are used, the clubs and and given orally, transdermally (skin patches), epi- raves that define turn-of-the-century youth cul- durally (into the area around the spinal canal), and ture. Because of the diversity and pleasure seeking parenterally (by injection)—to decrease anesthetic inherent to the club world, no list of club drugs can requirements and to effect less respiratory depres- pretend to be comprehensive but most lists include sion than OPIOIDS alone. drugs like MDMA,GHB,KETAMINE,ROHYPNOL, METHAMPHETAMINE and LSD. Most of these drugs are perceived by users as relatively benign com- pared to ‘‘older’’ drugs like COCAINE. As might be CONCLUSION expected, this perception is often not borne out in Using clonidine for withdrawal distress allows reality. the brain to reestablish normal homeostatic pat- Many observers of the history of drug use in the terns when given as part of a long-term recovery United States have noted the cyclical nature of patterns of drug use. Few today recall that the co- program. It allows patients sufficient motivation to caine epidemic of the 1980s was in fact the second achieve and sustain drug-free existence. cocaine epidemic in this century, the previous one having ended in the 1930s. Indeed, the lack of a (SEE ALSO: Opioid Complications and With- cultural memory of the lessons of the previous drawal ) epidemic no doubt played a role in the reemergence of the belief that cocaine was a ‘‘safe drug’’ in the 1960s and 70s, a belief that had been popular in the early 1900’s until certain less palatable realities BIBLIOGRAPHY began to sink in. Club drugs seem to fit this pattern CHARNEY, D. S., HENINGER, G. R., & KLEBER,H.D. insofar as the lack of direct experience with the (1986). The combined use of clonidine and naltrex- negative consequences of their use (MDMA for in- one as a rapid, safe and effective treatment of abrupt stance was not recreationally used before the withdrawal from methadone. American Journal of 1980s) imparts the belief that they are a safe means Psychiatry, 143, 817–831. of entertainment. History suggests that such a view is unlikely to stand the test of time. GOLD, M. S. (1991). The good news about drugs and MDMA is new as psychoactive drugs go; it only alcohol. New York: Villard Books. emerged as a recreational drug in the mid-1980s. It GOLD, M. S., REDMOND, D. E., & KLEBER, H. D. (1978a). is an AMPHETAMINE derived HALLUCINOGEN, some- Clonidine in opiate withdrawal. Lancet I, 929–930. times described as an empathogen or entactogen GOLD, M. S., REDMOND, D. E., & KLEBER, H. D. (1978). due to the enhanced feelings of emotional and Clonidine blocks acute opiate symptoms. Lancet II, physical closeness to others it generates in many 599–602. users. Although it has a reputation as a benign 264 COCA-COLA

‘‘love drug,’’ MDMA has contributed to hundreds side of its intense psychological effects LSD has of deaths in its short time as an abused drug. It has few, if any, physiological side effects even when been linked to seizures as well as kidney and car- taken at doses well in excess of those used recrea- diovascular failure. MDMA has produced long- tionally. term neurotoxicity in animals and a number of Club drugs are hardly risk-free, and the next frequent human users have exhibited cognitive and decade or so will probably provide the public with emotional deficits. more evidence of their dangers. A particularly risky Both rohypnol and GHB have gained notoriety and difficult-to-analyze aspect of the club drug as ‘‘date-rape’’ drugs due to their criminally phenomena is that most club drug users use several abused propensity for impairing memory and in- of these drugs as well as TOBACCO and alcohol. ducing unconsciousness. Again, both are fairly new With such a variety of drugs being abused by indi- to the world of recreational drug use, although vidual users, toxic and other dangerous results are rohypnol belongs to the same class of drugs, the far more likely to occur and less predictable in BENZODIAZEPINES,asVALIUM, a drug with a well terms of long-term consequences. known history of abuse. These drugs are especially RICHARD G. HUNTER dangerous when used with ALCOHOL, which exac- erbates their depressant effects often leading to stupor, respiratory depression, and in some cases coma and death. Like alcohol, GHB and rohypnol COCA-COLA See Cola/Cola Drinks seem to cause an increase in violent behavior in some users. These drugs have been linked to such a disproportionate number of negative events that COCA PASTE Coca paste is the first crude many countries have opted to increase restrictions extraction product of coca leaves from the COCA on their use. PLANT; it is obtained in the process of extracting Methamphetamine is an exception to the rule COCAINE from these leaves. The leaves are mashed that club drugs are new; it has a long and well- with alkali and kerosene and then sulfuric acid documented history of abuse and toxic effects. Its (and sometimes also potassium permanganate). appearance on the club scene seems to be linked to The result is an off-white or light-brown paste con- its low cost and the present negative perception of taining 40 to 70 percent cocaine, as well as other cocaine as an alternative PSYCHOSTIMULANT. Meth- ALKALOIDS, benzoic acid, kerosene residue, and amphetamine is substantially more toxic to the sulfuric acid (ElSohly, Brenneisen, & Jones, 1991). brain and liver than cocaine, while sharing some of Peruvian and Bolivian paste is illegally exported to cocaine’s potentially lethal effects on the cardiovas- Ecuador or Colombia, where it is purified into co- cular system. Amphetamine use has also been caine hydrochloride and then illicitly shipped to linked to toxic psychosis. markets throughout the world. Although cocaine is Ketamine is a dissociative anesthetic formerly the major component of coca paste, the paste is used in humans but now largely restricted to veteri- chemically complex, reflecting additives used by nary use. Ketamine shares its major site of action the clandestine laboratories performing the extrac- with PHENCYCLIDINE (PCP) and, like the latter tion from the coca leaves. drug, can produce many of the symptoms of psy- Coca paste, also called cocaine paste or pasta, is chosis in humans including hallucinations and smoked, primarily in Latin American countries, by indifference to pain or death. Given that chronic mixing about 0.2 ounces (0.5 g) of it with TOBACCO PCP use has been associated with the development (called ‘‘tabacazo’’) or with MARIJUANA (called of long-term psychosis, it seems likely that this may ‘‘mixto’’) in a cigarette. When this dab of coca prove to be a risk with ketamine as well. Ketamine paste is smoked with tobacco, only 6 percent of the is thought to have few other toxic effects. cocaine reaches the smoker—but since most the LSD is another drug with a well-known history paste samples contain significant amounts of man- of misuse and abuse. Its major dangers lie in its ganese as well as several gasoline residues, the in- hallucinogenic properties, which may cause users haled condensate is an extremely toxic substance. to physically harm themselves or others. LSD also Despite the low bioavailability of cocaine from coca seems to aggravate depression and psychosis. Out- paste when it is smoked, use of this illegal sub- COCA PLANT 265

stance by the smoking route reached epidemic pro- PALY, D., ET AL. (1980). Cocaine: Plasma levels after portions in Latin America in the late 1970s. More cocaine paste smoking. In F. R. Jeri (Ed.), Cocaine recently, coca paste smoking has been reported in 1980. Lima: Pacific Press. the NETHERLANDS, the Antilles, Panama, and the VAN DYCK, C., & BYCK, R. (1982). Cocaine. Scientific United States, although the level of use remains American, 246, 128–141. very low. MARIAN W. FISCHMAN The effects of coca-paste smoking have been reported to be as toxic as those seen after intrave- nous or smoked cocaine (i.e., CRACK) in the United COCA PLANT The coca plant is a cultivated States. In fact, coca-paste smokers can achieve co- shrub, generally found in the Andean Highlands caine blood levels comparable to those seen in users and the northwestern areas of the Amazon in South injecting or smoking cocaine (Paly et al., 1980). America. The plant, however, can be grown in Smoking the paste leads to an almost immediate many parts of the world and in the early part of the euphoric response, and users smoke it repeatedly. twentieth century much of the cocaine used in med- As with smoking cocaine (FREEBASING), large icine was obtained from plants grown in Asia. Of quantities of the paste are taken repeatedly within the more than 200 species of the genus Erythroxy- a single smoking session, which is terminated only lon, only E. coca variety ipadu, E. novogranatense, when the drug supply is depleted. Users report a and E. novogranatense variety truxillense contain dysphoric response (unease, illness) within about significant amounts of COCAINE, ranging from 0.6 thirty minutes after smoking, so more paste is gen- to 0.8 percent. In addition to cocaine, the leaves of erally smoked at this time if available. the coca plant contain eleven other ALKALOIDS, al- Substantial toxicity has been reported for chron- though no others are extracted for their eu- ic use of the coca-paste—tobacco combination, phorogenic effects. with users smoking it repeatedly, and progressing Coca plants have long histories of use for both from stimulant-related effects and euphoria to their medicinal and stimulant effects. Coca leaves HALLUCINATIONS and paranoid psychoses. In fact, are believed to have been used for well over a studies carried out in Peru defined a mental disor- millenium, since archeological evidence from Peru- der of coca-paste smoking, made up of four distinct vian burial sites of the 6th century A.D. suggests phases—euphoria, dysphoria, hallucinosis, and coca use. In fact, ancient Indian legends describe its paranoid psychosis (Jeri et al., 1980). Since sub- origin and supernatural powers. The Inca called the stantial amounts of paste are smoked at one time, coca plant a ‘‘gift of the Sun God,’’ and attributed the paranoid psychosis seen after chronic stimulant to it many magical functions. The Inca and the use has also been reported for paste use. As with other civilizations of the Andes used coca leaves for cocaine abusers, experienced users of coca paste social ceremonies, religious rites, and medicinal usually turn to criminal activities to support their purposes. Because of their energizing property, illicit drug use. coca leaves were also used by soldiers during mili- tary campaigns or by messengers who traveled long (SEE ALSO: Bolivia, Drug Use in; Complications; distances in the mountains. Under the Spanish con- Crime and Drugs; Pharmacokinetics; Psychomotor quest of the sixteenth century, coca plants were Stimulants) systematically cultivated and the custom of chew- ing coca leaves or drinking coca tea was widely BIBLIOGRAPHY adopted as part of the Indian’s daily life in South America. Use of coca leaves as both a medicinal and ELSOHLY, M. A., BRENNEISEN, R., & JONES, A. B. (1991). a psychoactive substance continues to be an inte- Coca paste: Chemical analysis and smoking experi- gral part of the daily life of the Indians living in the ments. Journal of Forensic Sciences, 36, 93–103. Andean highlands. Substantial societal controls JERI, F. R., ET AL. (1980). Further experience with the have existed concerning the use of these leaves, and syndromes produced by coca paste smoking. In F. R. minimal problematic behavior related to use of the Jeri (Ed.), Cocaine 1980. Lima: Pacific Press. coca leaves has been reported. 266 COCAETHYLENE: IMMUNOLOGIC, HEPATIC, AND CARDIAC EFFECTS

BIBLIOGRAPHY

HOLMSTEDT, B., ET AL. (1979). Cocaine in the blood of coca chewers. Journal of Ethnopharmacology, 1,69– 78. PALY, D., ET AL. (1980). Plasma levels of cocaine in native Peruvian coca chewers. In F. R. Jeri (Ed.), Cocaine 1980. Lima: Pacific Press. MARIAN W. FISCHMAN

COCAETHYLENE: IMMUNOLOGIC, HEPATIC, AND CARDIAC EFFECTS Con- Figure 1 comitant cocaine and ethanol use produce the com- Coca Leaf pound cocaethylene. A 1995 study estimated that 60 to 80 percent of cocaine users consume ethanol In the highland areas of Peru and Bolivia, and simultaneously. Some users of cocaine mix it with less frequently, in Ecuador and Colombia, the dried ethanol together as they extend the euphoric sensa- leaves are mixed with lime or ash (called ‘‘tocra’’) tion and lessen the dysphoria associated with a and both chewed and sucked. A wad containing 0.4 cessation of cocaine. Cocaethylene, a compound to 1 ounce (10 to 30 g) of leaf is formed, and daily synthesized in vivo, was only identified in 1979. It consumption by coca-leaf chewers is between 1 and also has been named in literature as ethylcocaine, 2 ounces (30 and 60 g). The Indian populations in ethylbenzoylecgonine, and benzoylecgonine ethyl the Amazonean areas, however, crush the dried ester. In 1990, an NIAAA Survey reported that 5.3 leaves, mix the powder with an alkaline substance, million Americans had used cocaine concurrently and chew it. Coca leaves are chewed today in much (during the same period of time) with alcohol, and the same way that they were chewed hundreds of 4.6 million simultaneously (on the same occasion) years ago. with ethanol. Substantial cocaine plasma levels can be at- Although the mechanism by which the combina- tained when coca leaves are chewed along with an tion of cocaine and ethanol may be particularly alkaline substance, which increases the bioavail- deleterious to the cardiovascular system is un- ability of the drug by changing its pH. Volunteers known, two hypotheses have been proposed: allowed to chew either the leaf or the powdered form of coca mixed with an alkaline substance (1) It may markedly increase the determinants of reported numbing in the mouth and a generally myocardial oxygen demand and simulta- stimulating effect which lasted an average of ap- neously diminish supply, leading to a marked proximately an hour after the coca chewing was supply:demand imbalance; in human volun- begun (Holmstedt et al., 1979). This time-course teers, the use of both drugs produces a greater corresponded to the ascending limb of the cocaine increase in heart rate than either substance plasma-level curve, suggesting that the effect was alone. cocaine-induced. Absorption of cocaine occurs (2) The concomitant ingestion of cocaine and eth- from the buccal mucosa (inner cheek wall) as well anol may lead to the production of a metabolite as from the gastrointestinal tract after saliva-con- which induces marked coronary arterial vaso- constriction, leading to myocardial ischemia, taining coca juice is swallowed. In fact, plasma infarction, and/or sudden death. concentrations in coca chewers are about what would be predicted if a dose of cocaine equivalent While formed when cocaine and ethanol were to that in the leaves was administered in a capsule consumed simultaneously in humans, monkeys, (Paly et al., 1980). and mice, formation of cocaethylene resulted through transesterification of cocaine by hepatic (SEE ALSO: Bolivia, Drug Use in; Coca Paste; Co- carboxylesterases in the liver. Further studies must lombia As Drug Source) be done in species that resemble humans to deter- COCAINE 267

mine the pathways and significance of the cocaine SONG, N., PARKER, R. B., & LAIZURE, C. S. (1999). and ethanol combination. Cocaethylene formation in rat, dog, and human he- The toxicity that results from combined cocaine patic microsomes. Life Sciences, 64: 2101-2108. and ethanol use is not due to enhanced sensitivity to ALBERT D. ARVALLO alcohol in cocaine abusers. In rats cocaethylene ex- RONALD ROSS WATSON posure during the brain growth spurt period causes teratogenic effects slowing brain growth. Cocaethylene is a neuroteratogen as indicated by COCAINE The abuse of cocaine has become a altered concentrations of catecholamines and in- major public-health problem in the United States doleamines in developing brains. There was a re- since the 1970s. During that period it emerged gion-specific alteration in neurotransmitter levels from relative obscurity, described by experts as a in response to six days of cocaethylene exposure. It harmless recreational drug with minimal toxicity. also appears that cocaethylene is more similar to By the mid-1980s, cocaine use had increased sub- ethanol than cocaine in terms of neuroteratogeneis. stantially and its ability to lead to drug taking at Measured cocaine and cocaethylene concentration levels that caused severe medical and psychological in postmortem human cerebral cortex and that problems was obvious. Cocaine (also known as combined use of cocaine and ethanol increased the ‘‘coke,’’ ‘‘snow,’’ ‘‘lady,’’ ‘‘CRACK’’ and ‘‘ready risk of death 18-fold. rock’’), is an ALKALOID with both local anesthetic In the first primate study the effects of intrave- and PSYCHOMOTOR STIMULANT properties. It is gen- nously administered cocaine on extracellular dopa- erally taken in binge cycles, with periods of hours to mine in the primate was compared to the effects of days in which users take the drug repeatedly, alter- nating with periods of days to weeks when no co- cocaethylene. There are numerous biochemical and caine is used. Many users are recalcitrant to treat- pharmacological differences between primates, ro- ment, and the introduction of substantial criminal dents and dogs that make it important to study penalties associated with its possession and sale primates if immediate extensions to clinical re- have not yet been effective in reducing its preva- search studies in humans are to be made. Both lence of heavy use. In fact, although occasional use cocaethylene and cocaine are equipotent and were of cocaine diminished somewhat by the early found to increase extracellular dopamine in the 1990s, heavier use did not. caudate nucleus. Cocaethylene retains activity sim- ilar to cocaine including inhibition of dopamine HISTORY transporter. In most case studies, the potentiality of cocaine and cocaethylene seem to point to equal Cocaine is extracted from the COCA PLANT potency in in vitro experiments. The organs of 60 (Erythroxylon coca), a shrub now found mainly in percent of the addicts seeking medical attention in the Andean highlands and the northwestern parts emergency rooms, or examined postmortem speci- of the Amazon in South America. The history of mens, contain cocaethylene. coca plant use by the cultures and civilizations who lived in these areas (including the Inca) goes back more than a thousand years, with evidence of use BIBLIOGRAPHY found archeologically in their burial sites. The Inca called the plant a ‘‘gift of the Sun god’’ and be- CHEN, W. J. A., & WEST, J. R.. (1997). Cocaethylene ex- posure during the brain growth spurt period: Brain lieved that the leaf had supernatural powers. They used the leaves much as the highland Indians of growth restrictions and neurochemisty studies. Devel- South America do today. A wad of leaves, along opmental Brain Research, 100: 220-229. with some ash, is placed in the mouth and both PIROZHKOV,S.V.&WATSON, R. R. P.. (1993). Im- chewed and sucked. The ash helps in the extraction munomodulalting and hepatotoxic effects of cocaine of the cocaine from the coca leaf—and the cocaine and coaerthylene: enhancement by simultaneous eth- is efficiently absorbed through the mucous mem- anol administration. Alcologia, 5: 113-116. branes of the mouth. 268 COCAINE

added to many patent medicines. Physicians began prescribing it for a variety of ills including dyspep- sia, gastrointestinal disorders, headache, neuralgia, toothache, and more—and use increased dramati- cally. By the beginning of the twentieth century, cocaine’s harmful effects were noted and caused a reassessment of its utility. As part of a broader regulatory effort, the U.S. government began to control its manufacture and sale. In 1914, the HAR- RISON NARCOTIC ACT forbade use of cocaine in over- the-counter medications and required the registra- tion of those involved in the importation, manufac- ture, and sale of either coca or opium products. This had the effect of substantially reducing co- caine use in the United States, which remained relatively low until the late 1960s, when it moved Cocaine is usually distributed as a white into the spotlight once again. crystalline powder, usually cocaine hydrocholride, that is often diluted with a MEDICAL UTILITY variety of substances—sugars such as lactose, Cocaine is a drug with both anesthetic and stim- inositol and mannitol, and local anesthetics such ulant properties. Its local anesthetic and vasocon- as lidocaine. (Drug Enforcement Administration) striction effects remain its major medical use. The local anesthetic effect was established by Carl Kol- During the height of the Inca Empire (11th– ler in the mid-1880s, in experiments on the eye, but 15th centuries) coca leaves were reserved for the because it has been found to cause sloughing of the nobility and for religious ceremonies, since it was cornea, it is no longer used in eye surgery. Because believed that coca was of divine origin. With the it is the only local anesthetic capable of causing conquest of the Inca Empire by the Spanish in the intense vasoconstriction, cocaine is beneficial in 1500s, coca use was banned. The Conquistadors surgeries where shrinking of the mucous mem- soon discovered, however, that their Indian slaves branes and the associated increased visualization worked harder and required less food if they were and decreased bleeding are necessary. Therefore, it allowed to chew coca. The Catholic church began remains useful for topical administration in the up- to cultivate coca plants, and in many cases the per respiratory tract. When used in clinically ap- Indians were paid in coca leaves. propriate doses, and with medical safeguards in Although glowing reports of the stimulant ef- place, cocaine appears to be a useful and safe local fects of coca reached Europe, coca use did not anesthetic. achieve popularity. This was no doubt related to the fact that coca plants could not be grown in PHARMACOKINETICS Europe and the active ingredient in the coca leaves did not survive the long ocean voyage from South Cocaine can be taken by a number of routes of America. After the isolation of cocaine from coca administration—oral, intranasal, intravenous, and leaves by the German chemist Albert Niemann in smoked. Although the effects of cocaine are similar 1860 and the subsequent purification of the drug, it no matter what the route, route clearly contributes became more popular. It was aided in this regard to the likelihood that the drug will be abused. The by commercial endeavors in which cocaine was likelihood that cocaine will be taken for combined with wine (e.g., Vin de Coca), products nonmedical purposes is assumed to be related to for which there appeared many enthusiastic and the rate of increase in cocaine brain level (as mea- uncritical endorsements by notables of the time. sured by blood levels) associated with those routes Both interest in and use of cocaine spread to the that provide the largest and most rapid changes in United States, where extracts of coca leaves were brain level being associated with greater self- COCAINE 269 administration. The oral route of administration, not a route used by cocaine abusers, is character- ized by relatively slow absorption and peak levels that do not appear until approximately an hour after ingestion. Cocaine, however, is quickly ab- sorbed from the nasal mucosa when it is inhaled into the nose as a powder (cocaine hydrochloride). Because of its local anesthetic properties, cocaine numbs or ‘‘freezes’’ the mucous membranes, a Figure 1 quality used by those purchasing the drug on the Chemical Structure of Cocaine street to test for purity. When cocaine is used intra- nasally (‘‘snorting’’), cocaine blood levels, as well nous cocaine, in contrast, was limited to those able as subjective and physiological effects, peak at to acquire the paraphernalia and willing to put a about 20 to 30 minutes, and reports of a ‘‘rush’’ are needle in a vein. The toxicity of the smoked route of minimal. Intranasal users report that they are administration is in part related to the fact that a ready to take a second dose of the drug within 30 to potent dose of cocaine is available to anyone who 40 minutes after the first dose. Although this route can afford it. was the most common way for people to use cocaine Cocaine is frequently taken in combination with in the mid-1980s, it is not as efficient in getting the other drugs such as alcohol, marijuana, and OPI- drug to the brain as either smoking or intravenous ATES. In fact, almost 75 percent of cocaine deaths injection, and it has declined in popularity. reported in 1989 involved co-ingestion of other When taken intravenously, venous blood levels drugs. When taken in combination with alcohol, a peak virtually immediately and subjects report a metabolite—COCAETHYLENE—is formed, which substantial, dose-related rush. This route was, until appears to be only slightly less potent than cocaine the mid-1980s, traditionally the choice of the expe- in its behavioral effects. It is possible that some of rienced user, since it provided a rapid increase in the toxicity reported after relatively low doses of brain levels of cocaine with a parallel increase in cocaine might well be due to the combination of subjective effects. Blood levels of cocaine dissipate cocaine and alcohol. in parallel with subjective effects, and subjects re- Cocaine is broken down rapidly by enzymes (es- port that they are ready for another intravenous terases) in the blood and liver. The major metabo- dose within about 30 to 40 minutes. Users of intra- lites of this action (all relatively inactive) are BEN- venous cocaine are also more likely to combine ZOYLECGONINE, ecgonine, and ecgonine methyl their cocaine with HEROIN (e.g., a ‘‘speedball’’) ester, all of which are excreted in the urine. than are users by other routes. Cocaethylene is an additional metabolite when co- In the mid-1980s, smoked cocaine began to caine and alcohol are ingested in combination. Peo- achieve popularity. FREEBASE, or ‘‘crack,’’ is co- ple with deficient plasma cholinesterase activity— caine base, which is not destroyed at temperatures fetuses, infants, pregnant women, patients with required to volatilize it. As with intravenous co- liver disease, and the elderly—are all likely to be caine, blood levels peak almost immediately and, as sensitive to cocaine and therefore at higher risk for with intravenous cocaine, a substantial rush ensues adverse effects than are others. after smoking it. Users can prepare their own free- base from the powdered form they purchase on the PHARMACOLOGY street, or they can purchase it in the form of crack, or ‘‘ready-rock.’’ The development of a smokable Research has been focused on the neurochemical form of cocaine provided a more socially acceptable and neuroanatomical substrates that mediate co- route of drug administration (both NICOTINE and caine’s reinforcing effects. Although a number of MARIJUANA cigarettes provided the model for smok- NEUROTRANSMITTER systems are involved, there is ing cocaine), resulting in a drug that was both easy growing evidence that cocaine’s effects on dopa- to use and highly toxic, since the route allowed for minergic neurons in the mesolimbic and/or meso- frequent repeated dosing with a readily available cortical neuronal systems of the brain are most and relatively inexpensive drug. The use of intrave- closely associated with its reinforcing and other be- 270 COCAINE havioral effects. The initial site of action in the dose of cocaine, compulsive drug seeking can occur brain for its reinforcing effects has been hypothe- in which users think of little else but the next dose. sized to be the dopamine transporter of mesolimbocortical neurons. Cocaine action at the BEHAVIORAL EFFECTS DOPAMINE transporter has the effect of inhibiting dopamine re-uptake, resulting in higher levels of Nonhuman Research Subjects. One of co- caine’s characteristics, as a PSYCHOMOTOR STIMU- dopamine at the synapse. These dopaminergic LANT, is its ability to elicit increases in the motor pathways may mediate the reinforcing effects of behavior of animals. Single low doses produce in- other stimulants and opiates as well. A substantial creases in exploration, locomotion, and grooming. body of evidence suggests that dopamine plays a With increasing doses, locomotor activity decreases major role in mediating cocaine’s reinforcing ef- and stereotyped behavior patterns emerge (contin- fects, although it is clear that cocaine affects not uous repetitious chains of behavior). When admin- only the dopamine but also the SEROTONIN and istered repeatedly, cocaine produces increased lev- noradrenaline systems. els of locomotor activity, increases in stereotyped behavior, and increases in susceptibility to drug- TOXICITY induced seizures (i.e., ‘‘kindling’’). This sensitiza- In addition to blocking the re-uptake of several tion occurs in a number of different species and has neurotransmitters, cocaine use results in central been suggested as a model for psychosis or schizo- nervous system stimulation and local anesthesia. phrenia in humans. Although sensitization to co- This latter effect may be responsible for the neural caine’s unconditioned behavioral effects generally and myocardial depression seen after taking large occurs, such effects are related to dose, environ- doses. Cocaine use has been implicated in a broad mental context, and schedule of cocaine adminis- tration. For example, sensitization occurs more range of medical complications covering virtually readily when dosing is intermittent rather than every one of the body’s organ systems. At low doses, continuous and when dosing occurs in the same cocaine causes increases in heart rate, blood pres- environment as testing. sure, respiration, and body temperature. There Learned behaviors, typically generated in the have been suggestions that cocaine’s cardiovascu- laboratory using operant schedules of reinforce- lar effects can interact with ongoing behavior, re- ment in which animals make responses that have sulting in increased toxicity. Cocaine intoxication consequences (e.g., press a lever to get food), gener- has been associated with cardiovascular toxicity, ally show a rate-dependent effect of cocaine. As related to both its local anesthetic effects and its with AMPHETAMINE, cocaine engenders increases in inhibition of neuronal uptake of catecholamines, low rates of responding and decreases in high rates including heart attacks, stroke, vasospasm, and of responding. Environmental variables and be- cardiac arrhythmias. havioral context can modify this effect. For exam- Cocaine is generally taken in binges, repeatedly, ple, responding maintained by food delivery was for several hours or days, followed by a period in decreased by doses of cocaine that either had no which none is taken. When taken repeatedly, effect or increased comparable rates of responding chronic cocaine intoxication can cause a psychosis, maintained by shock avoidance. Cocaine’s effects characterized by paranoia, anxiety, a stereotyped can also be modified by drug history. Although re- repetitive behavior pattern, and vivid visual, audi- peated administration can result in the develop- tory, and tactile hallucinations. Less severe behav- ment of sensitization to cocaine’s effects on ioral reactions to repeated cocaine use include irri- unlearned behaviors, repeated administration gen- tability, hypervigilance, paranoid thinking, erally results in tolerance to cocaine’s effects on hyperactivity, and eating and sleep disturbances. In schedule-controlled responding. This decrease in addition, when a cocaine binge ceases, there ap- effect of the same dose after repeated dosing is pears to be a crash response, characterized by de- influenced by behavioral as well as pharmacologi- pression, fatigue, and eating and sleep distur- cal factors. bances. Initially, the crash is accompanied by little Human Research Subjects. A major behav- cocaine craving, but as time increases since the last ioral effect of cocaine in humans is its mood- COCAINE 271 altering effect, generally believed related to its po- state, and socioeconomic level, individuals receive tential for abuse. Traditionally, subjective effects the treatment being delivered by the particular have provided the basis for classifying a substance program they happen to attend. Treatment pro- as having abuse potential—and the cocaine-engen- grams that focus on specific target populations will dered profile of subjective effects is prototypic of be far more successful than those which cover all stimulant drugs of abuse. Thus, cocaine produces who apply. For example, patients with relatively dose-related reports of ‘‘high,’’ ‘‘liking,’’ and ‘‘eu- mild symptoms might do quite well in a behavioral phoria’’; increases in stimulant-related factors, intervention with some relapse-prevention instruc- such as increases on Vigor and Friendliness scale tions but those with more severe problems might scores; ratings of ‘‘stimulated’’; and decreases in require the addition of pharmacotherapy. various sedation scores. Subjective effects correlate Pharmacological approaches to treating cocaine well with single intravenous or smoked doses of abusers have focused on potential neurophysiologi- cocaine, peaking soon after administration and dis- cal changes related to chronic cocaine use. Thus, sipating in parallel with decreasing plasma concen- because dopamine appears to mediate cocaine’s re- trations. When cocaine is administered repeatedly, inforcing effects, dopamine agonists such as AM- tolerance develops rapidly to many of its subjective ANTADINE and bromocriptine have been tried. effects and the same dose no longer exerts much of METHYLPHENIDATE, a stimulant, has been an effect. This means that the user must take in- suggested as a possible substitution medication, creasingly larger amounts of cocaine to achieve the and ANTIDEPRESSANTS such as desipramine have same effect. Tolerance to the cardiovascular effects been studied because of their actions on the dopa- of cocaine is less complete; the result here is a minergic system. In addition, because cocaine potential for drug-induced toxicity, since more and blocks re-uptake of SEROTONIN at nerve terminals, more drug is taken when the subjective effects are serotonin-uptake blockers, such as fluoxetine, have not present but the disruptions in cardiovascular also been tested. Although most of the potential function are still present. medications have been shown to be successful in Although users of stimulant drugs claim that some patients under open label conditions, none their performance of many activities is improved by have been clearly successful in double blind cocaine use, the data do not support their asser- placebo-controlled clinical trials. tions. In general, cocaine has little effect on per- Clearly, no medication yet exists for the treat- formance except under conditions in which per- ment of cocaine abuse. It may well be that differ- formance has deteriorated from fatigue. Under ent medications may be effective for the various those conditions, cocaine can bring it back to target populations and that variations in dosages nonfatigue levels. This effect, however, is relatively and durations of treatment might be required, de- short-lived, since cocaine has a half-life of less than pending on a variety of patient characteristics. In one hour. fact, several medications have been shown to be effective only for small and carefully delineated TREATMENT populations (e.g., lithium for cocaine abusers di- Despite substantial efforts directed toward treat- agnosed with concurrent bipolar manic-depressive ment of cocaine abuse, in the mid-1990s we are still or cyclothymic disorders). An artificial enzyme has unable to treat successfully many of the cocaine been developed that inactivates cocaine as soon as abusers who seek treatment. For many years the it enters the blood-stream by binding the cocaine only approach to treating these people was psycho- and breaking it into two inactive metabolites, and logical or behavioral. As of 1994, the most promis- this has the potential for destroying much of the ing of these include behavioral therapy, relapse cocaine before it reaches the brain. As of 1994, prevention, rehabilitation (e.g., vocational, educa- this technique is unavailable for human use. In tional, and social-skills training) and supportive addition, and most importantly, cocaine abuse psychotherapy. A major problem with these treat- (and drug abuse in general) is a behavioral prob- ment approaches is related to their lack of selectiv- lem, and it is unlikely that any medication will be ity. Rather than tailoring programs to an individ- effective unless it is combined with an appropriate ual’s background, drug-use history, psychiatric behavioral intervention. 272 COCAINE EPIDEMICS

(SEE ALSO: Cocaine, Treatment Strategies; Colom- bia As Drug Source; Epidemics of Drug Abuse; Epi- demiology of Drug Abuse; National Household Sur- vey on Drug Abuse; Treatment:Cocaine )

BIBLIOGRAPHY

BOCK,G.,&WHELAN, J. (1992). Cocaine:Scientific and social dimensions. Ciba Foundation Symposium 166. Chichester: Wiley. JOHANSON, C. E., & FISCHMAN, M. W. (1989). Pharma- cology of cocaine related to its abuse. Pharmacologi- Figure 1 cal Reviews, 41, 3–52. Codeine KLEBER, H. D. (1989). Treatment of drug dependence: What works. International Review of Psychiatry, 1, and problems of abuse have often been linked to 81–100. codeine-containing cough medicines, since they LANDRY, D. W., ET AL. (1993). Antibody-catalyzed deg- were once easily obtained over the counter. Chronic radation of cocaine. Science, 259, 1899–1901. dosing with high codeine doses will produce TOLERANCE AND PHYSICAL DEPENDENCE, much like MARIAN W. FISCHMAN morphine.

(SEE ALSO: Papaver somniferum) COCAINE EPIDEMICS See Epidemics of Drug Abuse BIBLIOGRAPHY

REISINE, T., & PASTERNAK, G. (1996) Opioid analgesics CODEINE Codeine is a natural product and antagonists. In J. G. Hardman et al. (Eds.), The found in the opium poppy (Papaver somniferum). Pharmacological Basis of Therapeutics, 9th ed. (pp. An alkaloid of OPIUM, codeine can be separated 521–555). New York: McGraw-Hill. from the other opium ALKALOIDS, purified, and GAVRIL W. PASTERNAK used alone as an ANALGESIC (painkiller). It is how- ever most often used along with mild nonopioid analgesics, such as aspirin, acetominophen, and CODEPENDENCE The term codependence ibuprofen. These combinations are particularly ef- replaced an earlier term, coalcoholism, in the early fective; the presence of the mild analgesics permits 1970s and achieved widespread acceptance among far lower codeine doses. Using lower doses of co- the general public during the 1980s. Both terms deine has the advantage of reducing side effects, point to problematic beliefs and behaviors that such as constipation. Codeine is one of the most family members of chemically dependent people widely used analgesics for mild to moderate pain. tend to have in common, although the term code- Structurally, codeine is very similar to MOR- pendence broadens the concept to cover a wider PHINE, differing only by the presence of a methoxy range of family dysfunctions than chemical depen-

(-OCH3) group at position 3, instead of morphine’s dence alone. hydroxy (-OH) group. The major advantage of A rather large nonscientific literature has devel- codeine is its excellent activity when taken by oped on the topic of codependence. Much of it is mouth, unlike many opioid analgesics. Codeine it- couched in terms of the need to deal with injuries to self has very low affinity for opioid receptors, yet it emotions sustained during childhood—that is, to has significant analgesic potency. In the body, it is heal the wounds of the ‘‘inner child,’’ a term pop- metabolized into morphine, and it is believed that ularized by John Bradshaw. the morphine generated from codeine is actually Despite the current popularity of codependence, the active agent. Codeine has also been widely used awareness that one person’s alcoholism affects ev- as a cough suppressant. Codeine can be abused, eryone in the family is not new. The Big Book of CODEPENDENCE 273

Alcoholics Anonymous (1939; 1976) described the ‘‘I don’t need help. It’s his problem, not mine!’’ experience of family members of alcoholics in the The chemically dependent and those around him following manner: all have impaired judgment; they differ only in the degree of impairment [p. 30]. We have had a long rendezvous with hurt pride, frustration, misunderstanding and fear. These are not pleasant companions. We have been driven to DEFINITION maudlin sympathy, to bitter resentment. Some of Although considerable debate still remains us veered from extreme to extreme, ever hoping among professionals regarding the definition and that our loved one would be themselves once more. meaning of codependence, most addiction special- We have been unselfish and sacrificing. We ists agree that the concept has successfully ushered have told innumerable lies to protect our pride and huge numbers of people into recovery. Perhaps the our husband’s reputations. We have prayed, we best general definition of codependence is called the have begged, we have been patient. We have Scottsdale definition, after the conference location struck out viciously. We have run away. We have where several lecturers met to achieve consensus: been hysterical. We have been terror stricken. We Co-dependence is a pattern of painful depen- have sought sympathy. We have had retaliatory dence on compulsive behaviors and on approval love affairs with other men. from others in an attempt to find safety, self-worth Usually we did not leave. We stayed on and on and identity. [pp. 104–106]. In his book I’ll Quit Tomorrow (1973), Vernon CHARACTERISTICS Johnson described the same experiences when he The following five characteristics form the com- wrote that the ism of alcoholism is shared by other mon thread weaving through the lives of many, if family members. In his words, not most, family members of alcoholics and other While there may be only one alcoholic in a family, drug addicts: the whole family suffers from the alcoholism. For 1. Codependents change who they are, and what every harmfully dependent person, most often they are feeling, to please others. Codependents there are two, three, or even more people immedi- are chameleons who sacrifice their own identity ately around him who are just as surely victims of in an effort to get others to love them. They do the disease. They too need real help and should be this for two reasons. First, they fear being aban- included in any thoroughgoing model of ther- doned if people know how they really feel or apy. . . . With every drunk there is a sick dry who is who they really are. Second, they have so little almost a mirror image. [italics added] sense of who they are that they need to be in The people around the alcoholic person have relationships in order to organize their lives and predictable experiences that are psychologically feel complete. Unless they are in a relationship, damaging. As they meet failure after failure, their and can take their cues from another person, feelings of fear, frustration, shame, inadequacy, they feel desperately lonely and worthless. As a guilt, resentment, self-pity, and anger mount, and result, codependents are split between two so do their defenses. They too use rationalization worlds. One world is the facade they show other as a defense against these feelings because they are people—the false version of themselves. The threatened with a growing sense of self-worthless- other world is how chaotic, fearful, and empty ness. They too begin to project these masses of their life feels underneath. free-floating negative feelings about themselves 2. Codependents feel responsible for meeting other upon the children, back on the spouse, on other peoples’ needs, even at the expense of their own family members, on employees, and everybody needs. Codependents are so afraid of rejection else at hand. Their defenses have begun to operate that they will do anything to keep other people in the same way as the alcoholic’s, although they happy, including sacrificing their own needs to are unconscious of this, and they are victimized by keep people from leaving them. They actually their own defenses rather than helped. Out of get more upset if others are disappointed or hurt touch with reality, just like the alcoholic, they say, than if their own problems go unsolved. This 274 CODEPENDENCE

habit of focusing more on others often leads to 5. Codependents have the same use of denial and codependents’ enabling a family member’s distorted relationship to willpower that is typi- drinking. Enabling means that the codependent cal of active alcoholics and other drug addicts. protects the chemical dependent from the nega- Denial and an unwillingness to accept human tive consequences of their drinking and other limitations are the two most destructive parts of drug usage to keep the other person from having the ism of alcoholism described by Vernon John- to feel any pain or embarrassment. son. In their own way, codependent family 3. Codependents have low self-esteem. Most people members fall into the same distorted relation- who are chemically dependent feel ashamed of ship to reality and willpower as the chemical themselves and are inwardly very self-critical. dependent. Both deny reality and think they can So perhaps it is not strange that other family control alcoholism (their own or another’s) if members also begin to feel bad about them- they just use enough willpower. For example, if selves. For codependents, low self-esteem comes chemical dependents deny that they are abusing from two main places: alcohol or other drugs and remain unaware of (a) It comes from having very little sense of self its impact on their lives and their relationships to esteem. By always pleasing others and taking with family members, friends, and coworkers, their whole identity from others, codependents then codependents show exactly the same de- end up not knowing who they are apart from the nial. They often refuse to see that a family relationships they are in. It’s hard to respect member is chemically dependent, or they refuse people who are afraid to be themselves, even to acknowledge that their children are being when it’s you! hurt. Shame and the compulsion to keep things (b) Low self-esteem also comes from believing under control cause codependents to deny the that they truly are responsible for someone’s problem. Denial is a universal human trait, but alcohol/drug use. Once they believe this, they it is overused by every member of a chemically will always feel inadequate when they fail to dependent family. control the chemical dependent’s behavior. This mistaken sense of what should be under their Codependents are driven by the firm belief that control is at the very core of both codependence their coping strategies fail because of personal in- and chemical dependence. adequacy. When they cannot control the drinking 4. Codependents are driven by compulsions. Code- or other drug use of someone they love, they blame pendents feel they do not have any real choices themselves for not trying hard enough—or for not about what is happening to them. They typically trying the right way. When codependents take too feel compelled to keep the family together, to much responsibility for another person’s recovery, stop the drinking or other drug use, to save the it keeps the chemical dependent from seeing that family from shame, to work, to eat or diet, to only they can be responsible for their own recovery. take physical risks, to spend or gamble, to have affairs, to be religious, to keep the house clean, PSYCHIATRIC PERSPECTIVE and on and on. The driven quality of compul- sions accomplishes two things: In many ways, codependence is the mirror image (a) Compulsions create excitement and drama. of a chemical dependent’s self-centeredness and As people battle their compulsions, the adrena- grandiosity. Another term for such self-centered- line begins to flow, and simple decisions, such as ness is narcissism. Codependence is the comple- what to eat or how much to work, are turned ment of narcissism, just as a glove complements the into life and death struggles. This drama tempo- hand it is shaped to fit. rarily gives a feeling of purpose and vitality. In the Greek’s myth that gives us the prototype (b) Compulsions also occupy a lot of time and for self-centeredness, Narcissus had relationships block people from their deeper feelings. Code- only with people who shared his values and inter- pendents often get locked into compulsive be- ests. He was unable to feel a sense of human con- haviors to avoid more painful feelings of fear, nection with people who were separate from him, sadness, anger, and abandonment caused by a just as chemical dependents may break off relation- family member’s chemical dependence. ships with people who do not support their denial. COERCED TREATMENT FOR SUBSTANCE OFFENDERS 275

The myth of Narcissus also gives us the prototype COERCED TREATMENT FOR for other-centeredness in Echo—who is the perfect SUBSTANCE OFFENDERS The logic for reflection of Narcissus. The two fit together and coerced treatment is that substance abusers have seemed to complete each other. Their relationship limited internal motivation and consequently need had intense chemistry. to be externally motivated to enter treatment in In the eternal struggle within each individual be- order to change their behaviors. Expected change includes reduced arrests, reduced crime, and no tween the need to be nurtured and the need to drug use. It is important to keep in mind that, from nurture others, Narcissus and Echo (and chemical a criminal justice point of view, no drug use is dependents and codependents) strike a balance be- expected, which is different from a public health tween two extreme positions. Rather than balanc- harm reduction approach. Consequently, sub- ing the two needs within each of themselves, they stance offenders who have limited internal motiva- allot the need to be validated and appreciated to tion to change their behaviors are externally moti- Narcissus and the need to nurture and be in a vated to enter treatment using the authority of the relationship to Echo. Neither is capable of a truly criminal justice system. This authority includes mutual relationship—but, together, they create an probation, parole, diversion, and drug courts, intense experience of connectedness. which can include incentives for substance of- In healthy families, children remain comfortable fenders like reduced sentences or decreased time with the competing, normal childhood needs to be under criminal justice supervision. Coerced substance-abuse treatment has a tradi- unconditionally loved and validated as worthwhile tional relationship with community treatment. The (i.e., to be the center) and the opposite need to be history of drug-abuse treatment in the United completely dependent upon all powerful and good States can be traced to two U.S. Public Health parents (i.e., to have others be the center). When Service farms at Lexington, Kentucky and Fort parents are unable to tolerate not being the center Worth, Texas, which were opened in the late of relationships, even with their children (which 1930s. These facilities were established largely often happens with a chemically dependent par- through the effort of James V. Bennett, former ent), children often renounce their own need to be Director of the Federal Bureau of Prisons, when he focused on. They become the opposite of narcissis- recognized the need for treating drug abusers. tic; they become codependent. Drug-abuse treatment at these farms, which were renamed hospitals, was designed primarily for fed- eral prisoners, but volunteers without coercion (SEE ALSO: Adult Children of Alcoholics (ACOA); could also receive treatment. However, after with- Al-Anon; Alateen; Families and Drug Use) drawal from drugs, most volunteers did not stay, and with no community followup, there was a high BIBLIOGRAPHY relapse rate. With these high relapse rates and using the ALCOHOLICS ANONYMOUS WORLD SERVICES. (1939; California and New York civil commitment 1976). The Big Book of Alcoholics Anonymous. New coerced treatment programs as models, the Nar- York: Author. cotic Addict Rehabilitation Act (NARA PL BRADSHAW, J. J. (1988). Healing the shame that binds 89-793) was passed by Congress in 1966 as a you. Deerfield Beach, Fl: Health Communications. federal civil commitment program to reduce drug CERMAK, T. L. (1986). Diagnosing and treating use. For NARA Titles I (treatment in lieu of pros- co-dependence. Minnesota: Johnson Institute. ecution) and III (treatment with no formal CERMAK, T. L., (1990–1991). Evaluating and treating charges) court-ordered treatment was initially adult children of alcoholics. Minnesota: Johnson Insti- provided at the Lexington and Fort Worth hospi- tals after an evaluation period. Later, NARA in- tute. patient treatment facilities were opened in several JOHNSON, V. (1973). I’ll quit tomorrow. New York: cities. These facilities served as the foundation for Harper & Row. community-based drug abuse treatment. When TIMMEN L. CERMAK NARA was phased out, the U.S. Public Health 276 COERCED TREATMENT FOR SUBSTANCE OFFENDERS

Service facilities were transferred to the Federal CONTROL VERSUS TREATMENT Bureau of Prisons in the mid–1970s (Leukefeld & The relationship between treatment and control Tims, 1988). can cloud the overall perception of coerced treat- Another milestone in coerced substance abuse ment. Most community treatment providers per- treatment was establishment of the Treatment Al- ceive treatment and control as opposites with treat- ternatives to Street Crime (TASC) program, which ment on one side, as ‘‘the good guys,’’ and control is now called Treatment Accountability for Safer from the criminal justice system on the other side. Communities. The Special Action Office created In fact, many community treatment providers point TASC in 1972 for Drug Abuse Prevention, an office to criminal justice authority as disruptive to the with responsibilities similar to those of the current therapeutic relationship. However, this is largely White House Office of National Drug Control Pol- refuted by the literature that indicates drug of- icy. TASC can be described as a diversion program fenders under criminal justice authority generally and as case management that helps bridge commu- remain in treatment longer and consequently have nity corrections and the drug-abuse treatment sys- better treatment outcomes. In fact, criminal justice tem. TASC provides identification, assessment, ref- involved offenders remain in community treatment erral, case management and monitoring services for at least as long as others in treatment who are not drug/alcohol dependent offenders accused or con- criminal justice involved. There are other ways of victed of nonviolent crimes. TASC defuses some of thinking about treatment and control if the as- the friction between community corrections and sumption is that interventions incorporate both treatment and control. For example, a therapeutic drug treatment services and is now operating in community/residential treatment facility is very over 125 communities nationwide. Overall, TASC’s high in treatment and control, whereas outpatient effectiveness has been established in reducing drug treatment is low in both treatment exposure and abuse and keeping drug abusers in treatment for a control unless a participant is involved in criminal longer period of time. justice supervision. Nevertheless, treatment and control are usually discussed as opposite processes, THE DRUG–CRIME RELATIONSHIP with this depending on ideology, perceived public interest, and political needs. Coerced treatment is considered within the con- text of the relationship between drugs and crime CONTROVERSIES that has been well documented. For example, since the mid–1970s, both the National Institute on Coerced treatment and the use of court authority Drug Abuse and the National Institute of Justice within the criminal justice system have not been have supported projects to understand the drug– without controversy, particularly since many com- crime connection, with findings that suggest that munity drug treatment providers believe that sub- drug use enhances criminal careers. In fact, a sur- stance abusers should enter treatment voluntarily. vey of inmates in state and federal correctional As one early example of this controversy, Robert L. facilities indicates that 83 percent of state prisoners DuPont as Director of the National Institute on Drug Abuse, when addressing the Federal Bar As- reported previous drug use and 57 percent reported sociation in 1977, proposed setting up a trip wire, using a drug in the month before their offense (BJS, in the form of urine testing, that would identify 1998). The Drug Use Forecasting (DUF) system, heroin users who were on probation and parole. If renamed ADAM (Arrestee Drug Abuse Monitoring an addicted probationer or parolee did not stop Program) has consistently reported that 51 to 83 daily drug use, he or she would be referred for percent of male arrestees in major urban cities test compulsory drug abuse treatment. And if treatment positive for drugs (ADAM Annual Report, 1998). was refused or daily heroin use continued, the indi- In fact, two-thirds of prisoners are drug abusers vidual would be reincarcerated. Although the trip whereas over 60 percent of persons who come into wire proposal was modified by other proponents, it contact with jails and lock-ups use a drug other never got underway because of the ensuing contro- than alcohol at the time of arrest (ONDCP, 1995). versy. Controversy focused on three areas: COERCED TREATMENT FOR SUBSTANCE OFFENDERS 277

(1) the image problem created when a health (Field, 1985), and Key and Crest Programs in agency proposed a mechanism for behavioral Delaware (Martin et al., 1999); control using the criminal justice system, (3) the large number of chronic drug abusers who (2) the violation of probationers’ civil rights when are incarcerated; and tested, and (4) the need to understand interventions and re- (3) the inadequacy of the urine testing technology. tention for drug offenders and their related In spite of the controversy, practitioners interested costs. in the relationship between drugs and crime sup- ported the concept because of the large number of DRUG COURTS crimes committed by substance abusers The current interest in drug courts developed in (Leukefeld, 1985). response to the overlap between substance abuse and crime in order to provide treatment for defen- COMMUNITY SUBSTANCE- dants. The interest in drug courts increased re- ABUSE TREATMENT cently with the expanded number of courts that Drug abusers in community treatment are in- grew to 275 jurisdictions in 1998 from the first volved with community corrections. They are fre- drug court in Dade County, Florida, in 1989 quently on diversion, probation, parole, or manda- (Belenko, 1998). The benefits of drug courts have tory release. Early data from the Client Oriented been documented: reduced recidivism, decreased Data Acquisition Process (CODAP) indicates that drug use, increased birth rates of drug-free babies, 17 percent of clients who entered drug-abuse treat- high program retention, increased relapse preven- ment were on probation, parole, or mandatory re- tion, and cost efficient treatment. The drug court is lease. By 1982, CODAP reported an increase in a court-managed drug intervention and treatment community corrections involvement for 27 percent program designed to provide a cost-effective alter- of the males and 15 percent of the females. During native to traditional criminal case processing. Drug the 1980s, Hubbard et al. (1989) found that over courts are treatment-oriented and target clients 30 percent of clients in residential and outpatient whose major problems stem from substance abuse. treatment were referred to treatment by the crimi- However, although there are standards that are nal justice system; this finding remains valid in the required for each drug court program, each drug year 2000. court program is different.

COERCED TREATMENT OUTCOMES CHRONIC AND RELAPSING NATURE Drug treatment provided through the criminal OF SUBSTANCE ABUSE justice system has had successes. As a result, It is easy to forget that drug abuse can be chronic coerced drug treatment, for example, has been sep- and relapsing. Without proper followup and treat- arated into categories, including Civil Commitment ment, substance abusers often return to drug use. It (supervision of parolees with urine testing), Crimi- is no secret that recovery is a difficult process that is nal Justice Authority (community corrections), not completely understood, with or without coerced urine testing, offender community treatment ser- treatment. Intervention and treatment efforts need vices (community drug abuse treatment) and treat- to focus on those factors that keep individuals drug ment in prisons and jails. The research on drug free. These options can range from urine testing to treatment for drug offenders has grown. The inter- methadone treatment. Nevertheless, many people est in examining interventions comes from believe that substance-abuse treatment does not (1) the decreased anti-rehabilitation atmosphere work. They cite professional and/or personal expe- in the criminal justice system (Martinson, riences about individuals who immediately return 1974); to drug use during treatment and/or supervision. (2) data which have shown promise including the However, after discussion it becomes clear that the Stay’n Out Program in New York (Wexler et proper blend of treatment combined with followup al., 1992), the Cornerstone Program in Oregon supervision, relapse prevention, and self-help 278 COFFEE

groups like Alcoholics Anonymous was not used, OFFICE OF NATIONAL DRUG CONTROL POLICY. (1995). and/or attendance was minimal. National Drug Control Strategy. Washington, D.C.: Finally, there are no instant cures for substance U.S. Government Printing Office. abuse. Recovery for many can take a lifetime. De- WEXLER,H.K.,FALKIN,G.P.,LIPTON,D.S.,& creasing substance use during the course of an ad- ROSENBLUM, A. B. (1992). Outcome Evaluation of a dict’s life can combine the interventions of coerced Prison Therapeutic Community for Substance Abuse treatment, community treatment, and possibly in- Treatment, in Leukefeld, C. G., and Tims, F. M. carceration with twelve step groups. More emphasis (eds.). needs to be placed on matching substance abusers MARIE RAGGHIANTI with appropriate services as well as looking at ways REVISED BY CARL LEUKEFELD to mix and match interventions. In addition, both external motivation—coerced treatment—and in- ternal motivation that substance abusers bring to COFFEE Coffee is the world’s most common treatment at varying levels need to be better under- source of CAFFEINE, providing a little more than stood. Clearly, coercion can bring a substance of- half of all caffeine consumed daily. In the United fender to treatment, but it cannot be used to force a States, coffee is usually a beverage made by perco- substance offender to participate in treatment. lation or infusion from the roasted and ground or pounded seeds of the coffee tree (genus Coffea), a large evergreen shrub or small tree, which was BIBLIOGRAPHY native to Africa but now is grown widely in warm ARRESTEE DRUG ABUSE MONITORING PROGRAM ANNUAL regions for commercial crops. Caffeine from coffee REPORT. (1998). Washington, D.C.: U.S. Government accounts for an estimated 125 milligrams of the Printing Office. 211 milligrams of U.S. caffeine consumed per cap- BELENKO, S. (1998). Research on Drug Courts: A Critical ita per day. Recent estimates suggest that more Review. National Court Institute Review, 1:(1), 1-30. than 50 percent of the adolescents and adults in the BUREAU OF JUSTICE STATISTICS. (1998). Washington, United States consume some type of coffee bever- D.C.: U.S. Government Printing Office. age. Coffee is one of the main natural commodities DRUG ABUSE TREATMENT IN PRISONS AND JAILS (NIDA in international trade, ranking second only to pe- Monograph no. 118), pp. 156-75. troleum in dollar value. Approximately fifty coun- tries export coffee and virtually all of those coun- FIELD, G. (1985). The Cornerstone Program: A Client tries rely on it as a major source of foreign Outcome Study. Federal Probation 49, 50-55. exchange. An estimated 25 million people make HUBBARD,R.L.,ET AL. (1989). Drug Abuse Treatment:A their living in the production and distribution of National Study of Effectiveness. Chapel Hill, NC: Uni- coffee products. versity of North Carolina Press. In addition to caffeine, roasted coffee contains at LEUKEFELD, C. G. (1985). The Clinical Connection: least 610 other chemical substances, which may Drugs and Crime. The International Journal of the contribute to its smell, taste, and physiological ef- Addictions 25 (6), 621-640. fects. Nevertheless, coffee’s primary psychoactive LEUKEFELD, C. G., & Tims, F. M. (eds.). (1988). Com- ingredient is caffeine. The amount of caffeine in an pulsory Treatment for Drug Abuse:Research and individual cup of coffee varies considerably, de- Clinical Practice (NIDA Research Monograph No.86). pending on the type and amount of coffee used, the Rockville, MD: U.S. Government Printing Office. form of the final coffee product (e.g., ground MARTIN, S. S., BUTZIN, C. A., SAUM, C. A., & INCIARDI, roasted or instant), and the method and length of J. A. (1999). Three-year Outcomes of Therapeutic brewing. On average, a 6-ounce (177 milliliters) Community Treatment for Drug-Involved Offenders cup of ground roasted coffee contains about 100 in Delaware: From Prison to Work Release to After- milligrams caffeine; the same amount of instant care. The Prison Journal 79(3), 294-320. coffee typically contains about 70 milligrams caf- MARTINSON, R. (1974). What Works? Questions and An- feine. However, the caffeine content of any given swers about Prison Reform. The Public Interest 35, 6-ounce cup of coffee can vary considerably and 22-54. can reach as much as 210 milligrams. Drip coffee COGNITIVE-BEHAVIORAL THERAPY 279

more water is extracted. The beans are then ground and ready for use. To produce instant coffee, roasted and ground coffee is percolated to produce an aqueous coffee extract. That extract is dehy- drated by spray or freeze-drying to produce water- soluble coffee extract solids. Since this process re- moves flavor and aroma from the coffee, com- pounds are added to the extracts at the completion of the process to restore the lost characteristics.

BIBLIOGRAPHY

Figure 1 BARONE, J. J., & ROBERTS, H. (1984). Human consump- Coffee tion of caffeine. In P. B. Dews (Ed.), Caffeine. New York: Springer-Verlag. typically contains more caffeine than percolated; SPILLER,G.A.(ED.). (1984). The methylxanthine bever- decaffeinated coffee contains a small amount of ages and foods:Chemistry, consumption, and health caffeine, approximately 4 milligrams in a 6-ounce effects. New York: Alan R. Liss. cup. Individual servings of caffeinated coffee con- KENNETH SILVERMAN tain amounts of caffeine that have been shown ex- ROLAND R. GRIFFITHS perimentally to produce a range of effects in hu- mans including the alteration of mood and performance and the development of physical de- pendence with chronic daily use. COGNITIVE-BEHAVIORAL THERAPY Coffee cultivation probably began around 600 Cognitive-behavioral treatments represent a group A.D. in Ethiopia, but the drink was spread into the of approaches, grounded in social learning theories Middle East and Europe. Today, much of the of substance abuse, that hold that lack of effective world’s coffee is grown in South and Central Amer- coping skills may be one factor underlying the ica, particularly Brazil and Colombia, and in sev- development or perpetuation of substance use dis- eral African countries. Coffee beverages derive pri- orders. Cognitive behavioral treatments have been marily from the seeds of two species of Coffea among the most well defined and rigorously studied plants, Coffea arabica and Coffea canephora var. of the psychosocial treatments for substance abuse robusta. Robusta coffees contain approximately and dependence, and have a comparatively high twice as much caffeine as Arabicas. Arabica beans level of empirical support across the addictions. For are used in the majority of the coffee consumed example, in their review of cost and effectiveness today, particularly in the higher quality coffees. data for treatments for alcohol use disorders, Since processing for instant and decaffeinated cof- Holder and colleagues (1991) included social skills fee extracts flavor components from the bean, the training, self-control training, stress management stronger flavored beans, typically Robusta beans, training, and the Community Reinforcement Ap- are used for these coffee products. Caffeine ex- proach (Azrin et al., 1976), all broad-spectrum tracted in the decaffeination process is sold for use CBT approaches, as having good empirical evi- in soft drinks and medications. The coffee bean, covered with several layers of dence of effectiveness. Recent meta-analyses (Irvin skin and pulp, occupies the center of the coffee et al., 1999) and reviews of the effectiveness of berry. During the first part of coffee production, the treatments for substance abuse (APA Workgroup outer layers of the coffee berry are removed, leaving on Substance Use Disorders, 1996; DeRubeis & a green coffee bean. The beans are then roasted, Crits-Christoph 1998) have identified this group of removing between 14 and 20 percent of their water approaches as having among the highest level of and changing their color from green to various empirical support for the treatment of substance shades of brown; generally, the beans get darker as use disorders. 280 COGNITIVE-BEHAVIORAL THERAPY

OVERVIEW AND STRUCTURE OF CBT for coping with negative affect, awareness of anger and anger management, coping with criticism, in- Cognitive-behavioral treatments are typically creasing pleasant activities, enhancing social sup- highly structured in comparison to other ap- port networks, job seeking skills, and so on. proaches for substance use disorders. That is, these There are a variety of manuals available (Monti treatment approaches are typically comparatively et al.,1989; Kadden et al. 1992, Carroll, 1998) brief (12-24 weeks) and organized closely around which describe key CBT strategies and techniques, well-specified treatment goals. There is typically an as well as guidelines for its implementation with a articulated agenda for each session and discussion variety of types of substance users. The classic remains focused around issues directly related to resource in this area remains the Marlatt and Gor- substance use. Progress toward treatment goals is don’s (1985) landmark book on relapse prevention. monitored closely and frequently, and the therapist The goals of cognitive-behavioral treatments takes an active stance throughout treatment. tend to be somewhat broader than those of ‘strict’ Cognitive-behavioral approaches typically in- behavioral approaches, and the choice of treatment clude a range of skills to foster or maintain absti- goals will dictate the specific interventions imple- nence and to prevent relapse. These typically in- mented. For example, in broad spectrum cognitive- clude strategies for: behavioral treatments (e.g., Azrin et al., 1976; (1) reducing availability and exposure to the sub- Monti et al., 1989), the patient and therapist may stance and related cues, select a wide range of target behaviors in addition (2) fostering resolution to stop substance use to a treatment goal of abstinence, including im- through exploring positive and negative conse- proved social skills or social functioning, reduced quences of continued use, psychiatric symptoms, and reduced social isolation, (3) self-monitoring to identify high risk situations entry into the work force. Cognitive behavioral and to conduct functional analyses of sub- therapy also differs from cognitive therapy through stance use, greater emphasis on building specific behavioral (4) recognition of conditioned craving and devel- skills (e.g., coping with craving, avoiding high risk opment of strategies for coping with craving, situations, understanding behavioral patterns) and (5) identification of seemingly irrelevant decisions somewhat lesser emphasis on targeting and chal- which can culminate in high risk situations, lenging maladaptive cognitions in the earlier stages (6) preparation for emergencies and coping with a of abstinence. relapse to substance use, (7) substance refusal skills, and STRENGTHS AND WEAKNESSES (8) identifying and confronting thoughts about the substance. Strengths of cognitive-behavioral approaches have been summarized by Rotgers (1996) and in- The techniques of teaching these coping responses clude: include a combination of direct verbal instruction, modeling of appropriate skills through role play, (1) flexibility in meeting individual needs, and rehearsal of the skills within the therapy ses- (2) acceptability to a wide range of substance- sion (Marlatt & Gordon, 1985). Material discussed abusing individuals seen in clinical settings, during sessions is typically supplemented with ex- (3) solid grounding in established principles of be- tra- session tasks (i.e., homework) intended to fos- havior theory and behavior change, ter practice and mastery of coping skills. (4) an emphasis on linking science to treatment, (5) well-specified treatment goals and clear guide- Broad-spectrum cognitive-behavioral ap- lines for assessing treatment progress, proaches such as that described by Monti and col- (6) emphasis on building self-efficacy, and leagues (1989), and adapted for use in Project (7) a comparatively strong level of empirical sup- MATCH (Kadden et al., 1992), expand to include port. interventions directed to other problems in the in- dividual’s life that are seen as functionally related These approaches are highly flexible, and can be to substance use. These may include general prob- used in a number of treatment modalities and set- lem-solving skills, assertiveness training, strategies tings, can be applied across different types of sub- COLA/COLA DRINKS 281

stance use with minor modifications, and are com- of Consulting and Clinical Psychology, 46, 1092- patible with a wide range of other treatment 1104. approaches, including family therapy and phar- DERUBEIS, R. J., & CRITS-CHRISTOPH, P. (1998). Empiri- macotherapy. Another advantage is that these ap- cally supported individual and group psychological proaches have emphasized clear specification of treatments for adult mental disorders. Journal of Con- treatment and a variety of manuals are available, sulting and Clinical Psychology, 66, 37-52. thus allowing a high level of technology transfer. HOLDER, H. D., LONGABAUGH, R., MILLER, W. R., & Disadvantages of this group of approaches include: RUBONIS, A. V. (1991). The cost effectiveness of treat- ment for alcohol problems: A first approximation. (1) research evaluating these approaches have Journal of Studies on Alcohol, 52, 517-540. tended not to emphasize the importance of IRVIN JE, BOWERS CA, DUNN ME, WONG MC. Efficacy of isolating and evaluating the specific ‘active in- relapse prevention:A meta-analytic review . J Consult gredients’ associated with behavior change, Clin Psychology. 1999;67:563-570. (2) comparative underutilization of these ap- KADDEN, R., CARROLL, K. M., DONOVAN, D., COONEY, N., proaches outside of academic treatment set- MONTI, P., ABRAMS, D., LITT, M., & HESTER,R. tings (Rotgers, 1996), and (1992). Cognitive-behavioral coping skills therapy (3) lack of emphasis on patient motivation and manual: A clinical research guide for therapists treat- specific procedures for addressing the patient’s ing individuals with alcohol abuse and dependence. readiness for change. NIAAA Project MATCH Monograph Series Volume 3, DHHS Publication No. (ADM) 92-1895. Rockville, SUMMARY MD: National Institute on Alcohol Abuse and Alcohol- Cognitive behavioral treatments have emerged ism. in the last decade as a leading approach to the MARLATT, G. A., & GORDON, J. R., (Eds.). (1985). Re- treatment of substance use disorders. Solidly lapse prevention: Maintenance strategies in the treat- grounded in well-established principles of behavior ment of addictive behaviors. New York:Guilford . change, with strong empirical support, and appli- MONTI, P. M., ABRAMS, D. B., KADDEN, R. M., & COONEY, cable to a wide range of individuals with substance N. L. (1989). Treating alcohol dependence: A coping use disorders, these well-defined approaches skills training guide in the treatment of alcoholism. should be a part of any clinician’s treatment reper- New York:Guilford . toire. ROTGERS, F. (1996). Behavioral theory of substance abuse treatment: Bringing science to bear on practice. BIBLIOGRAPHY In F. Rotgers, D. Keller, & J. Morgenstern (eds.), Treating Substance Abusers:Theory and Technique AMERICAN PSYCHIATRIC ASSOCIATION, Work Group on (pp. 174-201). New York: Guilford. Substance Use Disorders (1995). Practice guideline KATHLEEN M. CARROLL for the treatment of patients with substance use disor- ders: Alcohol, cocaine, opioids. American Journal of Psychiatry, 152 (sup), 2-59. AZRIN, N. H. (1976). Improvements in the community- COGNITIVE THERAPY OF ADDIC- reinforcement approach to alcoholism. Behavior Re- TIONS See Treatment Types search and Therapy, 14,339-348. CARROLL, K. M. (1998). A Cognitive-Behavioral Ap- proach: Treating Cocaine Addiction. NIH Publication COLA/COLA DRINKS Cola drinks are car- 98-4308. Rockville, MD: National Institute on Drug bonated soft drinks, sodas, that contain some ex- Abuse. tract of the kola nut in their syrup. Kola nuts are CARROLL, K. M. (1999). Behavioral and cognitive behav- the chestnut-sized and -colored seeds of the African ioral treatments. In B. S. McCrady & E. E. Epstein kola tree (Cola nitida or Cola acuminata). For the (eds.), Addictions:A Comprehensive Guidebook (pp. softdrink industry, the trees are now grown on 250-267). New York: Oxford University Press. plantations throughout the tropics. Historically, CHANEY, E. F., O’LEARY, M. R., & MARLATT,G.A. kola nuts were valued highly among African socie- (1978) Skill training with problem drinkers. Journal ties for their stimulating properties. Kola nuts were 282 COLLEGE ON PROBLEMS OF DRUG DEPENDENCE (CPDD), INC.

available with sugar or artificial sweeteners, with or without caffeine, with or without caramel coloring (clear)—thus indicating that people seem to like the flavor regardless of the specific ingredients or the ‘‘effect.’’

BIBLIOGRAPHY

GRAHAM, D. M. (1978). Caffeine—its identity, dietary sources, intake and biological effects. Nutritional Re- view, 36, 97–102. LEWIN, L. (1964). Phantastica:Narcotic and stimulat- ing drugs, their use and abuse. New York: Dutton. Figure 1 MICHAEL J. KUHAR Kola cracked into small pieces and chewed for the ef- COLLEGE ON PROBLEMS OF DRUG fect—which increased energy and elevated mood in The College extremes of heat, hunger, exhaustion, and the like. DEPENDENCE (CPDD), INC. on Problems of Drug Dependence (Martin W. The European colonists in Africa learned of the Adler, Ph.D., Executive Officer, CPDD, effect and some chewed it. In the 1800s, Europeans brought kola nuts to various strenuous endeavors Department of Pharmacology, 3420 N. Broad in Africa and in other regions, and they began to Street, Philadelphia, PA 19140; 215-707-3242; increase the areas under cultivation. Kola nuts were http://views.vcu.edu/cpdd/) is the nation’s oldest soon finely powdered and made into syrups for ease organization devoted to the problem of drug use of use—with no loss of effect, it was claimed. and addiction. It is an incorporated, not-for- The active ingredient responsible for these stim- profit, scientific organization that acts indepen- dently of both the U.S. government and the phar- ulatory properties is CAFFEINE, a powerful brain stimulant, which is also present in other plants such maceutical industry while fostering an exchange as COFFEE, cocoa, TEA, mate´, and others. Besides of knowledge and resources across the academic, reversing drowsiness and fatigue, a heightened medical, governmental, and business communi- awareness of stimuli and surroundings may occur. ties. The CPDD is known internationally as a Studies have shown that less energy may be World Health Organization Collaborating Center expended by the musculature with equal or greater for research and training in the field of drug de- results—in animals as well as humans—but excess pendence. The CPDD also offers consulting ser- use causes TOLERANCE and dependence, often un- vices and, along with the National Institute on realized until deprivation results in severe head- Drug Abuse, supports drug-dependence testing aches. Large doses can cause nervous irritation, and research at several select U.S. universities. shaking, sleep disturbances, insomnia, and aggra- Among the goals of the CPDD are the following: vation of stomach ulcers or high blood pressure. (1) to support, promote, and carry out ABUSE-LI- In the late 1800s, in the United States, cola ABILITY research and testing, both at the pre- drinks came onto the market with other carbonated clinical and clinical levels; or phosphated (fizzy) drinks. Coca-cola, one of (2) to serve as advisor to both the public and pri- the first and most popular, contained extracts of vate sectors, nationally and internationally; both the COCA PLANT (cocaine) and the kola nut (3) to sponsor an annual scientific meeting in fields (caffeine)—but by the early 1900s, with the reali- related to drug abuse and chemical depen- zation of COCAINE’s dangers, this was removed and dence. replaced by additional caffeine. Drinking cola is part of American culture, emulated and enjoyed The annual scientific meeting of the CPDD has worldwide, with many brands competing for a huge become one of the few forums where scientists from and growing consumer market. Colas are now diverse disciplines can discuss problems of drug COLOMBIA AS DRUG SOURCE 283 abuse and drug dependence at a rigorous academic abuse. Sixteen institutions and professional and and scientific level. scientific societies are affiliated with or have liaison A primary goal of the CPDD is the publication of representation with the CPDD, including such di- data on the physical-dependence potential and verse groups as the American Chemical Society, the abuse liability of OPIOIDS, stimulants, and depres- American Medical Association, and the Food and sants, as well as the development of a new method- Drug Administration. ology for drug evaluation. These data provide an The members of the CPDD are involved in all independent scientific evaluation of drugs that the aspects of the effects of drugs subject to might have abuse liability. A number of scientists abuse—encompassing the enormous range from from various medical schools work collaboratively social, economic, and political issues through basic to assess these drugs. The data are collated in the research in molecular biology and the study of the Laboratory of Medicinal Chemistry, National Insti- interaction of these drugs with specific RECEPTORS tute of Diabetes, Digestive and Kidney Diseases in the central nervous system. Membership is di- (NIDDK), National Institutes of Health (NIH), Be- vided into four categories: Fellows, Regular Mem- thesda, MD. They are discussed by the Drug Evalu- bers, Associate Members, and Student Members. In ation Committee of the CPDD before publication. addition, corporations with an interest in the field Government agencies can use the data to help de- may join as Corporate Members. The CPDD spon- termine whether a medically useful drug should be sors the publication of the monthly journal, Drug scheduled under the CONTROLLED SUBSTANCES ACT and Alcohol Dependence, an international journal to restrict access and thus reduce possible abuse. covering the scientific, epidemiological, sociologi- The contemporary CPDD originated in 1913, as cal, economic, and political aspects of substance the Committee on Drug Addiction of the Bureau of abuse. Social Hygiene in New York City. In 1928, the Bureau of Social Hygiene provided funds to the (SEE ALSO: Drug Types; World Health Organiza- Division of Medical Sciences, National Research tion Expert Committee on Drug Dependence) Council (NRC), of the National Academy of Sci- ences (NAS), for the support of a chemical, phar- macological, and clinical investigation of narcotic BIBLIOGRAPHY drugs by the Committee on Drug Addiction, NRC, EDDY, N. B. (1973). The National Research Council in- NAS. This research continued until World War II. volvement in the opiate problem, 1928–1971. Wash- From 1939 to 1947, the Committee on Drug Ad- ington, DC: National Academy of Sciences. diction served as an advisory group to the U.S. MAY, E. L., & JACOBSON, A. E. (1989). The Committee Public Health Service (Eddy, 1973). on Problems of Drug Dependence: A legacy of the The Committee on Drug Addiction was reestab- National Academy of Sciences. A historical account. lished in 1947 as the Committee on Drug Addiction Drug and Alcohol Dependence, 23, 183–218. and Narcotics (CDAN), in the Division of Medical ARTHUR E. JACOBSON Sciences of the NRC, NAS. In 1965, CDAN’s name REVISED BY NANCY FAERBER was changed to the Committee on Problems of Drug Dependence (CPDD). The CPDD remained as an NRC, NAS committee until 1976, when it be- came an independent scientific organization, the COLOMBIA AS DRUG SOURCE Smug- Committee on Problems of Drug Dependence gling and the commerce in contraband have been a (CPDD), Inc. It was guided by a Board of Directors way of life in Colombia for nearly 500 years. Ap- with the sponsorship of nine major scientific orga- proximately 1,000 miles (1609 km) of largely nizations (May & Jacobson, 1989). In 1991, the unpatrolled Pacific and Caribbean coastline and CPDD underwent its most recent reorganization vast tracts of mostly uninhabitable territory— and its name was modified to reflect its contempo- ranging from tropical jungles in the south, to rug- rary role. Now known as the College on Problems of ged Andean mountain slopes in the east, to sparsely Drug Dependence, Inc., the CPDD has become a populated deserts in the north—have made Colom- scientific membership organization that enables its bia a haven for smugglers of illegal COCAINE,MARI- members to have a voice on issues relating to drug JUANA, and, most recently, HEROIN. Violence, cor- 284 COLOMBIA AS DRUG SOURCE ruption, inadequate control by the central government over much of its territory, and an inef- fective judicial system have hampered Colombia’s drug-control efforts. Consequently, Colombian co- caine is the single largest supply of that illicit drug to be smuggled into the United States. During the 1980s, despite positive law enforce- ment and crop-control programs, Colombian labo- ratories processed large volumes of (COCA PLANT) (Erythroxylon coca) into cocaine; by the 1990s, their sophisticated trafficking infrastructure had diversified into heroin production and distribution, adding to the already large Asian and Mexican supply in the United States. To reduce the level of violence and achieve peaceful coexistence through- out the country, the Colombian government offered a type of amnesty, or plea bargain, to major drug traffickers willing to surrender and cease their traf- ficking operations. However, by the late 1990s, the government had shifted its approach, employing the military and law enforcement to attack narcot- ics cultivation, processing, and trafficking. Colombia has powerful, often violent, trafficking By 1991, cocaine cartels in Colombia had organizations based in the major urban areas of diversified into the more lucrative heroin trade Medellin and Cali, as well as the oldest continuous by cultivating opium poppies on the slopes of the political insurgency in the Western Hemisphere, Andes. (Drug Enforcement Administration) the Revolutionary Armed Forces of Colombia (FARC). Although the extradition treaty with the ROLE AS COCAINE SUPPLIER United States is no longer constitutional, the Co- lombian government has implemented the stron- Proximity to the U.S. marketplace, remote and gest drug law enforcement efforts of any Andean vast tracts of unpatrollable land, powerful criminal country. In the 1990s, Colombia began efforts to organizations, indigenous entrepreneurial spirit, eradicate its burgeoning crop of opium poppy and a long tradition of violence and smuggling (Papaver somniferum), but met with little or no make Colombia an ideal source for illegal drugs. success. It also attempted to enhance the investiga- Coca production rose dramatically in the 1990s as tion of drug crimes through the development of a the governments of Bolivia and Peru pursed aggres- new code of criminal procedure; tougher chemical sive eradication programs. The U.S. government control; anti-money-laundering, asset-seizure, and estimated that Colombian coca cultivation doubled evidence-sharing procedures. between 1995 and 1999, constituting over two- Colombia was a signatory to the 1961 SINGLE thirds of the production in South America. Cultiva- CONVENTION ON NARCOTIC DRUGS and the 1971 tion takes place in the Llanos (plains) region, Convention on Psychotropic Substances. It has which encompasses almost half of eastern Colom- signed but not yet ratified the 1988 U.N. Conven- bia. Heavy growth also occurs in the Caqueta, tion Against Illicit Traffic in Narcotic Drugs and Guaviare, Putumayo, and Vaupes departments Psychotropic Substances. Although money laun- (counties or provinces), with evidence of crop ex- dering is not illegal in Colombia, the government is pansion in the Bolivar department and in south and actively tracking narcotics proceeds (e.g., exchang- southwest Colombia. In addition, new, more potent ing tax information and writing tougher financial strains of coca have been developed that reach disclosure laws) to improve its drug-investigative maturity more quickly and yield more product in capacity. the cocaine conversion process. COLOMBIA AS DRUG SOURCE 285

Colombia’s importance to the U.S. government’s fickers’ aims. In return, the political insurgents international narcotics control strategy lies in its ‘‘tax’’ the profits of the drug trade, thereby earning role as the world’s leading processor and distribu- hard currency and occasionally extracting payment tor of cocaine hydrochloride (HCl)—the cocaine in weapons. salt (powder) that is sniffed or snorted—and co- Elected in 1982, Colombia’s President Belisario caine base, or CRACK cocaine—the rock or crystal Betancur appointed a strong counternarcotics min- that has been converted from cocaine HCl. Colom- ister of justice, Rodrigo Lara Bonilla. In 1984, Lara bian cocaine-trafficking organizations are sophisti- Bonilla ordered a police raid on a Medellin cartel cated and well-organized industries; they derive laboratory complex in a remote area called their strength from longtime control of cocaine lab- Tranquilandia, which produced more than 3 tons oratories and the smuggling routes to North Amer- of cocaine per month. The police seized some 15 ica. Colombian traffickers operate a large number tons (13.8 metric tons) of cocaine, several air- of base and HCl labs—ranging from small simple planes, a variety of arms, and chemicals essential to operations to large sophisticated complexes. the processing of cocaine. One month later, the minister of justice was assassinated in the capital, HISTORICAL AND Bogota. In retaliation, President Betancur signed INSTITUTIONAL FACTORS the first extradition order for Carlos Lehder, the Medellin cartel’s transportation czar. Lehder was In the mid-to-late 1970s, the United States di- extradited in 1987, convicted in a Florida federal rected its international drug-control attention to court, and is serving a sentence of life plus 135 eliminating the heroin and marijuana crossing our years in the United States. border at Mexico. As the U.S.-Mexican crackdown Between 1984 and 1987, a total of fifteen drug began to achieve positive results and the number of traffickers were extradited to the United States. In U.S. smokers of Mexican marijuana diminished, 1984, 1988, and 1990, major traffickers met pri- Colombian traffickers seized the opportunity to vately with senior Colombian politicians to discuss break into the lucrative U.S. drug market by the possibility of a general amnesty and an end to smuggling large amounts of marijuana and small extradition—in return for ceasing the violence, packages of cocaine. In the early 1980s, Florida abandoning the cocaine business, and relin- became the destination of choice for smugglers quishing the assets used in the industry (e.g., because of its long coastlines, access to boats and planes, laboratories, airstrips). Although the first planes, location in the Caribbean, and large His- three offers were rejected, in September 1990, the panic population; by 1986, Colombia supplied an Gaviria administration gave the Extraditables the estimated 80 percent of the cocaine HCl. option of accepting reduced sentences and guaran- More than 150 Colombian drug groups orga- tees against extradition if they surrendered to the nized loosely into autonomous business cartels in authorities, confessed their crimes, and offered up the two principal urban areas of Colombia— their assets. Medellin and Cali—represent one of the most im- Under President Vergilio Barco, 1986 to 1990, portant power centers. The government of Colom- the violence throughout Colombia’s countryside in- bia and the roughly ten thousand members of the creased in response to the continuing extraditions. two antigovernment guerrilla groups called the In the 1980s, the murders in Medellin, a city of two Revolutionary Armed Forces of Colombia (FARC) million inhabitants, increased ten-fold—from and the National Liberation Army (ELN) are also seven hundred in 1980 to seven thousand by political forces there (Lee, 1989). 1991—due in part to a bounty of $300 offered by In controlling all stages of cocaine production, Medellin cartel boss Pablo Escobar in 1990 for from cultivation to sale, Colombian traffickers have every policeman killed. In August 1990, the pop- developed sometimes competitive, sometimes sym- ulist politician Luis Carlos Galan, a presidential biotic, relationships with each other and with in- contender, was assassinated at a political rally be- surgent groups. The guerrillas benefit from the il- cause of his strong support for the extradition licit drug trade by providing protection for the coca treaty and antidrug position. His murder mobilized fields, laboratories, and storage facilities; they carry the civilian population against the cartels and in- out kidnapping and terrorism to support the traf- censed Colombia’s national police and military. 286 COLOMBIA AS DRUG SOURCE

Through a series of raids on cartel laboratories, the ords on cash transactions of over 10,000 U.S. dol- government began an unparalleled crackdown, lars. culminating in the shooting of Medellin strongman Despite these promising efforts, the shift of coca Rodrigo Gacha and the destruction of one of their production from Bolivia and Peru to Columbia in largest cocaine-processing centers. the 1990s placed civil society in jeopardy. In addi- The Cali cartel, which was less violent and less tion, the destruction of the Medellin and Cali car- obtrusive than its Medellin counterpart, quickly tels has led to the proliferation of smaller, decen- began to move into the position vacated by the tralized drug-trafficking organizations. These Medellin leaders, many of whom were either im- traffickers are primarily located near Cali and on prisoned or killed. However, by 1996 the Colom- the Caribbean North Coast. In addition, these drug bian government had broken up the Cali cartel organizations have the support of well-armed and through the arrest or surrender of its leaders. well-organized guerrillas and paramilitary groups. President Andres Pastrana, elected in 1998, DRUG-REDUCTION EFFORTS formed a counterdrug joint task force with ele- ments from all the military services and the na- Among the principal Andean SOURCE COUN- tional police. Pastrana proposed a comprehensive, TRIES for coca, Colombia has become most com- integrated strategy called ‘‘Plan Columbia’’ to ad- mitted to defeating the cocaine cartels, since they dress the country’s drug-related, economic, and so- threaten to undermine its society. Colombians rec- cial troubles. At a cost of over $7 billion, the United ognize and fear that the violence and corruption States agreed to fund a large part of the plan, which endemic to drug trafficking are harming their econ- includes a massive eradication program and the omy, political system, and society. By the late interdiction of air transportation. United States 1990s, the government sought international assis- military forces provide technical assistance and the tance to overcome the growing power of drug orga- United States has also supplied helicopters and air- nizations. planes. In 2000, the U.S. Congress approved over Colombia’s national police, the military, and the $1 billion in funds toward continued eradication. security forces successfully broke up the Medellin and Cali cartels. In 1989, with the assistance of (SEE ALSO: Crop-Control Policies; Drug In- U.S. technical and material support, they attacked terdiction; Foreign Policy and Drugs; International and killed several mid-level Medellin traffickers, Drug Supply Systems; Source Countries for Illicit including Rodrigo Gacha. Colombia has also used Drugs) the extradition to incarcerate or immobilize major traffickers. In late 1990, President Cesar Gaviria’s BIBLIOGRAPHY offer of amnesty for major traffickers resulted in a decrease in violence and the surrender and impris- BAGLEY, B. M. (1988). Colombia and the war on drugs. onment of five traffickers and one terrorist— Foreign Affairs (Fall), 70–92. including Pablo Escobar and the three Ochoa BUREAU OF INTERNATIONAL NARCOTICS MATTERS, U.S. DE- brothers (Jorge Luis, Juan David, and Fabio). The PARTMENT OF STATE. (1991). International narcotics Medellin cartel lost its leader when Pablo Escobar control strategy report (INCSR). Washington, DC: was killed in a shoot-out in December 1993 after Author. having escaped from prison. The Cali cartel met its CRAIG, R. B. (1987). Illicit drug traffic: Implications for demise in the mid–1990s. South American source countries. Journal of Inter- As a signatory of the 1961, 1971, and 1988 U.N. american and World Affairs, 29 (2), 1–34. International Narcotics Control Conventions, Co- GUGLIOTTA, G., & LEEN, J. (1989). Kings of cocaine: lombia demonstrates its political commitment to Inside the Medellin cartel. New York: Simon & Schu- immobilizing drug traffickers and eradicating coca, ster. cannabis, and opium. In the early 1990s, the gov- LEE, R. W., III. (1991). Making the most of Colombia’s ernment created public-order courts and began to drug negotiations. Orbis 35(2), 235–252. share evidence, reform its judiciary, and track sub- LEE, R. W., III. (1989). The white labyrinth. New Bruns- stantial money flows—requiring banks to keep rec- wick, NJ: Transaction. COMMISSIONS ON DRUGS 287

WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- PORT, have guided British social and governmental ICY. (2000). National Drug Control Strategy:2000 policy toward the prevention and control of Annual Report. Washington, D.C. nonmedical usage of heroin and other opioid drugs. JAMES VAN WERT In North America, there have been a series of REVISED BY FREDERICK K. GRITTNER important commissions directed toward nonmedical drug use. In 1939, President Franklin D. Roosevelt asked Mayor of New York Fiorello LaGuardia to chair a scientific commission to in- COMMISSIONS ON DRUGS For vestigate the effects of marijuana and other drugs hundreds of years, governments have been using in communities, especially within urban areas of commissions of inquiry to help them investigate pressing social problems and to formulate plans for the United States. After looking into these issues for organized social and governmental responses to five years, the LaGuardia commission members these problems. One of the first government com- published their final report entitled The Marijuana missions on problems associated with drug use, Problem in the City of New York:Sociological, Med- appointed in 1893, was the Indian Hemp Drugs ical, Psychological and Pharmacological Studies. Commission—whose purpose was to investigate Based on interviews with hundreds of users, and the extent to which the hemp plant was cultivated, after sociological studies and laboratory investiga- the preparation of drugs from it, the trade in those tions, the commission concluded that marijuana drugs, the extent of their use, and the effects of was not an addictive drug as compared to mor- their consumption on the social, physical, and phine and that tolerance to marijuana was devel- moral conditions of the people. In addition, they oped to only a limited degree. Although the were asked to investigate certain economic aspects LaGuardia report is a significant contribution to of the use of hemp and also the potential political, the marijuana literature, its conclusions must be social or religious results of the prohibition of qualified because of various weaknesses in the ex- hemp. After one year of investigation, the commis- perimental methodologies available at that time. sion published a report summarizing its conclusion In 1962, President John F. Kennedy appointed that the occasional use of hemp in moderate doses the President’s Advisory Commission on Narcotics was not harmful but that excessive use did cause and Drug Abuse. This commission considered how injury. best to begin reexamination of the problem of drug Commissions often can create a firm basis for abuse in the United States, as well as what specific long-lasting social policy. One of the best examples recommendations to make regarding the control of relating to drugs is provided by the Shanghai Com- the problem of addiction by law enforcement. The mission and the Smoking Opium Act of 1909. Sev- commission’s final report in 1963 suggested that eral laws directed at the traffic in narcotics had psychological treatment might be useful against been introduced into the U.S. Congress before addiction. The report also marked a shift away 1908, but only after President Theodore Roosevelt from the trend to consider all NARCOTICS the same convened the Shanghai Opium Commission in under law. 1909 was federal enactment of any legislation ac- During the late 1960s and early 1970s, both the complished. The Shanghai meeting had been called United States and Canada launched commissions to aid China in its attempt to eliminate opium of inquiry into a growing problem of nonmedical addiction. Then the first U.S. federal legislation drug use among the young people of their coun- against American narcotic abuse, the Smoking tries. The Canadian LeDain Commission was Opium Exclusion Act of 1909, outlawed the impor- appointed in 1969 with the goals of referencing the tation into the United States of opium prepared for existing literature and data regarding the smoking. nonmedical use of drugs; reporting on the current Within Great Britain, the Rolleston Commission state of medical knowledge of these drugs; studying served the important function of establishing basic the motivation underlying such nonmedical use of principles for long-lasting social policy. For more drugs; investigating social, economic, educational than sixty years, the recommendations of the and philosophical factors related to such use; and Rolleston Commission, called the ROLLESTON RE- finally, recommending ways the Canadian govern- 288 COMMITTEES OF CORRESPONDENCE ment could act to reduce the problems associated organization originally founded in 1772 by Samuel with such use. Adams—to exchange ideas on building colonial Shortly afterward, in the United States, the NA- unity. The modern version was formed to build TIONAL COMMISSION ON MARIHUANA AND DRUG national unity by exchanging facts and ideas on ABUSE issued two important reports, the first enti- drug prevention, with a newsletter and letter cam- tled Marihuana:A Signal of Misunderstanding and paign to government favoring antidrug legislation. the second called Drug Use in America:Problem in The Moultons have served Massachusetts state Perspective. For the most part, the commission’s government and the U.S. government as advisors in recommendations about MARIJUANA fell on deaf the 1980s and 1990s. The Committees of Corre- ears. A most important recommendation of the spondence maintains a large library on drug-cul- commission was realized in the form of a well- ture history, with books, videotapes, and publica- funded national program of periodic epidemiologic tions to provide information for global requests; it surveillance concerning nonmedical drug use and also provides the public, policymakers, and the the consequences of such use, now apparent in the media with current research data in an ongoing MONITORING THE FUTURE studies and in the NA- effort to counter drug advocacy. TIONAL HOUSEHOLD SURVEY ON DRUG ABUSE. OTTO MOULTON

(SEE ALSO: Marihuana Commission; Opioids and Opioid Control; Shanghai Opium Conference of COMMUNITY PARTNERSHIPS See 1909; U.S. Government:The Organization of U.S. Parents Movement; Prevention Movement Drug Policy) JENNIFER K. LIN COMPLICATIONS This section has articles on some aspects of the physical and psychological COMMITTEES OF CORRESPONDENCE complications of substance abuse. It contains an This organization works toward a drug-free Amer- overview of Medical and Behavioral Toxicity and ica. It is a nonprofit organization that does not individual articles on the following: Cardiovascular accept government funding and is headed by Otto System; Cognition; Dermatological; Endocrine and and Connie Moulton, 24 Adams Street, Danvers, Reproductive Systems; Immunologic; Liver (Alco- Massachusetts 01923, (508) 774-2641. Drug hol); Liver Damage (Other Drugs); Mental Disor- Watch International and its subsidiary, the Inter- ders; Neurological; Nutritional; and those Due to national Drug Strategy Institute, were founded to Route of Administration. Each article is extensively expand the information gathering and dissemina- cross-referenced and will refer the reader to other tion efforts of the Committees of Correspondence. articles throughout the Encyclopedia that will ei- In 1977, Otto had been coaching little-league ther expand or simplify concepts introduced here, baseball and youth hockey and was uninformed on and to articles on the many other behavioral and the youth drug culture. After four of his players nonmedical complications that arise as a result of changed in attitute and ability, he discovered the alcohol and drug use. cause—MARIJUANA. The Moultons began learning about the health effects of marijuana, which was not an easy task. PRIDE and The American Coun- Cardiovascular System (Alcohol and Co- cil on Marijuana provided research reports and, caine) Since the 1960s, the effects of ALCOHOL armed with facts, the Moultons shared them in (ethanol) on the heart and blood vessels have been their local communities, alerting parents and stu- extensively studied. Clearly, the toxic effects of dents to marijuana’s effects. both acute and chronic ingestion are independent At the 1980 PRIDE conference, they joined with of nutritional and cardiovascular risk factors. In other groups to found a grass-roots PARENTS 1964, a relationship was established between the MOVEMENT called The National Federation of Par- duration and quantity of alcohol use and the degree ents for Drug-Free Youth. The Moultons also re- of heart disease in patients without nutritional or vived the Committees of Correspondence, an liver disease. Alcoholism, once felt to be coinciden- COMPLICATIONS: Cardiovascular System (Alcohol and Cocaine) 289 tal with heart muscle damage, is now among the tion—a very rapid and irregular but generally not most frequently identified causes, according to two life-threatening heart rhythm—was the most com- recent studies that report a 32 percent and a 45 mon heartbeat irregularity. Normal rhythm was percent incidence, respectively. restored in all cases, but recurrence of the syn- Attention was also paid to COCAINE abuse as the drome is common. popularity of this drug skyrocketed in the 1980s Cardiac patients who have already had at least (an estimated 30 million Americans had used it and one prior episode of heart failure, and who have not some 6 million were users in 1985). Here too came compensated by clinical means, usually with symp- the recognition that acute and chronic-use users toms of severe fatigue and shortness of breath, may were associated with cardiopulmonary manifesta- exhibit even greater sensitivity to acute alcohol tions. A 1998 survey estimated that nearly twelve consumption. Such individuals given six ounces of million Americans use cocaine and alcohol to- scotch over two hours exhibited a substantial in- gether, and researchers have found a unique prod- crease in measured internal heart pressures, sug- uct of the body when these two drugs are used in gesting poor heart function and reserve. combination—COCAETHYLENE. EFFECTS OF CHRONIC ALCOHOL USE ALCOHOL Subclinical Dysfunction. Results of studies Effects of Acute Administration in Those on alcoholic subjects without evidence of heart dis- With and Without Heart Disease. Even mildly ease suggest that a subclinical disease state may intoxicating levels of alcohol affect the cardiovas- exist. In this situation, recognition of the possibility cular system. The magnitude of effects may depend of disease exists, but no methodology has been on the chronicity of use. When six ounces of scotch developed to detect one in the clinic. In one study, were given to both alcoholics and nonalcoholics, those with at least a ten-year history of heavy alco- neither of which groups was suffering from previ- hol consumption were compared to controls. These ously recognized cardiac problems, over a two-hour patients had biopsy-proven fatty liver disease (a period, only the nonalcoholics demonstrated evi- common sequel to chronic alcohol use) without dence of diminished heart muscle contractility prior history of heart disease. The response of the (pumping less blood per contraction). This depres- heart’s main pumping chamber—the left ventri- sant effect is enhanced by increasing blood levels cle—to storehouses was assessed. Alcoholic hearts 75 milligrams/100 milliliters, but remains for only were found to have abnormally high internal pres- a few hours after ingestion ceases. However, the sures and could not appropriately compensate by amount of blood the heart can pump per minute increasing forward blood flow. An index of heart may actually increase in normal subjects acutely contractions in response to the stimulus was corre- exposed to alcohol, because of an acceleration of spondingly low in the alcoholics compared to con- the heart rate (increase of contractions per minute). trol. Doppler echocardiography, an ultrasound During the late-intoxication/early-withdrawal technique for assessing heart function, has also stage of acute alcohol consumption, blood pressure demonstrated an inability of the heart muscle to may be affected in the noncardiac alcoholic. Blood- relax and its chambers to fill properly with blood. pressure elevation is the rule. Blood levels of certain Therefore, the pumping chamber of the heart can- hormones, as well as urinary levels of certain not fill or expel blood in a proper manner. Not breakdown products, correlate directly with blood- surprisingly, autopsy specimens from these pa- pressure response, which appears to vary with the tients demonstrate fibrosis, development of abnor- degree of alcohol intake. mal and often harmful tissue, and scarring of the Arrythmias, abnormal heart rhythms, are also heart muscle. Consideration must also be given to commonly described in patients without cardiac cardiac status in cirrhotics, a group once thought problems during acute alcohol intoxication. The relatively resistant to heart muscle failure. A group so-called holiday heart syndrome represents an of thirty-seven patients with cirrhosis of the liver acute transient-rhythm disturbance in persons but no evidence of heart disease were studied. One without otherwise detectable heart disease who are subset with poor heart function at rest had an examined following heavy drinking. Atrial fibrilla- abnormal response to left ventricle stressors. The 290 COMPLICATIONS: Cardiovascular System (Alcohol and Cocaine) other subset, which had abnormally vigorous func- In either gender, heart failure is generally found tion at rest, also failed to respond appropriately to in those who continuously (chronically) ingest in- stressors, suggesting cardiac dysfunction in this toxicating amounts for a minimum of ten years. group of patients despite a lack of symptoms. Isolated studies do, however, suggest the potential for the beneficial effects of cessation of alcohol MECHANISMS OF ACTION ingestion. One study of thirty-one alcoholics matched for degree of heart size and symptoms The exact mechanism by which alcohol exerts its found that all twelve abstainers survived over sev- effects on the heart muscle, at the cellular level, eral years, while all nineteen who continued drink- remains speculative. It is believed that altered ing died. A study of sixty-four patients found a 9 movement of calcium ions within these cells may be percent mortality rate among abstainers over four of major importance. years and a 57 percent mortality rate in persistent The Picture of Clinical Heart Failure. A drinkers. full-blown cardiomyopathic picture, a complete Coronary Artery Disease. Chest pain in pa- observance of disease of the middle layer of the tients with alcoholic hearts is not uncommon, al- heart, although relatively uncommon among alco- though it had long been held that chronic alcoholics holics, is not unlike that seen with other causes of have less severe atherosclerotic coronary artery dis- this syndrome. Most commonly, complaints of ease, characterized by a hardening of the arteries weakness and fatigue are present before a history of accompanied by cholesterol and fatty blockages, exertional and nocturnal shortness of breath. En- than nonalcoholics. Yet, it has been postulated that gorgement of the veins of the neck, an enlarged, many heavy drinkers may have a higher incidence tender liver, and swelling of the legs and feet are of heart attacks (myocardial infarction). Heart at- other peripheral signs of heart failure frequently tacks have even been reported in a small number of seen in these patients. Heart size is variable. The patients without significant coronary disease— most significant cardiomegaly, enlargement of the possibly related to the scarring of coronary arteries heart, is seen in those patients who develop atrio- or the spontaneous formation of blood clots within ventricular valve regurgitation, a leaking of blood them. backward from the large to the small heart cham- Alcohol may exert at least an indirect effect on bers, as a result of muscle weakness. This abnormal coronary anatomy via interaction with fat metabo- flow creates heart murmurs and may give a clue to lism. Three major components of fat metabolism, the severity of disease. Blood clots are also a com- low density lipoprotein (LDL) cholesterol, high mon feature of this syndrome. They often form in density lipoprotein (HDL) cholesterol, and triglyc- the vein of the leg or along the walls of the heart erides all impact on coronary atherosclerosis or chambers and can travel to the lungs and brain plaquing. Levels of LDL cholesterol (the so-called causing near instantaneous death or stroke. bad cholesterol responsible for atherosclerosis) ap- Studies performed in the 1960s clearly docu- pear to be lowered by heavy alcohol use. Moderate mented these effects of alcohol on cardiac difficul- use (1–3 drinks per day) does not seem to affect ties that are left untreated. In one, a patient was fed levels of either triglycerides or LDL cholesterol. twelve to sixteen ounces of Scotch daily. Gradually, HDL cholesterol, the so-called good cholesterol over a four-month period, he developed the signs (believed to be protective against atherosclerosis), and symptoms of heart failure. These reversed has shown a consistent relationship with even mod- when the alcohol was discontinued. This sensitivity erate alcohol consumption. Alcohol is believed to to alcohol has individual variability and, unfortu- enhance the activity of the enzymes lipoprotein li- nately, the factors contributing to this are un- pase and hepatic triglyceride lipase—thereby fa- known. There may be some difference in suscepti- voring HDL production. Autopsy studies have bility between the sexes. In a study of matched shown a lower prevalence of atherosclerosis, block- subjects with alcoholic cirrhosis under age forty- ages, in alcoholics and cirrhotics. Whether this is five, measures of heart muscle performance were due to malnutrition or direct effects on fat metabo- significantly worse in men than in women. Experi- lism remains unclear. ence also shows that heart failure is rare in alco- A reduced degree of coronary disease has also holic women prior to menopause. been documented in light as compared to COMPLICATIONS: Cardiovascular System (Alcohol and Cocaine) 291 nondrinkers. Two recent studies both support the tromechanical dysfunction manifest as an abnor- hypothesis that light or moderate alcohol intake mally slow heart rate or acute pump failure. appears to reduce the risk of fatal and nonfatal Several controlled trials have assessed the acute heart attacks and the need for coronary angioplasty effects of cocaine on humans. Investigators have and bypass operations in both men and women. demonstrated a dose-related increase in heart rate Neither study included many heavy drinkers, and and blood pressure. Others have induced a signifi- multiple coronary-risk factors (including cigarette cant reduction in coronary blood flow in patients SMOKING) were accounted for. Although these stud- receiving intranasal (inhaled through the nose), co- ies supported the positive association between in- caine at 2 milligrams per kilogram, with coronary creased HDL cholesterol levels and alcohol intake, angiography, a test using a chemical that can be no consensus exists to promote alcohol use for the tracked and seen in the body using an x-ray, re- primary prevention of coronary artery disease, ow- vealing a diffuse reduction in vessel caliber (width). ing to its ease of addiction and other multiple Coronary vasospasm, a sudden constriction of the harmful effects. blood vessel, has also been documented with intra- nasal administration. The effects of chronic use COCAINE have been studied in animal models, with two ex- periments demonstrating that cocaine fed to rab- Cocaine abuse has dramatically increased in the bits on high cholesterol diets significantly increased United States since the 1980s. One consequence aortic atherosclerosis, or blockages, as compared to has been the recognition of cocaine’s unpredictable rabbits fed similar diets minus the cocaine. medical side effects—the most dramatic and dev- Since all the mechanisms discussed above either astating of which are cardiovascular. These include increase myocardial oxygen demand or decrease acute impairment of blood supply to the heart mus- myocardial oxygen supply, heart attacks are natu- cle, and heart attacks, as well as hypertension, ral consequences of cocaine toxicity. Many case accelerated arteriosclerosis, ruptured aorta artery, reports have temporarily related cocaine use to inflammation of heart muscle, cardiomyopathy myocardial infarction, frequently in patients with- (heart disease), cardiac arrythmia, and sudden out coronary artery narrowing. Thrombosis, the death. acute formation of an occlusive clot in a blood Cocaine has two separate primary pharmaco- vessel, has been documented in nearly one-third of logic effects on the heart and vascular system. First, cases. This is consistent with evidence that cocaine it causes an accumulation of CATECHOLAMINES— causes an increase in the aggregation, collection accomplished by increasing their release (which and buildup, of platelets, blood elements that cling include epinephrine [also called adrenaline], together to initiate blood clotting. Cocaine toxicity NOREPINEPHRINE, and DOPAMINE) from both brain may also cause rupture of pre-existing small lipid- and spinal cord stores and by blocking their reup- containing bulges on the arterial walls, as well as take at nerve endings. The result is a more pro- coronary spasm, both of which trigger thrombus nounced and long lasting stimulation of the sympa- formation. thetic nervous system, heart muscle, and vascular Case reports have also suggested that cocaine smooth muscle, represented clinically by an in- has a primary depressant effect on cardiac muscle. crease in heart rate, blood pressure, heart contrac- Otherwise healthy patients have developed acute tions, vasoconstriction, when blood vessels con- cardiac dilation and pump failure associated with strict, and coronary vascular resistance, a acute or chronic cocaine use. With abstinence, such resistance of the blood vessels to blood flow. Co- signs and symptoms resolved over days to weeks. caine may also induce vasoconstriction via direct Animal studies have confirmed this phenomenon. stimulation of calcium into smooth muscle cells. Autopsy studies on patients with cocaine in the Cocaine’s second pharmacologic property is a bloodstream have shown inflammation and scar- local anesthetic effect on cardiac tissue. Cocaine ring of heart muscle cells in up to 20 percent, as can paralyze the movement of the ions (like sodium compared with 4 percent of controls, suggesting a and potassium) required for the inherent electrical pathologic link. stimulation of heart-muscle function. Therefore, Ultimately, most cocaine-related deaths are severe toxicity may result—with acute elec- caused by cardiac arrhythmias. Abnormally fast 292 COMPLICATIONS: Cognition

and abnormally slow heart rates have been re- THOMAS, B. A., & REGAN, T. J. (1990). Interactions be- ported with cocaine use. Low and moderate doses tween alcohol and cardiovascular medication. Alco- often trigger the fast and massive doses the slow, hol, Health, and Resort World, 14, 333–339. including the complete cessation of heart beats TIMOTHY REGAN (termed asystole). The combination of alcohol and ROBERT SAPORITO cocaine may be even more dangerous than cocaine REVISED BY ANDREW J. HOMBURG alone. In the presence of alcohol (ethanol), in hu- mans, cocaine is metabolized to the compound COCAETHYLENE. This chemical renders the combi- Cognition PSYCHOACTIVE DRUGS of abuse, nation of cocaine and alcohol more lethal than ei- used for their perceived mind-altering effects, often ther alone, and a twenty-one times greater risk of have additional cognitive effects of which the drug sudden death exists in people with associated coro- user may not be aware. A cognitive effect is an nary artery disease. impact on mental functions—including processes Cerebrovascular Disease. The effects of al- of learning, perceiving, imagining, remembering, cohol and cocaine on vascular physiology do not feeling, thinking, reasoning, knowing, and judging. bypass the brain. Epidemiologic studies indicate a Psychoactive drugs produce cognitive effects by passive association between the amount consumed causing chemical changes in the brain. These ef- and the risk of cerebral vascular accidents, gener- fects are mostly short-lived and correspond to the ally presenting as intracranial hemorrhage, blood duration and intensity of the chemical changes in vessel ruptures in the head. In one study, heavy the brain. However, cognitive effects can persist drinkers were twice as common among men and after the drug has been eliminated from the body, seven times as common among women who had and some can be irreversible. The common cogni- sustained intracranial hemorrhage than in the gen- tive effects of some psychoactive drugs of abuse are eral population. Furthermore, heavy drinkers were summarized below. more likely to have been intoxicated in the twenty- four hours prior to their event. Young adults and ALCOHOL women, generally unlikely candidates for intracra- nial hemorrhage, are not immune when subjected Ethanol (also called ethyl alcohol) is the drink- to acute, or heavy intoxication. ing ALCOHOL of BEERS AND BREWS, wine, distilled The mechanism for this remains unclear. Hyper- spirits, or medicinal compounds; it acts by de- tension is a known risk factor for stroke in general pressing or reducing cognitions. Initially, alcohol and alcohol-induced hypertension may be a caus- reduces inhibitions, and this results in more spon- ative factor. The same may be postulated with taneity or impulsivity and a feeling of relaxation. cocaine use. As with alcohol-induced cardiomyopa- As the amount of alcohol acting on the brain in- thy, individuals who reduce their alcohol intake creases, the ability to perceive, remember, reason, have a significantly lower risk of developing hemor- and judge is progressively impaired. Further in- rhagic stroke than those who continue its use. creases in the amount of alcohol can depress the brain and cognitions to the point of loss of con- (SEE ALSO: Alcohol; Complications) sciousness. Due to cognitive impairment, the per- son may not perceive the impairment (e.g., ‘‘I’m not drunk’’) and take undue risks (e.g., DRUNK BIBLIOGRAPHY DRIVING, indiscretions). AHMED, S. S., & REGAN, T. J. (1992). Cardiotoxicity of Alcoholic blackouts are impairments of memory acute and chronic ingestion of various alcohols in for events that occurred while one was conscious cardiovascular toxicology. In D. Acosta, Jr. (Ed.), but under the influence of alcohol. Such black-outs Cardiovascular Toxicology (2nd. ed.). New York: Ra- are not limited to chronic alcoholics. Long-term use ven Press. of alcohol can lead to subtle impairment of per- REGAN, T. J. (1991). Alcohol and the heart. In K. ceiving, responding, and remembering that may Chatterjie & W. Parmley (Eds.), Cardiology. New not be detectable without special psychometric York: Gower Medical Publishing. tests. A particular form of impairment of memory, COMPLICATIONS: Cognition 293 called the amnestic syndrome, has been seen in evidence that long-term and repeated doses of alcoholics; they are unable to remember recent stimulants can severely damage the brain and af- events although memories from long ago remain fect concentration, mood, and reasoning reasonably intact. By contrast, in alcoholic demen- tia, deficits in all cognitive functions are seen. Some MARIJUANA deficits may persist for life even if the person stops Cannabis sativa is often used for the subjective drinking. effects of relaxation and a decreased awareness of Paranoid states of unfounded suspicion or jeal- conflicts. It is also known to distort perception of ousy may manifest or be aggravated under the influ- time and to reduce responsiveness. Long-term use ence of alcohol. In alcoholic, HALLUCINATIONS peo- of Cannabis has been associated with apathy, un- ple can have vivid but unreal perceptions while der-achievement, and lack of motivation. awake; these typically occur as a result of neuro- chemical changes in the brain when alcohol use is HALLUCINOGENS abruptly discontinued after periods of excessive drinking. Even after months have elapsed since Hallucinogenic drugs distort perceptions and their last drink, alcoholics can have cognitive defi- cause hallucinations. They include LYSERGIC ACID cits, especially in visual-spatial abilities, hand-eye DIETHYLAMIDE (LSD), PHENCYCLIDINE (PCP), coordination, abstract reasoning, and new learning. MESCALINE,PSILOCYBIN mushrooms, and several newer drugs with hallucinatory and stimulant ef- TRANQUILIZERS, SEDATIVES, fects (called ‘‘designer drugs,’’ e.g. ecstasy. Apart AND HYPNOTICS from profound effects on perceptions, responsive- ness, learning, and judgment are affected. Some These drugs are often collectively referred to as users experience flashbacks—spontaneous vivid ‘‘downers.’’ Persons taking them are at risk for the recollections of experiences that occurred while un- cognitive impairments discussed above, under ‘‘Al- der the influence of hallucinogens. cohol.’’ The ELDERLY are particularly at risk for confusion. USE DURING PREGNANCY

Psychoactive drugs used during PREGNANCY af- STIMULANTS fect the developing fetus. Prenatal exposure, partic- Stimulant drugs have effects that are the reverse ularly to alcohol but possibly to Cannabis, or stim- of depressant drugs—they arouse the nervous sys- ulants has been associated with cognitive tem. They include such drugs as COCAINE, impairments detectable early in the child’s life and AMPHETAMINES (speed), and CAFFEINE. In low eventually resulting in developmental problems doses, perception is heightened, attention is in- and school, social, and occupational difficulties. creased, and thought processes are speeded up, resulting in a feeling of greater alertness. MEMORY, (SEE ALSO: Imaging Techniques) however, may be affected, resulting in impaired recall of material learned while under the influence BIBLIOGRAPHY of stimulants. Higher doses intensify the above ef- fects, leading to restlessness and rapidity of MARTIN, P. R., & HUBBARD, J. R. (2000). Substance thoughts, which reduce attention. Vulnerable per- abuse and related disorders. Current Diagnosis and sons may become paranoid or even psychotic. Treatment in Psychiatry. Ebert, M. H., Loosen, P. T., Higher effective doses of stimulants may occur via Nurcombe, B., eds., McGraw-Hill, 233-259 intravenous administration or smoking of cocaine, MARTIN, P. R., LOVINGER, D. M., BREESE, G. R. (1995). affecting the brain rapidly and resulting in an Alcohol and other abused substances. Principles of abrupt ‘‘rush’’ or ‘‘high.’’ These effects are typi- Pharmacology:Basic Concepts and Clinical Applica- cally short-lived but are so intense (pleasurable) tions. Munson, P., and Mueller, R. A., eds. New York: that individuals may repeat doses. Discontinuation Chapman & Hall, 417-452. of stimulants after a long period of use often leads PETER MARTIN to a temporary period of DEPRESSION. There is GEORGE MATHEWS 294 COMPLICATIONS: Dermatological

Dermatological With the exceptions of the cellulitis may eventually cover most of the rashes and other skin conditions resulting from id- user’s body as new needle sites are used to avoid iosyncratic or allergic reactions to drugs, most drug painfulareas.Superficialcellulitis,septic use complications involving skin damage result thrombophlebitis, and simple needle abscesses can from the use of hypodermic needles or other means usually be treated with local heat, incision, and of drug injection that involve breaking the skin drainage, followed by culture and sensitivity testing surface. There are three primary types of injection: and appropriate antimicrobial therapy. (1) subcutaneous, also known as ‘‘skin-popping,’’ Repeated intravenous injection may produce an- wherein the needle is injected into or directly under aerobic infections or abscesses that produce a foul- the skin surface; (2) intramuscular (IM), wherein smelling discharge, sometimes gas formation, and a the needle is injected into muscle mass, often in the cellulitis that is characterized by a rapidly progres- shoulder or buttock; and (3) intravenous (IV), di- sing stony or wooden-hard tenseness, often some rect injection into a blood vessel. Skin damage can distance from the original needle site. Although the result from repeated injection in the same area, mechanism of these infections is unclear, it is failure to clean the injection site, nonsterile needles, thought to involve a disruption of blood supply to and/or impurities or insoluble materials in the sub- the area from edema (fluid collection) resulting stance injected. Adulterants in the drugs, liquids from the cellulitis. Treatment involves wide inci- used to dilute the drugs and contaminated injection sion and pressure reduction in the affected area. paraphernalia, and the surface of the injection site Kaposi’s Sarcoma. Kaposi’s Sarcoma is a malig- all provide sources of viruses, bacteria, and fungi. nancy arising in the skin usually in the cells lining The most common skin damage from repeated the blood vessels (endothelium). The lesions have a injection is needle-track scars. These are usually nodular or plaquelike appearance, may be localized caused by unsterile injection techniques or by the and indolent or disseminated, and involve aggres- injection of fibrogenic particulate matter— sive spreading to mucous membranes and visceral material often used by dealers to add bulk and organs, especially the gastrointestinal tract. weight to the drug or buffers in tablets that have Prior to 1980 and the advent of the human been ground up and liquified for injection. Carbon immunodeficiency virus (HIV) and AIDS, Kaposi’s deposited on needles by users who try to sterilize by sarcoma was considered a rare disease and primar- heating the needle tip with a match may produce a ily limited to elderly males of Mediterranean ethnic ‘‘tattoo’’ discoloration, accompanied by a mild in- flammatory reaction under the skin at the point of origin. Since that time, widespread dissemination entry. Such scars are found mostly on the arms, but of HIV and the epidemic of AIDS accompanying it they can occur anywhere on the user’s body that has made Kaposi’s sarcoma much more common. has been used as an injection site, including thighs, Substance abusers who administer their drugs par- ankles, neck, and penile veins. enterally (subcutaneously, intramuscularly, intra- Needle abscesses, characterized by redness; a venously) are a higher risk group for Kaposi’s sar- stinging, itching sensation; and swelling at the site, coma since many of these individuals inject drugs often result from repeated injection without clean- with unsterile needles that frequently are used in ing the injection site. Such skin flora as staphylo- common with others. They therefore have an excel- cocci and streptococci are driven beneath the skin lent opportunity of acquiring HIV from infected surface to infect the site, often with pus formation. blood. Forms of contact dermatitis can also result from The aggressive form of Kaposi’s sarcoma has allergic reactions, especially to fluids used to steril- occurred in at least one-third of patients with AIDS ize the skin at injection sites. Infections and allergic and has reached epidemic proportions in the reactions increase as an individual’s resistance de- United States and many African countries. In many creases with a drug-compromised immune system. AIDS patients, Kaposi sarcoma lesions may actu- Subcutaneous injection of SEDATIVE-HYPNOTIC ally be the first notable manifestation of the dis- drugs, such as BARBITURATES, can cause cellulitis— ease. The lesions usually first appear on the upper where the tissue becomes reddened, hot, painful, part of the body, but rapidly spread to lymph and swollen at the injection site. If not treated, the nodes, the mucosa of the mouth and the gastroin- cellulitis may last for a long time. In extreme cases, testinal tract and other visceral organs. COMPLICATIONS: Endocrine and Reproductive Systems 295

Chemotherapy is the treatment of choice, either fested only by an abnormal result from a laboratory a single agent or a combination of agents. Inter- (biochemical) test. The absence of a physical sign feron-a effectively slows the progression of lesions or a clinical symptom may lead to the false impres- and cures others. The injection of vincristine into sion that there is no endocrine/reproductive conse- the lesions is also useful. The course of the disease is quence. In addition, there are challenges in ascer- dictated by the level of immunosuppression that is taining whether the alcohol- or drug-abuse related present. endocrine/reproductive dysfunction is due to the drug itself or to the social context in which the drug (SEE ALSO: Allergies to Alcohol and Drugs; Compli- is used. Finally, endocrine or reproductive distur- cations:Route of Administration ) bances may also occur from the consequences of WITHDRAWAL syndromes when the drugs or alcohol BIBLIOGRAPHY ingestion is stopped or reduced. To the extent to which these issues have been clarified, we will note COHEN, S., & GALLANT, D. M. (1981). Diagnosis of drug them here. and alcohol abuse. Brooklyn: Career Teacher Center, State University of New York. HYPOTHALAMIC/PITUITARY SENAY, E. C., & RAYNES, A. E. (1977). Treatment of the drug abusing patient for treatment staff physicians. Most endocrine and reproductive function is in- Arlington, TX: National Drug Abuse Center. fluenced directly or indirectly by the BRAIN— SEYMOUR, R. B., & SMITH, D. E. (1987). The physician’s specifically by the functional interactions of the guide to psychoactive drugs. New York: Hayworth brain’s hypothalamus and pituitary with the target Press. endocrine organs. The hypothalamus produces pi- tuitary-regulating hormones; all are peptides ex- DAVID E. SMITH cept one (DOPAMINE). In response to each of these RICHARD B. SEYMOUR hypothalamic hormones, the pituitary releases a REVISED BY RALPH MYERSON hormone, which influences the function of an endo- crine or reproductive organ. Alcohol. The anecdotal reports of changes in Endocrine and Reproductive Systems sexual function following alcohol consumption was Many fundamental challenges remain in under- the stimulus for much of the research targeting standing the impact of ALCOHOL and drugs on en- hypothalamic-pituitary relationships, since im- docrine and reproductive function. This article pre- pairments here may often result in sexual dysfunc- sents what is currently known; before beginning, a tion. Although acute alcohol use has been reported few caveats deserve attention. in public surveys to be associated with increased Many factors may influence the degree to which sexual drive and functioning, clinical and animal illegal drug or alcohol abuse may cause an abnor- research have revealed major hormonal dysfunc- mality of endocrine or reproductive function. These tions in chronic or heavy alcohol users. factors include (1) the amount and duration of con- Prolactin (PRL)—the pituitary hormone associ- sumption; (2) the route of illegal drug administra- ated with preparation during pregnancy for tion; (3) whether there is preexisting or concurrent breastmilk secretion—is increased with heavy al- damage to an endocrine/reproductive organ; cohol use; however, chronic alcohol use inhibits the (4) concurrent use of another drug; and (5) the pituitary release of luteinizing hormone (LH) and genetic predilection for an endocrine disorder. Of- follicle-stimulating hormone (FSH). Both LH and ten, our knowledge about these factors and how FSH are important in regulating the sex hormones they interact with one another is more limited than produced by the testes in males and the ovaries in what is known about the range of endocrine and females. Yet, when alcohol is administered acutely, reproductive dysfunction associated with the there are no significant changes in PRL, LH, or chronic consumption of alcohol and the abuse of FSH serum levels. illicit drugs. Heavy alcohol consumption is associated with Knowledge is also limited because some endo- an increase in pituitary-secreted adrenocorticotro- crine or reproductive consequences may be mani- pic hormone (ACTH), partly explaining the 296 COMPLICATIONS: Endocrine and Reproductive Systems

‘‘pseudo-’’Cushing’s syndrome (moon faced ap- a variable LH response following a GnRH chal- pearance, central obesity, muscle weakness) and lenge. the increased melanocyte-stimulating hormone Some researchers have demonstrated normal (MSH), which possibly leads to darkening skin pig- functioning of the hypothalamic-pituitary-adrenal mentation. Although there is no consistent effect of (HPA) axis in former heroin addicts who were heavy alcohol use on the pituitary’s release of thy- maintained on methadone both long-term and only roid-stimulating hormone (TSH) or growth hor- for a number of months. However, there is also mone (GH), a rise in the blood alcohol level is evidence suggesting alteration of the normal bio- associated with the inhibition of antidiuretic hor- logical rhythm of hormonal secretion. mone (ADH) release from the posterior pituitary, resulting in increased urination. SEX HORMONES Drugs. Complaints of derangements of libido Diminished sexual drive and performance in (sex drive) and sexual functioning in OPIOID addicts opioid users have raised questions about the rela- (HEROIN) were among the first lines of clinical evi- tionship between such narcotic drug use and dis- dence to suggest the possible role of such narcotics turbances in the levels of sex hormones. Although in altering hypothalamic-pituitary functioning. Al- some reports show no significant differences in se- though most of what is known about drug-abuse rum-testosterone levels between heroin addicts, related hypothalamic-pituitary abnormalities fo- METHADONE-MAINTAINED patients, and normal cuses on heroin use, the epidemic proportions of controls, other studies have not confirmed these COCAINE abuse and dependency in the 1980s have results. Some researchers have reported plasma brought renewed scientific interest to this area. levels of testosterone to be consistently lower in Studies have shown that opioid use has been active heroin addicts, in addicts who self-adminis- associated with increased serum PRL without dis- ter heroin in controlled research settings, and to be turbances in serum GH or TSH levels; and cocaine within normal range in long-term methadone- use has been associated with both high and low maintained patients. Additionally, some evidence PRL levels. The contradictory findings in the case shows that plasma testosterone levels that are de- of cocaine use might be attributable to the varia- pressed under circumstances of heroin administra- tions in patterns of cocaine use. Animal studies tion followed by methadone maintenance and then have shown that gonadotropin-releasing hormone withdrawal gradually returned to preheroin-use (GnRH), released from the hypothalamus, did not levels. stimulate PRL following acute cocaine administra- Opioid effects on the estrogens of both males and tion, and it did not prevent acute cocaine-associ- females may be responsible for the clinical observa- ated PRL suppression. Elevated levels of dopamine tions of sexual dysfunction. In the male heroin ad- have been observed during acute cocaine adminis- dicts studied, the plasma estradiol concentrations tration, but chronic cocaine use may deplete dopa- were either low or within normal ranges; in the mine. females, the plasma estrogens are low. A clear ex- In patients receiving METHADONE therapy for planation of these observed derangements in opioid addiction, some investigators have reported plasma testosterone and estrogens is unknown. Fe- a normal rise in TSH released by the pituitary, in male heroin addicts frequently experience cessation response to stimulation by the hypothalamic hor- of or irregular menses. However, most regain nor- mone called thyrotropin-releasing hormone mal menstrual funcion when stabilized on metha- (TRH). Others have observed a blunted TSH and done and under these circumstances fertility seems PRL response following TRH administration in ac- unaffected. The anecdotal reports and, in limited tive heroin users. cases, experimental evidence of the influence of Although normal basal LH secretion has been MARIJUANA on sexual function and sex-hormone observed in cocaine abuse, opiate use is associated levels are also inconsistent and confusing. with decreased basal FSH and LH levels in males. The illicit drug-related disturbances discussed In female heroin addicts, these low levels of the above suggests that the narcotic-related depres- pituitary gonadotropins have clinical relevance, re- sions in sex-hormone production of the ovaries and sulting in a consistently normal FSH response and testes may occur because they reduce the pitu- COMPLICATIONS: Endocrine and Reproductive Systems 297 itary’s stimulation of these sex organs. Still, this has cortisol. In another study, there was a decreased not been a consistent finding. plasma-cortisol response to intravenous cosyntropin (an ACTH-like substance) stimulation REPRODUCTION AND PREGNANCY in methadone-treated patients. There are also re- ports of low normal or subnormal plasma-cortisol Impotence, atrophy of the testes, infertility, and levels in heroin users and disturbances in the day- decreased libido are not uncommon complaints in time cortisol secretion from the adrenal gland in male alcoholics. These observations are thought to methadone-maintained patients. be secondary to the direct effects of alcohol on tes- The variable findings from the several studies ticular tissue, to an alcohol-associated decrease in may be attributed to differences in the types of sperm motility, and to an alcohol-related decrease drugs used, in the state of stress-associated drug in Vitamin A and zinc. Both Vitamin A and zinc are withdrawal, in patterns of drug use, in study de- important in maintaining testicular tissue growth. sign, or to a combination of these and other as yet In young females, alcohol abuse is associated with unknown factors. There is also the well-known amenorrhea and anovulation; in chronic users, with problem of ACTH measurement, often resulting in early menopause. There is evidence that vaginal falsely low values. blood flow decreases as the alcohol serum level increases. CARBOHYDRATE METABOLISM Despite these clinical observations, when rigor- ously investigated, there were no consistent The opioids are virtually the only class of illegal changes in estradiol, progesterone, or testosterone. drugs for which there is information about the Consequently, it is difficult to determine whether pharmacologic effects on serum-glucose levels. We these observations were due to alcohol-related liver have long-standing reports of opiate-associated hy- disease, malnutrition, or the direct toxic effects of perglycemia, but the mechanisms explaining these chronic alcohol use. empirical observations are incompletely under- During PREGNANCY, alcoholism is associated stood. In association with chronic opioid use, there with increased risk of spontaneous abortion and the are reports of both low levels of serum glucose and development of FETAL ALCOHOL SYNDROME (FAS). high levels of insulin. The conflicting results of FAS is comprised of a characteristic pattern of some investigations may be due, in part, to differ- skin/facial abnormalities with growth and develop- ences in study design (e.g., nutritional state of the ment impairments, which are believed to be related research subjects, amount of the glucose used in to alcohol’s suppression of the sex hormone proges- clinical studies, or the time(s) administered). terone. While the features of FAS may vary, fetal To briefly review the regulation of glucose con- abnormalities associated with alcohol can be di- trol: The pancreas, an endocrine organ located in vided into the following four categories: (1) growth the upper abdomen, plays a central role by secret- deficiency; (2) central nervous system dysfunction; ing glucagon to raise serum-glucose levels and by (3) head and facial abnormalities, and (4) other secreting insulin to lower serum-glucose levels. Af- major and minor malformations. ter the discovery of endogenous opioid peptides in the human pancreas, subsequent research provided ADRENALS information that one such endogenous opioid, beta- endorphin, stimulates the secretion of glucagon and Our understanding of the relationship between a biphasic rise of insulin. This may, in part, explain opioid drug use and the functioning of the adrenal the observations of both elevated and reduced se- gland is based on incomplete and often contradic- rum-glucose levels in heroin users. Whatever the ting information. Some scientists have published nature of the exact mechanism, glucose metabolism reports of normal plasma cortisol levels (from the is deranged in both heroin and methadone use by adrenals) during heroin use and withdrawal, under some direct or indirect parameter of serum-glucose research conditions of heroin self-administration, regulation. and during methadone-maintenance treatment. In The alcohol-related aberrations of carbohydrate methadonetreated patients, ACTH produced by the metabolism are also quite complex. Some investi- pituitary stimulates the adrenal gland to produce gators have demonstrated that acutely adminis- 298 COMPLICATIONS: Endocrine and Reproductive Systems tered alcohol may result in a reversible and mild opiate use. To maintain an adequate range of bio- resistance to the glucose-lowering effects of insulin, logically active T4, the total T4 is increased when- perhaps explaining the observations of a rise in ever there is an increase in TBG. Perhaps the in- glucose following alcohol use. In fasting individu- crease in total T4 is the result of a direct opiate- als, alcohol administration can lead to severe de- induced elevation of TBG. It is also possible that the pressions of serum glucose, primarily by reducing altered liver function seen in chronic heroin and the liver’s production of glucose. Serum-glucose alcohol users may be responsible TBG abnormal- levels are also lower in chronic alcohol users with ities, leading to disturbances in T4 levels. Finally, it concurrent alcohol-related liver disease. Neverthe- is possible that opiate-related or alcohol-related less, serum levels are elevated in alcoholics with disturbances may be due to a combination of the concurrent alcohol-related destruction of the pan- above mechanisms as well as to some other still creas. Even without other concurrent diseases, al- undefined processes. cohol consumption may result in either no changes or in minimal to mild elevations or reductions in BONE METABOLISM serum glucose. The observations of increased fractures sus- tained by alcoholics has prompted investigations THE THYROID about the role alcohol may play in disturbances of Located in the anterior aspect of the neck, the the structure and mechanical properties of bone. thyroid gland secretes thyroxine (T4) and other Some studies have shown reduced bone mass in hormones whose principal purpose is to regulate alcoholics, while others have reported decreases in the metabolism of other tissues in the body. The compact and trabecular bone mass—a condition production of T4 by the thyroid is under the control called osteoporosis. Some of these disturbances in of the TSH produced by the pituitary. Therefore new bone formation may be mediated by alcohol’s alterations in thyroid function can be the result of impairment of calcium and Vitamin D metabolism, problems directly involving the gland or disrup- both of which are crucial to bone metabolism. Nev- tions in the TSH-mediated control of the thyroid ertheless, there does remain considerable doubt as gland. to whether the bone complications are due to alco- Despite the frequency, duration, or amount of hol itself or due to alcohol-related liver disease, to use, it appears that there are no clinical signs or malnutrition, or to a potential host of other factors. symptoms of thyroid dysfunction in chronic heroin Chronic liver disease unrelated to alcohol has also or alcohol users. Disturbances in biochemical in- been a cause of osteoporosis and other bone dis- dices (laboratory tests) of thyroid function are, eases. however, not uncommon in opiate or alcohol use. The total T4 is decreased while the amount of CONCLUSION biologically available T4 (free T4) and other indices of thyroid function are normal in heavy alcohol The endocrine and reproductive consequences of users. illicit drug and alcohol abuse are extensive and In active heroin users or during heroin with- profound. Both drug and alcohol abuse result in drawal, total T4 levels are increased in association clinically significant multiglandular derangements. with normal, subnormal, or high levels of other Although knowledge about the dimensions of such parameters of thyroid function. In methadone- disturbances to endocrine and reproductive func- maintained persons, there are reports of normal tion slowly increases, explanations of the scientific and slight-to-significant increases in total T4 in mechanisms accounting for these observations re- conjunction with increased levels of thyroxine- main to be elucidated. Given the role of alcohol and binding globulin (TBG), a protein that binds thy- illicit drugs in society, however, the spectrum of roid hormones in blood. Interestingly, successful related endocrine and reproductive complications methadone maintenance is associated with a cor- can be expected to expand and, thereby, increase in rection of these biochemical disturbances. public-health significance. There are a number of possible explanations for the biochemical derangements observed during (SEE ALSO: Complications:Liver Damage ) COMPLICATIONS: Immunologic 299

BIBLIOGRAPHY host defense. Recent evidence suggests that aber- rant regulation of the neuroimmune-endocrine net- FELIG, P., ET AL. (1987). Endocrinology and metabolism, works may be a major risk factor for the develop- 2nd ed. New York: McGraw-Hill. ment of alcohol-induced immunosuppression, HAMID, A., ET AL. (1987). Alcohol and reproductive func- leading to the collapse of host defense. Bidirectional tion: A review. Obstetrical and Gynecological Survey, communication can occur between the immune and 42(2), 69–74. neuroendocrine systems. Accordingly, stimulated LALOR, B. C., ET AL. (1986). Bone and mineral metabo- lymphoid cells send signals mediated by cytokines lism and chronic alcohol abuse. Quarterly Journal of and other immune products to inform the central Medicine, 59, 497–511. nervous system about the activity of the immune SMITH,C.G.,&ASCH, R. H. (1987). Drug abuse and system. Neuroendocrine molecules, in turn, may reproduction: Fertility and sterility. The American complete a feedback loop by modulating the im- Fertility Society, 48(3), 355–373. mune response via the pituitary-endocrine axis as LAWRENCE S. BROWN,JR. well as the autonomic neural output. Thus, effec- REVISED BY RALPH MYERSON tive feedback communications between the endo- crine and the immune system may be crucial to the host’s defense responses. Immunologic This article describes the ba- Clinical and experimental studies indicate a re- sic and clinical immunologic aspects of alcohol and lationship between excessive alcohol use and com- drug abuse. promised immune responses. Human studies have shown that chronic alcohol ingestion is associated ALCOHOL with abnormalities of both humoral and cellular immunity. These abnormalities include a depres- The physiological characteristics of ALCOHOL sion of serum bacteriocidal activity, alterations of (ethanol) allow it to interfere intensively with the immunoglobulin production, leukopenia, defects in functions of immune cells. Alcohol is completely chemotaxis, decreased antigen trapping and pro- miscible with water and, to some degree, is fat- cessing, and decreased T-cell mitogenesis. The soluble. It crosses membranes by diffusion across a clear association between alcoholism and infections concentration gradient. Historically, alcohol has such as tuberculosis and listeriosis indicates defec- been associated with lower host resistance and in- tive functioning of cell-mediated immunity. A creased infectious disease. For example, ALCOHOL- study has linked alcohol abuse and deficient T-cell ISM has been closely associated with lung abscesses, responsiveness. Skin-test reactivity using purified bacteremia, peritonitis, and tuberculosis. Although protein derivative and dinitrochlorobenzene has these infections might be a result of malnutrition or also demonstrated poor responses in alcoholics with poor living conditions, prolonged consumption of liver disease. Natural killer (or NK) cell activity is alcohol also results in alterations of immune re- impaired in acute alcohol intoxication and in sponses, ultimately manifested by increasing sus- chronic alcoholic liver disease; NK cells are pro- ceptibility to infectious agents. Overwhelming evi- grammed to recognize and destroy abnormal cells, dence shows that alcohol abuse broadly suppresses such as virus-infected or tumor cells. Some re- the various immune responses, seriously impairing searchers have speculated that decreased NK cell the body’s normal host defense not only to invading activity may be intimately involved in the increased microbes but also to its defenses against CANCER incidence of tumors in alcoholics. cells. Giving alcohol to animals also has a profound These disruptions are the combined result of effect on decreasing the weight of their peripheral direct toxic effects on the immune system and indi- lymphoid organs as measured by a decreased num- rect effects such as malnutrition, oxidative stress, ber of thymocytes and splenocytes. In mice, alcohol endocrine changes, and the complications of liver use produces thymic and splenic atrophy and alter- disease. The alcoholic’s predisposition to extracel- ations in the circulating lymphocytes and lympho- lular and intracellular infection indicates the effects cyte subpopulations, as well as alterations in cellu- of alcohol consumption at the local, humoral, and lar and humoral immunity and impaired cytokine cellular levels, inhibiting immune response and production. Also impaired by dietary alcohol are 300 COMPLICATIONS: Immunologic antibody-dependent cellular cytotoxicity, lympho- active polypeptide intercellular messengers that cyte proliferation, B-lymphocyte functions, and cy- regulate growth, mobility, and differentiation of tokine production by lymphoid cells (the lymph leukocytes. Thus, cytokines have extremely impor- and lymph nodes). Thus, alcohol-induced immu- tant roles in the communicating network that links nosuppression may render alcoholics more suscep- inducer and effector cells to immune and inflam- tible to tumorigenesis and infection. matory cells. Alcoholics are susceptible to infections by bacte- Since any perturbation in the tightly controlled ria such as Listeria monocytogenes, Vibrio cytokine regulatory system can result in immune vulnificus, Pasteurella multocida, and Aeromonas alterations modifying host resistance to infectious hydrophilia. The severity of these infections has disease and cancer, the influence of alcohol con- raised the possibility of a neutrophil (white blood sumption on cytokine secretion has been investi- cell) abnormality in these patients. The proper gated considerably. Several studies have indicated functioning of neutrophils is critical for host de- a correlation between circulating levels of macro- fense against microorganisms. Neutrophils are the phage-derived cytokines and disease progression chief phagocytic leukocyte of the blood; they are during chronic alcohol consumption. Increased short-lived cells having a life span of approximately plasma concentrations of tumor necrosis factor four days. Their production is a tightly regulated have been observed in cases of alcoholic liver dis- process centered in the bone marrow. Chronic alco- ease and, interestingly, relate significantly to de- holics have often been noted to be leukopenic (ab- creased long-term survival; plasma Interleukin-1 is normally low in leukocytes). The toxic effect of also significantly increased in these patients (rela- alcohol is now believed to be caused by the depres- tive to healthy controls) but does not correlate with sion of the T-cell-derived colony-stimulating factor increased mortality. rather than to direct suppression of myeloid (bone In a model of alcohol-fed mice, we found that, marrow) precursors secondary to bone marrow tox- compared to controls, production of all cytokines icity. was suppressed by chronic alcohol consumption, Neutrophils must recognize the invading patho- suggesting general immunosuppression. The ele- gens, engulf them, and destroy them using a num- vated levels of cytokines in some animals with mu- ber of killing mechanisms, which include adher- rine (mice and rats) AIDS were, however, increased ence, chemotaxis, locomotion, phagocytosis, and further by alcohol ingestion as compared to con- intracellular killing. Several functions of neutro- trols that indicated alcohol-induced aggravation of phils are affected by alcohol in vitro, including some AIDS symptoms. Similarly, those cytokines impairment of chemotaxis, decreased migration of suppressed by murine AIDS were further sup- neutrophils within vessels, altered adherence to ny- pressed by alcohol. Thus, alcohol exacerbated their lon fibers in vitro, impaired phagocytosis, and de- immune dysfunction. Several pathways may be in- creased intracellular killing of bacteria. In human volved in mediating the interaction between the with advanced cirrhosis from chronic (prolonged endocrine system and the immune system. Recent and excessive) ingestion of ethanol and impaired findings indicate that pituitary peptide hormones phagocytic capacity, decreased metabolic activity can directly influence immune response. In addi- was observed in the liver’s reticuloendothelial sys- tion, when a neurotransmitter is released in lym- tem; there also were impairments of neutrophil phoid tissues, it may locally modify the functional chemotaxis, bacterial phagocytosis and killing, and properties of lymphocytes and release of cytokines. alterations of neutrophil-antigen expression. Neu- In human studies regarding alcohol, all parame- trophil dysfunction is therefore responsible for ag- ters, such as hormone levels and immune responses gravating the susceptibility to secondary infections to monitor changes of immune response and neuro- seen in alcoholics. transmitter, are usually detected in serum. Since The balance of cellular and humoral immune the serum levels of these parameters cannot accu- response to antigens is controlled by communica- rately reflect the real situation in the lymphoid or- tion between immunocompetent cells. They are gans or tissues, some results from them, therefore, regulated to a great extent by soluble mediators could be misleading. No animal model for alcohol (termed cytokines) produced mostly by T-helper studies can mimic the complications of alcoholic cells and macrophages. Cytokines are biologically liver disease often observed in human alcoholics. COMPLICATIONS: Immunologic 301

Furthermore, the facts that different hormonal sta- suppressor cytotoxic cells, B cells, and monocytes tus in individual animals, even within same strain were not elevated. of animal, and difficulty in defining hormonal sta- Cocaine causes neuroendocrine-mediated effects tus in animals indicate that some results from ani- on the immune response. It stimulates the brain’s mal studies could also be misleading. Therefore, hypothalamus to increase secretion, producing po- the research on the mechanism of alcohol’s effects tentiated secretion of beta-endorphin. As a result of on the neurological system at cellular and systemic cocaine administration, beta-endorphin binds to levels and the interaction between endocrine and opioid receptors on monocytes and lymphocytes immune system should continue if we are to under- and exerts multiple stimulating and suppressing stand the complex changes caused by the direct and effects on these cells, including secretion of immu- indirect effects of alcohol consumption. noregulatory cytokines. The net outcome of the reactions related to the immune response of the COCAINE host is difficult to assess because other determi- nants of these interactions (such as the psychologi- COCAINE acts directly on lymphoid cells (the cal and social situation of the cocaine user) are also lymph and lymph nodes) and indirectly modulates possible. the immune response by affecting the level of neu- roendocrine hormones. The first studies about the There are other mechanisms that might be oper- impact of cocaine use on the immune response were ating to mediate cocaine-induced im- initiated because epidemiological data demon- munomodulation, including nutritional deficien- cies and their impact on lymphoid cells. As early as strated a high prevalence of ACQUIRED 1870, the French physician Charles Gazeau sug- IMMUNODEFICIENCY SYNDROME (AIDS) in polydrug users. Depending on the different administration gested that coca leaves might be used to suppress routes, the plasma levels of cocaine in humans ap- the appetite. With food deprivation, which is com- pear to be in the range of 0.1 to 1 micrograms per mon under conditions of habitual drug use, the milliliter (␮g/ml). Such concentrations last only for self-administration of cocaine by rats increased. Al- thirty to sixty minutes at these levels and then though data indicate a poor nutritional status for decline because of cocaine’s short biological half- cocaine users, no study has yet assessed the nutri- life of about 1 hour. The direct effects of cocaine tional status of drug users as it contributes to a and its metabolites on immune cells should occur compromised immune competence. Cocaine clearly only during a short time, except in heavy cocaine modifies hormones with immunoregulatory proper- users who use the drug several times a day every ties via neurological effects. In addition, malnutri- day. Besides the direct effects on immune cells, tion could be a factor on cocaine use, resulting in cocaine could indirectly affect the immune re- altered disease and tumor resistance. Intravenous sponse via its impact on the neuroendocrine sys- use of drugs, including cocaine, is associated with tem—and both have been shown. the transmission of HUMAN IMMUNODEFICIENCY VI- Short-term exposure of mice to cocaine by daily RUS (HIV), and ultimately the development of intraperitoneal injection for fourteen days reduced AIDS. Immunomodulation by cocaine after HIV in- body, spleen, and thymus weight in the animal. fection could accelerate disease development as Cocaine increased the responsiveness of lympho- well as overall resistance to a variety of pathogens cytes to mitogens (cell proliferation initiators) and found frequently in intravenous drug users. the delayed hypersensitivity responsiveness, but it suppressed the antibody response. All the animal TOBACCO studies, however, suggest that the immune system requires continuous exposure to cocaine to demon- Although it is now well known that the use of strates its suppressing or stimulating effects. After a TOBACCO is a major health hazard, millions of single dose of cocaine (0.6 mg/kg), nonhabitual Americans still continue to smoke and the popular- cocaine users showed a significant stimulation of ity of smokeless tobacco is on the rise. Tobacco use natural killer cell activity, which is vital to defend is the chief cause of lung cancer in smokers and is against cancers. The levels of natural killer cells strongly linked with the oral cancers of those who were also increased, but the levels of T-helper and use chewing tobacco or SNUFF. 302 COMPLICATIONS: Immunologic

The pulmonary alveolar macrophage (PAM) is smokers have indicated that smokers have altered the cellular component of the immune system com- immunoglobulin levels. Elevated levels of immuno- prising the first line defense of the lung, offering globulin E (IgE) were present in a high proportion protection against inhaled particles, including irri- of the smoke-exposed animals but in none of the tants and microbial invaders. Because PAM has ex- controls. Studies on human subjects have also re- posure to both the bloodstream and the atmo- vealed that IgE levels were higher in smokers than sphere, it is uniquely suited to perform its in nonsmokers. A study of coal workers indicated protective functions, which include clearance, im- that both mining and nonmining smokers had de- mune modulation, and modulation of surrounding pressed serum IgA and IgM levels as compared with tissue. There is general agreement that the number similar groups of nonsmokers. A disturbing finding of PAMs in smokers’ lungs is increased two to in relationship to increased immunoglobulin levels twenty times above that found in the lungs of non- in smokers is the effect that maternal smoking may smokers. It also appears that there is a difference in have on the fetus. In newborn infants of mothers the morphology and certain aspects of the function who smoked during pregnancy, IgE was elevated of alveolar macrophages between the two groups. three-fold. Tobacco smoke affects fetal immuno- In general, PAMs from smokers are larger, contain globulin synthesis, stresses the fetal immune sys- more lysosomes and lysosomal enzymes, and are tem, and can predispose the infant to subsequent more metabolically active than those nonsmokers, sensitization. Thus, 34 percent of the reported suggesting that they may be in a chronically stimu- asthma in childhood may be caused by maternal lated, more active state. This might lead to the smoking. inference that there would be greater phagocytic Natural killer cells, thought to serve important capacity in the lungs of smokers, resulting in in- antitumor and antiviral functions in the body, have creased clearance of foreign matter. However, the been found to be decreased in smokers. Studies of responsiveness of smokers’ macrophages to foreign the white blood cells called basophils in the periph- bodies or bacteria was equal to or less than that of eral blood indicated that there are alterations nonsmokers, leading researchers to conclude that linked to tobacco smoking as well. chronic stimulation of PAMs by cigarette smoke When considering the effect that tobacco use has may be harmful rather than beneficial to the im- on immunocompetence, other confounding vari- muno-competence of the lung. ables must also be accounted for, including genetic There is some disagreement as to whether smok- factors, preexisting disease, and nutritional status. ing affects the phagocytic and bactericidal activity Smoking has been observed to cause deficiencies of of PAMs. The question of whether tobacco smoke vitamin C, beta-carotene (vitamin A), and other alters the tumoricidal ability of PAMs has not yet nutrients that have important functions in protect- been answered. Thus, the relationship between cig- ing immunity. arette smoking, neutrophil accumulation in the Tobacco smoking causes deleterious effects on lung, and lung destruction continues to be re- the pulmonary and systemic immune systems of searched. It is known that particles from cigarette experimental animals and in humans. Aspects of smoke are present in the PAMs of smokers, and both cell-mediated and humoral immunity are af- researchers have found that the PAMs of cigarette fected. It is often difficult to compare studies di- smokers released a potent chemotactic factor for rectly because of the variability in smoking behav- neutrophils, whereas those of nonsmokers did not. iors and the differences among tobacco products. Therefore, cigarette smokers had an increased Although it is expected that heavy smoking causes number of neutrophils in the lavage fluid and in the most amount of immune system damage, that lung biopsy tissue as compared to nonsmokers. does not mean light to moderate smoking is safe. Neutrophils store and release elastase, a substance Thus, if some alterations due to smoking are re- implicated in the development of certain lung dis- versible, it is not yet known whether long-term eases. Smokers’ lungs are exposed to a large chron- smoking may cause the impairment of the immune ic burden of elastase from neutrophils, which may system to become permanent. Further, simulta- predispose them to lung destruction. neous exposure to other air contaminants or air A number of animal and human studies compar- pollution may exert damaging synergistic effects on ing peripheral blood samples of smokers and non- local or systemic immune defenses. COMPLICATIONS: Immunologic 303

MORPHINE AND OTHER OPIOIDS Several studies have shown that neither mari- juana smoking nor THC is immunosuppressive. Several studies have drawn a parallelism be- Nevertheless, other immune alterations have been tween MORPHINE abuse and immune inhibition. In vitro studies have shown that polymorphonuclear associated with marijuana or THC, including sig- cells and monocytes form in patients subjected to nificantly reduced serum IgG levels in chronic morphine treatment but that they were severely smokers; inhibition of natural killer cell activity; depressed in their phagocytic and killing properties inhibition of phagocytic activity; elevation of serum as well as in their ability to generate superoxide. IgD levels; and reduced T-cell numbers. THC also OPIOID addiction also caused alterations in the fre- inhibited DNA-, RNA-, and protein synthesis in quencies of T-cells and null lymphocytes in human stimulated human lymphocytes. peripheral blood. Studies performed in animals have produced There is convincing evidence of the presence of more consistent findings than those in humans. In opioid receptors on various types of human im- most cases, THC is associated with immunosup- mune cells. The presence of opioid receptors on pression of various immune parameters. The immune cells may allow for modulation of specific greater consistency observed in animal studies immune functions in the presence of exogenous probably reflects the influence of genetic factors, opiates. Various administration schedules for opi- consistent dosage levels, and controlled diets and oids were shown to potentiate infections by other conditions. Klebsiella pneumoniae and Candida albicans. The Animal studies have thus provided strong evi- increased susceptibility was partly due to a de- dence of the immunosuppressive effects of THC. crease in reticuloendothelial-system activity as well Such effects were clearly demonstrated when ani- as a reduction in the number of phagocytes, not by mals exposed to THC were more susceptible to a direct cytotoxic effect of the opioid. infections than were others. THC has also exacer- Chronic administration of morphine has also in- bated viral infection, as has been shown in mice hibited a primary antibody response of mice. These and guinea pigs, and it has reduced resistance to effects were worsened by naloxone (a nonaddictive analog of morphine), indicating that morphine in- bacterial pathogens. hibits the immune system in a specific manner— Obvious differences in the susceptibility of hu- via its interaction with opioid receptors. Other mans versus animals to the effects of marijuana studies in animals have shown that morphine can and THC will be resolved when other, more regu- affect NK cell activity, perhaps yielding reduced lated research studies are carried out in immuno- resistance to tumors. suppression and decreased disease resistance. Such changes, which can also include morphine suppression of spleen and body weight, show evi- BIBLIOGRAPHY dence of significant changes in immune functions. MACGREGOR, R. R. (1986). Alcohol and immune defense. MARIJUANA Journal of the American Medical Association, 256, 1474–1479. Several approaches have been used to study the WALLACE,C.L.,&WATSON, R. R. (1990). Im- effects of MARIJUANA or its active component, munomodulation by tobacco. In Drugs of Abuse and TETRAHYDROCANNABINOL (THC), on human im- Immune Function. Boca Raton, FL: CRC Press. mune systems. These include using cells isolated W ATZL,B.,&WATSON, R. R. (1990). Im- from chronic marijuana smokers, from volunteers munomodulation by cocaine—A neuroendocrine me- who have been only exposed to marijuana smoke, diated response. Life Sciences, 46, 1319–1329. or from nonexposed donors but exposing their cells YAHYA,M.D.,&WATSON, R. R. (1987). Minireview: Im- to THC in the laboratory. A survey of chronic mari- munomodulation by morphine and marijuana. Life juana smokers showed that the response of their cells was depressed to stimulation with mitogens Sciences, 41, 2503–2510. (substances that cause cell division). RONALD R. WATSON 304 COMPLICATIONS: Liver (Alcohol)

Liver (Alcohol) For all the attention being proteins, and other nutrients; they act as a provider directed toward HEROIN and COCAINE, the favorite of empty calories. mood-altering drug in most human societies is As shown in Figure 1, because of its large energy ALCOHOL. Alcohol, in different quantities for dif- load, alcohol decreases the appetite for food and ferent people, is also a toxic drug—its over- displaces other nutrients in the diet, thereby pro- consumption taxes the body’s economy, produces moting primary malnutrition (Lieber, 1991a). Nu- pathological changes in liver and other tissues, and trition is also impaired because alcohol affects the can cause disease and death. In urban areas of the gastrointestinal tract. Alcohol-induced intestinal United States, just one of the complications— lesions, including pancreatitis, are associated with namely scarring or cirrhosis of the liver—is the maldigestion and malabsorption, causing secon- fourth to fifth most frequent cause of death for dary malnutrition. Moreover, malnutrition itself people between the ages of twenty-five and sixty- will create functional impairment of the gut. Fi- five. In recent years, changes in liver and other nally, alcohol (ethanol or its metabolite acetalde- tissues have been directly associated with specific hyde) also adversely affects nutritional status by steps in the metabolism of alcohol (also called etha- altering the hepatic activation or degradation of nol or ethyl alcohol), giving some hope that rational essential nutrients. methods can be developed for prevention and treat- Indeed, in experimental animals, malnutrition ment. may produce a variety of liver alterations, includ- ing fatty liver and fibrosis; however, the extent to PATHOLOGY OF ALCOHOL ABUSE which malnutrition contributes to the development of liver disease in the alcoholic remains unclear. Alcohol abuse affects all organs of the body (Lie- Furthermore, studies conducted in the past three ber, 1992a). It atrophies many tissues, including decades have shown that either the initial liver le- the brain and the endocrine glands. Indeed, altered hepatic (liver) metabolism plays a key role in a sion—the fatty liver—or the ultimate stage of cir- variety of endocrinological imbalances (such as go- rhosis can be produced by excess alcohol, even in nadal dysfunctions and reproductive problems). the absence of dietary deficiencies (Lieber & De- Alcohol also exerts toxic effects on the bone marrow Carli, 1991), because ethanol (via its metabolism and alters hematological status (e.g., macrocytic and/or its metabolite acetaldehyde) exerts direct anemias), and it scars the heart and other muscles. hepatotoxic effects. Thus, malnutrition plays a per- This article focuses mainly on the liver and gastro- intestinal tract, since this is where alcohol pene- trates into the body and has its most vicious effects; this focus will also allow exemplification of the in- sights and possible benefits that can be derived from the application of newly acquired knowledge in biochemistry, pathology, and molecular biology. Liver disease, one of the most devastating com- plications of alcoholism, was formerly attributed exclusively to the malnutrition associated with ALCOHOLISM. Indeed, nutritional deficiencies are common in the alcoholic for various reasons, some socioeconomic, but also because alcohol is a unique compound. Alcohol is a drug, a psychoactive drug, but unlike other drugs, which have negligible en- Figure 1 ergy value, alcohol has a high energy content— Interaction of Direct Toxicity of Ethanol on Liver each gram of alcohol contributes 7.1 kilocalories, and Gut with Malnutrition Secondary to Dietary which means that a cocktail or a glass of wine will Deficiencies, Maldigestion and Malabsorption. provide 100 to 150 kilocalories. Thus, alcoholic SOURCE: Lieber, C. S. (1991a). Alcohol, liver, and beverages are similar to food in energy terms, but, nutrition. Journal of the American College of unlike food, they are virtually devoid of vitamins, Nutrition, 10 602–632. COMPLICATIONS: Liver (Alcohol) 305 missive, but not an obligatory, role in alcohol-re- be lost, in part, in the alcoholic, because of a de- lated somatic pathology. crease in gastric ADH (Di Padova el al., 1987). Similar effects may also result from gastric ADH METABOLISM OF ETHANOL AND inhibition by some commonly used drugs. For ex- SOME INTERACTIONS ample, aspirin, or some H2-blockers such as those used in treatment of ulcers (Di Padova et al., 1992) Ethanol is readily absorbed from the gastroin- were found to inhibit gastric ADH activity and to testinal tract. Only 2 percent to 10 percent of that result in increased blood levels of ethanol when absorbed is eliminated through the kidneys and alcohol was consumed in amounts equivalent to lungs; the rest is oxidized in the body, principally in social drinking. Women also have a lower gastric the liver. Except for the stomach, extrahepatic ADH activity than do men (Frezza et al., 1990); as (outside the liver) metabolism of ethanol is small. a consequence, for a given intake, women’s blood This relative organ specificity probably explains ethanol levels are higher, an increase that is com- why, despite the existence of intracellular mecha- pounded by their body composition (more fat, less nisms to maintain homeostasis (equilibrium), etha- water than men) and, on average, a lower body nol disposal produces striking metabolic imbal- weight. Their higher blood ethanol levels, in turn, ances in the liver (Lieber, 1991b). These effects are may therefore contribute to women’s greater sus- aggravated by the lack of a feedback mechanism to ceptibility to alcohol. adjust the rate of ethanol oxidation to the metabolic Alcohol dehydrogenase converts ethanol to acet- state of the hepatocyte (liver cell) and the inability aldehyde and hydrogen. Hydrogen is a form of fuel of ethanol, unlike other major sources of calories, to that can be burned (oxidized). Normally, the liver be stored in the liver or to be metabolized or stored burns fat to produce the energy required for its own to a significant degree in peripheral tissues. As functioning but, when alcohol is present, its hydro- summarized here, the displacement by ethanol of gen displaces fat as the preferred fuel. When the the liver’s normal substrates and the metabolic dis- liver stops burning fat and instead burns the hydro- turbance produced by the oxidation of ethanol and gen from the ethanol, however, fat accumulates, its products explain many of the hepatic and meta- and a fatty liver develops, which is the first stage of bolic complications of alcoholism. alcoholic liver disease (Lieber, 1992a). Once a fatty liver has developed, fat accumulation does not in- A major pathway for ethanol disposition in- crease indefinitely, even though alcohol consump- volves alcohol dehydrogenase (ADH), an enzyme of tion may be continued (Salaspuro et al., 1981). Fat the cell sap (cytosol) that catalyzes the conversion deposition is offset, at least in part, by lipoprotein of ethanol to acetaldehyde. Liver ADH exists in secretion, resulting in hyperlipemia—elevated multiple molecular forms that arise from the asso- amounts of fat in blood. Hyperlipemia of a moder- ciation in various permutations of different types of ate degree is commonly associated with early stages subunits. Extrahepatic tissues contain isozymes of of alcoholic liver injury, but it wanes with the pro- ADH with a much lower affinity for ethanol than gression of liver disease (Lieber & Pignon, 1989). the hepatic isozymes; as a consequence, at the levels In some individuals, marked hyperlipemia may de- of ethanol achieved in the blood, these extrahepatic velop, sometimes associated with Zieve’s syn- enzymes are inactive, and therefore, extrahepatic drome—hemolytic anemia, fatty liver, and jaun- metabolism of ethanol is negligible, with the excep- dice. This represents the potentiation, by alcohol, tion of gastric metabolism. Because of the extraor- of an underlying abnormality in the metabolism of dinary high gastric ethanol concentration after al- either lipids (essential hyperlipemia) or carbohy- cohol consumption, even the gastric ADH with low drates (prediabetes, pancreatitis). In addition, the affinity for ethanol becomes active, and significant degree of hyperlipemia is also influenced by the gastric ethanol metabolism ensues. This decreases duration of alcohol intake. The capacity for a hy- the bioavailability of ethanol and represents a kind perlipemic response develops progressively and is of protective barrier against systemic effects, at accompanied by an increased activity of enzymes of least when ethanol is consumed in small social- the endoplasmic reticulum (within the living cells) drinking amounts. This gastric barrier disappears engaged in lipoprotein production. This hy- after gastrectomy (Caballeria et al., 1989) and may perlipemia involves all lipoprotein classes, includ- 306 COMPLICATIONS: Liver (Alcohol) ing high-density lipoproteins (HDL), which have anesthetics, analgesics (painkillers), and chemical been said to be involved in the protection against carcinogens. The latter contribute to the increased atherosclerosis and in the lesser incidence of coro- incidence of various cancers in the alcoholic. nary complications in moderate drinkers (com- Alcohol has a major impact on gastrointestinal pared to total abstainers). However, factors other cancers, with a significant increase in the incidence than alcohol may also contribute to this apparent of neoplasms of the oropharynx, the esophagus, the protection. The ability of the liver to respond with stomach, the liver, and the colon (Garro & Lieber, hyperlipemia reflects the integrity of the hepa- 1990). There is also activation to toxic metabolites tocytes; its capacity decreases with the develop- of commonly used drugs and even over-the-counter ment of more severe liver injury. analgesics (acetaminophen or paracetomal) (Sato Elucidation of the hepatic redox (contraction of et al., 1981) and vitamins, such as Vitamin A. In oxidation reduction) associated with ethanol oxida- the heavy drinker, there are both increased break- tion via the alcohol dehydrogenase pathway has down and hepatic depletion of Vitamin A (Leo & also furthered our understanding of associated dis- Lieber, 1982), with adverse consequences. In addi- orders in carbohydrate, purine, and protein metab- tion, alcohol potentiates the toxicity of Vitamin A olism—including hypoglycemia (low blood sugar), (Leo et al., 1982), which complicates supplementa- hyperlactacidemia (excessive levels of lactic acid in tion with the vitamin in the presence of alcohol the blood) and acidosis, as well as hyperuricemia abuse. Alcohol abuse also promotes the microsomal (elevated uric acid levels in blood) (Lieber, 1992a). breakdown of testosterone and its conversion to In addition to the enzyme ADH, alcohol is also estrogens, which, together with testicular toxicity oxidized in the liver by the enzyme system referred and decreased testosterone production, results in to as the microsomal ethanol-oxidizing system hypoandrogenism—the loss of masculinity (Lie- (MEOS), which involves a specific cytochrome ber, 1992a). P-450 (P450IIE1) (Lieber, 1987). Contrary to ADH, this pathway is inducible by chronic alcohol In addition to environmental factors, there are consumption. In rat livers (Lieber et al., 1988) and individual differences in rates of ethanol metabo- in human liver biopsies of heavy drinkers lism that appear to be genetically controlled, and (Tsutsumi et al., 1989), a five to tenfold increase of the possible role of heredity in the development of this alcohol-inducible form was found. This induc- alcoholism in humans has been emphasized. The tion represents one of the most striking biochemical induction of the MEOS pathway also leads to in- differences between heavy drinkers and normals creased conversion of alcohol to acetaldehyde, a and provides an explanation for the metabolic tol- highly reactive and thus potentially toxic com- erance to ethanol—a more rapid metabolism—that pound. develops after alcohol abuse. The induction spills over to microsomal systems that metabolize other TOXICITY OF ACETALDEHYDE substrates, resulting in cross-tolerance to other drugs—not only sedatives and tranquilizers but Acetaldehyde causes injury through the forma- also many commonly used medications such as tion of adducts with proteins, resulting in antibody anticoagulants and hypoglycemic agents. Thus, formation, inactivation of many key enzymes, de- heavy drinkers require an increased dosage of creased deoxyribonucleic acid (DNA) repair, and many commonly used medications, at least at the alterations in cell structures such as microtubules, initial stage, prior to the development of severe mitochondria, and plasma membranes (Lieber, liver disease, which, when it develops, it will offset 1988, 1992a). Acetaldehyde also promotes synthe- the enzyme induction, at which time drug dosage sis of hepatic collagen—the key protein of scar tis- may have to be decreased. What complicates treat- sue; furthermore, it causes glutathione depletion, ment of heavy drinkers even further is the fact that thereby exacerbating the toxicity mediated by free the microsomal enzymes (especially P450IIE1) radicals, which results in lipid peroxidation and also activate many xenobiotic agents (substances other tissue damage (Lieber, 1991b). Because of from outside the body) to highly toxic compounds. the far-reaching toxicity of this metabolite of etha- This explains the increased vulnerability of heavy nol, some of the liver cells die; this attracts inflam- drinkers to the hepatotoxicity of industrial solvents, matory cells, which results in the more severe stage COMPLICATIONS: Liver (Alcohol) 307 of alcoholic hepatitis, one of the precursors to the two drinks a day in men—with a drink being 12 ultimate scarring or cirrhosis. ounces of regular beer, 5 ounces of wine, or 1.5 Once there is cirrhosis, a number of complica- ounces of distilled spirits (80 proof) (Dietary tions ensue, including obstruction of blood flow— Guidelines, 1990). It is important, however, that with portal hypertension (elevated pressure in the ‘‘excess’’ be defined individually, taking into ac- veins leading from the intestine to the liver) and count not only gender, but also heredity and per- internal, life-threatening bleeding of distended sonal idiosyncrasies. veins, so-called varices. There is also a buildup of water in the abdominal cavity, so-called ascites (SEE ALSO: Addiction:Concepts and Definitions; (Lieber, 1992a). Alcohol:Complications; Cancer, Drugs, and Alco- Acetaldehyde is particularly elevated if drinking hol; Complications:Liver Damage; Social Costs of occurs in pregnancy; it crosses the placenta (Karl et Alcohol and Drug Abuse) al., 1988) and has been incriminated in the patho- genesis of the FETAL ALCOHOL SYNDROME (FAS), BIBLIOGRAPHY the most common preventable cause of cogenital abnormalities. CABALLERIA.J.ET AL. (1989). The gastric origin of the The bulk of acetaldehyde is oxidized to acetate first pass metabolism of ethanol in man: Effect of by an acetaldehyde dehydrogenase of the liver mi- gastrectomy. Gastroenterology, 97, 1205–1209. Di- tochondria. Lack of the active form of the enzyme etary Guidelines. (1990). Nutrition and your health: in some Asians explains their high blood acetalde- Dietary guidelines for Americans (3rd ed.). Washing- hyde and flushing reaction after alcohol. DI- ton, DC: U.S. Department of Agriculture. SULFIRAM (Antabuse—a drug used in recovering DI PADOVA,C.ET AL. (1987). Effects of fasting and alcoholics) is an inhibitor of acetaldehyde dehydro- chronic alcohol consumption on the first pass metabo- genase. It raises the acetaldehyde levels after drink- lism of ethanol. Gastroenterology, 92, 1169–1173. ing and thereby causes flushing and several adverse DI PADOVA,C.ET AL. (1992). Effects of ranitidine on effects that can be utilized to sustain abstinence in blood alcohol levels after ethanol ingestion: Compari- patients motivated to take the compound. son with other H2-receptor antagonists. Journal of the American Medical Association, 267, 83–86. FREZZA,M.ET AL. (1990). High blood alcohol levels in TREATMENT AND CONCLUSION women: Role of decreased gastric alcohol dehydroge- Alcoholics suffer commonly from malnutrition. nase activity and first pass metabolism. New England Therefore, nutritional deficiencies, when present, Journal of Medicine, 322, 95–99. should be corrected—although such efforts were GARRO, A. J., & LIEBER. C. S. (1990). Alcohol and can- found to be ineffective in fully preventing liver cer. Annual Review of Pharmacology and Toxicology, disease in view of the intrinsic toxicity of ethanol 30, 219–249. (Lieber, 1991b; Lieber & DeCarli, 1991). KARL,P.I.ET AL. (1988). Acetaldehyde production and Although progress is being made at offsetting transfer by the perfused human placental cotyledon. the direct toxicity of ethanol through chemical Science, 242, 273–275. means (Lieber, 1992b), at present, the single fully LEO, M. A., & LIEBER, C. S. (1982). Hepatic vitamin A effective way of preventing somatic alcoholic injury depletion in alcoholic liver injury. New England Jour- remains control of the toxic agent—ethanol— nal of Medicine, 307, 597–601. through control of consumption. Full abstinence is LEO, M. A., ARAI, M., SATO, M., & LIEBER, C. S. (1982). required in those who are genetically (or otherwise) Hepatotoxicity of vitamin A and ethanol in the rat. prone to develop craving or to exhibit dependence, Gastroenterology, 82, 194–205. or those who are predisposed to develop the major LIEBER, C. S. (1987). Microsomal ethanol oxidizing sys- somatic complication with chronic use of alcohol. tem (MEOS). Enzyme, 37, 45–56. For the others, moderation is recommended. LIEBER, C. S. (1988). Metabolic effects of acetaldehyde, What is considered ‘‘moderate’’ or ‘‘excessive’’ has Biochemical Society Transactions, 16, 241–247. been the subject of debate. One view is that on the LIEBER, C. S. (1991a). Alcohol, liver and nutrition. Jour- average, moderate drinking represents no more nal of the American College of Nutrition, 10, 602– than one drink a day in women and no more than 632. 308 COMPLICATIONS: Liver Damage (Other Drugs)

LIEBER, C. S. (1991b). Hepatic, metabolic and toxic ef- If illness pushes the liver beyond the ‘‘point of no fects of ethanol: 1991 update. Alcoholism:Clinical return,’’ the person dies. and Experimental Research, 15, 573–592. The liver has a multitude of complex functions LIEBER,C.S.(ED.). (1992a). Medical and nutritional and is justly called the ‘‘laboratory’’ of the human complications of alcoholism:Mechanisms and man- body. It secretes a digestive juice into the intestine, agement. New York: Plenum Press. called bile; it produces a number of essential pro- LIEBER, C. S. (1992b). Hepatotoxicity of alcohol and im- teins, clotting factors, and fatty substances; it stores plications for the therapy of alcoholic liver disease. In and conserves energy-producing sugars; it detox- J. Rodes & V. Arroyo (Eds.), Therapy in liver disease ifies both internally produced and external toxins (pp. 348–367). Barcelona: Ediciones Doyma. and drugs that would otherwise be poisonous to the LIEBER, C. S., & DECARLL L. M. (1991). Hepatotoxicity human organism—just to name some of its impor- of ethanol. Journal of Hepatology, 12, 394–401. tant functions. LIEBER, C. S., & PIGNON, J-P. (1989). Ethanol and lipids. What can seriously jeopardize this very impor- In J. C. Fruchart & J. Shepherd (Eds.), Human plasma lipoproteins:Chemistry, physiology and pa- tant organ and consequently the well-being and thology (pp. 245–280). New York: Walter De survival of the individual? For one, there are dis- Gruyter. eases—both congenital and acquired—over which LIEBER,C.S.ET AL. (1988). Role of acetone, dietary fat we have little or no control, such as some geneti- and total energy intake in induction of hepatic micro- cally determined and developmental abnormalities, somal ethanol oxidizing system. Journal of Pharma- circulatory liver problems, certain tumors, and in- cology and Experiment Therapeutics, 247, 791–795. fections. SALASPURO M. P. ET AL. (1981). Attenuation of the etha- A very large part of hepatology (the technical nol induced hepatic redox change after chronic alco- term to describe the study and treatment of liver hol consumption in baboons: Metabolic consequences diseases) is, however, devoted to liver problems in vivo and in vitro. Hepatology, 1, 33–38. created by a peculiar human behavior—the abuse SATO, C., MATSUDA, Y., & LIEBER, C. S. (1981). In- of ALCOHOL and drugs. Whereas discussions as to creased hepatotoxicity of acetaminophen after chron- whether ALCOHOLISM and DRUG ABUSE are truly ic ethanol consumption in the rat. Gastroenterology, self-inflicted problems elicit a variety of opinions, 80, 140–148. the liver disease that results from substance abuse TSUTSUMI,R.ET AL. (1989). The intralobular distribu- in a given individual could have been avoided if the tion of ethanol-inducible P450IIE1 in rat and human substance-abusing behavior had not occurred. Be- liver. Hepatology, 10, 437–446. yond the psychosocial consequences of substance CHARLES S. LIEBER abuse, diseases of the liver (and brain) represent EVISED BY ALPH YERSON R R M the major COMPLICATIONS of alcohol and drugs. The morbidity (disease incidence) and mortality (death incidence) from alcoholic and drug-induced Liver Damage (Other Drugs) The liver is liver injury are very high. In the scientific literature, the largest organ of the human body, normally it is well established that the mortality from alco- weighing about 3.3 pounds (1.5 kg). It occupies the holic liver disease is correlated with the per capita right upper quadrant of the abdominal cavity just alcohol consumption; in fact, the prevalence of al- below the diaphragm. As befitting its anatomical coholism in a given society has been calculated prominence, its function is essential to maintain from liver mortality statistics. While alcohol is a life. If we surgically removed the entire liver from direct liver toxin, most of the other commonly any animal (including humans), it will fall into a abused psychoactive substances are generally not coma shortly and die. The absence of a certain known to affect the liver directly to a great extent; critical mass of functioning liver tissue is incompat- ible with life. While the human liver has a remark- their major contribution to liver morbidity and able resilience and regenerative capacity after in- mortality is via exposing people to viral hepatitis— jury or illness, this is true only up to a certain point. a potentially fatal disease. COMPLICATIONS: Liver Damage (Other Drugs) 309

ALCOHOLIC LIVER DISEASES known by their initials: SGOT (or AST) and SGPT (or ALT). These enzymes are elevated because Another article in this encyclopedia discusses the some of them tend to leakout of the fatty liver cells relationship between alcohol and the liver in great into the blood. detail. In any article dealing with the effects of If a person stops drinking, the fat disappears drugs on the liver, however, alcohol must be ad- dressed. from the liver cells, the swelling subsides and the The gamut of alcoholic liver diseases and their AST and ALT levels become normal. The two-way interrelationship is illustrated in Figure 1. arrow in the diagram of Figure 1 indicates that Alcoholic Fatty Liver. Fat accumulation in fatty liver is reversible with abstinence, and the the liver is an almost universal response to exces- condition may fluctuate backand forth between sive alcohol consumption. It occurs in the majority normal and fatty liver with abstinence and drink- of heavy drinkers. How and why fat accumulates in ing, respectively. Thus, this, per se is not likely a liver cells is complicated and not completely under- serious situation; it is an early warning that ‘‘your stood; but we know for sure that it happens. If you liver does not like alcohol’’ and that possibly worse examine a piece of biopsied liver tissue from an things might yet come. There was a time when fatty alcoholic under the microscope, you see that many liver was regarded as the precursor of the end-stage liver cells are loaded with big bubbles consisting of liver disease called cirrhosis (indicated by the bro- fat, almost totally occupying the cell. In most cases, ken arrow and question mark on Figure 1), but in this fatty change does not matter too much as far as the 1990s, most physicians do not believe that this the patient’s health is concerned. It is an almost direct connection exists. invariable response to too much alcohol consump- Alcoholic Hepatitis. This is a potentially tion and an early warning. The person who has more serious form of alcoholic liver disease. A cer- nothing worse than an alcoholic fatty liver may not tain proportion of alcoholics, in addition to accu- feel sickat all, and only if a biopsy is done can the mulating fats in their livers when drinking, will fatty liver be diagnosed. The doctor may feel an develop inflammation (hepatitis means liver in- enlarged liver by palpation, which may be a bit flammation)-consisting of an accumulation of tender. The laboratory test may show a slight ele- white blood cells, the death (necrosis) of some of vation in the blood of some liver enzymes, best the liver cells, and the presence of some very char-

Figure 1 Interrelationships between Various Forms of Alcoholic Liver Disease Figure 1 Interrelationships between Various Forms of Alcoholic Liver Disease 310 COMPLICATIONS: Liver Damage (Other Drugs) acteristic material (called Mallory bodies). Again, Some of these overloaded blood vessels, especially all this can be seen under the microscope in a those on the border of the stomach and esophagus biopsied piece of tissue. (called esophageal varices), can rupture any time, The clinical picture of alcoholic hepatitis can be causing a major hemorrhage. very variable. At one extreme is the person who Those who develop the cirrhotic stage of alco- feels perfectly well and only the biopsy could tell holic liver disease present their symptoms in vari- that something is wrong. At the other extreme is the ous ways. Some of them lookquite normal and only patient with a swollen and painful liver, yellow the biopsy will reveal the presence of cirrhosis. jaundice (a yellowing of the entire body from bile Others are jaundiced, the yellow color coming from pigment leaking into the blood), fever, and dis- bile pigment leaking out of the damaged liver into turbed consciousness—who dies. Between these ex- the blood, thus staining the skin and the whites of tremes are people with varying degrees of serious- the eyes. Still others have large fluid accumulations ness of the illness; for example, with or without in their extremities (edema) or in their abdominal some jaundice, with or without pain and fever, etc. cavity (ascites); the latter may make these pa- The blood’s white cell count is usually elevated. tients—men or women—looklikethey are nine The bilirubin (bile pigment) level may be elevated months pregnant. Some may vomit blood, because in patients who are yellow (a pale to deep mustard). of the hemorrhaging. In most advanced cases, there The liver enzymes are higher than normal in the is just not enough functioning liver tissue left; the blood, because they leakout of the inflamed liver liver no longer can perform its ‘‘laboratory’’ func- cells. However, these values are not as high as in tion, and the person slips into a coma and may die. viral hepatitis and, characteristically, in alcoholic When cirrhotic patients are examined by doc- hepatitis AST (SGOT) is higher than ALT (SGPT), tors, their livers do not feel smooth on palpation, which helps to distinguish alcoholic hepatitis from but bumpy from all those nodules that formed. At viral hepatitis (difficult to do at times). In viral first the liver may be swollen and enlarged, but at hepatitis not only are the absolute enzyme values the later stages it shrinks. The ultrasound picture higher, but the ratio is reversed: ALT is higher than suggests a patchy, disorganized architecture of the AST. liver. The spleen may enlarge from the increased Thus, the outcome of alcoholic hepatitis can be pressure in the blood vessels. The liver enzymes death (worst scenario) or recovery (best scen- (AST and ALT) may be moderately elevated as in ario)-as shown on Figure 1. Repeated episodes of other forms of alcoholic liver disease, but this has drinking and alcoholic hepatitis, however, even if no prognostic importance. More ominous signs the patient does not die in a given episode, can lead pointing toward severely compromised liver func- to the endstage of alcoholic liver disease: cirrhosis. tions are the following: a decrease in blood level of Alcoholic Cirrhosis. In terms of histology albumin (an important protein manufactured by (tissue damage) this indeed is an end-stage disease: the liver), deficiency in blood-clotting factors that a cirrhotic liver cannot become normal; in Figure 1, are also made in the liver, and the presence of there is no arrow between cirrhosis and normal anaemia (low hemoglobin and red blood cell liver. Clinically, cirrhosis is a serious disease, po- count). tentially fatal, but not inevitably so. Alcoholism is What Can Kill a Cirrhotic Patient? Ascites (fluid not its only cause, but it is by far the most common. accumulation in the abdomen) is very uncomfort- Under the microscope a cirrhotic liver shows a able and unsightly but, by itself, usually does not disorganized architecture: the dead (necrotic) liver kill—unless it gets spontaneously infected, which is cells have been replaced by scar tissue. The liver always a threat. Generally, cirrhosis compromises tries to repair itself: In a somewhat haphazard fash- the immune system, rendering cirrhotic alcoholics ion it attempts to produce new liver tissue in the susceptible to all sorts of potentially overwhelming form of nodules, which are separated from each infections. Portal hypertension is a serious compli- other by scar. These newly formed liver nodules cation of the cirrhotic fibrosis. The obstruction to may indeed sustain liver function and thus life for a portal vein flow through the liver results in the time, but at a price: the liver’s blood circulation is development of other vein channels to accommo- mechanically compressed. Thus, the pressure in- date the return of blood from the abdominal organs creases in the blood vessels leading to the liver. which comprise the blood in the portal vein. The COMPLICATIONS: Liver Damage (Other Drugs) 311 result is the development of varices (enlarged, young age or after a relatively short drinking ca- engorged veins) in the stomach and esophagus. reer. These enlarged, thin-walled veins are prone to rup- Prognosis and Treatment. The issues of ture leading to one of the most serious complica- prognosis and treatment cannot be separated from tions of cirrhosis of the liver—bleeding varices. each other. The cornerstone of treatment is com- This constitutes an emergency and calls for imme- plete abstinence from alcohol; achieving abstinence diate intervention in the form of measures to con- can arrest the progression of liver disease, even in trol the bleeding. A variety of therapies are avail- established cirrhosis. Continued drinking leads to able, all of which have all been employed with a deterioration and death. varying degree of success that depends on the se- One therapeutic issue relating to alcoholism it- verity of the hemorrhage and the skill and experi- self, should be addressed here because it is relevant ence of the physician. Once the bleeding has been to liver disease. The drug DISULFIRAM (Antabuse) is controlled, the patient should be considered for an sometimes prescribed to reinforce abstinence: its appropriate permanent venous shunt procedure unpleasant, sometimes severe interaction with al- whereby venous blood bypasses the liver. Finally, cohol is used as a deterrent against drinking. Since total decompensation of liver-cell function may disulfiram (as so many other drugs) has been occa- cause coma and death. sionally reported to produce liver toxicity of its The good news is that even when there is irre- own, the presence of alcoholic liver disease is some- versible cirrhosis at the tissue level, death may not times regarded as a relative contraindication be inevitable. Survival depends mainly on two fac- against the prescription of disulfiram. The liver tors: luckand alcohol abstinence. Abstaining alco- toxicity caused by alcohol far outweighs any risk holics with cirrhosis can stabilize and survive on that may be caused by disulfiram. what’s left of their liver tissue without necessarily Are there any other treatment techniques avail- and relentlessly progressing to one of the fatal out- able beyond abstinence that can help the recovery comes. A famous Yale University study many years from alcoholic liver damage? In the late 1980s, a ago showed clearly the correlation between absti- Toronto research group reported the beneficial ef- nence and survival in cirrhosis. fect of propylthiouracil (PTU). This is a drug nor- Who Gets Which Alcoholic Liver Disease? mally used for the treatment of thyroid disease, but There are still no certain answers to this question. by reducing oxygen demand in the body (including Fatty liver is an almost universally predictable re- in the liver), it might help to repair the damage sponse to heavy alcohol consumption, but this by caused by alcohol. The early results were promising itself is seldom a serious problem. A smaller num- but it is still not a widely accepted treatment. Other ber of people develop alcoholic hepatitis and still drugs, such as corticosteroids (to decrease inflam- fewer (variously estimated in different populations mation) or colchicine (to decrease scar formation) between 5 to 25% of alcoholics) end up with cirrho- have dubious value. sis. Considering the large number of alcoholics in There are relatively effective treatments avail- our society, the minority who develop cirrhosis still able for some of the complications of alcoholic liver represents huge numbers; cirrhosis is one of the disease so that the patient may survive and thus leading causes of all deaths. begin his or her abstinence program. The fluid ac- Still, why do some alcoholics develop alcoholic cumulation in the extremities (edema) or in the hepatitis and cirrhosis, while others who drink abdomen (ascites) can he helped by diet modifica- equally heavily do not? The amount of alcohol con- tions (salt restriction), water removing drugs (di- sumption and the length of time of heavy drinking uretics), albumin infusion, or tapping the abdo- is certainly one riskfactor. Gender may be another: men. Infections can be treated with antibiotics. The Women’s livers generally are more vulnerable to brain syndrome of liver failure (so-called hepatic the effects of alcohol than those of men, given equal encephalopathy or, in severe cases, hepatic coma) alcohol exposures. Finally, there may be a geneti- can improve with dietary means (protein restric- cally determined (but still unclarified) individual tion) or some drugs (e.g., neomycin, lactulose). The susceptibility, which may explain why some people potentially or actually bleeding esophageal varicose never get cirrhosis, why some do after many years veins can be obliterated by certain injections of alcoholism, and why still others get cirrhosis at a through a gastroscope (so-called sclerotherapy), 312 COMPLICATIONS: Liver Damage (Other Drugs) and the bleeding riskcan be lessened by beta- son at the same time also happens to use or abuse a blocking drugs or some surgical procedures to de- sedative, the sedative can have an exaggerated ef- crease pressure. fect. Finally, in the 1990s we have the possibility of Generally speaking, the normal liver transforms liver transplantation. If all else fails, a successful or inactivates drugs (detoxification) to less active or liver transplant cures alcoholic liver disease. Apart harmless forms. A notable and important exception from the general problems of donor matching and is acetaminophen, one of the most commonly used supply, some people have raised objections on ethi- medications against PAIN and fever (e.g., the vari- cal grounds to offering transplantation for alcoholic ous Tylenol preparations). The liver can transform (i.e., ‘‘self-inflicted’’) liver disease. This is not an acetaminophen into a toxic metabolic derivative acceptable objection and goes against medical eth- that might cause a potentially lethal, acute liver ics. Well-motivated recovering alcoholics are enti- injury. Generally, this does not happen at ordinary tled, as much as anybody else, to a life-saying pro- therapeutic acetaminophen dose levels. In the case cedure. In fact, studies have shown that the very of an acetaminophen overdose, however, such se- dramatic and heroic nature of this operation may vere liver toxicity can occur that a person will die be an extremely powerful motivator for future ab- within days. Most of such overdoses are, of course, stinence by liver recipients. Numerous successful suicidal attempts. transplants have been carried out on alcoholics. Acetaminophen itself does not have any psycho- active (mind-altering) properties; thus people do DRUGS AND THE LIVER not abuse it for such reasons. Many marketed acet- aminophen preparations, however, are combined There are many drugs in medicinal use that can with CODEINE (a NARCOTIC). People seeking nar- have direct liver toxicity. Peculiarly, most of the cotic ‘‘highs’’ from such preparations might ingest psychoactive drugs that people tend to abuse are not known to be particularly harmful to the liver. them in large enough quantities to subject them- Occasional liver damage has been reported with selves to potentially severe liver injury. It is the codeine they are after, but it is the bystander acet- SOLVENT sniffing and COCAINE use, but this is not a common problem. Narcotics (opioids), anti-anxi- aminophen that may kill them. There is an antidote against acetaminophen poisoning (called acetyl- ety, and other sedative drugs (such as BARBITU- cysteine), but it is effective only if it is given within RATES), MARIJUANA, and HALLUCINOGENS do not usually cause liver injury. a few hours (less than a day) after the ingestion of There are, however, several relevant secondary the drug. The person who is overdosing with a issues concerning drug abuse and the liver. For one, suicidal intent is more likely to be discovered and a damaged liver (for example from alcohol or hepa- brought to quickmedical attention than an unin- titis) results in poor tolerance of SEDATIVES, be- tentionally overdosing drug abuser. An additional cause good liver function is necessary to eliminate issue in the acetaminophen story is that there is sedatives properly; impaired liver function can strong evidence of increased riskwhen alcohol and therefore result in exaggerated sedative effect. Con- acetaminophen are combined. In alcoholics, rela- versely, some sedatives, notably BARBITURATES tively low, even therapeutic, doses of acetamino- (which were often abused in the past and some- phen can cause severe and potentially fatal liver times still are), actually stimulate (‘‘induce’’) cer- damage. tain liver enzymes, which can result in increased Apart from acetaminophen, direct liver toxicity elimination (i.e., decreased effect) of another thera- is not a major feature of substance abuse except in peutically necessary drug. For example, a barbitu- the case of alcohol. The liver disease that is very rate user (or abuser) may have poor effect from a commonly associated with drug use is viral hepati- clotting preventative (anti-coagulant) drug that is tis (liver inflammation) which is not caused by the necessary in heart disease or after a stroke. Some drugs themselves but by infection with a virus. It is drugs do the opposite—they inhibit liver enzymes. then transmitted from person to person through For example, the anti-ulcer drug cimetidine contaminated needles and syringes. The problem of (Tagamet), which per se has no PSYCHOACTIVE viral hepatitis, then, is largely that of injecting drug effect, can cause such enzyme inhibition; if a per- users (IDUs). COMPLICATIONS: Liver Damage (Other Drugs) 313

VIRAL HEPATITIS IN DRUG ABUSERS The majority of people who get infected with hepatitis B do recover and acquire protective anti- In the mid-1990s, at least five types of disease- bodies. A sizable minority of those who survive, causing hepatitis viruses have been identified, and however, perhaps 10 percent, will continue to carry they are designated by the letters of the alphabet, the virus (remain ‘‘antigen positive’’); and some of A–E. Table I summarizes some of their important these will have a chronic liver inflammation that characteristics. Of the five, hepatitis A and E are can end up in cirrhosis. The cirrhosis caused by not particularly associated with injecting drug hepatitis B is essentially similar to alcoholic cirrho- abuse; but the other three very much are and they sis, with the same consequences and potential com- will be discussed in some detail in that context. plications described above. Moreover, hepatitis B Hepatitis B. This virus (which used to be has the potential to cause liver cancer in some of called ‘‘serum hepatitis’’) is endemic to some parts those who develop cirrhosis. Not only is hepatitis B of the world, such as Southeast Asia, where as in such chronically infected individuals a threat to much as 10 percent of the population may be in- their own survival, but it is also a source of infec- fected. In the Western world, IDUs represent the tion to others, particularly to their needle-sharing greatest reservoir for hepatitis B virus. It is trans- partners, to their sexual partners, and to their de- mitted through a direct blood-borne route, such as veloping fetuses and newborn babies. (1) contaminated needles and syringes (which drug Hepatitis C. Until about 1990, this was called addicts notoriously did not sterilize in the past); ‘‘non-A-non-B hepatitis,’’ because we knew that (2) from an infected mother across the placenta there were viral hepatitis cases that were caused by and through the umbilical cord of a developing FE- neither of the two identifiable viruses, A or B. An TUS; (3) from blood contaminating accidental nee- antibody test can now identify this virus, which is dle-stickinjuries in health-care workers;and called hepatitis C. The antibody detected is not a (4) from any blood to blood contact occurring dur- protective antibody, but it is similar to the AIDS ing sexual intercourse. At one time blood transfu- (HIV) antibody in that it indicates the presence of sions were a common source of infection, but since the virus. A lot of the viral hepatitis caused by the 1970s we have had a reliable test to screen out blood transfusions in the past was due to hepatitis infected donors. C infection; the antibody test can eliminate this The symptoms of hepatitis B infection vary. In source of transmission, since it is used to screen the its severest form, it can cause general unwellness, donor blood supply. fever, jaundice, coma, and death. The majority of Injecting drug users, however, remain a major patients, even with marked jaundice and fever, do reservoir and source for the spread of this virus. not die. Many infected people do not even have an Hepatitis C is transmitted similarly to hepatitis B— overt illness; they may not feel sickat all or may and, for that matter, to HIV—primarily through just have transient ‘‘flu-like’’ symptoms. There direct blood to blood contact (by contaminated in- may be a tender enlargement of the liver. If such jection PARAPHERNALIA) and to a lesser extent, but people are tested in the laboratory, they have ele- still possibly, via sex and from mother to fetus. The vated enzymes, such as AST (also known as SGOT) primary infection goes very often unnoticed. The and ALT (also known as SGPT), which are usually laboratory tests, in addition to hepatitis C antibod- much higher than the values found in alcoholic ies, will show elevated ALT and AST levels. Since liver disease (in contrast to alcohol, viral hepatitis this is a newly identified virus, the natural history tends to cause more elevation in ALT than in AST). of hepatitis C is not yet clear. A fair amount of The bilirubin (bile pigment) level will be high if the evidence suggests that chronic hepatitis, eventual person has yellow jaundice. cirrhosis, and liver cancer may be an even greater There are now quite good serological tests for riskwith hepatitis C than it is with hepatitis B. hepatitis B. A virus particle (hepatitis B’s antigen) Some studies in the current medical literature indi- can be identified in infected people. Those who cate that 50 to 80 percent of intravenous drug recover from the illness and clear the virus out of addicts may be positive for hepatitis C, so we are their body will develop a protective antibody that not talking about a trivial problem here. will prevent their reinfection. The antibody can be Hepatitis D. This is a very peculiar virus, detected in a laboratory test. which was originally called ‘‘delta agent’’ and later 314 COMPLICATIONS: Medical and Behavioral Toxicity Overview

renamed hepatitis D. It is an incomplete virus that SHAPIRO, C. N. (1994). Transmission of hepatitis viruses. can exist only in the presence of hepatitis B. When Annals of Internal Medicine, 120, 82. the two organisms combine, the outcome is a par- WOOLF, G. M., & LEVY, G. A. (1988). Chronic viral hep- ticularly nasty, potentially lethal hepatitis, both in atitis. Medicine in North America, 21, 3379. terms of acute mortality and chronic consequences. PAUL DEVENYI Discovered in Italy about 1990, in North America REVISED BY RALPH MYERSON hepatitis D is known to be primarily harbored by the injection drug-using population. Prevention and Treatment of Viral Hepati- tis. Obviously the best prevention for injection Medical and Behavioral Toxicity Over- drug users would be to stop injecting drugs. Other, view Alcohol and other drugs of abuse have often more realistic prophylactic measures—which caused and continue to cause considerable adverse are now all familiar from the HIV scene—are the health effects to both the individual and to society. use of sterile (or at least bleached) needles and Both legal and illegal drugs (substances) of abuse syringes, needle-exchange programs, and condoms are taken to modify mood, feeling, thinking, and for sexual activities. perception. As with most drugs (medications), both Immediately after a known or suspected expo- acute and chronic toxicities occur. In general, the sure to hepatitis B, the injection of an antibody term acute refers to the short period of time when preparation (known as ‘‘hepatitis B immune globu- the drug is present in the body, exerting its main lin’’) can prevent illness. A more permanent pro- effects. The term chronic refers to a longer term, phylaxis in high-riskpopulations is provided by the usually years. hepatitis B vaccine, which gives long-term immu- Acute toxicity results in the impairment of be- nity in previously uninfected individuals. IDUs cer- havior leading to other complications (e.g., tainly represent one of these high riskpopulations, trauma) and, in the case of some drugs, high doses although the widespread use of the hepatitis B vac- can decrease breathing (respiratory depression) or cine in this group raises some obvious ethical and change the rhythm of the heart, leading to acciden- logistic dilemmas. At the present time, there is no tal or intentional death. Chronic use can result in passive or active immunization available for hepa- organ damage, which may lead to chronic illness or titis C. death (as with alcoholic cirrhosis of the liver). Per- The acute phase of any form of viral hepatitis sistent use of many classes of drugs also leads to cannot be treated effectively. Chronic hepatitis B TOLERANCE (an increased amount is required to and C infection may respond, to a certain extent, to produce the same effects) and physiologic (physi- some antiviral drugs known as interferons, which cal) dependence, so that a WITHDRAWAL syndrome are currently widely studied. Finally, as mentioned is associated with sudden cessation of drug use. under alcoholic liver disease, the most radical form Drug users who employ hypodermic needles and of therapy in the end-stages is liver transplantation. syringes (injecting drug users [IDUs]) are at risk for blood-borne diseases associated with the use of (SEE ALSO: Complications: Liver (Alcohol); Needle unsterile equipment, such as hepatitis and human and Syringe Exchanges; Social Costs of Alcohol immunodeficiency virus (HIV 1 and 2—the viruses and Drug Use; Vulnerability As Cause of Substance responsible for AIDS; see ACQUIRED IMMUNODEFI- Abuse) CIENCY SYNDROME). This article focuses on ALCOHOL as the represen- BIBLIOGRAPHY tative drug, but other drugs of abuse will be re- GOLD, M. S. (1991). The Good News about Drugs and ferred to where appropriate. In North America, Alcohol. New York: Villard. diagnosis of alcohol and other psychoactive sub- LIEBER, C. S. (1992). Medical disorders of alcoholism. stance abuse/dependence is usually made accord- New York: Plenum. ing to the DIAGNOSTIC AND STATISTICAL MANUAL MEZEY, E. (1982). Alcoholic liver disease. In H. Popper (DSM) of the American Psychiatric Association & F. Shaffner (Eds.), Progress in liver diseases. New (APA). The fourth edition, called DSM-IV, defines York: Grune & Stratton. psychoactive substance dependence as at least COMPLICATIONS: Medical and Behavioral Toxicity Overview 315 three of the following (occurring in the same work, school, or home (e.g., repeated 12-month period): absences or poor workperformance re- lated to substance use; substance-related 1. tolerance, as defined by either of the fol- absences, suspensions, or expulsions lowing: from school; neglect of children or a. need for markedly increased amounts of household) the substance to achieve intoxication or 2. recurrent use in situations in which it is desired effect physically hazardous (e.g., driving an b. markedly diminished effect with contin- automobile or operating a machine ued use of the same amount of the sub- when impaired by substance use) stance 3. recurrent substance-related legal prob- 2. withdrawal, as manifested by either of the lems (e.g., arrests for substance-related following: disorderly conduct) a. the characteristic withdrawal syndrome 4. continued substance use despite having for the substance persistent or recurrent social or interper- b. the same (or closely related) substance sonal problems caused or exacerbated is taken to relieve or avoid withdrawal by the effects of the substance (e.g., ar- symptoms guments with family members about 3. the substance is often taken in larger consequences of intoxication; physical amounts or over a longer period than was fights) intended B. Has never met criteria for Substance De- 4. a persistent desire for or unsuccessful ef- pendence for this class of substance. forts in cutting down or controlling sub- stance use These criteria continue to evolve and are likely 5. a great deal of time is spent in activities to be somewhat changed in the future. Clearly the necessary in obtaining the substance (e.g., lackof one of the above diagnoses does not visiting multiple doctors or driving long preclude a given person from being at riskfor distances), using the substance (e.g., chain- complications of alcohol or drug use (e.g., trauma smoking), or recovering from its effects as a result of intoxication). 6. important social, occupational, or recrea- tional activities are given up or reduced be- THE ACUTE EFFECTS OF ALCOHOL cause of substance use 7. continued substance use despite knowledge At the level of the cell, very high doses of alcohol of having had a persistent or recurrent (ethanol) seem to act by disrupting fat (lipid) physical or psychological problem that was structure in the central nervous system (anesthetic likely to have been caused or exacerbated effect). Lower doses are thought to interact with by the substance (e.g., recurrent cocaine various proteins and NEUROTRANSMITTERS (which use despite recognition of cocaine-induced act as RECEPTORS), such as GLUTAMATE, GABA depression; continued drinking despite rec- (GAMMA-AMINO BUTYRIC ACID), cyclic AMP (aden- ognition that an ulcer was made worse by osine mono-phosphate), and G proteins. Other ac- alcohol consumption) tions may involve ion (calcium) channels. The rein- forcing (rewarding) effects of alcohol may be The diagnosis of alcohol and other substance abuse mediated via DOPAMINE (a neurotransmitter) in (as opposed to dependence) relies on: specific brain regions; dopamine acts as an inter- A. A maladaptive pattern of substance use mediary compound in the reinforcement process. leading to clinically significant impairment The reinforcement of responses to other drugs of or distress as manifested by one or more of abuse, such as COCAINE, are also thought to be the following occurring at any time during mediated via dopamine. the same twelve-month period: For most persons at least some of the acute ef- 1. recurrent substance use resulting in a fects of alcohol are well known on the basis of failure to fullfill major obligations at personal experience. Low doses cause blood vessels 316 COMPLICATIONS: Medical and Behavioral Toxicity Overview to dilate. The skin becomes flushed and warm. incidence of coronary heart disease compared with There is relaxation and mild sedation. Persons be- no drinks, while higher doses result in an increased come talkative with loss of inhibitory control of riskof infarction as well as the well-knownprob- emotions. Small doses (one to two drinks) do not lems produced by alcohol excess. impair complex intellectual ability; however, as the Inasmuch as most American households already dose increases (two or more drinks or as the blood are exposed to alcohol (Thun et al., 1997). advice alcohol concentration approaches and exceeds the as to the benefits of moderation may be offered legal limit) impairment at multiple levels of the without reserve. In the case of abstainers, however, nervous system occurs. All types of motor perform- the risks of initiating alcohol appear to outweigh its ance are eventually affected, including mainte- potential benefits. This is especially applicable in nance of posture, control of speech, and eye move- families that include adolescents. ments. These movements become slower and more inaccurate. There is a decrease in mental function- ACUTE EFFECTS OF OTHER DRUGS ing, such that there is impairment in attention and OF ABUSE concentration, and a diminishing ability to make mental associations. There is a decreased ability to Other drugs of abuse can be classified into stim- attend to incoming sensory information. Night and ulants, depressants, OPIOIDS, and drugs that alter color vision are impaired. Judgment and discrimi- perception (including HALLUCINOGENS). The ef- nation and the ability to thinkand reason clearly fects of any drug depends on the dose taken at any are adversely affected. Even higher doses result in a one time, the previous drug experience of the user, stuporous condition associated with sleeping, vom- the circumstances in which the drug is taken, and iting, and little appreciation of surroundings. This the manner (route of administration) in which the is followed by coma and sometimes death from drug is taken. decreases in the functioning of the brain centers Stimulants such as cocaine and AMPHETAMINE that control respiration. produce euphoria, increased confidence, increased sensory awareness, increased ANXIETY and suspi- ciousness, decreased appetite, and a decreased need DOES ALCOHOL IN MODERATION for sleep. Physiological effects include increases in HAVE A BENEFICIAL EFFECT? heart rate, blood pressure, and pupil size, and de- The impact of alcohol has been further en- creases in skin temperature. hanced recently by an impressive amount of evi- Depressants such as the minor tranquillizers (in- dence from epidemiological and clinical case-con- cluding the BENZODIAZEPINES,BARBITURATES, and trol and cohort studies over the last two decades other SEDATIVE-HYPNOTICS) produce acute effects demonstrating an inverse relationship between of a similar nature to alcohol—also a depressant. moderate alcohol consumption and coronary heart Actual effects vary according to drug, so that ben- disease. Individuals find themselves caught in a di- zodiazepines (such as diazepam/Valium) produce lemma between the oft-preached dangers of drink- less drunkenness compared to alcohol or barbitu- ing and its recently acclaimed benefits. rates. Early investigators, impressed by France’s rela- The term opioid refers to both drugs derived tively low incidence of coronary heart disease de- from OPIUM (opiates) and other synthetic drugs spite an intake of saturated fats at least three times with similar actions—those acting on the same re- that of the United States (the so-called ‘‘French ceptor system. The term NARCOTIC is usually syn- paradox’’), focused their studies on the potential onymous with opioid, but it can technically also cardioprotective properties of red wine. Based on include other drugs included in the HARRISON NAR- other studies, however, the present consensus is COTIC ACT (e.g., cocaine). Opioids produce eu- that all alcoholic beverages—wine, beer, and li- phoria, sedation (to which rapid tolerance devel- quor, in moderation, are associated with a lower ops), itching, increased talkativeness, increased or coronary artery disease risk(Rimm et al., 1996). In decreased activity, a sensation of stomach turning, dose-range studies, a J or U shaped curve has been nausea, and vomiting. There are minor changes in demonstrated whereby the equivalent of two alco- blood pressure and the pupils become constricted holic drinks per day is associated with a decreased (made smaller). COMPLICATIONS: Medical and Behavioral Toxicity Overview 317

Drugs that alter perception include those above PCP, are also associated with accidents mostly re- as well as MARIJUANA,PHENCYCLIDINE (PCP), and lated to an impaired sense of judgment. LYSERGIC ACID DIETHYLAMIDE (LSD). In general, Crime. Associations between criminal activity most drugs of abuse can cause hallucinations under and alcohol use have been established; however, some circumstances. The drugs which more specifi- methodological inadequacies of studies in this area cally affect perception (hallucinogens) produce a preclude a clear causal relationship between alco- combination of depersonalization, altered time per- hol use and crime. The strongest association be- ception, body-image distortion, perceptual distor- tween crime and alcohol use occurs in young males. tions (usually visual), and sometimes feelings of Other forms of drug abuse (e.g., HEROIN and co- insight. Physiological effects such as changes in caine) have much higher associations with crimi- heart rate and blood pressure may also occur. nality. For example the majority of persons en- rolled in METHADONE programs have extensive criminal careers. Those involved in drug dealing HARMFUL EFFECTS are at a high riskof being both a perpetrator or a Accidents. Alcohol is a significant factor in victim of homicide. accident-related deaths. The main causes are mo- Family Violence. Several studies indicate an tor-vehicle ACCIDENTS, falls, drownings, and fires association between alcohol use/abuse and spousal and burns. Approximately 50 percent of motor- abuse; however, the nature of this interaction is not vehicle fatalities (driver, pedestrian, or cyclist) in well understood. Intoxication is associated with an the United States are alcohol-related, with the inci- increase in negative behavior for episodic drinkers dence having fallen a little in recent years. These while less negative behavior is seen in steady drink- alcohol-related accidents are more common at ers, suggesting that drinking may be a short-term nights and on weekends. Falls are the most fre- solution to problems for regular drinkers. Clearly, quent cause of nonfatal accidents and the second alcohol use is associated with physical VIOLENCE in most frequent cause of fatal accidents. According to some families, and there also appears to be a link various surveys of fatal falls, those that are alcohol- between alcohol and child abuse. Female caregivers related range from 17 to 53 percent; for nonfatal with a diagnosis of alcohol abuse, alcohol depen- falls, from 21 to 77 percent (Hingson & Howland, dence, recurrent depression, or ANTISOCIAL PERSONALITY are more likely to report physical 1987). The higher the blood alcohol content abuse of their children than those without these (BAC), the higher is the riskfor falls. The third diagnoses (Bland & Orn, 1986). leading cause of accidental death in the United Suicide. From 20 to 36 percent of SUICIDE States is drowning. About half (47–65%) of adult victims have a history of alcohol abuse or had been deaths by drowning are alcohol-related (Eighth drinking prior to death. Alcohol use is linked more Special Report to U.S. Congress, 1993). Fires and to impulsive than to premeditated suicides, and to burns are the fourth leading cause of accidental the use of firearms, rather than to other modes of death in the United States. Studies on burn victims killing. Death from OVERDOSE of illicit drugs is show that alcohol intoxication is common. Ciga- common; most of these are thought to be accidental rette smoking while drinking is an additional cause but some are intentional. of fires and burn injuries. Estimates of the rates of Trauma or Severe Injuries. A history of intoxication range from 37 to 64 percent. trauma has been found to be a marker for (sign of) Users of other drugs of abuse (e.g., cocaine and alcohol abuse. Emergency room trauma victims of- opioids) also have higher rates of accidents in com- ten have high rates of intoxication. Furthermore, parison to the nondrug-abusing population. The heavy alcohol use both interferes with recovery combination of cocaine and alcohol has been re- from serious injuries and increases rates of mortal- ported to be commonly associated with motor-vehi- ity for a given injury. Users of illicit drugs have a cle deaths. Between 1984 and 1987 in New York higher age-adjusted rate of mortality than do non- City, 18 percent of motor-vehicle deaths showed users. Many of these deaths result from trauma. evidence of cocaine use at autopsy. Cigarette Fetal Alcohol Syndrome (FAS). Since the smokers have higher rates of accidents than do 1970s, alcohol has become firmly established as a non-smokers. Drugs that alter perception, such as teratogen (an agent that produces defects in the 318 COMPLICATIONS: Medical and Behavioral Toxicity Overview developing fetus). It is considered the most com- which alcohol enhances the onset of cancer. Alcohol mon known cause of mental retardation. FAS de- appears to modify the immune response to cancers, fects range from specific structural bodily changes facilitate delivery of carcinogens (substances which to growth retardation and subtle cognitive-behav- enhance cancer onset), and impair protective re- ioral abnormalities. The diagnostic criteria for FE- sponses. Overall, alcohol is considered to act as a TAL ALCOHOL SYNDROME are the following: pre- co-carcinogen; for example, it increases the likeli- natal (before birth) and postnatal (after birth) hood of certain smoking-induced cancers. growth retardation; characteristic craniofacial de- Smoking is, of course, well established as a cause fects; central nervous system dysfunction; organ of lung as well as other cancers. Smoking is respon- system malformations. When only some of these sible for 85 percent of lung cancers and has been criteria are met, the diagnosis is termed fetal alco- associated with cancers of the mouth, pharynx, lar- hol effects (Eighth Special Report to U.S. Congress, ynx, esophagus, stomach, pancreas, uterine cervix, 1993). The abnormalities in physical appearance kidney, ureter, and bladder (Bartecchi et al., seem to decrease with age whereas the cognitive 1994). Chewing tobacco (SMOKELESS TOBACCO)is deficiencies tend to persist. There is no clear dose- associated with mouth cancer. The chewing of BE- response relationship between alcohol use and ab- TEL NUTS with lime is common in Asia and results normalities. The safe amount of drinking during in absorption of arecoline (a mild stimulant). This pregnancy (if it exists at all) is unknown. The peak practice also causes cancer of the mouth. It has level of blood (or brain) alcohol attained and the been suggested that MARIJUANA smoking also timing in relation to gestation (and particular or- causes lung cancer, since high tar levels are present gan development) are probably more important in the smoked products. than the total amount of alcohol consumed during pregnancy. Genetic and maternal variables also seem to be important. Native-American and Afri- ALCOHOL USE AND ABUSE can-American children seem to be at high risk. AMONG ADOLESCENTS While the public is generally aware of the relation- Alcohol use among adolescents is a serious ship between alcohol consumption and fetal abnor- world-wide problem. Surveys indicate that up to 54 mality, surveys reveal that there is a need for percent of eighth graders, and up to 84 percent of greater public education in this area. twelfth graders report having consumed alcohol Smoking is associated with low birthweight. Co- (O’Malley et al, 1998). There is little doubt that caine use in PREGNANCY has been associated with parents’ attitudes and habits concerning drinking complications (e.g., placental separation and in are important influences on adolescent drinking utero bleeding), and it appears to be associated (Ary et al, 1993). However, there is also evidence with congenital abnormalities. Heroin use in preg- that adolescents who abuse alcohol often have co- nancy is associated with premature delivery and low birthweight; often there is a withdrawal syn- existing psychopathology such as sociopathy, and drome in the baby at birth. Methadone (a long- bouts of depression and anxiety (Clarkand acting opioid) usually reduces rates of prematurity Bukstein, 1998). and low birthweight but still causes as much or Another significant reason for concern about al- more opioid withdrawal in the newborn. cohol ingestion by adolescents is the close associa- Cancer. There is clear epidemiologic evidence tion of alcohol abuse with the use of other drugs. for an increased riskof certain types of C ANCER in There is considerable evidence that alcohol use association with alcohol consumption. These in- tends to precede use of illicit drugs, and some re- clude cancer of the esophagus, oropharynx, and searchers argue that, based on long-term studies, liver. Other cancers possibly associated with alco- alcohol serves as a ‘‘gate-way’’ to the use of illicit hol consumption include cancer of the breast, substances. As early as the eighth grade, alcohol stomach, prostate, and colon (Geokas, 1986). Alco- users were found to have a significantly higher hol plays a synergistic (additive) role with smoking prevalence of cigarette smoking, and use of mari- TOBACCO in the development of cancer, particularly juana and cocaine than non-users of alcohol. This with respect to the head, neckand esophagus. difference persists through grade 12 and thereafter There are several possible mechanisms through (Kandel and Yamaguchi, 1993). COMPLICATIONS: Medical and Behavioral Toxicity Overview 319

THE EFFECTS OF ALCOHOL ON acute hepatitis) may also contribute to this neuro- BODILY SYSTEMS logic impairment. Computerized tomography (CT) scans reveal that many alcoholics have cerebral Neurologic. Acute alcohol consumption atrophy—this consists of decreased brain weight, causes impairment as described above. Alcohol po- an increase in spaces (sulci) between various re- tentiates the action of many drugs that produce gions of the brain, and an increase in size of ventri- acute effects on the brain. High blood-alcohol lev- cles (spaces filled with cerebrospinal fluid). In a els can result in ‘‘blackouts.’’ This condition is due minority of cases, these structural changes are re- to acute loss of memory associated with intoxica- versible with abstinence. Seizures are associated tion, although the person usually behaves in ap- with heavy alcohol consumption and usually occur parently normal fashion during this period. Black- in association with alcohol withdrawal. Abstinence outs are also seen with the taking of other central from alcohol is usually the only treatment needed nervous system depressants, such as the barbitu- for this type of seizure. The hallucinations that are rates and the benzodiazepines. mostly associated with alcohol withdrawal are usu- The main adverse consequences of chronic alco- ally treated with drugs—benzodiazepines and phe- hol consumption with respect to the nervous system nothiazines. are the following: brain damage (manifested by Peripheral neuropathy is seen in association dementia and alcohol amnestic syndrome); compli- with chronic alcoholism. Peripheral neuropathy cations of the withdrawal syndrome (seizures, usually refers to toxic damage to peripheral nerves. HALLUCINATIONS); and peripheral neuropathy. Concurrent nutritional deficiencies often contribute Chronic alcohol consumption results in tolerance, to this damage. This neuropathy results in changes followed by an increased long-term consumption in sensation and occasionally motor function, usu- that likely leads to tissue damage. PHYSICAL ally in the legs. Sometimes this can occur acutely DEPENDENCE may also develop (i.e., a withdrawal with intoxication. For example, the abnormal pos- syndrome occurs on sudden cessation of drinking). ture in association with a drunken stupor can result The brain damage, when severe, is usually classi- in radial nerve (‘‘Saturday night’’) palsy. Alcohol- fied as one of two main disorders. The first is a type ics are also at increased riskof subdural hema- of global (general) dementia. It is estimated that 20 tomas (blood clots due to ruptured intracranial percent of admissions to state mental hospitals suf- veins secondary to trauma) and of stroke. fer from alcohol-induced dementia (Freund & The neurologic complications associated with Ballinger, 1988). The second is an alcohol-induced the acute use of other drugs of abuse include sei- amnestic (memory-loss) syndrome, more com- zures (convulsions) and strokes in association with monly known as Wernicke-Korsakoff syndrome. cocaine. High doses of some opioids, such as This is related to thiamine (Vitamin B1) deficiency. propoxyphene (Darvon) or MEPERIDINE (Demerol) The Wernicke component refers to the acute neuro- can also cause seizures. Substances which can logic signs, which consist of ocular (eye) problems cause delirium (reversible disorientation) include such as a sixth cranial nerve palsy (disturbed lat- Cannabis (MARIJUANA), phencyclidine (PCP), eral gaze), and ataxia (impaired balance); the Kor- lysergic acid diethylamide (LSD), and atropine. sakoff component refers to the memory impair- Sudden cessation of use of central nervous system ment, which tends to be selective for short-term depressants (benzodiazepines, barbiturates, and memory and is usually not as amenable to treat- alcohol) can result in seizures and hallucinations. ment once it has become manifest. Chronic use of other substances of abuse can also Milder forms of these disorders are also detect- result in neurologic complications. Tobacco use is able with neuropsychologic testing or brain IMAG- associated with increased rates of stroke (but it ING TECHNIQUES (CAT scans; MRI). Studies of de- appears to be associated with lower rates of Parkin- toxified alcoholics (without other evidence of son’s disease—a progressive disorder affecting organic brain damage) reveal that 50 to 70 percent control of movement). Solvent abuse (inhaling) can have impairments in neuropsychologic assessment cause damage to the cerebellum (the part of the (Eckardt & Martin, 1986). In most of these cases brain controlling movement) and to peripheral there is reversibility with abstinence from alcohol. nerves. A form of ‘‘synthetic heroin,’’ MPTP Severe liver disease (e.g., advanced cirrhosis or (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine), 320 COMPLICATIONS: Medical and Behavioral Toxicity Overview an analogue of meperidine (Demerol), has been order is a common diagnosis in those who abuse demonstrated to cause a severe form of Parkinson’s drugs. disease. Endocrine and Reproductive. Alcohol pro- Psychiatric. Alcohol-related diagnoses are duces both acute and chronic effects on virtually all common among psychiatric patients. For example, endocrine organs (glands). Acutely, alcohol raises a recent study (Moore et al., 1989) showed that 30 plasma catecholamines, which are chemicals re- percent of those admitted to a psychiatric unit had leased from nerve endings that are responsible for a concurrent alcohol-related diagnosis. Alcohol certain emotional reactions—‘‘fear, flight, and alone may produce symptoms and signs that mimic fight’’. Epinephrine (adrenaline) is released from psychiatric disorders. Examples include depres- the inside of the adrenal gland (medulla) and nor- sion, anxiety disorder, psychosis, and antisocial epinephrine (noradrenaline) from sympathetic personality disorder. Alternatively, an alcohol-re- NEURONS (nerve cells) and the adrenal glands. Al- lated disorder may co-exist with one of these or cohol also causes release of cortisol from the outside may aggravate the psychiatric disorder. (cortex) of the adrenal gland both acutely and Alcohol as a central nervous system (CNS) de- chronically. Cortisol is a hormone (chemical mes- pressant tends to cause low mood states (hy- senger) responsible for multiple effects on the body, pophoria) with chronic use. It does not commonly including changes in the immune response, glucose cause long-lasting significant clinical depression, regulation, fat breakdown, blood pressure, and but it may aggravate it. If alcohol is the primary mood. Alcohol-induced cortisol excess can mimic cause of a low mood state, then abstinenee from Cushing’s disease (a condition associated with ex- alcohol, as the sole treatment, rapidly improves the cess cortisol production, often caused by a tumor disorder. Hallucinations may occur during alcohol on the adrenals) and is known as pseudo-Cushing’s withdrawal, mimicking a psychotic disorder. Simi- disease. Alcohol affects the hypothalamus (an area larly, the anxiety associated with alcohol with- of the brain), where it modifies chemical-releasing drawal may mimic an anxiety disorder. Anxiety factors, which in turn control release of hormones and hallucinations may also be seen during with- from the pituitary (a gland in the brain linked to drawal from sedative-hypnotics. Behavior associ- the hypothalamus by a special blood supply), ated with alcoholism may lead to an erroneous di- which in turn affect endocrine organs throughout agnosis of antisocial personality disorder. the body. Acutely, alcohol also inhibits the release When alcohol is used for self-medication in some psychiatric conditions, such as anxiety disorders, it antidiuretic hormone (ADH) from the posterior pi- tends only to be of short-term help and leads to tuitary, which results in an increase in urine pro- more long-term problems. Other drugs of abuse, duction. such as the stimulants cocaine and amphetamine, The best documented chronic endocrine effect of also produce anxiety and occasionally may produce alcohol is male hypogonadism. This is a condition a psychotic state associated with acute intoxication. resulting from low sex-hormone function. Signs of This usually disappears rapidly as the drug effects this are small testes and decreased body hair. wear off. Withdrawal following chronic use of stim- Symptoms include loss of libido and impotence. ulants may be associated with depression, excessive Hypogonadism can occur as a result of alcohol low- fatigue, and somnolence (a ‘‘crash’’). Tobacco ering testosterone levels. Alcohol acts both directly smoking also appears to be somewhat associated on the testes and indirectly via the hypothalamus. with depression. (Individuals with a history of de- Alcoholic liver disease may also produce fem- pression are more likely to smoke, and may develop inization in men, as a result of impaired metabo- depression when they try to stop.) The nature of lism (breakdown) of female sex hormones such as this relationship is unclear, but patients with psy- estrogen. Signs of such feminization in men include chiatric diagnoses have higher rates of smoking gynecomastia (enlarged breasts) and female fat than the general population. Hallucinogens (such distribution. In women who drinkalcohol exces- as LSD and PCP) may also cause an acute psy- sively, there is a high prevalence of gynecologic chotic disorder which typically disappears as drug disorders (missed periods and problems in func- effects wear off; however, in some cases there may tioning of ovaries) and a possibly earlier onset of be longer lasting effects. Antisocial personality dis- menopause than in nondrinkers. In women, also, COMPLICATIONS: Medical and Behavioral Toxicity Overview 321 alcohol is metabolized at different rates according coordinated contraction of the atria). This is usu- to the particular phase of the menstrual cycle. ally not life-threatening and mostly disappears Abnormalities of both growth hormone (im- without specific treatment. High levels of alcohol paired release) and prolactin (increased release) consumption are associated with increased rates of have been described in association with acute alco- coronary (blood vessels which supply heart muscle) hol ingestion. Thyroid function (which controls heart disease, while low levels of consumption (in rate of body metabolism) can be indirectly affected comparison to complete abstinence) may be associ- as a result of alcoholic liver disease. This results in ated with a mild protective effect (the so-called impaired conversion of T4 (one version of thyroid U-curve relationship). However, low levels of con- hormone) to T3 (a more active form of thyroid sumption are not recommended as a preventive hormone). Furthermore, in alcoholism there are measure against coronary heart disease. Cigarette abnormalities in the proteins to which thyroid hor- smoking is a much greater risk factor for coronary mone binds. This results in making thyroid func- heart disease than is alcoholism. It should be noted tion tests difficult to interpret. Overall thyroid however, that 80 to 90 percent of alcoholics are also function is usually normal despite mild abnormal- cigarette smokers. ities in the tests. Multiple epidemiologic studies have established Other drugs, particularly the opioids, also have a relationship between alcohol and high blood pres- multiple effects on the endocrine system. Opioids sure (hypertension). Somewhere between 5 and 24 produce a degree of hypogonadism as a result of percent of hypertension is considered to be alcohol lowered testosterone in males and disturbed men- related (Klatsky, 1987). The relationship seems to strual function in females. This results from opioid hold most strongly for white males over the age of inhibition of gonadotropin releasing hormone 55 consuming at least 3 standard drinks per day on (GRH) in the hypothalamus, which in turn inhibits a chronic basis. Many cases resolve with absti- release of LH (lutenizing hormone) and FSH (folli- nence. Acute alcohol withdrawal has also been as- cle stimulating hormone) from the pituitary. Opi- sociated with hypertension, but this usually lasts oids also inhibit corticotropin releasing factor for only a few days. (CRF), which results in decreased adrenocor- The acute use of cocaine (a stimulant) results in ticotrophic hormone (ACTH) and decreased corti- increases in heart rate and blood pressure and sol. Nicotine causes release of epinephrine and nor- causes narrowing of peripheral and coronary artery epinephrine, which in turn increase blood pressure blood vessels. Repeated use of cocaine has been and heart rate. Nicotine also enhances the release of associated with abnormal heart beats, myocardial ADH from the hypothalamus, which decreases infarction (heart attack), and possibly myocardial urine output (i.e., counteracts alcohol’s effects). fibrosis (an increase of scar tissue within the heart). Cardiovascular. Alcohol has direct effects on Acute tobacco use also results in constriction both cardiac muscle and cardiac electrophysiology (narrowing) of blood vessels and an increase in (electrical functioning). These effects are also de- heart rate because of the nicotine. Chronic tobacco pendent on prior history of alcohol use (i.e., use is the most important of the preventable causes whether there have been underlying changes due to of coronary heart disease. The coronary arteries chronic use) and whether there is any evidence of supply the heart muscle. Long-term tobacco use underlying heart disease. Acutely, alcohol is a myo- results in an increase in atherosclerosis (build up of cardial depressant (decreases muscle function) fat and other products inside the walls of blood and, chronically, it may cause a degeneration of vessels) in most of the arteries throughout the body cardiac muscle (known as cardiomyopathy), which and increases coagulation (clotting). This has im- can lead to heart failure (condition due to excess portant effects on the following blood vessels: the body fluids because of inadequate pumping func- coronary (causes angina [chest pain] and infarction tion of the heart). Abstinence from alcohol leads to [heart attack]; the aorta (causes aneurysms, the improvement in function in some cases. ballooning effect on the arterial wall, which can be Both acute alcohol intoxication and acute with- fatal); the carotid (cause of strokes); the femoral drawal can lead to cardiac arrhythmias (abnormal (causes intermittent claudication, pain on walk- heart beats). The most frequent association is with ing); and the kidney (cause of kidney failure and atrial fibrillation (frequent uneven and un- some hypertension). Acute use of opioids have mi- 322 COMPLICATIONS: Medical and Behavioral Toxicity Overview nor effects on blood pressure. There are not esophageal reflux. Alcohol alone does not appear to thought to be important chronic adverse effects of cause peptic ulcers (cigarettes do), but alcohol in- opioids on the cardiovascular system. Marijuana terferes with healing. Alcohol disrupts the mucosal acutely causes increases in heart rate and blood barrier in the stomach and causes gastritis (inflam- flow. mation of the stomach) which can lead to hemor- Respiratory System. Acutely, alcohol does rhage, especially when combined with aspirin. Al- not usually interfere with lung function; however a cohol also interferes with the cellular junctions decrease in cough reflexes, a predisposition to within the small intestine, which can result in the reflux of stomach fluids, and the impairment of disturbance of fluid and nutrient absorption, pro- bacterial clearance in the respiratory tract occur ducing, diarrhea and malabsorption. Any resulting after intoxication. For some persons with asthma, nutritional deficiencies can further aggravate this alcoholic beverages can induce bronchospasm (air- process. way narrowing). This is thought to be related to Heavy alcohol use interferes significantly with nonalcoholic components in the beverage. Acute al- pancreatic structure and function. Alcohol abuse cohol consumption also has a direct depressant ef- and gallstone disease are the major causes of pan- fect on the respiratory center located in the creatitis, and alcoholism alone is responsible for brainstem. Accordingly, an overdose (intentional most cases of chronic pancreatitis. Alcohol changes or unintentional) can result in death from respira- cellular membranes, resulting in changes in trans- tory failure (decreased ability to breathe). Alcohol port mechanisms and the permeability of vital ions also contributes to respiratory depression when and nutrients essential for normal cellular function. taken with other central nervous system depres- Acetaldehyde, which is a breakdown product of sants such as barbiturates and benzodiazepines alcohol (and also present in cigarette smoke), is (minor tranquillizers). Acute alcohol intake in- toxic to cells and has been proposed as a causative creases sleep apnea (period of time not breathing) agent in the development of this disorder (Geokas, in those who suffer from this disorder. 1984). Acute pancreatitis is life-threatening; pa- Chronic alcohol consumption is associated with tients have abdominal pain, nausea, and vomiting. several pulmonary infectious diseases (in addition Increased levels of pancreatic enzymes, such as to risks associated with tobacco smoking). These amylase and lipase, accompany this disorder. include pneumonia, lung abscess, and tuberculosis. Treatment is usually by conservative measures, Aspiration pneumonia occurs in association with such as replacement of fluids and pain relief. high levels of alcohol intoxication; it is thought to Chronic pancreatitis can be without symptoms; can be caused by the inhalation of bacteria caused by become evident with chronic abdominal pain and the impairment of the usual reflexes, such as evidence of malabsorption (weight loss, fatty stools, coughing. Pancreatitis and alcoholic cirrhosis are nutritional deficiencies); or, uncommonly, with di- associated with pulmonary effusions (build-up of abetes mellitus as a result of the destruction of the fluid on the lung). endocrine as well as the exocrine function of the Among the other drugs, cigarette smoking pancreas. causes emphysema, chronic bronchitis, and lung Liver. Alcoholic liver disease is a major cause cancer. The smoking of marijuana on a frequent of morbidity and mortality in the United States; in long-term basis may also increase the likelihood of 1986, cirrhosis of the liver was the ninth leading these disorders. Acute use of opiate drugs intrave- cause of death. Alcohol causes three progressive nously may cause pulmonary edema (accumulation pathological (abnormal) changes in the liver— of fluid in the lungs). which can be life-threatening. fatty liver, alcoholic hepatitis, and cirrhosis. These Chronic use of intravenous drugs may cause pul- changes are useful in a prognostic sense but can monary fibrosis (increased scar tissue). This is only be diagnosed with a liver biopsy, which is not probably related to impurities, such as talc, associ- always feasible or practical. More than one patho- ated with the cutting of the drug (diluting the dose logical condition may exist at any one time in a with fillers) prior to its sale and eventual injection. given patient. Fatty liver is the most benign of the Gastrointestinal Tract and Pancreas. three conditions, and is usually completely revers- Acutely, alcohol alters motor function of the esoph- ible with abstinence from alcohol; it occurs at a agus. Chronic use of alcohol increases gastro- lower threshold of drinking compared to alcoholic COMPLICATIONS: Medical and Behavioral Toxicity Overview 323 hepatitis and cirrhosis. Alcoholic hepatitis ranges in drinkheavily to specific types of infection. With severity from no symptoms at all to severe liver respect to host factors, alcohol alone can reduce failure with a fatal outcome; it can be followed by both the number and function of white blood cells complete recovery, chronic hepatitis, or cirrhosis. (both polymorphonuclear leucocytes and lympho- Treatment is primarily supportive. Similarly, the cytes). This both predisposes toward infection symptoms and signs of cirrhosis range from none at while it interferes with the ability to counteract all to coma and death. Cirrhosis consists of irre- infection. Mechanical factors are also of impor- versible changes in liver structure resulting from an tance. For example intoxication with alcohol and a increase in scar tissue. A consequence of this is an depressed level of consciousness (and depressed abnormal flow of blood through the liver (shunts), cough reflex) predisposes toward aspiration pneu- which can result in the adverse health conse- monia. Specific infections that alcoholics are at quences of bleeding and presentation of toxic sub- higher riskfor, compared to the population at stances to the brain. This, in turn, may result in large, include pneumococcal pneumonia (the most effects ranging from impaired thinking to coma common form of pneumonia), other lung infections and death. Abstinence from alcohol can prevent (Hemophilus influenzae, Klebsiella), abscesses (an- progression of cirrhosis and reduces mortality and aerobic infections,), and pulmonary tuberculosis. morbidity (illness) from this condition. Medica- Alcoholics with liver disease are at increased risk tions may also help to reduce mortality from alco- of spontaneous bacterial peritonitis (inflammation holic liver disease. These include propothiouracil of the lining of the abdominal cavity). Other infec- (an antithyroid drug) and prednisone (a steroid). tions possibly associated with alcoholism include The former reduces the oxygen requirements for bacterial endocarditis (infection of the heart areas of the liver that are poorly perfused. The valves), bacterial meningitis, pancreatitic abscess, latter reduces inflammation. Women appear to be and diphtheria. HIV infected drug abusers are at at higher riskfor liver damage than are men. increased riskof tuberculosis as well as a multitude Opioid use alone has not been associated with of other infections. As mentioned above, injecting liver disease, but some opioids such as morphine drug users are also susceptible to a variety of infec- can cause spasm of the bile duct, which results in tions associated with use of unsterile equipment. acute abdominal pain. Tobacco use is associated Changes in immune function have been reported with a more rapid metabolism (breakdown) of cer- tain drugs in the liver. This means that sometimes to occur in users of other drugs of abuse, including higher or more frequent dosing of medicatons is heroin, cocaine, and marijuana. The precise rela- required for smokers. This effect is thought to re- tionship of the immune function change to the drug late to the tars in tobacco rather than to the nic- of abuse is not yet understood. Lifestyle factors otine. High doses of cocaine have been associated such as poor nutrition are also likely to contribute with acute liver failure. to this. Acute and chronic hepatitis (types B, C, and D) Nutrition. In heavy alcohol consumers, mal- is common in users of intravenous drugs. It is not nutrition as a result of poor dietary habits is com- usually the drug itself that causes hepatitis (inflam- mon. In women, heavy alcohol consumption is as- mation of the liver) but rather the introduction of sociated with lower than usual body weight to a disease-producing organisms associated with the degree similar to that also associated with tobacco sharing of needles. Viruses and bacteria introduced smoking. There is less of a weight-lowering effect in by injecting drugs cause other problems, such as men. Specific nutritional disorders associated with HIV infection and AIDS, endocarditis (infection of alcoholism include anemia (due to iron or folate heart valves), cellulitis (skin infection), and ab- deficiency); thiamine (Vitamin B1) deficiency— scesses. causing beri-beri or Wernicke’s encephalopathy or Immune System. Alcohol affects the immune neuropathy; malabsorption; and defective immune system both directly and indirectly. It is often diffi- and hormonal responses. Alcohol also interferes cult to discern the direct effects of alcohol from with the absorption of vitamins (such as pyridoxine concurrent conditions, such as malnutrition and and Vitamin A), minerals (such as zinc), and other liver disease. Alcohol affects host defense factors in nutrients (such as glucose and amino acids) a general way; it also seems to predispose those who (Mezey, 1985). 324 COMPLICATIONS: Medical and Behavioral Toxicity Overview

Metabolic. Alcohol is metabolized (broken suppressed by alcohol, resulting in prolonged down) in the liver to acetaldehyde and hydrogen, bleeding times. and then to carbon dioxide and water. Acetalde- Other drugs also exert hematologic effects. Ex- hyde is toxic to many different cellular functions. perimental addiction to opioids results in a revers- Alcohol affects carbohydrate, lipid (fat), and pro- ible anemia and a reversible increase in erythrocyte tein metabolism. Alcohol can cause low blood glu- sedimentation rate (a nonspecific indicator of dis- cose (hypoglycemia) due to inhibition of glycogen ease process). Smoking allows carbon monoxide to (liver stores of carbohydrate) metabolism. Alcohol enter the body and bind to hemoglobin (car- also raises blood sugar and acids (alcoholic boxyhemoglobinemia), which consequently causes ketacidosis). By interfering with the elimination of an increase in red cell production (erythrocytosis). uric acid, alcohol may precipitate acute attacks of The hematocrit value and the plasma fibronogen (a gout. Increased urinary excretion of magnesium clotting factor) rise and increase blood viscosity; can result in muscle weakness. Alcohol causes dis- platelets (sticky constituents of blood important in turbances in blood lipids, with mostly an increase wound healing) aggregate more in smokers. These in triglycerides and high density lipoprotein (HDL) thickening factors, together with damage to the in- cholesterol. sides of blood vessels, increase the probability of Acute alcohol consumption can decrease, both stroke and heart attack (myocardial infarc- whereas chronic consumption can increase, the me- tion) in smokers. White cells are also at increased tabolism of certain drugs. Tobacco smoking also levels in smokers (leucocytosis). increases the metabolism of some drugs, such as Skeletal Muscle. Chronic alcohol consump- theophylline and caffeine. This results from the tion can result in muscle cell necrosis (death). Two main patterns are seen: (1) An acute alcoholic increased activity of various liver enzymes as dis- myopathy (disturbance of muscle function) occurs cussed above. in the setting of binge drinking, sometimes associ- Hematologic (Blood) System. The effects of ated with stupor and immobilization. This results alcohol on the hematologic system can either be in severe muscle pain, swelling elevated creatine direct, or it can be indirect (as a result of liver kinase (a muscle enzyme), and myoglobinuria disease or nutritional deficiencies). Uncommonly (muscle protein in the urine which can cause kid- acute alcohol consumption (a very large dose in a ney failure). (2) This pattern consists of a more short span of time) has direct effects on the bone slowly evolving syndrome of proximal muscle marrow, resulting in decreased production of red (those closest to the trunk) weakness and atrophy cells, white cells, and platelets. (decreased size). Milder degrees of muscle injury The most frequent effect seen in alcoholics fol- are quite common and consist of elevated levels of lowing chronic consumption is an increase in the the muscle enzyme creatine kinase. size of the red blood cells (macrocytosis). This is Cocaine use can also cause muscle damage mainly due to direct toxic effects on the red cell (rhabdomyolysis), resulting in abnormalities of membrane rather than to folate (a vitamin found in creatine kinase. Most drugs of abuse (especially green vegetables) deficiency, which also causes depressants) may indirectly cause muscle damage macrocytosis. A folate deficiency, however, is some- as a result of prolonged abnormal posture, for ex- times seen in alcoholics caused mainly by impaired ample, sleeping in an intoxicated state on a hard intake and absorption of folate. Iron deficiency surface. anemia is also seen because of impaired intake of Kidney. Alcohol abuse causes a variety of elec- iron and because of frequent bleeding (due to a trolyte and acid-base (blood chemistry) disorders, variety of factors, such as coagulation defects, gas- which include decreases in the levels of phosphate, tritis, and the impaired healing of peptic ulcer). magnesium, calcium, and potassium. These abnor- Iron-overload syndromes are also diagnosed in al- malities relate to disorders within the functioning coholics and are due to a multiplicity of causes. kidney tubules (involved in secretion and reabsorp- Chronic alcohol consumption can also lead to he- tion of minerals). The abnormalities usually disap- molytic (excess breakdown of red blood cells) ane- pear with abstinence from alcohol. mia, which is mainly seen in association with liver Chronic use of other abused substances is also disease. Platelet production and function can be associated with kidney (renal) damage and failure. COMPLICATIONS: Mental Disorders 325

Long-term consumption of pain-relieving medi- KANDEL D. B., & YAMAGUCHI K. (1993). From beer to cines (daily use over many years) has been associ- crack: developmental patterns of drug involvement. ated with kidney failure (analgesic nephropathy). American Journal of Public Health 83, 851-5 This is especially associated with the combination KLATSKY, A. L. (1987). The cardiovascular effects of products—those that include two or more of CO- alcohol. Alcohol and Alcoholism, 22(suppl. 1), 117– DEINE,CAFFEINE, aspirin, and phenacetin. The re- 124. warding effects that perpetuate this form of drug MEZEY, E. (1985). Effect of ethanol on intestinal mor- use most probably relate to the codeine (an opioid) phology, metabolism, and function. In H. K. Seitz & and the caffeine (a stimulant). Heroin use has been B. Kommerell (Eds.), Alcohol related diseases in gas- associated with a form of kidney failure known as troenterology. Berlin: Springer-Verlag. heroin nephropathy. Its precise relationship to her- MOORE, R. D., ET AL. (1989). Prevalence, detection, and oin use is unclear. Secondary effects on the kidneys treatment of alcoholism in hospitalized patients. Jour- from drug and alcohol abuse also occur (for exam- nal of the American Medical Association, 261, 403– ple, from effects of trauma or muscle damage as 407. described above). O’MALLEY P. M., JOHNSTON L. D., & BACHMAN J. G. (1998). Alcohol use among adolescents. Alcohol (SEE ALSO: Crime and Alcohol; Crime and Drugs; Health & Research World 22, 85-93 Family Violence and Substance Abuse; Inhalants; RIMM, E. B., KLATSKY A., GROBBEE D., et al. (1996). Social Costs of Alcohol and Drug Use; Substance Review of moderate alcohol consumption and reduced Abuse and AIDS; Tobacco: Complications) riskof coronary heart disease: Is the effect due to beer, wine, or spirits? British Medical Journal, 312, 731-6. BIBLIOGRAPHY THUN M. J., PETO R., LOPEZ A. D., et al. (1997). Alcohol consumption and mortality among middle-aged and AMERICAN PSYCHIATRIC ASSOCIATION (1994). Diagnostic elderly U.S. adults. New England Journal of Medicine and statistical manual of mental disorders-fourth edi- 337, 1705-14. tion. Washington, DC: Author. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. ARY D. V., et al. (1993). The influence of parent, sibling, (1993). Eighth special report to the U.S. Congress on and peer modeling and attitudes on adolescent use of alcohol and health. Washington, DC: U.S. Govern- alcohol. International Journal of Addiction 28:859- ment Printing Office. 80. JOHN T. SULLIVAN BARTECCHI, C. E., MACKENZIE,T.D.,&SCHRIER,R.W. 1994. The human costs of tobacco use. New England REVISED BY RALPH MYERSON Journal of Medicine, 330, 907–912. BLAND, R., & ORN, H. (1986). Family violence and psy- chiatric disorder. Canadian Journal of Psychiatry, Mental Disorders Psychiatric disorders 31, 129–137. have long been recognized as being associated with CLARK D. B., & BUKSTEIN O. G. (1998). Psychopathology psychoactive-substance-use disorders (commonly in adolescent alcohol abuse and dependence. Alcohol referred to as drug or alcohol abuse). The term dual Health & Research World 22, 117-126. diagnosis is frequently used to describe people with ECKARDT, M. J., & MARTIN, P. R. (1986). Clinical assess- substance-use disorders combined with other psy- ment of cognition in alcoholism. Alcoholism (NY) chiatric disorders. The term COMORBIDITY is also 10(2), 123–127. used to describe the situation in which an individ- FREUND,G.,&BALLINGER, W. E. (1988). Loss of cholin- ual has two or more distinct disorders. Anxiety ergic muscarinic receptors in the frontal cortex of disorders and mood disorders are generally the dis- alcohol abusers. Alcoholism (NY), 12(5), 630–638. orders thought to occur in individuals with sub- GEOKAS,M.C.(ED.). (1984). Ethyl alcohol and disease. stance abuse, but other psychiatric disorders also Medical Clinics of North America, 68(1), 1–246. demonstrate high rates of psychoactive-substance HINGSON, R., & HOWLAND, J. (1987). Alcohol as a risk use also, including eating disorders (particularly factor for injury or death resulting from accidental BULIMIA), posttraumatic stress disorder (PTSD), falls: A review of the literature. Journal of Studies in personality disorders, somatization disorder, and Alcohol, 48, 212–219. SCHIZOPHRENIA. Children with ATTENTION DEFICIT 326 COMPLICATIONS: Mental Disorders hyperactivity disorder (ADHD) may also be at in- ing to different studies. The reason for the lackof creased riskof substance abuse as adults. Various agreement regarding such rates involves problems relationships may exist between drug and alcohol shared by all combinations of dual diagnosis. Two use and the development of these psychiatric dis- such problems include the means of assessment turbances. In understanding the relationships be- (both of substance abuse and psychiatric symp- tween substance abuse and psychiatric disorders, toms), and the timing of the assessment of psychi- the concepts of primary and secondary are of criti- atric symptoms (i.e., in relationship to the last oc- cal importance. The primary-secondary dichotomy currence of substance use). is based on the time sequence in which each disor- The effect that the means of assessment has der developed. When a disorder is referred to as upon psychiatric comorbidity is well illustrated by primary, this would indicate that it presented first. depression. Different rates of depression in alcohol- The rationale for using the primary-secondary con- ics are seen if one uses standard clinical interviews, cept involves improved prediction of familial clus- structured research interviews or self-report mea- tering of the psychiatric disorder, implications for sures. Such methodological differences have led to treatment, and improved outcome prediction. widely differing conclusions regarding both In addition to the primary-secondary distinc- comorbidity rates and comorbid influence. How- tion, the approach to the individual with both a ever, recent estimates from a number of sources substance use and a nonsubstance use psychiatric suggests that 40 percent of all alcoholics in the U.S. disorder should incorporate a similar but slightly are also battling depression (Larson, 1998). more encompassing approach. The drug or alcohol The critical importance of the timing of the psy- use in such individuals may be involved as a form chiatric assessment and its relationship to of self-medication for the psychiatric disturbance; comorbidity is demonstrated by studies from the it may itself induce psychiatric symptoms in an Alcohol Research Center in San Diego (Brown, otherwise unaffected individual; or the individual 1988; Schuckit, 1990). Symptoms of depression in may be affected by both disorders (substance abuse 191 alcoholics were recorded within 48 hours of and other psychiatric disorders) through separate admission for alcohol detoxification and again after routes of VULNERABILITY. 4 weeks of abstinence (Brown, 1988). Significant As can be anticipated from this introduction to levels of depression were noted in 42 percent of dual diagnosis issues, the relationship of psychiat- alcoholics in the first assessment, but in only 6 ric disorders and substance abuse is complex. De- percent in the follow-up evaluation irrespective of spite this complexity, the extent of such problems any specific antidepressant therapy. underscores the need for attention to this area. These studies demonstrate that for a number of Studies have shown higher prevalence rates of sub- alcoholics, psychiatric symptoms are directly in- stance abuse in individuals with psychiatric disor- duced by the intake of alcohol, and that these ders than in the general population, and conversely symptoms should be regarded as secondary to the patients seeking care for substance abuse have alcoholism. This is important for two reasons. First, shown high rates of other psychiatric disorders. if the psychiatric symptoms are secondary to the Large epidemiologic studies of community samples alcoholism, treatment of the psychiatric symptoms in the United States reveal that greater than 50 alone will not treat the main disorder (alcoholism). percent of substance abusers have at least one other Second, riskfor relapse of the alcoholism is high. mental illness (Regier, 1990). Data from this same Another complication of alcoholism in regard to study indicate that approximately one third of depression is poor treatment response to standard those identified as having a mental disorder also ANTIDEPRESSANT therapy, both pharmacologic and have a substance-abuse disorder. nonpharmacologic in type. The reason for this is unknown, but may be related to adverse social complications of the alcoholic behavior (e.g., legal ALCOHOLISM AND MOOD DISORDERS problems, job difficulties, marital separation, and DepressionandAlcoholism. The rate of de- divorce) (Cook, 1991). pression in individuals with alcoholism and rate of Mania and Alcoholism. Individuals with bi- alcoholism in individuals affected with mood disor- polar affective disorder (manic-depressive disor- ders (depression and mania) varies greatly accord- der) have been noted to have increased use of alco- COMPLICATIONS: Mental Disorders 327

hol during their manic episodes. Two studies have abuse are ANTISOCIAL PERSONALITY DISORDER and suggested that alcoholic bipolar patients have high borderline personality disorder. rates of alcoholism in their families as compared to Antisocial Personality and Alcoholism. A nonalcoholic bipolar patients (Morrison, 1974; great deal is known regarding the relationship of Dunner, 1979). This fact suggests that the riskfor antisocial personality disorder and alcoholism. alcoholism in bipolar disorder may occur due to a This diagnostic combination is estimated to involve familial predisposition (e.g., genetic predisposition, as many as 2 percent of the male population of the behavior modeling, etc.), and not necessarily from United States. Most studies of this combination of a complication of the manic episode itself. Regard- illnesses indicate that the antisocial alcoholic has less, impulsive behavior during manic episodes an earlier onset of drinking difficulties, more family clearly includes riskfor excessive alcohol use. history of alcoholism, more social complications of alcoholism, and a greater number of symptoms of SUBSTANCE ABUSE AND other psychiatric disturbances, e.g., drug abuse, MOOD DISORDERS depression, mania, schizophrenia, and psychotic symptoms. Antisocial alcoholics have also been re- Nearly all substances of abuse have the potential ported to attempt suicide more frequently. In addi- to alter mood symptoms. Classically, tion to these more severe symptoms at the time of PSYCHOSTIMULANTS, such as AMPHETAMINES and initial evaluation, antisocial personality disorder COCAINE, may induce an appearance of elevated influences the natural history of the substance use mood, racing thoughts, increased energy, and sense disorders and alcoholism. This change in course is of well-being. Individuals who have developed tol- demonstrated by the following studies. erance to stimulants will experience, upon their Schuckit (1985) utilized standardized research discontinuation, withdrawal. These withdrawal criteria to divide a group of 541 alcoholics into symptoms will overlap characteristic depressive those who were primary alcoholics, primary drug symptoms, including severe dysphoria, insomnia abusers, primary antisocials, and primary affective followed by hypersomnia, irritability, and fatigue. disorders. Intake and one-year outcome were then OPIATES induce a sense of elevated mood, and in- evaluated. The primary antisocial, along with the creased self-esteem. A sense of decreased anxiety is primary drug abusers, had a poorer one-year out- also frequently reported. Upon withdrawal, depres- come in terms of drug use, police and social prob- sive symptoms are accompanied by characteristic lems, and higher scores (worse outcome) on a clin- physical symptoms such as muscle aches, drug ical-outcome scale. Schuckit concluded from this CRAVING, lacrimation (secretion of tears), and study that antisocial personality predicted a poor piloerection (goose flesh). prognosis in terms of continued alcohol problems. In a carefully designed study, Rounsaville and SUBSTANCE ABUSE AND coworkers (1987) evaluated 266 alcoholics one PERSONALITY DISORDERS year after treatment. Multiple-outcome measures were utilized in this study and over 84 percent of Personality disorders by definition involve mal- the original cohort were reevaluated. In this study, adaptive patterns of relating to one’s environment it was found that in males, an additional diagnosis and self that lead to conflict. To meet the definition of major depression, antisocial personality disor- of a disorder, these patterns should be enduring der, or drug abuse were associated with poor prog- qualities, and the onset of such disorders is late nosis at one year. Further analysis in this study also adolescence. Behavior induced by substance abuse supported the conclusion that the diagnosis was the should be carefully separated from behavior dem- factor that conveyed the poor prognosis, not gen- onstrated during periods of abstinence. This is im- eral severity of psychopathology or degree of alco- portant, since maladaptive behavior associated hol dependence. with personality disorders will persist through Another study that looked at outcome of alcohol adulthood, while maladaptive behavior that is in- problems in subtypes of antisocials was conducted duced by substance abuse should subside during by Liskow (1991). In this study, antisocial alcohol- abstinence from the substance. Two personality ics were subtyped as to presence of additional diag- disorders that are closely associated with substance noses of drug abuse and depression. An alcoholism- 328 COMPLICATIONS: Mental Disorders only group was included as a control group. In this POSTTRAUMATIC STRESS DISORDER study, the alcoholism-only group had the best out- (PTSD) AND SUBSTANCE ABUSE come on a number of measures, while the antisocial Following extreme stresses beyond the realm of alcoholic with drug abuse had the worst outcome. normal human experience, symptoms of anxiety The antisocial alcoholic with no other diagnosis including intrusive recollections of the trauma, au- and the antisocial alcoholic with depression were tonomic hyperactivity, and nightmares have long similar in outcome—and intermediate in outcome. been observed, but PTSD as a psychiatric diagno- Overall, the differences in the alcoholism-only sis is much newer. Following recognition of this compared to the antisocial-only and the antisocial disorder, the linkwith substance abuse has been depressed alcoholics were small compared to the the subject of a number of studies. Rates of alco- differences between the antisocial plus drug group holism in PTSD range from 40 to 80 percent, and all other groups. This study suggests that the while other forms of substance abuse may range poor prognosis in antisocial alcoholics may depend from 20 to 50 percent. This high rate of substance in part on other additional psychopathology (i.e., abuse has led to the hypothesis that the drug use drug abuse). may be explained by a self-medication theory. Antisocial Personality Disorder and Sub- Jelinek(1984) has proposed that in the treatment stance Abuse. Individuals with antisocial per- of PTSD, those with substance abuse be divided sonality disorder have high rates of drug use. Con- into groups with abuse that preceded the trauma versely, the dysfunctional lifestyle of an individual and those whose abuse followed the trauma. This actively involved with substance abuse frequently latter group is considered as a ‘‘self-medication involves lying, joblessness, and the inability to group,’’ and in this group treatment of the PTSD comply with social norms concerning issues such as is felt to be the primary goal. Following treatment child care, finances, and the legal system. This for the PTSD, it is believed that the substance makes disentangling these disorders difficult. If one abuse in this group will then decrease or end. In looks for evidence of conduct disturbance, particu- the former group, detoxification from the sub- larly during the late adolescence that predates the stance abuse and abstinence is felt to be the pri- substance abuse, then the diagnosis of antisocial mary goal, and that following this the PTSD personality disorder is much more reliable. The symptoms will improve. implication for this distinction involves improved ability to predict changes in the individual should SUBSTANCE ABUSE AND OTHER long-term abstinence be achieved. The abstinent ANXIETY DISORDERS antisocial will likely continue to demonstrate be- Alcohol and Anxiety. Individuals with anxi- havior problems in a variety of areas, whereas ety disorders (e.g., generalized anxiety disorder, someone with an intact personality would be expec- panic disorder, phobic disorders, obsessive-com- ted to have a better prognosis. pulsive disorder) find that alcohol provides tempo- Borderline Personality Disorder. Less is rary relief from some of their anxiety symptoms. known about borderline personality disorder and Large community studies of individuals with pho- substance abuse or alcoholism. Individuals with bias suggest over a twofold increase in alcoholism borderline personality disorder clearly have high risk. Panic disorder patients have rates of alcohol- rates of substance abuse, and the criteria published ism approaching 20 percent, and male relatives of in the DIAGNOSTIC AND STATISTICAL MANUAL OF individuals with panic disorder have a two to three MENTAL DISORDERS, 3rd edition, revised (DSM- times increased rate of alcoholism when compared III-R) (American Psychiatric Association, 1987) to controls, further suggesting a relationship be- for this personality disorder include self-damaging tween alcoholism and anxiety disorders. Another behavior—such as substance abuse—as one of the known fact is that anxiety symptoms are experi- five symptoms required to make the diagnosis. enced during withdrawal. Schuckit (1990), in a Dulit (1990) has suggested that drug abuse may be study of anxiety symptoms during withdrawal, an important factor in the development of this dis- evaluated 171 alcoholics for anxiety and panic order. symptoms. Nearly all subjects had at least one COMPLICATIONS: Mental Disorders 329 anxiety symptom during heavy drinking, or upon eating disorders who seekpsychiatric treatment, as abrupt discontinuation of drinking, but only 4 per- many as 35 percent have a significant substance- cent fulfilled DSM-III-R criteria for generalized abuse history. Alcoholism, particularly in bulimia anxiety disorder when three or more months of and bulimic anorectic patients, appears to be com- abstinence were achieved. mon. Substance abuse in eating disorders is gener- Anxiety and Substance Abuse. Panic attacks ally thought to convey a poor prognosis for recov- have been shown to be induced by psychostimu- ery. lants, particularly COCAINE. The rate of panic at- tacks among users of cocaine has been reported to SUBSTANCE ABUSE AND ATTENTION be as high as 64 percent. Anxiety symptoms during DEFICIT DISORDER the withdrawal phase from cocaine also increases the riskfor alcohol abuse and/or benzodiazepine Children with attention deficit hyperactivity dis- abuse. These substances are frequently used to ease order (ADHD) have been noted to be at riskfor the ‘‘crash’’ phase. development of alcoholism and cocaine abuse as they grow into adolescence and adulthood. Family studies of children with ADHD and alcoholism SUBSTANCE ABUSE have demonstrated higher rates of alcoholism in AND SCHIZOPHRENIA family members than that seen in the general popu- Only recently has the high prevalence of alco- lation. Goodwin (1975) compared previously hy- holism in schizophrenia been noted. Likewise, the peractive adult adoptees with and without alcohol- recognition of high rates of other substance abuse ism. As children, these alcoholics were hyperactive, in the schizophrenic population was not appreci- truant, shy, aggressive, disobedient, and friendless. ated until the 1980s. A review of published esti- In these adoptees, those with alcoholism clearly had mates of the prevalence of alcohol abuse in schizo- an excess of alcoholism in their biological parents. phrenia reported a range of 8.4 to 47 percent No alcoholism was found among the biological par- (Mueser, 1990). Stimulant abuse in this review ents of the nonalcoholic hyperactive adoptees. was reported between 4 and 15 percent. The ques- These findings suggest that in the case of alcohol- tion of whether substance abuse induces a chronic ism and hyperactivity, the riskfor alcoholism schizophrenic-like psychosis even after the drugs comes from a genetic basis and not necessarily from are stopped is still open to debate. It is generally just having ADHD. held, however, that individuals who develop schiz- It has been estimated that 15 to 20 percent of ophrenia coupled with drug abuse would most cocaine users might also be afflicted with ADHD. likely have developed schizophrenia regardless, Studies have been conducted using Ritalin to treat but the abuse may have caused an earlier onset. cocaine users suffering ADHD—indeed, one such The early drug use may represent efforts at self- study by the New YorkState Psychiatric Institute treatment. Treatment of the schizophrenic with showed a 66 percent drop of ADHD symptoms and drug abuse presents a major clinical challenge. a decline of 75 percent in the craving of cocaine Such patients tend to be disruptive, prone to fre- (New YorkState Psychiatric Institute (1996). De- quent relapse of psychosis and drug use, and do spite those encouraging statistics, counseling and not easily fit into conventional treatment settings. other treatment methods are obviously still very Optimal care is thus difficult, and improved strate- much in need. gies for treatment are needed. SUBSTANCE ABUSE AND SUBSTANCE ABUSE AND OTHER COMPLICATIONS EATING DISORDERS Suicide. Alcoholics have a 15 percent lifetime Individuals with eating disorders (ANOREXIA and riskof S UICIDE. Alcohol is involved in at least 50 BULIMIA) abuse a number of drugs and alcohol. percent of successful suicides. Substance abusers During the course of their lives, they often use are also recognized to have an elevated riskof agents to reduce weight, such as laxatives, emetics, suicide, and it has been reported that 70 percent of diet pills, and diuretics. Of those individuals with suicides in young people are associated with sub- 330 COMPLICATIONS: Mental Disorders

stance abuse. Studies of successful suicides demon- BIBLIOGRAPHY strate the ambivalent nature of this act. Alcohol or AMERICAN PSYCHIATRIC ASSOCIATION. (1987). Diagnostic substance abuse may act as the weight that tips the and Statistical Manual of Mental Disorders-3rd ed.- scale toward suicide, or may induce the psychiatric rev. Washington, DC: Author. symptoms that elicit the suicidal urge. Regardless, BROWN, S. A., & SCHUCKIT, M. A. (1988). Changes in substance abuse is among the strongest riskfactors depression among abstinent alcoholics. Journal of the for suicide. Study of Alcohol, 49, 412–417. Organic Brain Syndromes. A variety of or- COOK, B. L., ET AL. (1991). Depression and previous ganic brain syndromes, including DELIRIUM and alcoholism in the elderly. British Journal of Psychia- dementia are associated with acute and chronic use try, 158, 72–75. of drugs and alcohol. Abrupt WITHDRAWAL from DULIT, R. A., ET AL. (1990). Substance abuse in border- alcohol or sedative-hypnotic drugs can cause with- line personality disorder. Psychiatry, 147, 1002– drawal delirium (DTs). These organic effects from 1004. DUNNER, D. L., HENSEL, B. M., & FIEVE, R. R. (1979). drug use must be carefully separated from the psy- Bipolar illness: Factors in drinking behavior. Ameri- chiatric conditions discussed earlier, and from neu- can Journal of Psychiatry, 136, 583–585. rologic conditions which can overlap their symp- GOLD, M. S., & SLABY, A. E. (1991). Dual diagnosis in toms. The impact of chronic drug use and substance abuse. New York: Marcel Dekker. personality is an area in need of further study. GOODWIN, D., ET AL. (1975). Alcoholism and the hyper- Acquired Immunodeficiency Syndrome active child syndrome. Journal of Nervous and Mental (AIDS). Intravenous drug use, needle sharing, Disorders, 160, 349–353. and high-risksexual practices among drug users JELINEK, J. M., & WILLIAMS, T. (1984). Post-traumatic are major riskfactors for AIDS. Psychiatric mani- stress disorder and substance abuse in Vietnam com- festations of AIDS may present in a number of bat veterans: Treatment problems, strategies and rec- ways, including mood disorders, dementia, psycho- ommendations. Journal of Substance Abuse Treat- sis, and behavioral impairment. Suicide riskamong ment, 1, 87–97. AIDS victims is high. In evaluating the substance KEELER, M. H., TAYLOR, C. I., & MILLER, W. C. (1979). abuser with neuropsychiatric changes, HIV testing Are all recently detoxified alcoholics depressed? American Journal of Psychiatry, 136, 586–588. should be completed and treatment for AIDS LARSON, J. (1998). Alcoholism: The Biochemical Con- should incorporate educating the patient about nection. Women in Engineering and Science News. these risks. LISKOW, B., POWELL, B. J., & NICKEL, E. (1991). Diag- nostic subgroups of antisocial alcoholics: Outcome at SUMMARY 1 year. Comparative Psychiatry, 31, 549–556. LOWINSON, J. H., ET AL. (1992). Substance abuse: A Substance abuse of all kinds and many psychiat- comprehensive textbook, 2nd ed. Baltimore, MD: Wil- ric disorders have been shown very conclusively to liams & Wilkins. be associated one with the other. The combination MORRISON, J. R. (1974). Bipolar affective disorder and of these disorders, as generally agreed, make such alcoholism. American Journal of Psychiatry, 131, individuals more difficult to treat from the stand- 1130–1133. point of both their psychiatric and their substance- MUESER, K. T., YARNOLD, P. R., & LEVINSON,D.F. abuse problems. Research is being conducted to (1990). Prevalence of substance abuse in schizophre- determine better ways of understanding the origins nia: Demographic and clinical correlates. Schizophre- of these associations. nia Bulletin, 16, 31–56. NEW YORK STATE PSYCHIATRIC INSTITUTE. (1996). Who Gets Addicted to Cocaine and Why? New York Psychi- (SEE ALSO: Conduct Disorder; Research: Mood and atric Institute Newsletter, 15. Drugs; Social Costs of Alcohol and Drug Abuse; REGIER, D. A., ET AL. (1990). Comorbidity of mental Structured Clinical Interview for DSM-III-R; Vul- disorders and other drug abuse: Results from the nerability) epidemiology catchment area (ECA) study. Journal of COMPLICATIONS: Neurological 331

the American Medical Association, 264(19), 2511– ALCOHOL: ACUTE EFFECTS 2518. BLOOD ALCOHOL CONCENTRATIONS (BAC) above ROUNSAVILLE, B. J., ET AL. (1987). Psychopathology as a the legal limit (0.08%) typically impair the opera- predictor of treatment outcome in alcoholics. Archives tion of complex machinery, as should be obvious of General Psychiatry, 44, 505–513. from public information and programs regarding SCHUCKIT, M. A. (1985). The clinical implications of pri- DRIVING while intoxicated. The signs of intoxica- mary diagnostic groups among alcoholics. Archives of tion, such as impaired judgment, slurred speech, General Psychiatry, 42, 1043–1049. and motor incoordination, are due to CNS depres- SCHUCKIT, M. A., IRWIN, M., & BROWN, S. A. (1990). The sion. Sensitive testing also reveals impairments in a history of anxiety symptoms among 171 primary al- number of specific cognitive operations, including coholics. Journal of the Study of Alcohol, 51, 24–51. selective attention, decision making, and hand-eye WINOKUR, G., RIMMER, J., & REICH, T. (1971). Alcohol- coordination, at lower blood alcohol concentra- ism IV: Is there more than one type of alcoholism? tions. Intoxication can increase risk-taking, aggres- British Journal of Psychiatry, 118, 525–531. sive, or dangerous behaviors because of diminished inhibitory control coupled with the person’s inabil- BRIAN L. COOK ity to evaluate the consequences of his or her ac- GEORGE WINOKUR tions. Therefore, it is not surprising that intoxica- REVISED BY DANIEL P. HAYES tion is frequently associated with traumatic injuries, including traumatic brain injuries, and is a common factor in fatal motor vehicle accidents and Neurological Alcohol (ethanol, also called violent incidents. ethyl alcohol) and other psychotropic drugs are A binge of heavy drinking can lead to MEMORY taken because of their ability to affect the central lapses or alcoholic blackouts, in which the individ- nervous system (CNS) and thereby alter mental ual is unable to recollect events that tookplace functioning. However, the possible reinforcing ef- during the period of intoxication even though he or she may have seemed ‘‘normal’’ to observers at the fects are offset by a cost: it is now well established time. Although the pathogenesis of these episodes is that CNS structural and functional integrity can be not yet defined, it appears that the mechanisms compromised by heavy or prolonged intake of underlying memory storage are temporarily many abused substances. This article addresses the disrupted during the blackout. Less severe difficul- effects of alcohol and other psychotropic drugs on ties with storage of new information can be seen nervous system structure and function. It will even when drinking is below the legal limit of intox- briefly review and synthesize information from ication. studies using various methods and technologies, Very high doses of alcohol depress conscious- including neurological examination, postmortem ness, leading to sleepiness, coma, respiratory de- examination of the brain, neuropsychological tests, pression, and death. The acute effects outlined here and neuroradiological techniques such as magnetic are clearly dose-dependent and are due to depres- resonance imaging (MRI), which shows the living sion of successively more regions of the nervous brain in fine detail, and positron-emission tomog- system with the increasing dose. raphy (PET), which indicates the level of function- ing of particular brain regions while the individual ALCOHOL: TOLERANCE is at rest or is engaged in a cognitive task. Both AND WITHDRAWAL acute and chronic effects of substances on brain Dependence on alcohol, and many other drugs, and behavior and the reversibility of drug-related is characterized by TOLERANCE and WITHDRAWAL. impairments are addressed. Because most of the Tolerance refers to the fact that with chronic use, relevant research on this issue has been conducted increasing doses of the drug are needed to achieve with ALCOHOL, more limited information is pre- the same behavioral effects. Thus, the degree of sented regarding the effects of other drugs of abuse acute impairment outlined above will vary with the on CNS. individual’s tolerance. People who have developed 332 COMPLICATIONS: Neurological alcohol tolerance also show cross-tolerance to other drinking more than thirty standard drinks (each CNS depressants, including general anesthetics. containing 13.6 grams of ethanol) per weekand at Loss of tolerance appears to occur in the ELDERLY least a five-year history of such use. and in alcoholics who have developed organic brain Victor and his colleagues (1989) have made the impairments due to alcohol use or other factors, definitive studies of the best-known disorder asso- such as head injury. However, tolerance does not ciated with alcohol abuse, the Wernicke-Korsakoff appear to develop to the direct neurotoxic effects of syndrome (WKS). There are three major symptoms long-term alcohol abuse. in the acute phase, known as Wernicke’s encepha- Following heavy drinking, many alcoholics ex- lopathy: abnormalities of eye movements; ataxia; perience a tremulous-hyperexcitable withdrawal and a confusional state that includes poor respon- syndrome, which is characterized by postural sivity, disorientation, and deficits in attention and tremor, agitation, confusion, and ataxia. General- memory. The disorder has been demonstrated to be ized seizures can also appear in withdrawal, typi- caused by a thiamin (Vitamin B1) deficiency that is cally 10 to 48 hours after cessation of drinking. It probably due to decreased B1 in the diet and de- has been hypothesized that long-term alcohol use creased absorption or utilization of B1 induced by may establish an epileptogenic state of the brain alcohol-related gastrointestinal disorders or other that becomes manifest upon alcohol withdrawal. mechanisms. These symptoms usually improve For this reason, it has become common practice in substantially when the patient is immediately many treatment facilities to guard against with- treated with thiamin. The chronic phase, known as drawal seizures in patients with known susceptibil- Korsakoff’s syndrome, is marked by a profound ity by giving prophylactic anticonvulsants or tran- memory deficit that includes both retrograde am- quilizers. Long-term treatment is usually not nesia (an inability to recall information from the indicated because the withdrawal syndrome is self- remote past) and anterograde amnesia (an inability limiting. In some patients, the acute withdrawal to learn and retain new information). It should be syndrome can progress to DELIRIUM TREMENS noted that there is frequently no prior Wernicke’s (DTs). This more severe form of withdrawal is encephalopathy recognized in Korsakoff patients. characterized by delirium, HALLUCINATIONS, and a Although there may be difficulties in other cogni- hyperautonomic state manifested by sweating and tive capacities, the levels of general intellectual tachycardia. DTs are associated with approxi- functioning, verbal abilities, and many other spe- mately 15 percent mortality rate, possibly due to cific skills remain intact in these patients. Although cardiac toxicity caused by the hyperadrenergic partial or complete recovery from the amnesia is state. Treatment of the disorder involves rehydra- seen in some individuals, at least 50 percent of tion and haloperidol (a neuroleptic drug) as well as cases show slight or no recovery. medication to control withdrawal. Postmortem analysis indicates that the lesions in Korsakoff patients generally involve diencephalic areas known to be important to memory function- ALCOHOL: CHRONIC EFFECTS ing. These include the mammillary bodies and the Alcohol has direct toxic effects on neurons and, dorsomedial nuclei of the thalamus. Neuronal loss in association with other medical consequences of is also prominent in other areas surrounding the alcohol abuse, such as liver damage and inadequate cerebral ventricles, such as the periaqueductal gray nutrition, can result in significant and lasting cog- of the mesencephalon, hippocampus, and basal nitive deficits. There is no clear indication of the forebrain. Modern imaging techniques that permit level of consumption that might put one at riskfor in vivo examination of the neuropathology of WKS such consequences, but ‘‘safe’’ drinking guidelines are consistent with the neuropathological data. of no more than twelve to fourteen drinks per week Analysis of MRI scans reveals small or absent probably represent a minimum level. Although mammillary bodies, as well as more general cere- there are no precise data on the incidence of neuro- bral atrophy. logical or cognitive impairment in alcohol abusers, Estimates of the prevalence of WKS, based on it is estimated that 50 to 70 percent of individuals hospital records, suggest that it is relatively rare. seeking treatment may present with some form of However, it appears that the diagnosis is often neurocognitive impairment. Most of these report missed during life, despite its seemingly dramatic COMPLICATIONS: Neurological 333 presentation. Autopsy series by Harper and his Many investigators recognize a more severe and colleagues (1987) have indicated that less than 20 global impairment in mental functioning that is percent of patients with the characteristic brain different from both the ‘‘typical’’ picture of chronic lesions of WKS had been correctly identified ante- alcoholic brain dysfunction and from WKS. This is mortem. generally referred to as alcoholic dementia, to un- A second profile of alcohol-related brain dys- derscore the severe and global nature of the cogni- function, which is much more common than WKS, tive deficits. However, it is not known whether has been described by many investigators since the alcoholic dementia exists as a separate pathological 1970s. These individuals may not show overt neu- entity, which represents the end point of chronic rological symptoms, but selective impairments are alcoholism in some older individuals, or is an ex- seen in cognitive functions when sensitive neuro- tension of WKS to other brain regions and cognitive psychological tests are used. Extensive reviews of domains. Some research at the end of the 1990s these effects are available in a bookedited by Par- suggested that alcoholic dementia may be a more sons, Butters, and Nathan (1987). The most promi- severe form of WKS. nent deficits are in complex visual-motor functions, There is no clear set of clinical diagnostic or particularly when speed of response is important. neuropathological criteria for alcoholic dementia. Thus, visual search, manual tracking, symbol However, a relatively high prevalence of alcohol- copying, and other psychomotor functions are related dementias among residents of several long- marked by imprecision and slowness. Problem- term care institutions in northern Ontario were solving abilities, such as abstraction, hypothesis found. In that study, 24 percent of cognitively im- generation, and mental flexibility are also deficient. paired residents fit this diagnostic profile, a figure Mild deficits are apparent in new learning and substantially higher than had been reported previ- memory, especially for nonverbal material. The ously. Given that the proportion of elderly individ- memory difficulties are increased when the task uals in North America is growing, we might expect requires the patient to use strategies for organizing an increase in research activity associated with this and retrieving the information. disorder in years to come. Studies of BRAIN STRUCTURES in these chronic alcoholics reveal apparent atrophy of the cortex, ALCOHOL: RECOVERY OF FUNCTION with enlargement of ventricles and sulci. For exam- ple, autopsy studies demonstrate that cerebral atro- When alcoholics stop drinking, their presenting phy and low brain weight are associated with alco- neurocognitive impairment can often show marked holism, and some studies even show loss of cerebral recovery over weeks to months with maintained tissue in ‘‘moderate’’ drinkers. Although such dam- abstinence. Substantial recovery has been demon- age may be relatively widespread, several lines of strated in only a minority of patients with WKS, research implicate a predominant involvement of given appropriate thiamin treatment and absti- frontal cortical regions in alcohol-related cerebral nence from alcohol use. In 1978, Carlen and col- dysfunction. Autopsy studies show significant re- leagues were the first to report reversibility in mea- duction in neuronal counts in the superior frontal sured cerebral atrophy on computerized cortex but not the motor cortex. Research with MRI tomography (CT) scans in chronic alcoholics after and PET scanning in vivo reveals a consistent de- several months of abstinence. This reversibility has crease in brain volume and functioning at rest in been replicated by several other research groups. frontal regions, although most studies have impli- Many studies have also reported recovery in the cated other brain areas as well. This evidence is cognitive performance deficits for a majority of pa- generally consistent with studies using neuropsy- tients, with improvements depending critically on chological techniques, which also suggest impair- abstinence. In general, the more novel, complex, ments through tests sensitive to frontal-lobe dys- and rapid the information-processing requirements function. However, further research is necessary to of the task, the longer the time for recovery to refine and correlate these different sources of evi- normal levels of function. As of the mid-1990s, dence before strong conclusions can be made re- only modest correlations between the measures of garding selective effects of alcohol on localized cor- brain atrophy and cognitive functioning had been tical regions. shown. The mechanisms underlying the pathogen- 334 COMPLICATIONS: Neurological esis and reversibility of cerebral atrophy remained can be associated with adverse behavioral changes, under study. particularly in older individuals. In acute adminis- tration, they can cause impaired memory, slowing ALCOHOL: SUMMARY AND of reaction time and decision making, and FURTHER QUESTIONS disrupted attention. These effects are similar to those produced by drinking alcohol, and the effects Chronic alcohol ingestion has potentially devas- of these two drugs taken together can be additive. tating effects on neurocognitive functioning. Im- Although patients appear to develop some toler- pairments associated with alcohol use range from ance to the sedating effects of benzodiazepines transient deficits observed in acute intoxication to when they are administered for long periods, new potentially permanent and severe disorders, such as evidence suggests that memory and cognitive im- alcoholic dementia. There are also various other pairments can remain or even increase with chronic neurological conditions associated with chronic al- administration. At present, it does not appear that cohol abuse. Some of these are relatively common these drugs have direct toxic effects on brain struc- in alcoholics, including cerebellar degeneration, tures, so that their effects on behavior are likely peripheral neuropathies, movement disorders, and mediated by a temporary and reversible pharmaco- hepatic encephalopathy. Alcohol-related condi- logical blocking of normal routes of neural infor- tions that are relatively rare include central pontine mation processing. myelinolysis, pellegra encephalopathy, and Marchiafava Bignami disease. Although some im- CANNABIS portant relationships between alcohol misuse and neurocognitive functioning have been discerned Cannabis (MARIJUANA) intoxication leads to since the 1970s, many important questions remain. widespread changes in cognitive functioning, in- Outstanding issues include the prevalence of im- cluding disrupted attention, memory, and percep- pairment in the alcohol-dependent population; in- tual-motor abilities. For example, individuals may dividual riskfactors that mediate the expression of be unable to remember information learned while deficits; the relation between levels and patterns of intoxicated, even when tested in drug-free condi- consumption and resulting impairments; the rate tions. Like alcohol, there is also impairment in the and extent of recovery of function and treatments complex visual, motor, and decision-making skills that may enhance recovery; precise specification of needed to operate complex machinery. Numerous the profiles of cognitive impairment in different reports from the 1970s indicated a lackof enduring clinical syndromes and their relation to measures of cognitive impairment associated with chronic can- brain damage; and implications of cognitive dys- nabis use. However, later workreported poor function for prevention and treatment of substance learning and memory in newly abstinent users, abuse. with recovery of function documented over a six- weekperiod. Although further research is needed, OTHER CNS DEPRESSANTS there is clearly not the same degree of brain and behavioral dysfunction that has been associated Several other classes of drugs act as depressants with alcohol. on the central nervous system. The profile of im- pairment with barbiturate intoxication largely re- OPIOIDS sembles the acute effects of alcohol. Because of the relatively high abuse potential and severe with- Primarily used for therapeutic management of drawal associated with these drugs, the severe pain, the OPIOIDS can have a profound BENZODIAZEPINES have largely displaced BARBITU- mood-altering euphoric effect that can lead to de- RATES in prescriptions for SEDATIVE-HYPNOTIC pendence. Administration of opioids (HEROIN, drugs. Currently the most prescribed class of MORPHINE, or Demerol) to relatively naive users PSYCHOACTIVE drugs in Western industrialized leads to a generalized depression of cognition that countries, they are typically used for muscle relaxa- can be referred to as ‘‘mental clouding.’’ Impair- tion, sedation, and reduction of ANXIETY. It has ments in perception, learning and memory, and become clear that benzodiazepines (e.g., Valium) reasoning accompany the drowsiness and mood COMPLICATIONS: Neurological 335 changes induced by the drug. Generally, tolerance setting. These chemicals are unique in their ability develops to the depression in mentation with to cause damage to the CNS after fairly limited chronic administration. Thus, there appears to be exposure. Clinical observation of acute effects of little long-term performance or brain dysfunction these drugs shows that users experience euphoria, associated with this drug class. dizziness, and ‘‘drunkenness,’’ which are usually accompanied by fatigue, muscle weakness, and im- AMPHETAMINES AND COCAINE pairments in concentration, memory, and rea- soning. This can progress through loss of self-con- AMPHETAMINES and COCAINE act as CNS stimu- trol, disorientation, and coma. Chronic lants, which means that they generally increase neuropsychological impairments are seen in a vari- arousal and psychomotor activity. As might be ex- ety of domains, including motor coordination, pected, acute administration can improve perform- memory, and attention, and can resemble the ance on many tasks, particularly when vigilance or symptoms of dementia. Neurological impairments speed of response is important. It can also reverse include diminished sensitivity to pain and touch, the effects of fatigue, which suggests that atten- shrinkage of the cortex, and lesions in the cerebel- tional resources are enhanced. However, this in- lum. Although there is not yet sufficient evidence to crease in arousal can be coupled with a dysfunction be conclusive, it is likely that much of the damage in higher-order control processes used to monitor and disruption to function are permanent. or inhibit ongoing behavior, such that there is a corresponding increase in errors, impulsivity, and SUMMARY hyperactivity. Neurological consequences of a sin- gle dose of cocaine can include intracerebral hem- Although much is known about the effects of orrhages, seizures, and strokes. These complica- drugs on the brain and behavior, many important tions appear in only a small proportion of cocaine questions remain to be answered. Even given the users, but the factors that place one at riskare not intensive research on alcohol, there is still lackof yet known. Although there is little research on the consensus regarding the durability of impairments, existence or nature of cumulative effects of chronic the riskfactors that determine individual suscepti- stimulant use, some recent evidence indicates mild bility, and the relationship between consumption impairments in memory and attention. A few stud- and brain damage. In particular, the separation of ies have documented the recovery of function with any neurocognitive dysfunction that may precede abstinence and a correlation between the level of drug abuse from that which is consequent to chron- consumption and impairment, suggesting a direct ic drug use remains an important issue that is diffi- relationship between drug use and behavioral defi- cult to address without prospective studies. Re- ciency. Convergent evidence for a transient disrup- search attempting to discover the relationships tion in brain function is provided by the workof among a given drug’s effects on various indices of Volkow and colleagues (1988). Their PET studies brain integrity is also a relatively new area and indicated decreased blood flow in the prefrontal requires further elaboration. For example, only a cortex of cocaine users and an apparent return to few studies attempting to relate brain atrophy in normal levels with abstinence. In animal models, specific regions to particular cognitive impairments high doses of amphetamines, particularly in chronic alcoholics have shown significant and METHAMPETAMINE, can produce damage to seroto- reliable correlations. It is also increasingly common nergic and dopaminergic neurons. to find that individuals will use and abuse several different drugs, yet research on the interacting ef- fects of various drug combinations is in its infancy. SOLVENTS In the final analysis, much of the worksummarized Solvents are chemical compounds, such as ben- here prepares us to askbetter questions regarding zene and toluene, typically used to dissolve oils or the consequences of drug use on neurocognitive resins. Although a small proportion of young peo- functioning. ple voluntarily abuse or inhale these substances (e.g., sniffing glue or gasoline), many more individ- (SEE ALSO: Accidents and Injuries from Alcohol; uals are exposed to them as workers in an industrial Imaging Techniques) 336 COMPLICATIONS: Nutritional

BIBLIOGRAPHY Nutritional This entry discusses nutritional complications in alcoholics, smokers, and abusers CARLEN, P. L., ET AL. (1978). Reversible cerebral atro- of other addictive drugs. phy in recently abstinent chronic alcoholics measured by computed tomography scans. Science, 200, 1076– 1078. ALCOHOL CHESHER, G. B. (1989). Understanding the opioid anal- Alcoholic beverages were long used as a source gesics and their effects on skills performance. Alcohol, of nourishment for the sick, as a means of promot- Drugs and Driving, 5, 111–138. ing appetite, and as a treatment for pain and infec- EMSLEY, R., ET AL. (1996). Magnetic resonance imaging tion—all before other means and medications were in alcoholic Korsakoff’s syndrome: evidence for an developed for these situations. Traditionally, wine association with alcoholic dementia. Alcohol, 5, 479– and BEER were foods, used ceremonially and as 486. part of ceremonial healing for the ailing (and preg- FORNAZZARI, L., WILKINSON, D. A., KAPUR, B. M., & nant) who refused or could not tolerate a solid diet. CARLEN, P. L. (1983). Cerebellar, cortical, and func- Eventually, alcoholic beverages moved from purely tional impairment in toluene abusers. Acta Neurolog- ceremonial occasions to a reason for social occa- ica Scandinavica, 67, 319–329. sions in some cultures, among some classes, and for HARPER, C. G., KRIL, J., & DALY, J. (1987). Are we drink- some individuals. Alcoholic beverages have a habit- ing our neurons away? British Medical Journal, 294, forming or addictive element for some people that 534–536. may become life threatening to fatal. HARTMAN, D. E. (1988). Neuropsychological toxicology: Use of Alcohol in Medicine: Recent History. Identification and assessment of human neurotoxic In 1900, Atwater and Benedict reported on their syndromes. New York: Pergamon. experiments at Wesleyan University, which at- LISHMAN, W. A. (1990). Alcohol and the brain. British tempted to define whether ALCOHOL could actually Journal of Psychiatry, 156, 635–644. be considered a food; they showed that alcohol is MODY, C. K., ET AL. (1988). Neurologic complications of oxidized in the body and that the energy so derived cocaine abuse. Neurology, 28, 1189–1193. can be used as a fuel for metabolic purposes. Before O’MALLEY, S., ADAMSE, M., HEATON,R.K.,&GAWIN, that, F. E. Anstie (1877) had written his treatise F. H. (1992). Neuropsychological impairment in On the Uses of Wine in Health and Disease, and, in chronic cocaine abusers. American Journal of Drug fact, the long tradition of using alcoholic beverages and Alcohol Abuse, 18, 131–144. within the medical profession persisted into the PARSONS, O. A., BUTTERS, N., & NATHAN, P. E. (1987). twentieth century. Sir Robert Hutchison, a noted Neuropsychology of alcoholism: Implications for diag- British physician, wrote in 1905 that there was nosis and treatment. New York: Guilford Press. reason to believe (not that there was evidence) that THOMAS, P. K. (1986). Alcohol and disease: Central ner- alcohol increases disease resistance. Alcohol was vous system. Acta Medica Scandinavica (suppl.), actually used to treat serious infectious disease, 703, 251–264. such as typhus, into the late 1920s—until it was VICTOR, M., ADAMS,R.D.,&COLLINS, G. H. (1989). The shown that patients treated with milkand beef tea Wernicke-Korsakoff syndrome and related neurologi- had greater survival rates. cal disorders due to alcoholism and malnutrition (2nd The use of alcohol to treat such disease was ed.). Philadelphia: F. A. Davis. linked to a supposition that debility would some- VOLKOW, N. D., ET AL. (1988). Cerebral blood flow in how be overcome and strength regained. Other chronic cocaine users: A study with positron emission than this, the major indication for alcohol was for tomography. British Journal of Psychiatry, 152, 641– analgesia (pain suppression). The basic analgesic 648. properties of alcohol and alcoholic beverages were WOODS, J. H., KATZ, J. L., & WINGER, G. (1992). Benzo- utilized for hundreds of years in the management of diazepines: Use, abuse and consequences. Pharmaco- the injured and those requiring surgery. For exam- logical Reviews, 44, 151–347. ple, prior to the time of anesthetics, patients were PETER L. CARLEN offered brandy to reduce the agonizing pain of am- MARY PAT MCANDREWS putations. Decline and cessation of these medical REVISED BY MARY CARVLIN uses of alcohol came about with the development of COMPLICATIONS: Nutritional 337 inhalation anesthetics and more efficient analge- Alcohol and Malnutrition. Diet-related sics. causes of malnutrition in alcoholics include low di- Alcohol, Obesity, and Wasting. In nonalco- etary intake of calories and nutrients—because of holics, calories from alcohol are utilized as effi- poor appetite, inebriation, and diversion of food ciently as calories from carbohydrates or fats (and dollars into support of the alcohol habit. In addi- alcohol provides more calories per gram than does tion, malnutrition may be caused by impaired ab- carbohydrate). Indeed, while carbohydrate yields 4 sorption of nutrients, poor nutrient utilization, and kilocalories per gram (kcal/gm) on combustion, increased nutrient losses in body wastes. In 1940, it when alcohol is combusted in a bomb calorimeter it was suggested that ALCOHOLISM is the major cause yields 7.1 kcal/gm. This suggests that when alcohol of malnutrition in the industrialized world (Jolliffe, is consumed in addition to a diet that maintains 1940). Malnutrition in alcoholics may be caused by body weight, weight gain occurs. Fictitious charac- impaired absorption of nutrients because of the ters such as Shakespeare’s Sir John Falstaff provide reduced absorptive capacity of the alcohol-dam- evidence that obesity was already in the 1600s aged gut. Nutrients that are poorly absorbed by considered a characteristic of heavy drinkers. alcoholics include the B vitamins—folic acid, thi-

The realization came about gradually that in amin (Vitamin B1), and riboflavin (Vitamin B2). fact chronic heavy drinking leads not to obesity but Folic acid deficiency, which causes an anemia, is to weight loss and an inability to sustain adequate particularly common in heavy drinkers. Multiple nutritional status. Wasted alcoholics were first por- nutritional deficiencies, including deficiencies of trayed by artists such as William Hogarth (1697– water and fat-soluble vitamins, are also common in 1764) who were intent on showing both the social those alcoholics who have pancreatic and liver dis- and medical evils of drinking gin—a recent import ease. Chronic alcoholic pancreatitis (inflammation from Holland that became a fad. All ages and of the pancreas) develops commonly in people who classes indulged in the new drinkat all hours of the consume 150 grams or more of alcohol per day for day and night. In eighteenth and nineteenth cen- at least ten years and at the same time eat a high-fat tury England, when artists were portraying the diet. The digestive functions of the pancreas be- physical deterioration associated with heavy gin come impaired, and therefore food is not broken drinking, it was assumed that drinking eventually down into nutrients that can be absorbed. This type led to wasting only because the drunkard was dis- of pancreatitis is a major cause of malabsorption of interested in food. This idea persisted into the nutrients in alcoholics. Alcoholic cirrhosis is a con- twentieth century. By the 1940s, it was also well dition in which liver cells that are responsible for recognized that chronic alcoholics are the conversion of nutrients to active forms are re- malnourished because of impaired utilization of placed by fibrous tissue. Cirrhosis develops slowly nutrients. in heavy drinkers and is a special risk in those who It is well-known today that, whereas obesity consume about 35 percent or more of their total may occur in heavy eaters who consume alcohol, caloric intake as alcohol. Cirrhosis is the chief cause chronic alcoholics are undernourished. Further- of impaired nutrient utilization (Morgan, 1982); more, studies have shown that long-term, heavy however, cirrhosis is caused not by a nutritional consumption of alcohol in addition to food is not deficiency but by the toxic effects of alcohol on the associated with the gain in body weight that would liver (Lieber, 1988). be expected from the calorie intake (Lieber, 1991). Mineral and trace-element deficiencies, particu- In addition, if dietary carbohydrate is replaced by larly zinc deficiency, are common in alcoholics. alcohol, weight loss occurs (as in the so-called Contributory causes are low intake and increased Drinking Man’s Diet of the 1960s and 1970s). This losses in the urine. energy deficit has been attributed to induction of Alcohol, Nutrition, and Brain Damage. the system that metabolizes alcohol and at the same Alcoholics are at riskfor brain damage when they time uses chemical energy and generates heat. Lie- go on drinking sprees without food. Evidence exists ber, in reviewing current knowledge of the ques- for this condition only in Caucasians who are ge- tion, notes that this does not explain the fact that netically predisposed. An acute confusional state there is little or no weight deficit when alcohol is may occur, called Wernicke’s encephalopathy; this consumed with a very low-fat diet. condition can be rapidly reversed if the patient is 338 COMPLICATIONS: Nutritional given massive doses of thiamin, intravenously, leading questions, they provide answers that the within a period of forty-eight hours from the onset question indicates are correct or ideal. They may of the symptoms. If this acute condition is not provide the questioner with an account of a make- treated with thiamin, a chronic state of irreversible believe diet, or they exaggerate the amounts of food brain damage develops, in which there is moderate they have eaten. These responses, which are worth- to severe dementia (Victor et al., 1957). less for the purpose of assessing the amount of Alcohol and Heart Disease. Through the calories consumed from food or for assessing the 1990s, evidence indicated that while moderate nutrients consumed, are given by alcoholics who drinking may reduce the risk of heart disease, alco- may not remember what was eaten and also be- hol abuse is associated with an increased riskof cause they may want to please the dietitian, physi- heart disease. Alcohol has the effect of increasing cian, or nurse seeking information. Not only do blood (plasma) levels of high-density lipoproteins alcoholics confabulate, they may also exaggerate (HDL)—and elevation of these blood lipids is asso- the amount they eat, reporting what is served to ciated with a lower riskof heart disease. In a British them rather than what was consumed. (This is also study (Razay et al., 1992), it was shown that the type of over-reporting of food intake frequently women consuming a moderate amount of alcohol found in people consuming other drugs that sup- (1–20 gm/day) have lower fat (triglyceride) levels press appetite.) in their blood and higher HDL levels. The authors The presence of malnutrition is assessed in alco- consider this strong evidence for supporting a lower holics (as well as nonalcoholics) by using anthropo- riskof heart disease. It is important to note that in metric (body) measurements—including weight- this study the women who were the moderate for-height measurements, calculation of the drinkers were slimmer than the non-drinking body—mass index (the weight/height squared), group. Lower body weight, found in this study and the circumference of the upper arm and the among the moderate drinkers, is also a known fac- thickness of the fat on the back of the arm. Alcohol- tor in reduced riskof heart disease. Heart disease in ics show muscle wasting in the upper arms, which alcoholics is due to the direct toxic effects of alcohol may suggest malnutrition even when body weight is on heart muscle (Brigden and Robinson, 1964). not markedly decreased. Although alcoholics with Alcohol and Osteoporosis. The formation of advanced liver disease are frequently wasted, new bone tissue is reduced in heavy drinkers, and weight loss may not register in numerical terms this causes a marked decrease in bone mass and because of fluid retention within the abdominal strength, leading to severe osteoporosis. Alcohol cavity (ascites). abuse is recognized as a riskfactor for osteoporosis Biochemical measurements are valuable for as- in both men and women. Because inebriation is also sessing the nutritional status of alcoholics. The associated with a high riskof falls, alcoholics who measurement of plasma albumin levels is particu- have osteoporosis are likely to sustain hip fractures. larly important—a value of less than 3.5 grams per Low intake of calcium in foods is an additional risk 100 milliliters of plasma indicates that protein-en- factor for osteoporosis in alcoholics (Bikle et al., ergy malnutrition exists. 1985). Nutrient Intolerance in Alcoholics with Methods for Assessing Nutritional Status in Liver Disease. Alcoholics with liver disease are Alcoholics. The methods required for the assess- very intolerant of high-protein diets. If high-pro- ment of caloric and nutrient intake in actively tein diets are provided during periods of nutritional drinking alcoholics include direct observation (sel- rehabilitation, such alcoholics may develop signs of dom feasible outside a treatment facility) and liver failure. Such alcoholics are also intolerant of so-called tray weigh back(also feasible only in the Vitamin A if this vitamin is taken in amounts that detoxification section of a rehabilitation facility, exceed 10,000 international units (IU) per day. hospital, or nursing home). The term tray weigh Continued intake of Vitamin A at a high daily back means weighing the food served to a patient, dosage level leads to further liver damage and may weighing the uneaten food, then computing intake also precipitate liver failure (Roe, 1992). from the difference. Nutritional Rehabilitation of Alcoholics. When alcoholics are asked to recount what they Nutritional rehabilitation of alcoholics can be car- have eaten, they tend to confabulate: When asked ried out successfully only when abstinence is en- COMPLICATIONS: Nutritional 339 forced or the alcoholic voluntarily stops drinking. If and duration of use/abuse, and the time in life the alcoholic has advanced liver disease or impair- when the drug or drugs are abused. NARCOTIC ment of pancreatic function such that digestion and drugs, such as HEROIN, impair appetite—so food absorption of nutrients is impaired, optimal nutri- intake is often diminished. If the drug is injected tional status cannot be maintained. The goal of intravenously, malnutrition may be secondary to nutritional rehabilitation is the treatment of exist- blood-borne bacterial infection or ACQUIRED IMMU- ing protein-energy malnutrition by increasing calo- NODEFICIENCY SYNDROME (AIDS). AMPHETAMINE ric intake from carbohydrates and the treatment of (‘‘speed’’) is the stimulant drug that has the most existing vitamin, mineral, and trace-element defi- inhibitory effect on appetite; if taken in large doses, ciencies. Appetite returns after alcohol withdrawal it also prevents sleep and stimulates activity— symptoms have abated; however, recovery of effi- therefore energy expenditure may be high and cient absorption of vitamins may not occur until weight loss is common. COCAINE and CRACK are ten to fourteen days after drinking ceases. Initially, also stimulants, they reduce appetite and may in intolerance of milkand other dairy foods is com- addition induce gastrointestinal symptoms such as mon during rehabilitation, because of lactose intol- nausea, which further lessen food intake (Brody et erance, and extreme caution has to be exercised in al., 1990). diet prescription because of protein intolerance Substance Abuse and Nutrition in Preg- (Roe, 1979). nancy. Relationships between substance abuse and impaired nutrition of the fetus and newborn have been summarized in a 1990 report by the TOBACCO National Academy of Sciences, Nutrition during Smoking diminishes appetite and on average, Pregnancy. smokers have lower body weights than nonsmok- Alcohol use during PREGNANCY has led to poor ers. Nevertheless, on average, smokers have greater birth outcomes. One condition is infants with spe- waist-to-hip circumference ratios than nonsmok- cific defects in neuronal and cranial development, ers. This suggests that smoking may have an effect designated FETAL ALCOHOL SYNDROME. Even the on body-fat distribution. Central (torso) adiposity, daily drinking of more than two glasses of wine or a reflected by this change in circumferential mea- daily mixed drinkhas led to fetal alcohol syn- surements, has been shown to worsen the riskof drome, but this condition is most common among cardiovascular disease. Cessation of smoking is the offspring of mothers who are chronic drinkers usually associated with moderate weight gain, or binge drinkers. caused at least in part by increased food intake Alcohol use during pregnancy is also known to (Troisi et al., 1991). be associated with prenatal and postnatal growth retardation. After birth, infants of heavy drinkers OTHER ADDICTIVE DRUGS may fail to suck, either because of the presence of withdrawal symptoms or because of cleft palate Multiple Substance Abuse and Nutrition. Drug (which may be part of the fetal alcohol syndrome). abuse includes the experimental use of various ad- Cigarette smoking during pregnancy can affect dictive drugs as well as chronic addiction to one or both maternal and fetal nutrition (Werler et al., more of these social drugs. The term addiction here 1985). Effects are due to increased metabolic rate refers both to PHYSICAL DEPENDENCE on the drug, in smokers and to toxic effects from tobacco that such that when the drug is withdrawn specific impair the mother’s utilization of certain nutrients, physical withdrawal symptoms occur, and to PSY- including iron, Vitamin C, folic acid (part of the B CHOLOGICAL DEPENDENCE on the drug—even with- complex), and zinc. Low-birthweight infants are out physical dependence. Alcohol has been called more likely to be the offspring of smokers than of the GATEWAY DRUG, because its early use is fre- nonsmokers—because their caloric intake is likely quently accompanied by and/or followed by use of to be less and because the transfer of nutrients from other drugs. the mother to the fetus via the placenta may be Effects of multiple-drug use on nutrition depend reduced in smokers. on the properties and toxic characteristics of the Cocaine and amphetamine use in pregnancy also drug most used, as well as on doses, frequencies, lead to increased numbers of low-birthweight in- 340 COMPLICATIONS: Route of Administration

fants. This may be caused by low food intake by the RAZAY, G., ET AL. (1992). Alcohol consumption and its mother, since these drugs reduce appetite. The risk relation to cardiovascular riskfactors in British of malnutrition in the newborns of women who women. British Medical Journal, 304, 80–83. have used cocaine during pregnancy is caused by ROE, D. A. (1992). Geriatric nutrition. Englewood Cliffs, the abnormal development of the infant’s small in- NJ: Prentice Hall. testine. These intestinal disorders in the infant may ROE, D. A. (1979). Alcohol and the diet. Westport, CT: be extremely severe and may be associated with AVI. enterocolitis or bowel perforation, which may be SPINNAZOLA, R., ET AL. (1992). Neonatal gastrointestinal fatal. If these infants survive, special methods of complications of maternal cocaine abuse. New York feeding via a vein are required. Although drugs State Journal of Medicine, 92, 22–23. other than cocaine are known to cause constriction TELSEY, A. M., MERRIT, A., & DIXON, S. D. (1988). Co- of blood vessels in the pregnant woman, none other caine exposure in a term neonate: Necrotizing en- than cocaine have been shown to produce these terocolitis as a complication. Clinical Pediatrics, 27, bowel disorders in infants (Telsey et al., 1988; 547–550. Spinazzola et al., 1992). TROISI, R. J., ET AL. (1991). Cigarette smoking, dietary intake and physical activity: Effects on body fat dis- (SEE ALSO: Alcohol History of; Complications: Liver tribution—the Normative Aging Study. American [Alcohol]; Overeating and Other Excessive Behav- Journal of Clinical Nutrition, 53, 1104–1111. iors) VICTOR, M., ADAMS,R.D.,&COLLINS, G. H. (1971). The Wernicke-Korsakoff syndrome: A clinical and patho- logical study of 245 patients, 82 with post-mortem BIBLIOGRAPHY examination. Philadelphia: F. A. Davis. ANSTIE, F. E. (1877). On the uses of wine in health and WERLER, M. M., POBER, B. R., & HOLMES, L. B. (1985). disease. London: Macmillan. Smoking and pregnancy. Teratology, 32, 473–481. ATWATER,W.O.,&BENEDICT, F. B. Experiments on the DAPHNE ROE metabolism of matter and energy in the human body. REVISED BY MARY CARVLIN (Bulletin No. 69). Washington, DC: U.S. Department of Agriculture. BIKLE,D.D.ET AL. (1985). Bone disease in alcohol Route of Administration The mode of abuse. Annals of Internal Medicine, 103, 42–48. drug administration—ingestion (by mouth), in- BRIGDEN, W., & ROBINSON, J. (1964). Alcoholic heart sufflation (snorting), inhalation (smoking), or in- disease. British Medical Journal, 2, 1283–1289. jection (intravenous, subcutaneous, or in- BRODY, S. L., SLOVIS, C. M., & WRENN, K. D. (1990). tramuscular)—can be responsible for a number of Cocaine-related medical problems: Consecutive series medical complications to alcohol and other drug of 233 patients. American Journal of Medicine, 88, use. In the following, these complications are dis- 325–330. cussed as direct and indirect results of the various HUTCHISON, R. (1905). Food and the principles of die- modes (route) of administration in the above order. tetics. New York: W. Wood. JOLLIFFE, N. (1940). The influence of alcohol on the adequacy of B vitamins in the American diet. Quar- COMPLICATIONS DUE TO INGESTION terly Journal of the Study of Alcohol, 1, 74–84. Ingestion is the way ALCOHOL, liquid medicines, LIEBER, C. S. (1991). Perspectives: Do alcohol calories pills and capsules are usually taken. Ingested drugs count? American Journal of Clinical Nutrition, 54, enter the gastrointestinal (GI) system, undergo 976–982. some digestive processing, and enter the blood- LIEBER, C. S. (1988). The influence of alcohol on nutri- stream through the walls of the stomach and intes- tional status. Nutrition Review, 241–251. tines. Most medical complications from drug inges- MORGAN, M. Y. (1982). Alcohol and nutrition. British tion are a result of the corrosive and irritant effects Medical Bulletin, 38, 21–29. of the drugs on the GI system. Alcohol and a variety NUTRITION DURING PREGNANCY. (1990). Washington, of medicines, including aspirin, can cause intense, DC: National Academy Press. localized irritation to the GI mucous membranes, COMPLICATIONS: Route of Administration 341 leading to ulceration and GI bleeding. Pharmaceu- Smoking. Smoke from any material will act as tical manufacturers attempt to decrease the danger an irritant to the lungs and bronchial system, even- of GI irritation by adding buffers to their pills and tually causing problems that can range from chron- capsules. Buffers are inert or nonactive ingredients ic bronchitis to emphysema or cancer of the mouth, that cushion the corrosive effect of the active ingre- throat and/or lungs. Both tobacco and marijuana dients. However, if drug users attempt to dissolve contain a number of tars and potential carcinogens pills intended for oral use and inject them, these (cancer-triggering substances) and both produce buffers will often cause problems, such as abscesses potentially toxic concentrations of carbon monox- or embolisms. ide. While it has been argued that tobacco is the worst danger because it is smoked very frequently, COMPLICATIONS DUE TO it has also been pointed out that the use mode of INSUFFLATION (SNORTING) marijuana is worse—holding the smoke in the lungs for a long time. The argument is moot, since Medical complications from insufflation (snort- both can produce profound damage. As a vasocon- ing) are usually caused by stimulant drugs, such as strictor, nicotine in tobacco promotes mouth ulcer- the AMPHETAMINES or COCAINE. These drugs are ation and gum disease. It can be said that people breathed into the nose and absorbed into the blood- who smoke lose their teeth, while those who don’t, stream through the capillaries in the nasal mucous don’t. Besides its irritant effects, the smoking of membrane. While these drugs cause a certain tobacco may also promote respiratory disease by amount of surface irritation, the major damage is weakening the immune system and by paralyzing caused by their action as vasoconstrictors—they the cilia (the tiny hairlike organs) in the lungs that reduce the diameter of blood vessels, and with push out foreign matter. chronic use can severely limit the delivery of blood Inhalation (Sniffing). The inhalation (sniff- through the capillaries to the inner membranes of ing) of volatile hydrocarbons, such as solvents, can the nose. The result of this is that tissue damaged cause death by asphyxiation or suffocation, can by contact with the drugs is unable to repair itself, impair judgment, and may produce irrational, and progressive necrosis (tissue death) follows. reckless behavior. Abnormalities also have oc- With chronic cocaine use, this process can result in curred in liver and kidney functions, and bone- actual holes through the septum (the dividing tis- marrow damage has occurred. These may be due to sue) between the nostrils. When tobacco is in- hypersensitivity to the substances or chronic heavy sufflated as snuff, the riskof cancer of the nasal exposure. Chromosome damage and blood abnor- passages is increased. malities have been reported, and solvents have been cited as a cause of gastritis, hepatitis, jaun- COMPLICATIONS DUE TO dice, and peptic ulcers—such effects are due more SMOKING (INHALING) to the actions of the drugs than to the route of administration. Chronic users have developed The fastest delivery of large amounts of drug slow-healing ulcers around the mouth and nose, directly to the brain is through smoking (inhaling). loss of appetite, weight loss, and nutritional disor- Drugs taken in this way go directly to the lungs and ders. Irreversible brain damage has been reported, are absorbed along with oxygen directly into the too. Many deaths attributed to solvent inhalants are blood heading for the brain. The two terms, smok- caused by suffocation when users pass out with the ing and inhaling, as a means of drug intake, are plastic bags containing the substance still glued to clearly differentiated when, on the one hand, mate- their noses and mouths. There is also a very real rial is actually burned and the resulting smoke is danger of death from acute solvent poisoning or taken into the lungs—as with TOBACCO or MARI- aerosol inhalation. The mere provision of adequate JUANA—or on the other hand, when fumes from ventilation and the avoidance of sticking one’s head volatile substances are inhaled, such as glue or in a plastic bag are by no means sufficient safe- gasoline. They may be confused or used inter- guards against aerosol dangers. changeably, however, when material is vaporized Other hazards may include freezing the larynx through heat and the vapor is inhaled—as with or other parts of the airway when refrigerants are cocaine FREEBASE (crack). inhaled, and potential spasms as these areas de- 342 COMPLICATIONS: Route of Administration frost. Blockage of the pulmonary membrane, ing, and the insertion of an eyedropper, tubing and through which oxygen is absorbed into the lungs, bulb, or any means of squirting the drug into the can occur. Death may also result from the ingestion resultant wound. In extremes, addicts have used of toxic ingredients along with the aerosol sub- such implements as a pencil, ballpoint or fountain stance. The possibility is made more likely by the pen, or the sharpened end of a spoon. fact that commercial products not produced for Intra-arterial Injection. Injections are never human consumption are not required to list their made intentionally into arteries. Accidental intra- ingredients on the label. Individual substances may arterial injection will produce intense pain, swell- produce a spectrum of toxic reactions depending on ing, cyanosis (blueness), and coldness of the body their contents. These have included gastric pain, extremity injected. Intra-arterial injection resulting headaches, drowsiness, irritability, nausea, mu- in these symptoms is a medical emergency and, if cous-membrane irritation, confusion, tremors, untreated, may produce gangrene of the fingers, nerve paralysis, optic-nerve damage, vomiting, hands, toes, or feet and result in loss of these parts. lead poisoning, anemia, and so on. The inhaling of Transmittal of Disease through Injection. aerosol fluorocarbons can cause ‘‘sudden-sniffing The greatest number and variety of medical com- death’’ (SSD), wherein the heart is hypersensitized plications of drug use caused by the mode of ad- to the body’s own hormone epinephrine (adrena- ministration occur as a result of injection. Among line), leading to a very erratic heartbeat, increased the highest risk, and that with the most frequent pulse rate, and cardiac arrest. fatal and disabling consequences is the transmittal The inhaling of amyl, butyl or isobutyl nitrites of disease through the use of unsterile needles and can cause intense headaches, an abrupt drop in the sharing of such needles. blood pressure, and loss of consciousness through Human Immunodeficiency Virus (HIV). Needle-us- orthostatic hypotension (increased heart rate and ing drug abusers comprise one of the primary high- palpitations), with a threat of myocardial infarc- riskpopulations for contracting human immuno- tion (heart attack). deficiency virus (HIV). The primary recognized routes of transmission for HIV are (1) sexual con- COMPLICATIONS DUE TO INJECTION tact through unprotected anal or vaginal inter- course—particularly if there are damaged tissue or The injection of drugs generally involves the use sores present that provide direct access to the of the hypodermic needle, first invented in the early bloodstream; (2) contact with infected blood nineteenth century and used initially for the medi- through needle sharing or through transfusions of cal delivery of the opiate painkiller MORPHINE, for blood or blood products; and (3) in utero or the rapid control of intense PAIN. This combination at-birth transmission from a mother to her baby. was first used extensively for battlefield wounds ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS), during the Crimean War (1853–1856) and the the most severe and life-threatening result of HIV American Civil War (1861–1865). As its name infection, involves the destruction of a person’s implies, the hypodermic needle pierces the skin— immune system and the development of cancers the dermis. Hypodermic injections may be subcu- and infections that can no longer be fought off. taneous, directly beneath the skin surface; in- The incidence of HIV infection among needle- tramuscular, into the muscle tissue; or intravenous, using drug abusers is closely related to local use into a blood vessel. (Note: Although a number of traditions, habits, and the prevalence of HIV infec- injection-related medical complications are directly tion among other addicts. The highest incidence is skin-related, these are discussed in the article Com- in areas such as New YorkCity, where there is a plications: Dermatological. tradition of needle sharing or where ‘‘shooting While the hypodermic needle is the primary galleries’’—places where users can rent or share means of drug injection, drug addicts who do not ‘‘works’’—are commonly utilized and where there have access to hypodermics have made use of a was a high prevalence of HIV among the homosex- number of ingenious, and often very dangerous, ual population. Users in other geographical loca- substitutes. Nonhypodermic-needle means of injec- tions, such as San Francisco, seem to be more con- tion may involve such paraphernalia as lancets or servative in their social-usage patterns, and when scalpels, or any small sharp blade to make an open- they do share needles, tend to keep the same COMPLICATIONS: Route of Administration 343

‘‘shooting partners’’ over a longer period of time. nutritional support, and avoidance of alcohol or HIV-prevention efforts in some areas have focused any other substance that may further irritate the on NEEDLE AND SYRINGE EXCHANGE, while others, liver. Caregivers should wear rubber gloves for particularly where needle exchange is not legalized, handling patients. Patients with any form of hepa- have community-outreach workers teaching users titis should avoid preparing food for others and use how to sterilize their needles between each use with separate towels, bedlinens, and eating utensils until household bleach. The gist of both campaigns is symptoms disappear. Toilet seats and any spilled that users who share their needles or who use dirty bedpan matter should be disinfected and hands needles are at riskfor contracting HIV through should then be washed thoroughly with soap. Con- their drug use. Those who use sterile needles are doms should be used for any genital contact. not. Both approaches are considered stopgap, how- Hepatitis can cause hepatic fibrosis—the devel- ever, and are apt to be condemned as ‘‘encouraging opment of fibrous tissue in the liver. It can also of drug abuse.’’ cause or exacerbate cirrhosis (scarring of the liver), All needle-using drug abusers are considered at although this is most often a result of chronic alco- extremely high riskfor HIV infection, and HIV hol abuse. Symptoms of cirrhosis include jaundice screening is performed routinely at most drug- (yellowish skin and eye whites), fatigue, ankle treatment centers. The virus has a very long incu- swelling, enlargement of the abdomen, and a full bation period and may be present for seven or more feeling in the right upper abdomen. years before active symptoms of opportunistic dis- Tetanus and Malaria. According to Senay and ease appear. Early symptoms may include: a per- Raynes, the first case of tetanus associated with sistent rash or lesion; unexplained weight loss; per- needle-using substance abuse was reported in En- sistent night sweats or low-grade fever; persistent gland in 1886. By the 1990s, between 70 and 90 diarrhea or fatigue; swollen lymph glands: DEPRES- percent of tetanus cases have occurred to drug SION or states of mental confusion. abusers. As a medical complication to drug injec- Hepatitis and Other Liver Disorders. Hepatitis B, tion, tetanus most often occurs from ‘‘skin-pop- and related strains, often referred to as serum ping’’—which is cutaneous injection. A majority of (fluid-related) hepatitis, are the most common cases occur in women, and this is attributed to less- medical complication of needle drug use. Like HIV, substantial venous development than in men and a hepatitis can spread in other ways than needle use, smaller population with tetanus immunization. such as sexual intercourse or other direct sharing of Malaria (caused by the Plasmodium parasite) blood and bodily fluids. Several strains, however, was first reported among drug users in the United can be spread by contaminated foods, particularly States in 1926. It affects intravenous drug abusers shellfish, or by unhygenic practices in food han- and was brought to this country by needle-sharing dling. Current research indicates that some forms sailors who had been exposed to malaria in Africa. of hepatitis spread via an anal/oral progression— The initial outbreakin New Orleans spread to New so it is recommended that hands are washed thor- YorkCity in the 1930s and resulted in several oughly after all bowel movements or any other hundred deaths from tertian malaria among drug anal-area or fecal-matter handling, as a means of abusers. A second outbreakoccurred in the 1970s, prophylaxis. as a result of malaria-infected veterans returning Unlike AIDS, hepatitis is often not fatal if it is from Vietnam. detected and treated at an early stage. Symptoms of The spread of both these diseases among needle- all forms of hepatitis include fatigue, loss of appe- sharing drug abusers has been kept somewhat in tite, pain in the upper abdomen, jaundice—yellow check, particularly on the East Coast and in Chi- skin and a yellowish-to-chartreuse tinge to the cago, by the inclusion of 15 to 30 percent quinine sclerae (white of the eye), general itching, dark (a natural antimalarial), as filler, to stretch profits urine reaching the color of cola drinks with light- in illicit opioid drug mixtures in those areas. Qui- tan to cream-colored feces, and mental depression. nine (an alkaloid from chinchona bark) is a proto- Gamma globulin injection can provide short-term plasmic poison that prevents the germination of the immunity to all forms of hepatitis and can reduce fastidious tetanus anaerobe, Clostridium tetani, the symptoms of serum hepatitis if it is given during under the skin and in adjacent muscle tissue. Al- the gestation period. Treatment includes bed rest, though the quinine amount is not sufficient to erad- 344 COMPULSIONS icate malaria once it has taken hold in the body, it grene can develop from cutting off circulation to does help prevent the disease by killing the malarial the extremities and may necessitate amputation or parasites in the hypodermic syringe. be fatal.

COMPLICATIONS TO HEART AND (SEE ALSO: Inhalant Abuse and Its Dangers; Needle BLOOD VESSELS and Syringe Exchange and HIV/AIDS) Drug abuse is related to a number of heart and blood vessel medical complications. Some of these, BIBLIOGRAPHY such as alcohol cardiomyopathy, are a direct result COHEN, S., & GALLANT, D. M. (1981). Diagnosis of drug of the drug’s toxic effects. Others are at least par- and alcohol abuse. Brooklyn: Career Teacher Center, tially related to needle use. State University of New York. Endocarditis, an infection of the tissues in the SENAY, E. C., & RAYNES, A. E. (1977). Treatment of the heart, usually a heart valve, is a progressive disease drug abusing patient for treatment staff physicians. characterized by frequent embolization (obstruc- Arlington, VA: National Drug Abuse Center. tion of blood vessels) and severe heart-valve de- SEYMOUR, R. B., & SMITH, D. E. (1990). Identifying and struction that can be fatal if not treated. This dis- responding to drug abuse in the workplace. Journal of ease can result from repeated injection of the Psychoactive Drugs, 22(4), 383–406. infective agents into the blood system, usually from SEYMOUR, R. B., & SMITH, D. E. (1987). The physician’s nonsterile needles and/or unusual methods of injec- guide to psychoactive drugs. New York: Hayworth. tion. Infective endocarditis is highly prevalent WILFORD, B. B. (1981). Drug abuse: A guide for the among drug abusers and should be suspected in any needle-using abuser who shows such symptoms primary care physician. Chicago: American Medical as the following: fever of unknown origin; heart Association. murmur; pneumonia; embolic phenomena; blood DAVID E. SMITH cultures that are positive for Candida, Staphylo- RICHARD B. SEYMOUR coccus aureus or enterococcus, or Gram-negative REVISED BY RALPH MYERSON organisms.

MISCELLANEOUS COMPLICATIONS COMPULSIONS A compulsion is a persis- Blood-vessel changes caused by necrotizing tent, irresistible impulse to perform a repetitive, angiitis (polyarteritis—the inflammation of a num- irrational behavior or mental act. Common behav- ber of arteries) or a swelling that leads to tissue loss ioral compulsions include hand-washing, cleaning, have been demonstrated in intravenous amphet- checking, ordering, and touching. Common mental amine abusers, resulting in cerebrovascular occlu- act compulsions include counting, praying, and re- sion (blockage in brain blood vessels) and intracra- peating words silently. Compulsive acts may need nial hemorrhage or stroke. to be performed to exacting specifications. The goal Problems in the lungs often develop from inert of compulsive behaviors or mental acts is to prevent materials that are included as cutting agents or as or reduce anxiety. There is no pleasure or gratifica- buffers and binding agents in drugs that come in tion derived from performing the compulsive be- pill form but are liquified and injected. These sub- havior or mental act. Often, the person feels com- stances do not dissolve, so their particles may be- pelled to perform the compulsive act in order to come lodged in the lungs, causing chronic pulmo- reduce the anxiety associated with an obsessive nary fibrosis and foreign-body granulomas. These thought. Alternatively, compulsive acts are per- same buffers and binding agents may as well be- formed as a way to prevent a feared event or situa- come lodged in various capillary systems, including tion. Compulsions are excessive (e.g. washing the the tiny blood vessels in the eye. hands until the skin is raw in order to relieve Finally, injection-induced infections reaching obsessive fears of contamination) or they are unre- the skeleton can be responsible for such bone dis- lated to the obsessive thought they were designed to eases as septic arthritides and osteomyelitis. Gan- negate or prevent. CONDITIONED TOLERANCE 345

BIBLIOGRAPHY solution in the context of a different set of stimuli for several days. Each day, the rats’ body tempera- AMERICAN PSYCHIATRIC ASSOCIATION (2000). Diagnostic tures were measured. Alcohol lowered body tem- and statistical manual of mental disorders: peratures the first time it was given, but this effect DSM-IV-TR. Washington, D.C.: American Psychiatric diminished over the course of the repeated alcohol Association. administrations—that is, tolerance developed to SADOCK, B. J., & SADOCK, V. A. (2000). Kaplan & the hypothermic effect of alcohol. To determine if a Sadock’s comprehensive textbook of psychiatry. Phil- drug-compensatory CR was elicited by the usual adelphia: Lippincott Williams & Wilkins. predrug cues, the rats were given a placebo CR test. BELINDA ROWLAND In a placebo CR test, saline solution is administered instead of the drug. The placebo CR test was given to some rats under conditions where they were ex- COMPULSORY TREATMENT See Civil pecting alcohol; that is, saline was administered Commitment; Coerced Treatment for Substance with the usual predrug cues. For the remaining Offenders; Narcotic Addict Rehabilitation Act rats, the placebo CR test was given under condi- (NARA) tions where there should have been no expectancy of alcohol, that is saline was administered with cues that had previously signaled only saline. Rats given saline with the usual predrug cues had elevated Tolerance CONDITIONED TOLERANCE body temperatures, while rats given saline without refers to the diminishment or the loss of a drug the usual predrug cues showed little temperature effect over the course of repeated administrations. change. Thus, it was possible to directly observe the Some researchers have postulated that an impor- drug-compensatory CR, in this case hyperthermia tant factor in the development of tolerance is Pav- opposed to the hypothermic effect of alcohol. Other lovian conditioning of drug-compensatory re- experiments similar to the one just described have sponses. The administration of a drug may be found drug-compensatory CRs following the devel- viewed as a Pavlovian conditioning trial. The stim- opment of tolerance to various effects of OPIATES, uli present at the time of drug administration are BARBITURATES,andBENZODIAZEPINES (Siegel, the conditional stimulus (CS), while the effect pro- 1983). duced by the drug is the unconditional stimulus Conditioned responses occur only when the con- (UCS). Many drug effects involve disruption of the ditional stimulus is presented. If drug-compensa- homeostatic level of physiological systems (e.g., al- tory CRs contribute to tolerance, then tolerance cohol lowers body temperature), and these disrup- should only be evident in the presence of the usual tions elicit compensatory responses that tend to re- predrug cues that are the CS. This expectation was storefunctioningtonormallevels.The tested in the experiment by Crowell, Hinson, and compensatory, restorative response to a drug effect Siegel (1981), involving tolerance to the hypother- is the unconditional response (UCR). Repeated ad- mic effect of alcohol. After all rats had developed ministrations of a drug in the context of the same tolerance to the hypothermic effect of alcohol, a test set of stimuli can result in the usual predrug cues was given in which some rats received alcohol with coming to elicit as a conditional response (CR) the the usual predrug cues, while other rats received compensatory, restorative response. The condi- alcohol when the usual predrug cues were not pres- tional drug-compensatory CR would tend to reduce ent. Although all rats had displayed tolerance prior the drug effect when the drug is administered with to the test, only those rats given alcohol in the the usual predrug cues—thus accounting for toler- presence of the usual predrug cues (i.e., with the ance, or at least some aspects of tolerance. CS) showed tolerance during the test. The explana- One test of the Pavlovian conditioning model of tion of this ‘‘situational specificity’’ of tolerance is tolerance is whether conditional drug-compensa- that when alcohol is given with the usual predrug tory responses are elicited by predrug cues. In one cues, the drug-compensatory CR occurs and re- experiment with rats (Crowell, Hinson, & Siegel, duces the drug effect—but when alcohol is given 1981), injections of alcohol in the context of one set without the usual predrug cues, the drug-compen- of stimuli were alternated with injections of saline satory CR does not occur and the drug effect is not 346 CONDUCT DISORDER AND DRUG USE

reduced. Other research has demonstrated situa- BIBLIOGRAPHY tional specificity with regard to tolerance to opiates, CROWELL, C., HINSON, R. E., & SIEGEL, S. (1981). The barbiturates, and benzodiazepines (for a complete role of conditional drug responses in tolerance to the review see Siegel, 1983). hypothermic effects of alcohol. Psychopharmacology, In order to eliminate a CR, it is necessary to 73, 51–54. present the CS not followed by the UCS, a proce- HINSON, R. E., & SIEGEL, S. (1980). The contribution of dure termed extinction. Research indicates that the Pavlovian conditioning to ethanol tolerance and de- loss of tolerance occurs as a result of extinction of pendence. In H. Rigter & J. C. Crabbe (Eds.), Alcohol drug-compensatory CRs. Again referring to the ex- tolerance and dependence. Amsterdam: Elsvier/ periment of Crowell, Hinson, and Siegel (1981), North Holland Biomedical Press. rats were given alcohol in the presence of a consis- SIEGEL, S. (1983). Classical conditioning, drug toler- tent set of cues until tolerance developed. Then, all ance, and drug dependence. In F. B. Glaser et al. drug injections were stopped for several days. Dur- (Eds.), Research advances in alcohol and drug prob- ing this period some animals were given extinction lems, vol. 7. New York: Plenum. trials, in which the usual predrug cues were pre- RILEY HINSON sented but only saline was injected. The other ani- mals did not receive extinction trials and were left undisturbed during this time. Subsequently, all an- CONDUCT DISORDER AND DRUG USE imals were given a test in which the drug was given A behavior pattern characterized by such behaviors with the usual predrug cues. The animals that had as stealing, violence, running away from home, and received extinction trials were no longer tolerant, truancy occurs in about 10 percent of children whereas animals that had not been given extinction under 16 years of age. Within the frameworkof the trials retained their tolerance. Similar results—in DIAGNOSTIC AND STATISTICAL MANUAL of Mental which tolerance is retained unless extinction trials Disorders, 4th edition, (DSM-IV), this serious and are given—occur for tolerance to opiates, barbitu- persistent pattern of antisocial behavior is diagnos- rates, and benzodiazepines (Siegel, 1983). tically labeled conduct disorder (CD). CD is the The drug-compensatory CRs that contribute to most common psychiatric disorder in emotionally tolerance may also be involved in withdrawal-like disturbed youth, present in about 75 percent of cases. Boys outnumber girls in ratios of 4:1, but 8:1 symptoms that occur in detoxified drug addicts. for property and violent crimes. Emerging evidence Detoxified addicts often report experiencing with- suggests, however, that the gender gap is narrow- drawallike symptoms when they return to places ing; and by adolescence, commonly associated where they formerly used drugs, although they are problems include alcoholism, drug addiction, crim- now drug free. The places where the addict for- inality, incarceration, sexually transmitted diseases merly used drugs act as CSs and still elicit drug- (STDs), pregnancies, prostitution, traumatic inju- compensatory CRs; even when the addict is drug ries, dropping out of school, and comorbid psychi- free, the drug-compensatory CRs achieve expres- atric disorders. sion. Thus, it is postulated that the drug-compen- satory CRs elicited by the usual predrug cues in the DIAGNOSIS drug-free postaddict result in a withdrawal-like syndrome (Hinson & Siegel, 1980). This condi- In the American Psychiatric Association classifi- cation system for diagnosing mental disorder tional postdetoxification withdrawal syndrome (DSM-IV), conduct disorder is defined as ‘‘a repeti- may motivate the postaddict to resume drug taking tive and persistent pattern of conduct in which the (to alleviate the symptoms). basic rights of others or major age-appropriate so- cietal norms or rules are violated’’ (American Psy- (SEE ALSO: Addiction: Concepts and Definitions; chiatric Association, 1994). Conduct disorder has Causes of Drug Abuse: Learning; Tolerance and become one of the most valid and reliably diag- Physical Dependence; Wikler’s Pharmacologic nosed psychiatric disturbances. The problem be- Theory of Drug Addiction) havior is transsituational—it is manifested in the CONDUCT DISORDER AND DRUG USE 347 home, at school, and in daily social functioning. disorder may also be accompanied by any other Often, CD youth are suspicious of others and, con- psychiatric disorder. sequently, they misinterpret the intentions and ac- Among those who have CD with attention deficit tions of others. By adolescence, aggression may disorder, the onset age of behavior problems tends become so severe that violent assault, rape, and to be earlier and more severe than in cases with homicide are committed. Precocious sexual behav- either disorder alone. In the situation where both ior and sexual misbehavior, especially among fe- are present, children are also at greater riskfor males, are also common. Denial and minimization developing criminal behavior and substance abuse generally occur when the youngsters are confronted by adolescence or young adulthood. about their behavior. Typically, feelings of guilt are The coexistence of CD and substance abuse has not experienced. been frequently observed. It is estimated that as Other, less severe, types of behavior disorders many as 50 percent of serious offenders are sub- are also known. The most common that resemble stance abusers. In these cases, CD usually preceded CD are the onset of substance abuse. Some evidence has been marshaled to suggest that, for many individu- (1) adjustment disorder with disturbances of con- als, substance abuse and CD are the overt expres- duct; sions of a common underlying predisposition. Only (2) childhood (or adolescent) antisocial behavior; in some cases, does the onset of CD follow the onset and of substance abuse. Drug use during adolescence, (3) oppositional defiant disorder. by virtue of its pattern of illegal behavior plus Substantial differences in the behavioral mani- association with nonnormative peers, increases the festations of CD have prompted efforts to develop riskfor violent assault as well as getting arrested subtypes. The most well-known subtyping criteria and convicted for drug possession or distribution. are In effect, the use of drugs in this circumstance socializes a person to a deviant lifestyle by early to (1) socialized versus unsocialized; mid-adolescence. (2) aggressive versus nonaggressive; and Approximately 30 percent of boys with CD also (3) overt versus covert. qualify for a diagnosis of DEPRESSION. In this Just one variant of CD, the solitary aggressive type, comorbid condition, there appears to be a lower characterizes approximately 50 percent of incar- riskof depression in adulthood compared to cases cerated youth; they are usually socioeconomically of depression in childhood without CD. Since the disadvantaged and typically derive from dysfunc- outcome of depressed children with comorbid CD is tional families. Moral development is arrested, cog- similar to nondepressed CD children, this suggests nitive abilities are low, and behavior is often dan- that the affective disturbance is a secondary condi- gerous both to self and others. This CD variant tion. should not be confused with adaptive delinquency, CD in childhood is associated with an increased in which the behavior is an attempt to adjust to the riskfor antisocial personality disorder in adult- manifold disadvantages of inner-city living. hood. Compared to other psychiatric disorders of childhood, CD is the most likely to remain stable. NATURAL HISTORY Persistence of conduct problems into adulthood is most likely if the behavior problems are serious, are Other psychiatric disorders frequently occur in generalized across multiple environments or situa- conjunction with conduct disorder. The most prev- tions, have an early age onset, and lead the person alent comorbid (coexisting) psychiatric disorder is into the criminal-justice system (Loeber, 1991). attention deficit disorder. By adolescence, the comorbid conditions of psychoactive substance use ETIOLOGY disorder with depressive disorders often emerge; however, virtually any type of psychiatric disorder Adoption and family studies implicate a genetic can be present concurrently with CD (Rutter, predisposition for the development of antisocial 1984). By adulthood, an ANTISOCIAL PERSONALITY behavior in many. A genetic propensity does not, disorder is the most common outcome of CD; this however, appear to invariably ensure this adverse 348 CONDUCT DISORDER IN CHILDREN

outcome. Other complicating factors include being RUTTER, M. (1984). Psychopathology and develop- a child in a dysfunctional family where the parents ment. I. Childhood antecedents of adult psychiatric are abusive, neglectful, or absent or where there are disorder. Australian and New Zealand Journal of poor parenting skills. Alcoholic and physically abu- Psychiatry, 18, 225–234. sive parents have been frequently linked to CD in ADA C. MEZZICH their own childhoods. Neurologic injuries (e.g., RALPH E. TARTER trauma) and neurodevelopmental disability (e.g., REVISED BY MARY CARVLIN dyslexia) can exacerbate the expression of CD. So- cioeconomic and ethnic factors (e.g., POVERTY, street GANGS) also influence the development of CONDUCT DISORDER IN CHILDREN CD. One of several childhood behavioral disturbances, CONDUCT DISORDER refers to repeated patterns of TREATMENT conduct by a child that violate the basic rights of The following are generally inadequate for the others or transgress age-appropriate societal rules. treatment of youth with CD: individual psychother- The behavior is socially disruptive and generally apy, behavior modification, group counseling, fam- more serious in its consequences than typical child- ily therapy, milieu therapy, and immersion in a hood mischief. The duration of the behavior, its long-term therapeutic community. The most prom- severity, and the kinds of actions involved distin- ising approaches emphasize training parents in the guish conduct disorder from general misbehavior. skills necessary to promote normal socialization in Conduct disorder is the most common behavioral their children, accompanied by training children in problem seen in child psychiatric settings in North the use of problem-solving strategies (Kazdin et al., America. 1987). The complexity and severity of The behaviors that characterize this disorder CD-associated problems dictate the need for mul- include theft, vandalism, physical fights— timodal treatment. Primary consideration should sometimes with weapons—fire setting, running be given to containment and limit setting—which away from home, truancy, repetitive lying, forcing create the conditions for treatment, to provide sexual activity on others, physical cruelty to ani- safety, and to delineate a comprehensive program mals and to people, and substance abuse. Legal of intervention encompassing behavioral and so- involvement may ensue. Different children may cial-skill building, family therapy, and educational manifest different combinations of these behaviors, assistance. and these in turn may change at different points of child development. Conduct disorder appears to be (SEE ALSO: Adolescents and Drug Use; Crime and more common in boys than in girls. Drugs; Families and Drug Use; Family Violence and The etiology of conduct disorder is considered Substance Abuse; Vulnerability As Cause of Sub- multifactorial. Psychological and social factors be- stance Abuse) lieved to contribute to its development include the child’s particular temperament, a family history of ANTISOCIAL PERSONALITY disorder or alcohol de- BIBLIOGRAPHY pendence (or both), poor parenting skills, a chaotic AMERICAN PSYCHIATRIC ASSOCIATION (1994). Diagnostic home environment, and lower socioeconomic sta- and statistical manual of mental disorders-4th ed. tus. Mild central nervous system abnormalities (DSM-IV). Washington, DC: Author. have been found in children with a history of vio- KAZDIN, A. E., ET AL. (1987). Effects of parent manage- lent behavior, and they are thought to contribute to ment training and problem-solving skills combined in the children’s impulsivity. ATTENTION-DEFICIT HY- the treatment of antisocial child behavior. Journal of PERACTIVITY DISORDER and specific developmental the American Academy of Child and Adolescent Psy- disorders are common associated diagnoses. Chil- chiatry, 26, 416–424. dren who display significant antisocial behavior LOEBER, R. (1991). Antisocial behavior: More enduring have a poorer long-term prognosis with greater than changeable? Journal of the American Academy of psychiatric impairment in adulthood (including Child and Adolescent Psychiatry, 30, 393–397. antisocial personality disorder), poorer educational CONTROLLED SUBSTANCES ACT OF 1970 349

achievement, overt criminal behavior, higher rates ZEITLIN, H. (1999). Psychiatric comorbidity with sub- of unemployment, impaired social functioning— stance misuse in children and teenagers. Drug and and considerably higher rates of smoking and alco- Alcohol Dependence, 55, (3) 225–234. hol abuse, illicit drug use and dependence. MYROSLAVA ROMACH Treatment of conduct disorder in children and KAREN PARKER adolescents can include family therapy, parent REVISED BY REBECCA J. FREY management training, behavioral and cognitive therapies, residential treatment programs, and, less frequently, pharmacotherapy. CONTROLLED SUBSTANCES ACT OF 1970 Until 1970, psychoactive drugs were regu- (SEE ALSO: Crime and Drugs) lated at the federal level by a patchworkof stat- utes enacted since the turn of the century. These statutes were shaped by an evolving conception of BIBLIOGRAPHY congressional power under the U.S. Constitution. AMERICAN PSYCHIATRIC ASSOCIATION. (1994). Diagnostic The first federal law on the subject was the Pure and Statistical Manual of Mental Disorders-4th ed. Food and Drug Act of 1906, which required the (DSM-IV). Washington, DC: Author. labeling of substances such as patent medicines if BEERS, M. H., & BERKOW, R. (Eds.) (1999). The Merck they included designated NARCOTICS (e.g., OPI- Manual of Diagnosis and Therapy, 17th ed. ATES and COCAINE) and were shipped in interstate Whitehouse Station, NJ: MerckResearch Laborato- commerce. In 1909, Congress banned the impor- ries. tation of smoking opium. Then in 1914, in the CANTWELL, D. P. (1989). Conduct disorder. In H. I. HARRISON NARCOTICS ACT, Congress deployed its Kaplan & B. J. Sadock(Eds.), Comprehensive text- taxing power as a device for prohibiting the distri- book of psychiatry, 5th ed., Vol. 2. Baltimore, MD: bution and use of narcotics for nonmedical pur- Williams & Wilkins. poses. (The taxing power was used because U.S. CHAMBERLAIN, C., & STEINHAUER, P. D. (1983). Conduct Supreme Court decisions implied that Congress disorders and delinquency. In P. D. Steinhauer & would not be permitted to use its power to regulate Q. R. Grant, (Eds.), Psychological problems of the interstate commerce in banning ‘‘local’’ activities, child in the family, 2nd ed. rev. New York: Basic such as the production and distribution of narcot- Books. ics.) The scheme established by the Harrison Act CONNOR, D. F., BARKLEY, R. A., & DAVIS, H. T. (2000). A required the registration and payment of an occu- pilot study of methylphenidate, clonidine, or the com- pational tax by all persons who imported, pro- bination in ADHD comorbid with aggressive opposi- duced, or distributed narcotics; it imposed a tax on tional defiant or conduct disorder. Clinical Pediatrics each transaction; and it made it a crime to engage (Philadelphia), 39, (1) 15–25. in a transaction without paying the tax. Mere pos- MALONE, R. P., ET AL. (2000). A double-blind placebo- session of narcotics without a prescription was controlled study of lithium in hospitalized aggressive presumptive evidence of a violation of the act. The children and adolescents with conduct disorder. Ar- Marihuana Tax Act of 1937 utilized the same chives of General Psychiatry, 57, (7) 649–654. model. OFFICE OF THE SURGEON GENERAL. (2000). Mental In 1965, Congress prohibited the manufacture Health: A Report of the Surgeon General. Washing- and distribution of ‘‘dangerous drugs’’ (stimulants, ton, DC: U. S. Government Printing Office. depressants, and hallucinogens) for nonmedical SCHUBINER, H., ET AL. (2000). Prevalence of attention- purposes. By this time, Congress’s constitutional deficit/hyperactivity disorder and conduct disorder authority to enact such legislation under the com- among substance abusers. Journal of Clinical Psychi- merce clause was no longer in doubt. (In 1968, atry, 61, (4) 244–251. Congress made simple possession of the drugs a WEINBERG, N. Z., & GLANTZ, M. D. (1999). Child psy- misdemeanor.) All important feature of the 1965 chopathology riskfactors for drug abuse: overview. ‘‘dangerous drug’’ legislation was its delegation of Journal of Clinical Child Psychology, 28, (3) 290– authority to the secretary of Health, Education and 297. Welfare (HEW) to control previously uncontrolled 350 CONTROLS: SCHEDULED DRUGS/DRUG SCHEDULES, U.S. drugs if they had a ‘‘potential for abuse’’ due to and scientific aspects. The House version prevailed their depressant, stimulant, or hallucinogenic in the 1970 law as it was finally adopted. properties. (In 1968, this scheduling authority was After enactment of the federal Controlled Sub- transferred to the U.S. attorney general.) stances Act, the National Conference of Commis- All this legislation was replaced by a compre- sioners on Uniform State Laws promulgated a Uni- hensive regulatory structure in the 1970 Con- form Controlled Substances Act, which was trolled Substances Act (CSA). Under the new stat- modeled after the federal act. (Earlier state laws utory scheme, all previously controlled substances were modeled on the 1934 Uniform Narcotic Drug were classified—in five schedules—according to Act, which had also been promulgated by the Na- their potential for abuse and accepted medical tional Conference.) Every state has enacted the utility; an administrative process was then estab- Uniform Controlled Substances Act. lished for scheduling new substances, building on the model of the 1965 act. Schedule 1 lists drugs (SEE ALSO: Anslinger, Harry J., and U.S. Drug Pol- that have no traditional recognized medical use, icy; Controls: Scheduled Drugs; Legal Regulation of such as HEROIN, LSD, and cannabis (MARIJUANA). Drugs and Alcohol ) Schedule 2 lists the drugs with medical uses that have the greatest potential for abuse and depen- BIBLIOGRAPHY dence, such as MORPHINE and cocaine. The re- BONNIE, R. J., & WHITEBREAD, C. H., II. (1974). The maining schedules use a sliding scale that balances marihuana conviction. Charlottesville, VA: Univer- each drug’s ABUSE POTENTIAL and its legitimate sity Press of Virgina. medical uses. MUSTO, D. F. (1987). The American disease. New York: Different degrees of control are applied to Oxford University Press. manufacturers, distributors, and prescribers— SONNENREICH, M. R., ROCCOGRANDI, A. J., & BOGOMOLNY, depending on the schedule in which the drug has R. L. (1975). Handbook on the 1970 federal drug been placed. The regulatory structure of the Con- act. Springfield, IL: Charles C. Thomas. trolled Substances Act is predicated on the assump- RICHARD BONNIE tion that tighter controls on legitimate transactions will prevent diversion of these substances and will thereby reduce the availability of these substances for nonmedical use. The drafting of the Controlled Substances Act CONTROLS: SCHEDULED DRUGS/ reflected a continuing controversy regarding the lo- DRUG SCHEDULES, U.S. The Compre- cus of administrative authority for scheduling new hensive Drug Abuse Prevention and Control Act of drugs and for rescheduling previously controlled 1970, commonly known as the CONTROLLED SUB- drugs. Under the bill passed by the Senate, this STANCE ACT (CSA) establishes the procedures that responsibility would have rested with the U.S. at- must be followed by drug manufacturers, research- ers, physicians, pharmacists, and others involved in torney general, who was required only to ‘‘request the legal manufacturing of, distributing of, pre- the advice’’ of the secretary of HEW (now Health scribing of, and dispensing of controlled drugs. and Human Services, HHS) and of a scientific advi- These procedures provide for accountability for a sory committee; the attorney general was not re- drug from its initial production through distribu- quired to follow this advice although the various tion to the patient and are intended to reduce wide- criteria in the act require primarily scientific and spread diversion of controlled drugs from legiti- medical judgments. The Senate rejected an amend- mate medical or scientific use. ment that would have made the recommendations of the ‘‘advisor’’ binding on the attorney general. CRITERIA FOR CONTROLLING AND Under the bill passed in the House of Representa- SCHEDULING DRUGS tives, however, the secretary’s decision declining to schedule a new drug was binding on the attorney Several factors are considered before a drug is general, and the secretary’s recommendation con- controlled under this act. These factors include the cerning rescheduling was binding as to its medical potential for abuse (i.e., history, magnitude, dura- CONTROLS: SCHEDULED DRUGS/DRUG SCHEDULES, U.S. 351 tion, and significance), riskto public health, and PRESCRIBING AND DISPENSING OF potential of physical or psychological dependence. CONTROLLED DRUGS Drugs controlled under this act are divided into five Medical practitioners have to follow specific Schedules (I–V) according to their potential for rules for each schedule when prescribing or dis- abuse, ability to produce dependence, and medical pensing controlled drugs. Drugs in Schedule I can utility. Drugs in Schedule I have a high potential for only be obtained, prescribed, and dispensed to an abuse and/or dependence with no accepted medical individual after special approval is obtained from use or they lackdemonstrated clinical safety. Those the Food and Drug Administration (FDA). Drugs in in Schedules II–V may have a high potential for Schedule II cannot be refilled or dispensed without abuse or ability to produce dependence but also a written prescription from a practitioner, except in have an accepted medical use. (However, some an emergency. When they are dispensed in an substances which have no accepted medical use but emergency, a written prescription must be obtained which are precursors to clinically useful substances within 72 hours. Drugs in Schedule III and in may also be found in Schedules II–V. For example, Schedule IV may not be dispensed without a writ- thebaine, found naturally in OPIUM, has no medical ten or an oral prescription. Prescriptions for these use but it is a substance used in the manufacture of drugs may not be filled or refilled more than six CODEINE and a series of potent OPIOID compounds months after their issue date or refilled more than as well as opioid ANTAGONISTS.) The potential for five times unless authorized by a licensed practi- abuse and the ability to produce dependence is tioner. Drugs in Schedule V can be refilled, with a considered to be the greatest for Schedule I and II practitioner’s authorization, without the limitation drugs and progressively less for Schedule III, IV, on number of refills or time. Certain Schedule V and V (see Table 1). drugs may be purchased directly from a pharma- The amount of controlled drug in a product can cist, in limited quantities, without a prescription. also determine the schedule in which it is placed. The purchaser must be at least 18 years of age and For example, AMPHETAMINE,METHAMPHETAMINE, furnish appropriate identification and the transac- and codeine, as pure substances, are placed in tions must be recorded by the dispensing pharma- Schedule II; however, these same drugs in limited cist. quantities and in combination with a noncontrolled When drugs in Schedule II, III, and IV are dis- drug are placed in Schedules III and V. Drugs in pensed, a warning label stating ‘‘Caution: Federal Schedule V generally contain limited quantities of law prohibits the transfer of this drug to any person certain narcotic drugs used for cough and other than the patient for whom it was prescribed,’’ antidiarrheal purposes and can only be distributed must be affixed to the dispensing container. The warning label regarding transfer does not apply to or dispensed for medical purposes. Schedule V drugs.

LISTS OF SCHEDULED DRUGS REGISTRATION, ORDERING, QUOTAS, Drugs controlled under the CSA are listed by AND RECORDS OF schedule and drug class in Table 2 (Schedules I and CONTROLLED DRUGS II) and Table 3 (Schedules III, IV, and V). A listing Each individual or institution engaged in manu- of controlled chemical derivatives, immediate pre- facturing, distributing, or dispensing any con- cursors (chemical which precedes the active drug), trolled drug must be authorized by and register and chemicals essential for making a controlled annually with federal and state drug-enforcement drug, along with drugs exempt from control can be agencies, unless specifically exempted. A unique found in the most current edition of the Controlled registration number is assigned to each individual Substances Handbook. Brand names for drugs in or institution registered under the act. A separate Schedules II–V are not included in the Tables but registration is required for practitioners who dis- can also be found in the latest edition of the Con- pense narcotic drugs to individuals for the purpose trolled Substances Handbook. of addiction treatment (such as METHADONE and 352 COPING AND DRUG USE

LAAM [L-ALPHA-ACETYLMETHADOL] for opioid CODE OF FEDERAL REGULATIONS (21 CFR Parts 1301– detoxification or maintenance). 1308). (1992). Food and drugs—Drug Enforcement All orders for Schedule I and II drugs must be Administration, Department of Justice. Washington, made using a special narcotic order form. Proof of DC: U.S. Government Printing Office. registration is required when ordering Schedule SIMONSMEIER, L. M., & FINK, J. L. (1990). The compre- III-V drugs. hensive drug abuse prevention and control act of Annual production quotas are established for 1970. In A. R. Gennaro (Ed.), Remington’s pharma- drugs in Schedule I and Schedule II. Everyone reg- ceutical sciences, 18th ed. Easton, PA: MackPublish- istered to handle controlled drugs must maintain ing Company. records, conduct inventories, and file periodic WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- reports specific to their business or professional ICY. (2000). National Drug Control Strategy: 2000 activity. Annual Report. Washington, D.C. ROLLEY E. JOHNSON SPECIAL ISSUES ANASTASIA E. NASIS The development of designer drugs has raised REVISED BY FREDERICK K. GRITTNER many concerns about policing drugs of abuse. Un- derground chemists who develop designer drugs seekto achieve two results: the creation of market- COPING AND DRUG USE Coping is the able drugs that mimic the effects of restricted drugs capacity to surmount negative emotional states, of abuse; and the creation of drugs that are not including ANXIETY,DEPRESSION, anger, loneliness, specifically listed as controlled substances by the and alienation. These aversive states are induced Drug Enforcement Administration. The most pop- by internal psychological conflict or by external ular designer drug of the late 1990s was MDMA STRESS. Effectiveness in appraising and overcom- (methylenedioxymeth-amphetamine), popularly ing emotional distress that results from predispos- known as Ecstasy. Despite efforts to evade federal ing or triggering stressors determines, to a large drug laws, the designers of these drugs eventually extent, psychological well-being. In contrast, inef- see them added to the CSA. For example, MDMA fectiveness in coping, as well as a subjective percep- was placed on Schedule I on an emergency basis in tion of ineffectiveness, exacerbates emotional dis- 1985 because of its neurotoxic effects and abuse tress, which comprises for some people an potential. important factor in promoting ALCOHOL,TOBACCO, State and local laws either parallel the federal and other drug (ATOD) consumption. regulations as described by the CSA, or impose The association between ATOD use and coping additional restrictions. Individuals registered to is complex. In some individuals there is a direct handle controlled drugs must abide by the law connection. In effect, PSYCHOACTIVE DRUGS are (state or federal) that is most stringent in governing consumed to reduce tension and associated nega- their business or professional activity. Examples tive emotions. The consumption of drugs is motiva- where state law may be more stringent than federal ted by their palliative effects. In most individuals, law include the requirement for TRIPLICATE however, the connection between drug consump- PRESCRIPTION forms or the placing of a drug in a higher schedule. tion and coping is more complicated. Numerous factors such as psychiatric illness, low self-esteem, deviant social values, maladaptive learned behav- (SEE ALSO: Addiction: Concepts and Definitions; Legal Regulation of Drugs and Alcohol ) iors, inadequate social support, poor social skills, and personality disposition moderate and mediate the relationship between ATOD use and coping. No BIBLIOGRAPHY specific association has been established between BAUMGARTNER,K.,&HOFFMAN,D.(EDS.) (1993). coping style and VULNERABILITY to drug use or Schedules of controlled substances. In Controlled sub- abuse. Thus, whereas it is generally recognized that stances handbook. Arlington, VA: Government Infor- a substantial proportion of the ATOD-using popu- mation Services, J. J. Marshall Publisher. lation is deficient in coping capacity, it is important CRACK 353 to understand that many factors influence this report evaluates the severity of the disorder in ten association. key domains: (1) substance use, (2) psychiatric Coping and substance use and abuse become so disorder, (3) behavior patterns, (4) health status, intertwined over time that cause-effect relation- (5) family system, (6) workadjustment, (7) social ships cannot always be discerned. Deficient coping competence, (8) peer relationships, (9) school ad- capacity initially may, directly or indirectly, lead to justment, and (10) leisure/recreation. A treatment ATOD consumption. Neurobehavioral, psycho- protocol to enhance coping has also been developed pathological, and social adjustment disturbances for alcoholics (Kadden et al., 1992); this practical that occur along with chronic ATOD consumption approach to intervention is also applicable for may also diminish coping ability. treating individuals with other types of drug abuse. Substantial variation among individuals occurs with respect to both coping capacity and drug-use (SEE ALSO: Relapse; Treatment Types: Cognitive behavior across the life span. Drug consumption Therapy of Addictions) among youth is most frequently related to negative feelings such as depression and anxiety, social BIBLIOGRAPHY deviancy, and interpersonal problems—whereas substance use among the ELDERLY is more com- FINNEY, J. W., & MOOS, R. H. (1992). The long-term monly associated with life crises, psychiatric disor- course of treated alcoholism: II. Predictors and corre- der, bereavement, sleep disturbances, and unremit- lates of 10-year functioning and mortality. Journal of ting pain. Studies on Alcohol, 53, 142–153. Drug-abusing youth and adults, as a group, ex- GETTER, H., ET AL. (1992). Measuring treatment process hibit less ability to cope than the general popula- in coping skills and interactional group therapies for tion (Peele, 1985). It is essential to emphasize, alcoholism. International Journal of Group Psycho- however, that ATOD use and abuse may also be therapy, 42, 419–430. motivated by reasons other than the need to cope. KADDEN, R., ET AL. (1992). Cognitive behavioral coping In this context, ATOD consumption often stems skills therapy manual. Project MATCH Monograph from the desire for a euphoric effect or some other Series,Vol.3,DHHSPublicationNo.(ADM) desirable state, a desire that may reflect accurate as 92-1895. well as inaccurate beliefs about the pharmacologi- KATZ, L., & EPSTEIN, S. (1989). Constructive thinking cal effects of the chosen drug. For example, ATOD and coping with laboratory induced stress. Journal of consumption may be motivated by perceived Personality and Social Psychology, 61, 789–800. APHRODISIAC effects, energy or alertness enhance- LAZARUS, R., & FOLKMAN, S. (1984). Stress, appraisal ment, or social facilitation. and coping. New York: Springer. Among those whose ATOD consumption is moti- PEELE, S. (1985). The meaning of addiction. Lexington, vated by deficient coping skills, it appears that aug- MA: Lexington Books. menting competency improves the likelihood of TARTER, R. (1990). Evaluation and treatment of adoles- successful treatment. In other words, treatments cent substance abuse. A decision tree method. Ameri- designed to enhance their coping skills are superior can Journal of Drug and Alcohol Abuse, 16, 1–46. to treatments that emphasize their exploration of feelings (Getter et al., 1992). Furthermore, active RALPH E. TARTER coping strategies present 2 years after treatment are associated with a superior outcome at 10-year posttreatment follow-up (Finney & Moos, 1992). CRACK Crack(sometimes called crack-co- The role of coping in ATOD use needs to be caine) is an illicit drug, the smokable form of CO- evaluated on a case-by-case basis. Assessment can CAINE, made by adding the bases ammonia or bak- be conducted using the Ways of Coping scale (Laz- ing soda and water to cocaine hydrochloride. The arus & Folkman, 1984) or the more comprehensive white powder illicitly purchased as cocaine is in the Constructive Thinking Inventory (Katz & Epstein, hydrochloride form; it cannot be smoked, because 1989). Severity of ATOD-use disorder can be effi- it is destroyed at the temperatures required for ciently quantified by employing the Drug Use smoking. Therefore, in order to be used by the Screening Inventory (Tarter, 1990). This brief self- smoked route, cocaine must be converted to the 354 CRAVING base state. A mixture is made and heated to remove the hydrochloride, resulting in a pellet-sized cake- like solid substance that can be smoked. This form of cocaine is inexpensive, available for purchase ‘‘on the street,’’ and is called ‘‘crack,’’ because of the cracks formed in the solid as it dries. Although crackcan be smokedin tobacco ciga- rettes or marijuana cigarettes, it is generally smoked in a special crack pipe. In its simplest form, this is a glass tube with a hole at the top of one end and a hole at the other end through which the smoke is inhaled. The crack pellet is placed on fine wire mesh screens that cover the hole distal to the smoker and a flame is applied directly to the pellet. Soda bottles, small liquor bottles, etc. are all used Smoking crack, the rock form of cocaine, to manufacture crackpipes. They have in common produces effects comparable to intravenous the use of fine mesh screens so that the crackis not injection; the effects, felt almost immediately, are lost as it melts. Temperatures of approximately very intense, and quickly subside. (Drug 200ЊF (93ЊC) are most efficient in providing the Enforcement Administration) largest amount of cocaine to the user. Higher tem- peratures destroy more of the cocaine. bined with its toxicity make this an extremely dan- Smoking cocaine began with the use of FREE- gerous substance. BASE cocaine, prepared by its users from the co- From a financial perspective, crackis more de- caine hydrochloride illicitly purchased by them. sirable for both the buyer and the seller. A gram of Soon after this form of cocaine had achieved its cocaine hydrochloride costs approximately 50 to 60 popularity, single doses of cocaine already pre- dollars. This gram can be turned into 10 to 25 pared for smoking (i.e., crack), became available crackpellets, each selling for 2 to 20 dollars. Thus, through the illicit drug market. Unlike the process a gram of cocaine can generate a substantial profit for forming freebase cocaine, the crackmanufac- for the seller, and, as well, is available in single- turing process does not rid the cocaine of its adul- dose units to anyone with only a few dollars to terants. Smoking cocaine rapidly became a popular spend. route of administration once crackbecame readily available, since it was so convenient to use. Blood levels peakrapidly when cocaine is smoked,be- (SEE ALSO: Coca Paste; Freebasing; Pharmacoki- cause of efficient respiratory absorption, and the netics; Street Value) smoked route of cocaine administration yields ef- fects (peak, duration of effect, half-life) compara- BIBLIOGRAPHY ble to the intravenous route of administration. This INCIARDI, J. A. (1991). Crack-cocaine in Miami. In S. means that the smoker of cocaine can achieve rapid Schober & C. Schade (Eds.), The epidemiology of onset of effect, including a cocaine ‘‘rush’’ and cocaine use and abuse. NIDA Research Monograph substantial cocaine blood levels, and can do this No. 110. Rockville, MD: National Institute on Drug repeatedly using a more socially acceptable route of Abuse. administration—one that requires none of the SIEGEL, R. (1982). Cocaine smoking. Journal of Psycho- PARAPHERNALIA associated with hardcore illicit active Drugs, 14, 271–359. drug use (e.g., syringes, needles, etc.). The more rapid the onset of the drug effect, the MARIAN W. FISCHMAN more likely it is that the drug will be abused. Thus, although the effects of smoking crack are no differ- ent than the effects of cocaine by any other route, CRAVING The term craving is generally de- the ease with which the drug can be taken, com- lined as a state of desire, longing, or urge for a drug CRAVING 355 that is responsible for ongoing drug-use behavior in was synonymous with loss of control over drug drug-dependent individuals. Craving is also viewed intake. Furthermore, withdrawal models of by many drug-abuse researchers and clinicians as craving could not account for the common obser- the main cause of relapse among drug users at- vation that many addicts experienced craving and tempting to remain abstinent. During periods of relapsed long after their withdrawal had disap- abstinence, drug-dependent individuals often com- peared. Finally, addiction research was increas- plain of intense craving for their drug. Several sys- ingly dominated by behavioral approaches that fo- tems for diagnosing drug abuse include persistent cused on the influence of environmental variables desire or craving for a drug as a major symptom of in the control of drug taking and avoided the use drug-dependence disorders. of subjective concepts, such as craving, to explain The belief that an addict’s inability to control addictive behavior. drug use is caused by craving and irresistible desire Even though many researchers questioned the was a prominent feature of descriptions of addic- value of using craving to explain addictive behav- tive disorders provided by many nineteenth-cen- ior, it persisted as an important clinical issue, as tury writers. Craving continued to be important in many addicts complained that craving was a major many models of addiction developed in the twenti- barrier to their attempts to stop using drugs. eth century. The use of craving as a key mechanism Craving continued to be cited as a major symptom in theories of addiction peaked in the 1950s, sup- of drug dependence in formal diagnostic systems of ported largely by E. M. Jellinek’s writings on the behavioral disorders, and the notion that craving causes of alcoholism. was responsible for compulsive drug use remained Jellineckcontended that sober alcoholics who at the core of several popular conceptualizations of consumed a small amount of alcohol would experi- drug addiction. Scientific interest on the role of ence overwhelming craving that would compel craving in addictive disorders reemerged in the them to continue drinking. The proposal that middle 1970s as a result of two developments. craving and loss of control over drinking were First, behavioral theories of addiction were increas- equivalent concepts was adopted by many clini- ingly influenced by social-cognitive models of be- cians and addiction researchers. Equally popular havior that were more sympathetic to the possibil- was the position, also supported by Jellinek, that ity that hypothetical entities such as craving might craving was a direct sign of drug withdrawal. be useful in explaining addictive processes. Second, WITHDRAWAL-based craving was often described as animal research on the contribution of learning physical craving, distinguishing it from craving processes to drug tolerance and drug withdrawal that led to relapse during long periods of abstinence provided support for the hypothesis that learned after withdrawal had subsided. Craving that oc- withdrawal effects might produce craving and re- curred after an addict no longer was experiencing lapse in abstinent addicts. withdrawal was typically viewed as the result of psychological factors. The craving concept was suf- THEORIES OF CRAVING ficiently controversial that a committee of alcohol- ism experts brought together by the World Health Although there is considerable disagreement Organization in 1954 (WHO Expert Committees across current theories regarding the processes that on Mental Health and on Alcohol, 1955) recom- supposedly control craving, nearly all models de- mended that the term craving not be used to de- scribe craving as, fundamentally, a subjective state scribe various aspects of drinking behavior seen in and agree on the impact of craving on drug use. alcoholics. With few exceptions, modern theories of craving The use of craving as a key process in theories assume that craving is a necessary, but probably of addiction decreased during the 1960s and early not sufficient, condition for drug taking among 1970s as a result of several factors. During this addicts. These theories suppose that addicts are period, many studies showed that alcoholics did driven to use drugs because of their craving, and not necessarily engage in loss of control drinking craving is generally described as the principal cause when they dranksmall doses of alcohol. The fail- of relapse in addicts trying to remain abstinent. ure to confirm Jellinek’s conceptualization of alco- Moreover, all the comprehensive models of craving holic drinking cast doubt on the idea that craving invoke some sort of learning or cognitive process in 356 CRAVING their descriptions of the mechanisms controlling ing mood states and access to drugs, generate craving, and these models make little distinction craving (Baker, Morse, & Sherman, 1987; Gawin, between physical and psychological forms of drug 1990). craving. It is important to note that, at the present In contrast to models that contend that craving time, research on craving is not sufficiently ad- is responsihle for all addictive drug use, a recent vanced to fully evaluate the validity of any of the cognitive theory suggests that drug use may operate major models of craving. independently of craving (Tiffany, 1990). Accord- Many modern theories associate craving with ing to this theory, as a result of a long history of drug withdrawal and suggest that craving may be repeated practice, most of an addict’s drug-use be- merely a part of drug withdrawal. For example, havior becomes automatic. That is, drug use may the diagnostic system published by the American be easily triggered by certain cues, difficult to stop Psychiatric Association in 1987 listed craving as once triggered, and carried out effortlessly with one of the symptoms of withdrawal for nicotine little awareness. Addicts attempting to withdraw and opiates. Other approaches assume that from drug use will experience craving as they try to cravings are distinct from withdrawal, but repre- stop these automatized actions from going through sent an addict’s anticipation of, and desire for, to completion. relief from withdrawal. To explain the presence of craving following long periods of abstinence, it has been posited that learning processes are responsi- MEASURES OF CRAVING ble for the maintenance of withdrawal effects. For Craving is generally measured through three example, Wikler’s conditioning model of drug types of behaviors—self-reports of craving, drug- withdrawal (see WIKLER’S PHARMACOLOGIC THE- use behavior, and physiological responding. In the ORY) hypothesizes that situations reliably paired most frequently used measure, self-report, addicts with episodes of drug withdrawal become condi- are simply asked to rate or describe their level of tioned stimuli that can produce conditioned with- craving for a drug. Recently, questionnaires have drawal responses. An addict who has been absti- been developed that askaddicts to rate a variety of nent for an extended period may reexperience questions related to craving. These questionnaires withdrawal if faced with these conditioned stimuli. produce results that are considerably more reliable This learned-withdrawal reaction will trigger drug than a single rating of craving and tend to show craving, that, in turn, may lead to relapse. A simi- that an addict’s description of craving may have lar theory is based on the suggestion that drug- multiple dimensions. Measures of drug-use behav- tolerance processes can become conditioned to en- ior have also been used to assess drug craving. This vironmental stimuli. Some have hypothesized that is entirely consistent with the common assumption conditioned drug-tolerance effects will produce that craving is responsible for drug use in addicts. withdrawal-like reactions that, as in Wikler’s the- ory, should promote craving and relapse to drug Finally, as several theories posit that craving use (Poulos, Hinson, & Siegel, 1981). should be represented by particular patterns of Another perspective on craving is that it is physiological changes, physiological measures, pri- strongly associated with the positively reinforcing, marily those controlled by the autonomic nervous or stimulating, effects of drugs. For example, system, have been included in several studies as an Marlatt (1985) has suggested that craving is a index of craving. These measures have included subjective state produced by the expectation that changes in heart rate, sweat gland activity, and use of a drug will produce euphoria, excitation, or salivation. In general, withdrawal-based theories stimulation. Similarly, Wise (1988) proposed that predict that the physiology of craving should look craving represents memories for the pleasurable like the physiology of drug withdrawal. In contrast, or positively reinforcing effects of drugs. There models that emphasize positive reinforcement in are also multiprocess models, in which expectan- the production of craving would associate drug de- cies of positive reinforcement and anticipation of sire with physiology characteristic of the excitatory withdrawal relief, as well as other factors, includ- effects of drugs. CREATIVITY AND DRUGS 357

RESEARCH ON CRAVING (SEE ALSO: Addiction: Concepts and Definitions; Causes Drug Abuse: Learning; Research: Condi- Two kinds of studies have been used to investi- tioned Drug Effects; Research, Animal Model: Con- gate drug craving. The first, naturalistic studies, ditioned Drug Effects) examine changes in addicts’ descriptions of craving as they are attempting to stop using drugs. These studies generally have shown that cravings are es- BIBLIOGRAPHY pecially strong in the first several weeks of absti- AMERICAN PSYCHIATRIC ASSOCIATION. (1987). Diagnostic nence, but decline over time as addicts stay off and statistical manual of mental disorders-3rd ed.- drugs. They also reveal that craving rarely remains rev. Washington, DC: Author. at a constant level throughout the day, but grows BAKER, T. B., MORSE, E., & SHERMAN, J. E. (1987). The stronger or weaker depending on the situations the motivation to use drugs: A psychobiological analysis addict encounters. These situations tend to be of urges. In P. C. Rivers (Ed.), The Nebraska sympo- strongly associated with previous use of drugs, such sium on motivation: Alcohol use and abuse (pp. 257– as meeting drug-using friends or going to locations 323). Lincoln: University of Nebraska Press. where the addict used drugs in the past. JELLINEK, E. M. (1955). The ‘‘craving’’ for alcohol. Laboratory studies attempt to manipulate Quarterly Journal of Studies on Alcohol, 16, 35–38. craving by presenting addicts with stimuli or cues KASSEL,J.D.,&SHIFFMAN, S. (1992). What can hunger that have been associated with their previous drug teach us about drug craving? A comparative analysis use. For example, a heroin addict may watch a of the two constructs. Advances in Behaviour Re- videotape of someone injecting heroin or smokers search and Therapy, 14, 141–167. may be asked to imagine a situation in which they MARLATT, G. A. (1985). Cognitive factors in the relapse would want to smoke. These cue-reactivity studies process. In G. A. Marlatt & J. R. Gordon (Eds.). Re- allow the measurement of self-reports of craving, lapse prevention (pp. 128–200). New York: Guilford drug-use behavior, and physiological reactions un- Press. der controlled conditions. Results from these stud- POULOUS, C. W., HINSON, R., & SIEGEL., S. (1981). The ies indicate that abstinence from drugs, drug-re- role of Pavlovian processes in drug tolerance and de- lated stimuli, and negative moods can influence pendence: Implications for treatment. Addictive Be- craving measures. haviors, 6, 205–211. Many of the results of naturalistic and labora- TIFFANY, S. T. (1990). A cognitive model of drug urges tory studies have presented a challenge to the dom- and drug-use behavior: Role of automatic and inant assumption that craving is directly responsi- nonautomattic behavior. Psychological Review, 97, ble for drug use in addicts (Kassel & Shiffman, 147–168. 1902; Tiffany, 1990). For example, across many WIKLER, A. (1948). Recent progress on neurophysiologi- cue-reactivity studies, there is not a very strong cal basis of morphine addiction. American Journal of correlation between addict’s reported levels of Psychiatry, 105, 329–338. craving and their level of drug consumption in the WISE, R. A. (1988). The neurobiology of craving: Impli- laboratory. Correlations between self-reported cations for understanding and treatment of addiction. craving and physiological reactions also tend to be Journal of Abnormal Psychology, 97, 118–132. weak. Other studies reveal that, although addicts WORLD HEALTH ORGANIZATION EXPERT COMMITTEES ON frequently complain that cravings are a major diffi- MENTAL HEALTH AND ALCOHOL. (1955). Craving for alcohol: Formulation of the Joint Expert Committees culty they face as they try to stay off their drugs, on Mental Health and Alcohol. Quarterly Journal of few addicts who relapse say that they experienced Studies on Alcohol, 16, 63–64. craving just before their relapse episode. These findings show that the exact function of craving in STEPHEN T. TIFFANY drug dependence remains a controversial issue. Despite these negative indications, millions of dollars are spent each year to develop pharmaco- CREATIVITY AND DRUGS Accounts of logical agents that might be capable of blocking, alcohol and drug use to stimulate creativity are preventing, or reducing craving for various drugs. apocryphal and anecdotal. For example, Samuel 358 CREATIVITY AND DRUGS

Taylor Coleridge reportedly composed much of his unfinished poem Kubla Khan while in an opium dream. In ancient Greece, however, the Pythian priestesses of the oracle at Delphi inhaled medici- nal fumes to facilitate revelatory trances—as did the priests and peoples of most ancient societies. The institutionalized twentieth-century Native American Church continues to use the PEYOTE of their ancestors to promote profound religious experiences. Psychedelic drugs, such as LYSERGIC ACID DI- ETHYLAMIDE (LSD), MESCALINE,PSILOCYBIN, and methylene dioxyamphetamine (MDA) have been used—both legally and illicitly—to increase aes- thetic appreciation, improve artistic techniques, and enhance creativity. MARIJUANA has been used to heighten the sense of meaning, foster creativity, and heighten perceptions (also both legally and illicitly); and ALCOHOL has been employed by countless people worldwide to relieve inhibitions, increase spontaneity, and stimulate innovation and originality. In the industrial West, the common belief in, Samuel Taylor Coleridge (1772–1834), depicted and positive association between, alcohol or drug here in a 1795 painting by Peter Van Dyke, use and creativity is strengthened by the popular reportedly composed much of Kubla Khan while stereotypes of artists, writers, actors, and others in in an opium dream. (᭧ Bettmann/CORBIS) the creative and performing arts as heavy users or abusers of such substances. Despite these anec- ulties; (8) a heightened sense of meaning and sig- dotal claims, little scientific evidence supports the nificance; (9) sense of the ineffable, in which the notion that alcohol and drug use actually increase experience cannot be expressed in words; and creativity. (10) feelings of rebirth and rejuvenation. When Part of the reason that creativity is attributed to people experience such features as these, it is un- drug use involves the actions of many psychoactive derstandable that they attribute creativity to cer- substances in producing altered states of conscious- tain drug experiences. ness. These altered states are characterized by some or all of the following features: (1) alterations in The immediate problem, however, in evaluating thinking, in which distinctions between cause and whether this is really so depends on the definition of effect become blurred and in which logical in- creativity. At the outset, three dimensions of crea- congruities may coexist; (2) disturbances in time tivity need to be distinguished: those pertaining to sense, whereby the sense of time and chronology the creative person, those pertaining to the creative may become greatly altered; (3) a sense of loss of process, and those pertaining to the creative prod- control, during which the person becomes less in- uct. If creativity pertains to an attribute of the per- hibited and self-possessed; (4) a change in emo- son (e.g., original thinking), then any unusual or tional expression; (5) body image change, with a extraordinary experiences should qualify as ‘‘cre- dissolution of boundaries between one’s self and ative,’’ even if nothing of social value emerges. If the world, resulting in transcendental or mystical creativity pertains to a process (e.g., discovery, in- experiences of ‘‘oneness’’ or ‘‘oceanic feelings’’; sight), then the testing and validation of the in- (6) perceptual distortions, including illusions, sights must take place as well. If creativity pertains pseudohallucinations, heightened acuity, and in- to a product, it not only should possess some mea- creased visual imagery; (7) hypersuggestibility, sure of social utility but should embody such quali- representing a decrease in the use of critical fac- ties as novelty, surprise, uniqueness, originality, CREATIVITY AND DRUGS 359 beauty, simplicity, value, and/or coherence. For used it in moderate amounts early in their careers both the creative process and the creative product, to remove certain roadblocks, to lessen depression there is no substantive evidence to indicate that or mania, or to modulate the effects of other drugs. alcohol or drugs have benefit, despite the ongoing With many anecdotal accounts to the contrary, belief of many that they do. The experience of the the weight of scientific and clinical evidence sug- sense of meaning or significance produced by drugs gests that long-term alcohol and drug use exert may have no bearing on whether that experience mostly negative effects on creativity. That drugs has true meaning or significance. The American and alcohol are used so widely within the creative philosopher and psychologist William James’s arts professions seems to have less to do with crea- claim that alcohol makes things seem more ‘‘utterly tivity than with social expectations and other extra- utter’’ is especially apt. This also happens with neous factors. In fact, people use pharmacological PSYCHEDELIC DRUGS, which have the capacity to substances for many reasons other than the stimu- induce a sense of profundity and epiphany (intui- lation of their imaginations. These reasons include tive grasp of reality), but usually without any sub- relaxation, the facilitation of sleep, self-medication, stantive or lasting benefit or practical value. social rituals, pleasure, or simply habituation or What, then, is the actual state of knowledge addiction. about the relationship between substance use and Because writers, artists, actors, or musicians creative achievement? What few studies exist, in may write about, portray, or act out certain aspects fact, indicate mostly detrimental effects of drugs on of their pharmacological experiences does not logi- creativity, especially when these substances are cally or necessarily mean that these experiences are taken in large amounts and over an extended pe- essential for the creative process. Creative people riod of time. The results of studies on the actions of often exploit all aspects of their experiences— alcohol typify this. As early as 1962, for example, whether pathological or healthy and whether drug- Nash demonstrated that small doses (about equal to two martinis) of alcohol, in normal volunteers, induced or not—in a creative way; they try to tended to facilitate mental associations, while large translate personal visions and insights within their doses (about equal to four martinis) had adverse own fields of expression into socially acceptable, effects. With the large doses, they had more trouble useful, or scientifically testable truths. Without in discriminating and assimilating details and per- some measure of social utility, unique drug- forming complex tasks. In another study, Hajcak induced experiences represent little more than idio- (1975) found that male undergraduates permitted syncratic to quasi-psychotic productions, having alcohol on an ad-lib basis (without limits or re- value and meaning only, perhaps, to the substance straints) showed greater initial productivity than user. when not allowed to drinkbut showed decreased appropriateness and decreased creative problem BIBLIOGRAPHY solving when intoxicated. In an anecdotal study with seventeen artists who HARMON, W. W., ET AL. (1966). Psychedelic agents in drank, Roe (1946) found that all but one regarded creative problem-solving. Psychological Reports, 19, the short-term effects of alcohol as deleterious to 211–227. their work, but they sometimes used it to overcome KOSKI-JANNES, A. (1985). Alcohol and literary creativity. various technical difficulties. The general senti- Journal of Creative Behavior, 19, 120–136. ment was that alcohol provided the freedom for KRIPPNER, S. (1969). The psychedelic state, the hypnotic painting but impaired the discipline. In a more trance and the creative act. In C. Tart (Ed.). Altered extensive study of thirty-four eminent writers, states of consciousness. New York: Wiley. Ludwig (1990) found that more than 75 percent of LUDWIG, A. M. (1990). Alcohol input and creative out- artists or performers who drankheavily experi- put. British Journal of Addiction, 85, 953–963. enced negative effects from alcohol—either directly LUDWIG, A. M. (1966). Altered states of consciousness. or indirectly, on creative activity, particularly when Archives of General Psychiatry, 15, 223–234. they did not refrain from drinking when they were LUDWIG, A. M. (1989). Reflections on creativity and working. More positive effects of alcohol were madness. American Journal of Psychotherapy, 43,4– found in a small number of cases, among those who 14. 360 CRIME AND ALCOHOL

MCGLOTHLIN, W., COHEN, S., & MCGLOTHLIN,M.S. is complex (involving multiple factors in addition (1967). Long-lasting effects of LSD on normals. Ar- to alcohol), and that alcohol is often blamed with- chives of General Psychiatry, 17, 521–532. out justification for criminal offenses. NASH, H. (1962). Alcohol and caffeine: A study of their psychological effects, Springfield, IL: Charles C. HOW OFTEN DOES DRINKING Thomas. PRECEDE THE COMMISSION ROE, A. (1946). Alcohol and creative work. Quarterly OF CRIMES? Journal of the Study of Alcohol, 415–467. The Bureau of Justice Statistics (BJS), an agency TART, C. T. (1971). On being stoned. Palo Alto. CA: Science and Behavior Books. of the U.S. Department of Justice, reviewed the role alcohol played in crime by looking at convicted ARNOLD M. LUDWIG offender data from 1996 (Greenfield, 1998). On an average day in 1996, an estimated 5.3 million convicted offenders were under the supervision of CRIME AND ALCOHOL The relationship criminal justice authorities. Nearly 40% of these between ALCOHOL and involvement in crime is not offenders, about two million, had been using alco- a simple one. Drinking is a very common activity, hol at the time of the offense for which they were and most drinking is not followed by criminal be- convicted. Whether the offender was on probation havior. Understanding the alcohol-crime relation- or was incarcerated in a local jail or a state prison, ship requires an identification of those drinking ef- offenders were about equally likely to have been fects and circumstances that are related to crime. drinking at the time of the crime. What they con- Alcohol’s relationship to crime also varies by the sumed was similar, with beer being the most com- type of crime. The major crime-type distinction is monly used alcoholic beverage: 30 percent of pro- between violent personal crime (such as homicide, bationers, 32 percent of jail inmates, and 23 forcible rape, and assault) and property crime percent of state prisoners said that they had been (such as burglary and larceny). Alcohol’s effects drinking beer or beer in combination with liquor differ with respect to violent crime and property prior to the commission of the current offense. Con- crime. Individual characteristics are also impli- sumption of wine alone was comparatively rare cated in the alcohol-crime relationship. Age and among the surveyed offender populations. gender, for example, affect whether drinking leads Surveys of crime victims also indicate that of- to criminal behavior. Young adult males are more fenders often had been drinking. The National likely than older adult males and females of all ages Crime Victimization Survey (NCVS) is one of two to engage in alcohol-related offenses. statistical series maintained by the Department of According to the available evidence, drinking is Justice to learn about the extent to which crime is more likely to be implicated in violent than in prop- occurring. The NCVS, which gathers data on crimi- erty crime. Moreover, violent offenses are often nal victimization from a national sample of house- thought of as expressive or instrumental. Expres- hold respondents, provides annual estimates of sive violent offenses are typically those that result crimes experienced by the public without regard to from interpersonal conflict that escalates from ver- whether a law enforcement agency was called bal abuse to physical AGGRESSION. Such violence about the crime. Initiated in 1972, the NCVS was often involves a drinking offender or drinking by designed to complement what is known about both (or multiple) parties in cases of violent con- crimes reported to local law enforcement agencies flict. Instrumental offenses have rational goals, typ- under the FBI’s annual compilation known as the ified by stealing to realize the value of the stolen Uniform Crime Reporting Program (UCR). 1998 money or goods. Alcohol is not thought to be an estimates from the NCVS indicate that victims of important causal factor in acquisitive crimes such about three million violent crimes each year, or as theft. about a quarter of all violent crimes, perceived the Research has shown that alcohol is an important offenders to have been drinking. factor in the occurrence of expressive interpersonal Most studies of alcohol and crime focus on of- violence, that alcohol use increases the riskof being fenses known to the police or on offenders serving a crime victim, that the alcohol-crime relationship sentences for crimes that resulted in conviction. A CRIME AND ALCOHOL 361 notable exception is a community study in Thunder et al. (1986) tested the alcohol levels of several Bay, located in the province of Ontario, Canada. thousand homicide victims; they found that 46 per- Pernanen (1976, 1981, 1991) collected informa- cent of the victims had consumed alcohol in the tion from a representative sample of 1,100 commu- period before being killed, and three of ten victims nity residents. Among those who had been victim- had alcohol levels beyond the legal intoxication ized, the assailant had been drinking in 51 percent level. of the occasions when violence occurred; two-thirds Roizen (1993) examined studies of alcohol use of the time (68%), the assailant was judged to have by robbery and rape victims. The percentage who been ‘‘drunk.’’ Pernanen also noted that the find- had been drinking before their victimization ings for the Thunder Bay study are consistent with ranged widely—from 12 to 16 percent for robbery many other North American studies using police victims and from 6 to 36 percent for rape victims. records. It is usually found that half of all violent Abbey (1991) and Muehlenhard and Linton offenders had been drinking at the time of the (1987) also found in their studies of date rape that offense. both offenders and victims had commonly been The most common pattern found in studies of drinking. Abbey suggested that drinking by the of- violent crimes is that 60 percent or more of the fender or by the victim contributes to rape by the events involve drinking by the offender, both the impaired communication and misperception that offender and the victim, or the victim only. The results from alcohol’s effects on cognitive ability results of Wolfgang’s classic study (1958) of crimi- (among other contributing factors). Males who nal homicides in Philadelphia are typical (see ta- have been drinking, for example, may mistakenly ble 2). The most common pattern when alcohol was attribute sexual intent to their date. present was for both victim and offender to have Alcohol may increase the riskthat the drinker been drinking. will be a crime victim because of effects that alcohol If the foregoing findings indicated the extent to has on judgment and demeanor. Someone who has which drinking was causally implicated in violent been drinking may take risks that might not be crime, it would be remarkable. It could then be taken when sober, such as walking in a dangerous argued that alcohol accounts for a majority of vio- area of a city at night. Alcohol also causes some lent offenses. But neither the presence of alcohol in individuals to be loud and verbally aggressive. a crime nor the intoxication of an offender is neces- Such demeanor can be offensive and might some- sarily an indication that alcohol influenced the oc- times precipitate physical attack. currence of the crime. Because drinking is such a common activity, it is likely that alcohol is some- DOES DRINKING GENERATE times simply present but not causally relevant. FAMILY VIOLENCE? Drinking is also sometimes offered by offenders as an excuse for the crime, as a way of avoiding being Unfortunately, violence is common in American held accountable. households, and alcohol is a contributing factor, according to research done by Kantor and Straus (1989) and by Straus, Gelles, and Steinmetz ALCOHOL USE AND (1980), among others. Hotaling and Sugarman CRIME VICTIMIZATION (1986) found that alcohol appears to be most rele- Alcohol use raises the likelihood that the drinker vant to the occurrence of husband-against-wife vi- will be a victim of violent crime. Substantial per- olence. Hamilton and Collins (1981) reviewed centages of homicide, assault, and robbery victims about 25 studies that examined the role of alcohol were drinking just before their victimization. Medi- in spouse and CHILD ABUSE. They found alcohol to cal examiners have done a significant number of be most relevant to wife beating, where it was pres- homicide studies by running toxicological tests of ent in one-quarter to a half of all such events. the body fluids of homicide victims. Separate re- (Alcohol was present in less than one in five inci- views by Greenberg (1981) and by Murdoch, Pihl, dents of child abuse.) The most common pattern and Ross (1990) found that the percentage of was for only the husband to be drinking or for both homicide victims who had been drinking ranges parties to have consumed alcohol. It was uncom- widely, but is usually about 50 percent. Goodman mon for only the wife to have been drinking. Stud- 362 CRIME AND ALCOHOL ies also indicate that husbands or partners with These possible explanations are not mutually alcohol problems were more likely to be violent exclusive. All may sometimes accurately describe against their wives/partners. how drinking causes crime. Two or more of the A 1998 BJS study on the relationship between explanations may even apply to the same incident. crime and alcohol found that two-thirds of victims Committing ‘‘income crimes’’—to obtain money who suffered violence by an intimate (a current or for drinking—is not thought to be an important former spouse, boyfriend, or girlfriend) reported explanation. Although the cost of maintaining an that alcohol had been a factor. Among spouse vic- addiction to relatively more expensive drugs (e.g., tims, three out of four incidents were reported to HEROIN and COCAINE) is high, the price tag for have involved an offender who had been drinking. supporting heavy drinking is usually modest. In By contrast, an estimated 31 percent of stranger most of the United States, for example, one could victimizations where the victim could determine support a habit of daily heavy drinking for 10 the absence or presence of alcohol were perceived to dollars or less. The majority of individuals could be alcohol-related. maintain such a habit without resorting to crime, Research by Jones and Schecter (1992) and by although many heavy drinkers spend more than Barnett and Fagan (1993) on family violence sug- this minimal amount on alcohol. There is virtually gests that violence against women may lead to their no information in the research literature about the likelihood or frequency of involvement in income own use of alcohol and drugs as a coping mecha- crime to support drinking, but alcohol is not nism. Drinking and/or drug use may be a response thought to be a major factor in income crimes. This to the physical and emotional pain and fear that does not mean it never happens, only that it is result from living in a violent relationship. Miller, uncommon. Downs, and Testa (1993) found that women in If alcohol is not an important factor in the occur- alcohol-treatment programs had higher rates of fa- rence of income-generating crime, why do so many ther-to-daughter violence than did the women in property offenders (approximately 30 percent of the comparison group. These findings underline the inmates in 1996) report they were under the influ- importance of interpreting the meaning of alcohol’s ence of alcohol at the time they committed such association with family (and other forms of) vio- offenses? At least two explanations are possible for lence carefully. As previously noted, alcohol is often the high correlation between drinking and property present but irrelevant to the occurrence of violence. crime. The first suggests that the correlation is sim- Some recent literature on family violence indicates ply coincidental, not causal. A second reason (put that alcohol use may sometimes be a response to forward by both Collins, 1988, and Cordilia, violent victimization. 1985), is that a property offender who has been drinking is more likely to be caught than is a sober HOW OR WHY DOES ALCOHOL one. This reason makes sense based on the known CONTRIBUTE TO CRIME? impairment effects of alcohol. A drinking offender may not be as competent or careful as a sober one, There are a number of possible explanations of- so drinking offenders may be overrepresented fered for alcohol’s role in crime: among offenders who are caught and thus known The need for money to support drinking may to criminal-justice officials. cause some individuals to commit crimes to gener- Alcohol impairs cognitive ability, including ate cash to support their habit. one’s own capacity to communicate clearly and the The pharmacological effects of alcohol can com- capacity to understand the verbal and behavioral promise drinkers’ cognitive ability and judgment cues of others. In addition, a person whose abilities and raise the likelihood of physical aggression. have been impaired by alcohol is less able to make Expectations that alcohol makes drinkers ag- decisions and carry out appropriate and effective gressive may increase the chance of violence. actions. Pernanen, in his early work(1976), dis- Standards of conduct and accountability for be- cussed how alcohol-impaired cognitive ability can havior may differ for sober and drunken activities lead to violence. When one or both parties who are (these differences can result in an increase in the interacting have been drinking, there is an in- likelihood of criminal behavior after drinking). creased potential for misunderstanding that can CRIME AND ALCOHOL 363 lead to conflict and that may in turn escalate to deviance disavowal potential of alcohol can ac- violence. One factor in such a scenario is what may count for a drinker’s involvement in crime in two be called a ‘‘reduced behavioral response reper- ways: individuals may drinkor say that they have toire.’’ Alcohol impairs a drinker’s capacity to con- been drinking as an advance excuse for their con- ceive and utilize the wide range of verbal and other duct, or drinking may be offered as an excuse after behavioral options that are available to sober indi- the fact. viduals. Alcohol-induced cognitive impairment may also diminish the drinker’s capacity to foresee SUMMARY the negative implications of violent actions. In sum- mary, one way that alcohol increases the likelihood Drinking alcohol and involvement in criminal of violence is its negative effect on cognitive capaci- behavior frequently occur together. Some of the ties, and these effects lead to an increased riskof time alcohol has a causal role in crime, but often it violence. is merely present. Drinking is most likely to be It has been demonstrated in laboratory experi- relevant causally to expressive interpersonal vio- ments that both actual alcohol use and the belief lence—including family violence. Drinking can in- that alcohol has been consumed can raise levels of crease the riskof being victimized as well. Drinking aggression. In laboratory experiments using com- may also sometimes help account for the commis- petitive encounters between opponents in which the sion of crimes to obtain money to support the habit, winner can apply an electrical shockto the loser, but alcohol is not a major factor in the occurrence subjects who have been given alcohol behave more of income crime. Drinking leads to criminal behav- aggressively. Evidence gathered by Bushman and ior in a number of ways, including the effects that Cooper (1990) and by Hull and Bond (1986) also alcohol use has on cognition and the rules that indicates that subjects who have been told they govern behavior and accountability for behavior. have received alcohol, but who actually have been The alcohol-crime relationship is complex. It is given a placebo, are more aggressive in their ad- clear that drinking is rarely the only cause of crimi- ministration of electrical shocks. These findings nal behavior, and that when it does contribute, it is suggest that beliefs about alcohol’s behavioral ef- usually only one of a number of relevant factors. fects can themselves affect behavior. Expectations that alcohol use leads to aggressive (SEE ALSO: Complications: Cognition; Crime and behavior probably have sociocultural roots. An- Drugs; Drunk Driving; Economic Costs of Alcohol thropologists such as Heath (1976a, 1976b) and Abuse and Alcohol Dependence; Expectancies; MacAndrew and Edgerton (1969), for example, Family Violence and Substance Abuse; Social Costs noted that societies differ in the behavior that oc- of Alcohol and Drug Abuse) curs after drinking. Some of these differences may be attributable to racial or ethnic differences in BIBLIOGRAPHY physiological reactions to alcohol, but it is also clear that there are normative variations in what ABBEY, A. (1991). Acquaintance rape and alcohol con- behaviors are expected or acceptable after drink- sumption on college campuses: How are they linked? ing. In fact, behavioral norms after drinking may Journal of American College Health, 39(4), 165–169. vary within societies. MacAndrew and Edgerton BARNETT, O. W., & FAGAN, R. W. (1993). Alcohol use in noted that during certain ‘‘time-out’’ periods, usual male spouse abusers and their female partners. Jour- standards of behavior are suspended. For example, nal of Family Violence, 8(1), 1–25. festivals or Mardi Gras celebrations are often char- BECK, A., ET AL. (1993). Survey of state prison inmates, acterized by high levels of drinking and behavior 1991, (NCJ-136949). Washington, DC: U.S. Depart- that is considered deviant or criminal during nor- ment of Justice, Office of Justice Programs, Bureau of mal times. Justice Statistics. Alcohol appears to be implicated in violence in BUSHMAN, B. J., & COOPER, H. M. (1990). Effects of alco- another indirect way. Drinking is sometimes used hol on human aggression: An integrative research re- as an excuse for crime or as a way to avoid account- view. Psychological Bulletin, 107(3), 341–354. ability after the fact. McCaghy (1968) has referred COLLINS, J. J. (1988). Alcohol and interpersonal vio- to this phenomenon as ‘‘deviance disavowal.’’ The lence: Less than meets the eye. In N. A. Weiner & 364 CRIME AND DRUGS

M. E. Wolfgang (Eds.), Pathways to criminal vio- MCCAGHY, C. (1968). Drinking and deviance disavowal: lence. Newbury Park, CA: Sage Publications. The case of child molesters. Social Problems, 16,43– CORDILIA, A. (1985). Alcohol and property crime: Ex- 49. ploring the causal nexus. Journal of Studies on Alco- MILLER, B. A., DOWNS, W. R., & TESTA, M. (1993). Inter- hol, 46(2), 161–171. relationships between victimization experiences and GOODMAN, R. A., ET AL. (1986). Alcohol use and interper- women’s alcohol/drug use. Journal of Studies on Alco- sonal violence: Alcohol detected in homicide victims. hol, Suppl. 11, 109–117. American Journal of Public Health, 76(2), 144–149. MUEHLENHARD, C. L., & LINTON, M. A. (1987). Date GREENBERG, S. W. (1981). Alcohol and crime: A method- rape and sexual aggression in dating situations: Inci- ological critique of the literature. In J. J. Collins Jr. dence and riskfactors. 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The role of relationships between alcohol consumption and crim- alcohol in wife heating and child abuse: A review of inal behavior. New York: Guilford Press. the literature. In J. J. Collins Jr. (Ed.), Drinking and PERNANEN, K. (1976). Alcohol and crimes of violence. In crime: Perspectives on the relationship between alco- B. Kissin & H. Begleiter (Eds.), The biology of alco- hol consumption and criminal behavior. New York: holism: Vol. 4. Social aspects of alcoholism. New Guilford Press. York: Plenum. HEATH, D. B. (1976a). Anthropological perspectives on ROIZEN, J. (1993). Issues in the epidemiology of alcohol alcohol: An historical review. In M. W. Everett, J. O. and violence. In S. E. Martin (Ed.), Alcohol and inter- Waddell, & D. B. Heath (Eds.), Cross-cultural ap- personal violence: Fostering multidisciplinary per- proaches to the study of alcohol. The Hague: Mauton. spectives. (NIH Publication No. 93-3496, Research HEATH, D. B. (1976b). Anthropological perspectives on Monograph 24). Rockville, MD: U.S. Department of the social biology of alcohol: An introduction to the Health and Human Services. literature. In B. Kissin & H. Begleiter (Eds.), The STRAUS,M.A.,GELLES, R. J., & STEINMETZ,S.K. biology of alcoholism: Vol. 4. Social aspects of alco- (1980). Behind closed doors: Violence in the American holism. New York: Plenum. family. Garden City, NY: Anchor-Doubleday. HOTALING, G., & SUGARMAN, D. (1986). An analysis of WOLFGANG, M. E. (1958). Patterns of criminal homicide. riskmarkersin husband to wife violence: The current Philadelphia: University of Pennsylvania Press. state of knowledge. Violence and Victims, 1, 101–124. ZAWITZ, M. W., ET AL. (1993). Highlights from 20 years HULL, J. G., & BOND, C. F. (1986). Social and behavioral of surveying crime victims: The National Crime Vic- consequences of alcohol consumption and expec- timization Survey, 1973–92, NCJ-144525. Washing- tancy: A meta-analysis. Psychological Bulletin, 99, ton, DC: U.S. Department of Justice, Office of Justice 347–360. Programs, Bureau of Justice Statistics. JONES, A., & SCHECHTER, S. (1992). When love goes JAMES J. COLLINS wrong: What to do when you can’t do anything right. REVISED BY FREDERICK K. GRITTNER New York: HarperCollins. KANTOR, G.-K., & STRAUS, M. A. (1989). Substance abuse as a precipitant of wife abuse victimizations. CRIME AND DRUGS Because of wide- American Journal of Drug and Alcohol Abuse, 15(2), spread public and political concern over drug-re- 173–189. lated crime, there has been an urgent need to un- MACANDREW, C., & EDGERTON, R. B. (1969). Drunken derstand the drugs-crime relationship. However, comportment: A social explanation. Chicago: Aldine. despite numerous studies on this topic, only re- CRIME AND DRUGS 365 cently have significant empirical advances in our single national drug problem, but rather different understanding emerged. local drug problems that vary from city to city. Authors of a comprehensive literature review published in 1980 concluded that the drugs-crime THE CRIMINALITY OF relationship was far more complex than originally DRUG ABUSERS believed (Gandossy et al.). While acknowledging significant contributions of previous research, the In examining the criminality of drug abusers, it authors felt that methodological problems in the is important to note that the onset of illicit drug use studies they reviewed had obscured an understand- typically does not result in the onset of criminal ing of the linkage between drugs and crime. As behavior. Rather, it is the frequency, not the onset, these and other reviewers have observed, perhaps of drug use that increases criminal activity. Fur- the most serious of these weaknesses was the use of ther, the positive relationship between drug-use official arrest records as indicators of criminal ac- frequency and crime frequency is not consistent tivity. Studies using confidential self-report meth- across all types of drug use and all types of crime. ods in settings in which there is immunity from Such a relationship has been observed with respect prosecution have consistently documented that less to only three types of drug abuse: heroin addiction, than 1 percent of offenses committed by drug abus- cocaine abuse, and multiple-drug use. In addition, ers result in arrest. such associations are more common for property With a subsequent emphasis on confidential crime than for violent crime. self-report data, studies conducted since 1980 have Narcotic Drug Use. Much of our knowledge permitted more realistic estimates of the extent of about the relationship between drugs and crime criminality among drug abusers. In addition, vic- comes from detailed self-report information on the tims of violent crime are now being asked whether type, extent, and severity of criminal activity of they perceived the offender to be under the influ- NARCOTIC (mainly heroin) addicts. Large-scale, in- ence of drugs or alcohol. The annual Bureau of dependently conducted studies have convincingly Justice Statistics (BJS) National Crime Victimiza- shown that increases in property crime and rob- tion Survey asks this question of crime victims. bery, which has components of both property crime Though a subjective inquiry, the 1998 survey re- and violence, are associated with increased heroin vealed that 30 percent of victims could not deter- use. Such a relationship, however, is less clear for mine whether the offender was under the influence violent crimes other than robbery. of a substance. Of those who could make a determi- Prevalence and Scope of Property and Violent nation, about 31 percent reported that the offender Crime. Several key studies reveal an exceptionally was under the influence of drugs or alchohol. high prevalence of property crime among narcotic In 1997, the National Institute of Justice (NIJ) addicts. Anglin and Speckart (1988) found that 82 established the Arrestee Drug Abuse Monitoring percent of a sample of 386 California male narcotic (ADAM) Program to measure drug use among ar- addicts reported involvement in property crime restees by calculating the percentage of arrestees over an average five-year period of daily narcotic with positive urine tests for drug use. ADAM data use. Anglin and Hser (1987) reported that 77 per- are collected voluntarily and anonymously at the cent of a sample of 196 female narcotic addicts time of arrest in booking facilities in thirty-five U.S. from California admitted to involvement in prop- cities. The ADAM program has given researchers a erty crime during an average six-year narcotic ad- powerful tool for obtaining empirical evidence of diction period. Inciardi (1986) noted that almost patterns of drug abuse. ADAM is the only national all of a sample of 573 male and female narcotic research program studying drug use that employs abusers from Miami had reportedly engaged in both drug testing and interviews, giving analysts theft during the year prior to interview. Inciardi the means of assessing validity of self-report data. also found that these individuals reported involve- Therefore, ADAM data are less susceptible either to ment in more than 77,000 property crimes (on av- exaggeration or denial of drug use than many other erage, 135 per subject) over a 12-month period surveys. Moreover, ADAM is the only national drug while at large in the community. This figure in- research program built upon data collection at the cluded 6,669 burglaries, 841 vehicle thefts, 25,045 local level. This data has revealed that there is no instances of shoplifting, and 17,240 instances of 366 CRIME AND DRUGS fencing. While these studies varied in sampling addiction. Such a relationship tends to be linear, methods and definitions of property crime (e.g., with the highest property-crime rates occurring at including and not including robbery), all provided the highest levels of narcotic use (three or more evidence that a substantial majority of narcotic times per day). In addition, although most addicts abusers routinely engage in property crime. commit property crime prior to addiction, the fre- Property crime comprises a considerable portion quency of such crime increases significantly from of the crime, other than drug distribution, com- preaddiction to addiction, remaining high over mitted by narcotic addicts. For instance, Nurco et subsequent addiction periods and low during inter- al. (1991a) found that of the nondistribution vening nonaddiction periods. While other factors crimes committed by a sample of 250 male narcotic also influence property-crime rates, the simplest addicts during an average 7.5-year addiction pe- explanation for these results is that property crime riod, approximately 48 percent were property is functionally related to narcotic addiction—since crimes. addicts need cash to support their habits. Research has also consistently documented that Evidence of a similar relationship between her- among heroin addicts, violent crime is less preva- oin use and violent crime is less conclusive. Studies lent and occurs with less frequency than property have consistently shown that rates for robbery, in crime. Earlier studies noted that addicts tended to which there are property-crime features, are con- prefer property crime over violent crime and ap- siderably higher during addiction periods than dur- peared to be less violent than other offenders. ing either preaddiction or nonaddiction periods. While findings from later studies have continued to However, when rates for composite measures of show that violence accounts for only a small pro- violence and rates of assault alone are examined, portion of all addict crime (approximately 1% to the relationship appears less clear. 3%, a rate that is much smaller than the property- In compiling composite measures of violence, crime figure), the actual number of violent crimes is Ball et al. (1983) found that for a sample of 243 still quite large because addicts commit so many male Baltimore addicts, the number of days on crimes. For example, in Inciardi’s 1986 sample of which violent crime was committed was considera- 573 Miami narcotic abusers, violent crime com- bly higher during the first addiction period than prised only 2.8 percent of all offenses (5% of non- during the first nonaddiction period. However, in distribution offenses) committed by the subjects in the year prior to interview. However, this relatively subsequent studies of 250 male addicts from Balti- small percentage amounted to 6,000 incidents of more and New YorkCity, most of whom had multi- violent crime (on average, 10.4 per subject), since a ple periods of addiction, more complex relation- total of 215,105 offenses were committed. ships were observed. Over an addiction career, Researchers have also suggested that heavy her- violent-crime rates for the total sample were signif- oin use and, more recently, heavy cocaine abuse icantly higher for combined addiction periods than have contributed to record numbers of homicides in for combined nonaddiction periods (Nurco et al., large cities in the United States. The ways in which 1986; Nurco et al., 1988a). This result stemmed drugs can contribute to violence is the basis for a largely from high levels of crime committed during prominent theory in the drugs-crime field, dis- the first addiction period; violent crime actually cussed later in this article. decreased over subsequent periods of addiction, a Crime and Frequency of Heroin Use. Recent studies finding that appeared to be age-related. The fact have provided consistent evidence of a direct, func- that mean rates for violence were found to be even tional relationship between the frequency of nar- higher for preaddiction (10 days per year) than for cotic drug (primarily heroin) use and the frequency addiction periods (8 days per year) also reflected an of property crime. These investigations have em- inverse relationship between age and violent crimi- ployed a unique longitudinal design in which crime nal activity. data are obtained for each subject over periods dur- The 1999 ADAM report on U.S. drug use of ing which the frequency of narcotic use may vary. arrestees reveals that opiate use among adult ar- These studies of addiction careers reveal that prop- restees remains relatively low compared to the erty-crime rates are significantly higher during nar- prevalence of cocaine and marijuana in the overall cotic addiction periods than during periods of non- sample. For female arrestees the median rate for CRIME AND DRUGS 367 testing positive to opiates was 8 percent in 1999 58 subjects classified as heavy cocaine users (8 or and for male arrestees it was 6 per cent. more doses per day) were 12, 14, and 320 for Nonnarcotic Drug Use. Investigation of the violent crime, major property offenses, and minor nonnarcotic drugs-crime relationship has only re- property crimes, respectively. These rates were cently emerged as a major research question. In the substantially higher than rates for the 90 subjects 1980 literature review, Gandossy and associates classified as ‘‘typical’’ users (4–7.99 doses per found that, of the few studies conducted on the day). For those forty-nine users who tookless than nonnarcotic drug-crime relationship, evidence four doses per day, the average adjusted annual linking the use of various nonnarcotic substances to rates for violence and major property crime were either property crime or violent crime was weak. less than one, and the rate for minor property Another reason for the unclear relationship be- offenses was twenty-four. tween nonnarcotic drug use and criminal behavior Increased cocaine use among narcotic addicts is that various narcotic and nonnarcotic drugs are has also been associated with increased property often used in combination. Thus, disentangling and violent-crime rates. Both Nurco et al. (1988b) their separate relationships to criminal activity, let and Shaffer et al. (1985) found that male narcotic alone determining cause and effect, is especially addicts who had higher rates of cocaine use tended problematic. Despite these difficulties, significant to have higher rates of property and violent crime advances have been made in understanding the than addicts who did not abuse cocaine. nonnarcotic drugs-crime relationship since 1980. The 1999 ADAM report found that cocaine use Cocaine. Data analyses on a nationwide probability among adult arrestees remained high, with cocaine sample of 1,725 adolescents strongly supported a found in more than one-third of adult arrestees in cocaine-crime connection (Johnson et al., 1991). twenty sites. There was substantial variation in the Adolescents who reported using cocaine in the year proportion of those testing positive for cocaine. In preceding the interview (comprising only 1.3% of three sites (Atlanta, Chicago, New YorkCity), more the sample) were responsible for a disproportion- than 60 percent of adult female arrestees tested ately large share of the property and violent crime positive for cocaine. In six other sites, however, committed by the sample during this period. The cocaine use was less than 25 percent. cocaine users accounted for 60 percent of all minor Other Nonnarcotic Drugs. The use of other non- thefts, 57 percent of felony thefts, 41 percent of all narcotic drugs appears to be unrelated to increased robberies, and 28 percent of felony assaults com- criminal activity. While there is considerable evi- mitted by the entire sample. dence that frequent users of multiple nonnarcotic Typological studies involving seriously delin- substances, including amphetamines, BARBITU- quent youth and female crack-cocaine abusers also RATES, marijuana, and PCP, typically have high revealed that subjects who reported the heaviest crime rates (although somewhat lower than rates levels of cocaine use also had substantially higher for heroin addicts), such is not the case for users of rates of property and violent crime than subjects single non-narcotic drugs. Although single use may who used crackless frequently. Among a sample of be related to offenses like disorderly conduct or 254 youth identified by Inciardi and coworkers driving while impaired, it is not generally associ- (1993a) as serious delinquents, the 184 CRACK ated with predatory crime. dealers (86% of whom were daily crackusers) were Marijuana. Research on the relationship between responsible for 45,563 property crimes (an average marijuana use and crime has found that, with the of 231 per user) during the year preceding the possible exception of the sale of the drug and disor- interview. In contrast, the seventy subjects who derly conduct or driving while impaired, the use of were not crackdealers and who used crackless marijuana is not associated with an increase in frequently (approximately three times per week) crime. Some studies have reported that marijuana averaged 135 property crimes per year. In addition, use may actually reduce inclinations toward violent the heavy cocaine users averaged ten robberies per crime. year, compared with one per year for the remaining A major problem in studying the association be- subjects. Similar results were reported for a sample tween marijuana use and criminal behavior is that of 197 female crackabusers (Inciardi et al., the exclusive use of marijuana is generally short- 1993b). The average adjusted annual rates for the lived. Further, like other illicit nonnarcotic sub- 368 CRIME AND DRUGS stances, marijuana is often used in combination theless, that the inconsistency of study findings with other drugs. Under such circumstances, it is may indicate that PCP use facilitates violence in a difficult to isolate the effects of heavy marijuana small proportion of users (Inciardi, 1986; Kinlock, use from those associated with the use of various 1991). There is agreement that biological, psycho- drug combinations. logical, situational, and other factors underlying The 1999 ADAM report disclosed that mari- seemingly drug-related aggressive behavior should juana remains a very popular drug for adult ar- be examined in future research. restees, particularly among young males between 15 and 20 years old. The median rate of marijuana THEORIES ON THE positives for this group of arrestees was 63 percent DRUGS-CRIME RELATIONSHIP compared to the overall adult male arrestee median rate of 39 percent and the overall adult female Inciardi (1986) has noted that numerous theo- arrestee median rate of 26 percent. ries have been posited to explain the drugs-crime Amphetamines. Literature reviews published dur- relationship. Many of these theories have dealt with ing the late 1970s and early 1980s (Gandossy et al., the etiology of drug use and crime. Early etiological 1980; Greenberg, 1976) reported that the associa- theories tended to be overly simplistic, focusing on tion between amphetamine use and crime was diffi- what Inciardi termed the ‘‘chicken-egg’’ question: cult to determine because, among other factors, of Which came first, drugs or crime? This question the diversity of amphetamine users. More recent polarized the drugs-crime field for over fifty years. ethnographic studies of drug abusers (Goldstein, It typically reflected two mutually exclusive posi- 1986) have reported that amphetamine use is re- tions: that addicts were criminals to begin with, lated to violent crime in some individuals. In the and addiction was simply another manifestation of general population, however, the association be- a deviant lifestyle; or that addicts were not crimi- tween amphetamine use and crime is not readily nals but, rather, were forced into committing crime apparent. Despite assertions of the media in the to support their drug habits. 1960s and 1970s, the prevalence of amphetamine- Reflecting a middle-ground position, more re- related violence among American youth is likely to cent theories argue for a diversity among narcotic be quite low. addicts with regard to the predispositional charac- The 1999 ADAM report indicated that metham- teristics and motives underlying drug-related crim- phetamine use among ADAM arrestees is concen- inal behavior. For example, on the basis of their trated mainly in the Western part of the United research with narcotic addicts, Nurco and his asso- States. A large number of sites had virtually no ciates (1991b) concluded that there is considerable presence of methamphetamine. However, preva- variation among addicts in their propensity toward lence rates exceeded 10 percent both for adult fe- criminal activity. Some addicts had been heavily male arrestees in twelve sites and for adult male involved in crime prior to addiction, whereas others arrestees in 9 sites. were extensively involved in crime only when ad- Psychedelic Substances. Most studies investigating dicted. the relationship between psychedelic-substance In the late 1970s, drugs-crime theories became abuse and crime have involved PHENCYCLIDINE increasingly complex, partly because studies (PCP). Much of this research has examined the tended to have fewer methodological problems that relationship between PCP and violence. As in the interfered with the measurement of both drug use coverage of many other nonnarcotic drugs, media and crime. With improvements in techniques, re- reports, principally in the 1970s and early 1980s, searchers gradually become more aware of hetero- emphasized a perceived linkbetween PCP use and geneity among drug abusers on many dimensions, violent behavior. However, the actual extent of this including the type and severity of drug-use patterns linkis greatly exaggerated. In his report on the and related criminal activity. Also, more recent subject, Kinlock(1991) noted that serious method- studies have found that drug use and crime, in most ological problems in some studies and contradic- instances, do not initially have a causal relationship tory findings in others disallowed a conclusive an- but, rather, are often the joint result of multiple swer to the question of whether PCP use increased influences. Among the many factors contributing to violent crime. Researchers have suggested, never- drug use and/or crime are those involving the fam- CRIME AND DRUGS 369 ily, such as lackof parental supervision, parental murdered as a result of drug-related activity rejection, family conflict, lackof discipline, and (Tardiff et al., 1986). The investigators contended parental deviance; association with deviant peers; that these percentages were higher than those pre- school dropout, failure, and discipline problems; viously reported in the United States. In a subse- and early antisocial behavior. Consistent with the quent study by Goldstein and his coworkers (1989) notion that all drug abusers are not alike, varying involving 414 homicides in New YorkCity that combinations of factors probably contribute to dif- occurred over an eight-month period, 53 percent ferent patterns of deviant behavior in individuals at were classified by the police and researchers as be- risk. ing drug-related. In both studies, most of the drug- However, as Inciardi and his associates (1993a) related homicides were attributed to systemic have noted, some limitations of these theories re- causes. Interestingly, in the former study, most of main. Most theories discuss drug abuse only as one the homicides involved heroin, whereas in the latter of several manifestations of delinquency. Further, study, most involved crack-cocaine. as in earlier years, the primary concern has been Drug Use and High-Rate, Serious Criminal- with the etiology of deviant behavior. Very little ity. As indicated earlier, the onset of illicit drug attention has been paid to explaining events that use typically does not result in the onset of criminal occur after the onset of drug use and criminal behavior. In most cases, both drug use and crime behavior, specifically how certain types of drug begin in the early teens. Generally, the less serious abuse increase the frequency of criminal activity. the drug or crime, the earlier the age at onset of Finally, theories have typically focused on adoles- involvement. For example, among illicit drugs, cence, without incorporating attributes and events marijuana is more commonly used at a younger age that influence behavior during childhood and than are sedatives or tranquilizers, and these drugs, adulthood. in turn, are typically used at a younger age than are Among the most prominent theories in the ‘‘hard’’ drugs, such as heroin and cocaine. Simi- drugs-crime field is that of Paul Goldstein (1986, larly, minor forms of crime (e.g., shoplifting, van- 1989) regarding the relationship between drugs dalism) have an earlier onset than more serious and violence. Goldstein’s theory is based on his types of crimes, such as assault, robbery, and drug numerous ethnographic accounts of violent drug- dealing. related acts obtained from both perpetrators and Most marijuana users do not become heroin ad- victims in New YorkCity. According to this theory, dicts, and most youths who commit minor property drugs and violence can be related in three separate crimes do not subsequently become involved in ways: psychopharmacologically, economic-com- more serious offenses. In both instances, the salient pulsively, and systemically. Within the psycho- variable appears to be age of onset—the younger pharmacological model, violent crime results from the individual is when first using a ‘‘soft’’ drug or the short- or long-term effects of the ingestion of committing a minor crime, the more likely he or she particular substances, most notably crack-cocaine will move on to more serious forms of deviance. In and heroin. According to the economic-compulsive general, the more deviant the environment (family, model, violent crime is committed as a means to peers, community), the earlier the onset of obtain money to purchase drugs, primarily expen- deviance. sive addictive drugs such as heroin and cocaine. Since 1980, independent studies have identified The systemic model posits that drug-related vio- several core characteristics of high-rate, serious of- lence results from the traditionally aggressive pat- fenders. According to Chaiken and Chaiken terns of interaction found at various levels within (1990), these studies have consistently found that systems of illicit-drug distribution. Examples in- predatory individuals tend to commit many differ- clude killing or assaulting someone for failure to ent types of crime, including violent crime, at high pay debts; for selling ‘‘bad,’’ or adulterated, drugs; rates, and to abuse many types of drugs, including or for transgression on one’s drug-dealing ‘‘turf.’’ heroin and cocaine. Also, research findings have Several key studies have analyzed data in the consistently reported that among heroin addicts, light of Goldstein’s concepts. In a study of 578 prisoners, and seriously delinquent youth, the homicides in Manhattan in 1981, 38 percent of the younger one is at onset of heroin and/or cocaine male and 14 percent of the female victims were addiction, the more frequent, persistent, and severe 370 CRIME AND DRUGS one’s criminal activity tends to be. In these studies, identified as drug users by urine testing conceal individuals with early onsets of addiction (typically their recent drug use, even in a voluntary, confi- before age 16) tended to abuse several types of dential interview having no bearing on their correc- drugs and to have disproportionately high rates of tional status. several types of crime, regardless of addiction sta- tus. Such findings have been observed in various (SEE ALSO: Antisocial Personality; Conduct Disor- geographic locations and are independent of ethnic der; Crime and Alcohol; Families and Drug Use; group. These results are similar for both males and Family Violence and Substance Abuse) females, with one notable exception: females with early onsets of addiction are more likely to commit BIBLIOGRAPHY prostitution, shoplifting, and other property crimes at high rates, whereas males with early onsets are ANGLIN,M.D.,&HSER, Y. (1987). Addicted women and more likely to commit violent acts. crime. Criminology, 25, 359–397. Chaiken and Chaiken’s 1982 study of over two ANGLIN,M.D.,&SPECKART, G. (1988). Narcotics use thousand male prisoners in three states was signifi- and crime: A multisample, multimethod analysis. cant for at least two reasons. First, it challenged the Criminology, 26, 197–233. long-held perception that drug abusers were less BALL, J. C., ET AL. (1983). The day-to-day criminality of violent than other arrestees. While 65 percent of heroin addicts in Baltimore: A study in the continuity Chaiken and Chaiken’s sample reported having of offense rates. Drug and Alcohol Dependence, 12, used illicit drugs during the one- to two-year period 119–142. preceding the arrest leading to the most recent CHAIKEN, J. M., & CHAIKEN, M. R. (1990). Drugs and incarceration, an even higher proportion (83%) of predatory crime. In M. Tonry & J. Q. Wilson (Eds.), high-rate, serious offenders, identified as ‘‘violent Drugs and crime. Crime and Justice: A Review of predators,’’ had used drugs during the same period. Research, Vol. 13. Chicago: University of Chicago Among the offenders studied, violent predators Press. were also most likely to have had histories of CHAIKEN, J. M., & CHAIKEN, M. R. (1982). Varieties of ‘‘hard’’ drug use (including heavy multiple-drug criminal behavior. Santa Monica, CA: Rand. use and heroin addiction) and to have had early ELLIOTT, D. S., ET AL. (1989). Multiple problem youth: onsets of several types of drug use and criminal Delinquency, substance use, and mental health prob- activity. Second, and perhaps more important, the lems. New York: Springer-Verlag. information on an offender’s drug history was more GANDOSSY, R. P., ET AL. (1980). Drugs and crime: A sur- likely than official arrest records to be related to the vey and analysis of the literature. National Institute of amount and seriousness of self-reported criminal Justice. Washington, DC: U.S. Department of Justice. activity. As in the results of drug-crime studies GOLDSTEIN, P. J. (1989a). Drugs and violent crime. In discussed earlier, official arrest data were poor in- N. A. Weiner & M. E. Wolfgang (Eds.), Pathways to dicators of the type, amount, and severity of crime criminal violence. Newbury Park, CA: Sage. committed by these respondents. GOLDSTEIN, P. J., ET AL. (1989b). Crackand homocide in These findings suggest a potential for using an New YorkCity, 1988: A conceptually-based event individual’s history of illicit drug use, including age analysis. Contempory Drug Problems, 16, 651–687. of onset, in identifying high-rate, dangerous of- GOLDSTEIN, P. J. (1986). Homicide related to drug traf- fenders. However, this approach has several limita- fic. Bulletin of the New York Academy of Medicine, 62, tions. First, a general caution is in order whenever 509–516. findings based on aggregate data are applied to the GREENBERG, S. W. (1976). The relationship between individual case. Second, although self-reports of crime and amphetamine abuse: An empirical review drug use and crime are generally valid when ob- of the literature. Contemporary Drug Problems, 5, tained from individuals who are either at large in 101–103. the community, entering a drug-abuse treatment INCIARDI, J. A., ET AL. (1993a). Street kids, street drugs, program, or already incarcerated, they tend to be street crime: An examination of drug use and serious less accurate for individuals being evaluated for delinquency in Miami. Belmont, CA: Wadsworth. initial disposition in the criminal-justice system. INCIARDI, J. A., ET AL. (1993b). Women and crack-co- Approximately one out of every two new arrestees caine. New Yokr: Macmillan. CROP-CONTROL POLICIES (DRUGS) 371

INCIARDI, J. A. (1986). The war on drugs: Heroin, co- CROP-CONTROL POLICIES (DRUGS) caine, and public policy. Palo Alto, CA: Mayfield. Eliminating drug crops at the source through crop INCIARDI, J. A. (Ed.). (1981). The drugs-crime connec- eradication and/or crop substitution has been a tion. Sage Annual Reviews of Drug and Alcohol central, or at least an integral, part of U.S. interna- Abuse, Vol. 5. Beverly Hills, CA: Sage. tional narcotics-control policy for the past twenty JOHNSON, B. D., ET AL. (1991). Concentration of delin- years. U.S. government policy officials maintain quent offending: Serious drug involvement and high that eradication of illicit narcotics closest to the delinquency rates. Journal of Drug Issues, 21, 205– source of the raw material represents the most cost- 229. effective and efficient approach to narcotics control KINLOCK, T. W. (1991). Does phencyclidine (PCP) use within the overall supply-reduction strategy. The increase violent crime? Journal of Drug Issues, 21, source of the illicit crop is believed to be the most 795–816. commercially vulnerable point in the chain from grower to user. Since 1990, however, U.S. govern- NURCO, D. N., ET. AL. (1991a). A classification of nar- cotic addicts based on type, amount, and severity of ment policy officials have shifted away from crop crime. Journal of Drug Issues, 21, 429–448. control in favor of enhanced interdiction and tar- geting major trafficking organizations. Despite the NURCO, D. N., ET AL. (1991b). Recent research on the best efforts of the United States and cooperating relationship between illicit drug use and crime. Be- drug-SOURCE COUNTRIES, controlling the crop has havioral Sciences and the Law, 9, 221–242. been a difficult, if not impossible, task. Several NURCO, D. N., ET AL. (1988a). Differential criminal pat- HEROIN and MARIJUANA crop-control successes terns of narcotic addicts over an addiction career. have occurred, most notably in MEXICO and Criminology, 26, 407–423. COLOMBIA, but these programs had their problems. NURCO, D. N., ET AL. (1988b). Nonnarcotic drug use over To date, notwithstanding minor, short-term suc- an addiction career: A study of heroin addicts in Balti- cesses in BOLIVIA, coca crop-control has remained more and New YorkCity. Comprehensive Psychiatry, an elusive goal in the Andes. Undertaking a drug 26, 450–459. crop-control program involves political as well as NURCO, D. N., ET AL. (1986). A comparison by ethnic economic costs for both the source country and the group and city of the criminal activities of narcotic United States. addicts. Journal of Nervous and Mental Disease, 12, 297–307. CROP-ESTIMATING METHODOLOGIES SHAFFER, J. W., ET AL. (1985). The frequency of non- narcotic drug use and its relationship to criminal ac- For more than a decade, the U.S. government tivity among narcotic addicts. Comprehensive Psychi- has estimated the total acreage under illicit-drug atry, 26, 558–566. cultivation at home and abroad, applying proven TARDIFF, K., ET AL. (1986). A study of homicide in methods similar to those used to estimate the size of Manhattan, 1981. American Journal of Public Health, legal crops. The government knows with less cer- 76, 139–143. tainty, however, actual crop yields (the amount of PIUM WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- coca leaf or O gum produced per acre). Soil fertility, weather, farming techniques, and plant ICY. (2000). National Drug Control Strategy: 2000 Annual Report. Washington, D.C. diseases can produce wide variations in crop yields. Given the clandestine nature of the drug business WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- and variations from year to year and place to place, ICY. (March,2000). Drug Related-Crime Fact Sheet. the government cannot estimate accurately the Washington, D.C. quantities harvested and available for processing. NATIONAL INSTITUTE OF JUSTICE. (1999). 1999 Annual Furthermore, wide variations in processing effi- Report on Drug Use Among Adult and Juvenile Ar- ciencies (depending on the orgin and quality of raw restees. Washington, D.C. material, technical processing method, size and so- DAVID N. NURCO phistication of laboratories, and the skill and expe- TIMOTHY W. KINLOCK rience of workers and chemists) make cocaine and THOMAS E. HANLON heroin production estimates extremely compli- REVISED BY FREDERICK K. GRITTNER cated. Using commonly believed processing effi- 372 CROP-CONTROL POLICIES (DRUGS)

ciencies, the government estimates a range for CO- CAINE and heroin production. Estimating the amount of this production that enters the United States poses still more difficult challenges. The government uses two principal methods of estimating illicit-drug acreage under cultivation: (1) photographic-based aerial surveys: and, (2) remote sensing from satellite surveillance. Both methods have validity and reliability problems, but aerial surveys matched by ground truth (the verifi- cation of cultivation in the areas photographed) produce the best estimates. Satellite surveillance data are problematic because of weather, instru- A Mexican federal policeman prepares to get off ment calibration, cultivation under foliage, the a helicopter as it lands near a large marijuana small size of fields, false positives and negatives field slated for destruction in Mocorito, Sinaloa, that result from color spectrum (signature) inaccu- Mexico, August 28, 1995. (AP Photo/Dario Lopez- racies, and lackof ground truth. Mills)

Crop-control strategies are important for co- EFFECTIVE CROP-CONTROL caine, heroin, and marijuana reduction, although STRATEGIES neither the United States nor the source govern- Many believe the illicit-drug trade is most sus- ments have much control over, or much access to, ceptible to disruption at the organizational center the largest opium-producing reigons of Southwest of gravity—the traffickers’ home country of pro- Asia (the Middle East) and Southeast Asia (espe- duction. Once the product leaves the production cially Myanmar [formerly Burma] and Afghani- area and enters the distribution networks, it be- stan, the world’s largest producers of illicit opium). comes more difficult to locate and control. Conse- The Peruvian government has exercised only lim- quently, the U.S. government’s drug-supply reduc- ited sovereignty over the world’s largest area of tion programs have historically focused major coca cultivation (for cocaine), the insurgent-con- attention on the drug source, which represents the trolled Upper Huallaga Valley (UHV). When gov- smallest, most localized point in the grower-to-user ernment commitment and ability exists for control- chain. ling the source of the illicit product, crop International supply-reduction efforts close to eradication and/or income substitution can be ef- the source of the drug also complement domestic fective ways to achieve a net reduction in the pro- supply-and-demand reduction efforts and give duction of the illegal crop. them a better chance of success. The U.S. 1991 National Drug Control Strategy states that when it COCA is judged to be feasible politically, particularly Both a legal and an illegal commodity, the COCA when the market price of the raw product has been PLANT is mainly grown in Andean South Amer- depressed below the cost of production, cooperative ica—in Peru, Bolivia, and Colombia; it belongs to efforts can and should be taken to reduce the net the genus Erythroxylon within the family Ery- cultivation of the NARCOTIC crops. Such crop con- throxylaceae. Most cocaine comes from the leaves trol, or eradication, would then occur through of 2 of the 250 identified species: E. coca Lam and manual or herbicidal means, crop substitution, in- E. novograntense. Each of these species, in turn, come replacement, and area-development projects has two varieties. Agriculturally speaking, coca is a that provide income and raise the standard of liv- hardy, relatively labor-free, subtropical perennial ing. Additionally, efforts would be made to con- plant that thrives at high to somewhat lower eleva- vince the cultivators to plough under or cut down tions and in dry to slightly humid climates, depend- their drug crops voluntarily or not to plant them in ing on variety. Coca plants are shallow-rooted, the first place. broad-leaved woody shrubs that grow to heights of CROP-CONTROL POLICIES (DRUGS) 373

3 to 10 feet (1 to 3 m) and live about 30 years adapted to do well in various soils and climates, (White, 1989; LaBattAnderson, 1990). It takes 30 ranging from southern Sweden to the Equator. De- to 36 months before the coca bush is mature pending on the soil and climatic conditions, the enough to produce leaves that can be used in the growers can harvest at least two crops per year production of cocaine. Once the plant is mature, (White, 1985). Although the opium poppy seems to three to four crops of coca leaves may be harvested flourish at about 3,000 feet (915 m) in low humid- per year for an estimated yield of 1 to 3 tons per ity, it also grows and survives in humid lowlands, acre (0.8 to 2.7 metric tons [MT] per hectare) of under foliage, or in full sunlight. With the aid of dry coca leaf cultivated per year. Actual yield de- irrigation and pesticides, the poppy growers have pends on microclimate, plant maturity, and spe- expanded the conditions and acreage in which the cies. After harvesting and drying, the leaves are plant will produce. The U.S. government estimated soaked in a mixture of solvents, and the resulting that 4,187 tons (3,800 MT) of opium, or approxi- COCA PASTE is precipitated, further refined to coca mately 418 tons (380 MT) of heroin—if the total base, and finally refined to cocaine hydrochloride were converted—were produced throughout the (HCl), the salt or white powder form of cocaine. source countries of Southeast Asia, the Middle East, Leaves weighing 1.1 tons (1MT) produce approxi- Mexico, Guatemala, and Colombia. mately 6.6 pounds (3 kg) of paste. These 6.6 pounds (3 kg) of paste, called pasta, are then con- CANNABIS verted to about 3.3 pounds (1.5 kg) of coca base, which is equivalent to 3.3 pounds (1.5 kg) of co- Marijuana, a by-product of the plant Cannabis caine HCl. The U.S. government estimates that the sativa, remains the most commonly used illicit sub- Andean countries produced approximately 900 stance in the United States, although its use has tons (816 MT) of cocaine for world consumption in been decreasing steadily for the past several years. 1991 (INCSR, 1992). Both the plant and its psychoactive ingredient TETRAHYDROCANNABINOL (THC) are controlled substances. The U.S. government estimates that OPIUM POPPY Mexico still supplies the majority of the marijuana Unlike the perennial coca bush, the opium available in the United States, perhaps as much as poppy flower is an annual that requires the plant- 63 percent. Domestic supply accounts for another ing of seeds for each crop. Poppies of many species 18 percent, Colombia for 5 percent, Jamaica for 3 grow throughout the world, but only Papaver som- percent, and the remaining 11 percent comes form niferum yields opium and its derivatives—the me- Belize, Laos, the Philippines, Thailand, Lebanon, dicinal analgesics CODEINE and MORPHINE as well Pakistan, and Afghanistan. Brazil and Paraguay as the now illicit addictive heroin. Once planted, also cultivate cannabis, but the majority is con- the life cycle of the labor-intensive poppy lasts for sumed locally or exported to neighboring countries, 120 to 150 days, from planting until the petals fall with very little, if any, finding its way to the United off. Day and night, certain nitrogen-containing States (NNICC, 1990). compounds, alkaloids, are produced by the plant The flowering tops and the leaves of the mari- and stored in its cells. After the petals fall, the seed juana plant are collected, dried, and used for psy- capsule swells and is incised while still green. A choactive effect—usually smoked as a cigarette or milky alkaloid-rich sap seeps from tiny tubes in the in a pipe but also ingested as an ingredient of food. capsule wall, which dries, darkens, and turns The plant is an annual; it is planted from seed and gummy—becoming a substance called opium gum. harvested traditionally in two seasons of five- to Raw opium gum is converted by crude refineries six-month cycles each year. Cannabis can grow into morphine base; a few pots, simple chemicals, almost anywhere outside of the ice-bound frigid and a source of fresh water are all that is needed to zones, if provided with adequate sunshine and wa- create the morphine base from which illicit heroin ter. As a chlorophyll-based green plant, it requires is made. About 22 pounds (10 kg) of opium make photosynthesis to grow and mature. Coating the 2.2 pounds (1 kg) of morphine base; treating the plant’s leaves with a contact herbicide such as base with acetic anhydride creates heroin. Papaver paraquat or glyphosate has been very effective in somniferum is cultivated in dozens of varieties killing the plant in Mexico, Belize, and Colombia. 374 CROP-CONTROL POLICIES (DRUGS)

Unlike the coca plant, which has a perennial root Manual Eradication. Manual eradication in- system, most types of marijuana can be destroyed volves physical removal or cutting. For coca, re- easily by digging, spraying, or cutting. moving the plant is more effective than cutting, because coca can sprout new shoots from the base CROP ERADICATION of the stump. The plants, however, are difficult to remove after three years of growth because of their Illicit crops probably constitute the least expense root systems. Coca, poppy, and marijuana plants in the narcotics chain. Producers devote few eco- can be removed only if grown in areas that are nomic resources to prevent detection, although it is easily accessible. Many of the illicit growing areas easier to locate and destroy crops in the field than to are in remote corners of the countryside, so trans- locate the processed drugs once they enter the porting personnel and equipment may be expensive smuggling routes or on U.S. city streets. Despite and hazardous. More importantly, the manual this belief, however, few effective crop-control poli- eradicators place themselves at great personal risk, cies have been implemented, and crop control re- as for example in coca-growing areas of Peru and mained a secondary approach, at best, in the U.S. Colombia—where violence directed at eradication government’s 1991 and 1992 National Drug Con- personnel have forced the suspension of such trol Strategy. It was easier for U.S. agencies to efforts. function at the border or within the United States Biological Control. Numerous biological con- than to get compliance on command from source trol agents—parasites, predators, pathogens— countries. DRUG INTERDICTION and immobilizing have been identified that may destroy coca and the trafficking organizations were the preferred poppy plants. Too little is known, however, about policy approaches. the effect of these agents on the ecology of the Crop eradication can be effected forcibly or vol- growing regions. Another issue is the possible nega- untarily (1) by manual plant removal, (2) by bio- tive impact on legitimate crops, which, if inadver- logical control through the use of pathogens or tently destroyed, could cause famine and/or severe predators, or (3) by the use of herbicides. Of the economic losses. Use of biological agents may be a three methods, herbicidal eradication has been the future possibility, but the current state of research most effective and efficient, though not the most on such pests and their potential impact does not neutral politically. Payment to the growers for the make this option feasible yet. labor of uprooting the plants voluntarily is an im- Herbicides. Control of coca by foliar applica- portant short-term element, while development as- tion of herbicides was attempted in Colombia in sistance is a longer-term component of the success- 1985, with inconsistent results. In 1987 and 1988, ful implementation of any eradication effort that further small-scale testing was conducted in Peru, invites voluntary reduction. involving both foliar- and soil-applied herbicides, Because the coca bush is a perennial, destroying which confirmed the efficacy of soil-applied herbi- the plant can have a devastating effect on the pro- cides. Two herbicides were chosen for further test- ductive capacity of the trafficking organizations. ing: tebuthiuron and hexazinone. Based on further After the plant dies, it would take nearly three years tests in Peru in 1989, researchers learned that for the grower to be reemployed on that land pro- aerial application of either pellet tebuthiuron or ductively. For the most part, the coca fields of Peru, granular hexazinone, at lower rates than used typi- Bolivia, and Colombia are remote relatively small cally in the United States, can kill a significant plots. There is little or no intercropping, where the percentage of coca plants in a field and force its grower mixes his coca fields with yucca or other abandonment. Environmental tests were con- agricultural produce, therefore, aerial herbicidal ducted in Peru for more than two years to measure eradication is an efficient option—but one that such ecological effects as translocation of the herbi- requires significant amounts of herbicide to kill the cide into the soil, water, and air; water solubility; hardy coca bush. The opium poppy and the mari- effect on the flora and fauna; and ability of the juana plant are easier to eradicate than coca bushes herbicide to leech on the clay molecules in the soil. but, because they are annuals and planted from Tebuthiuron and hexazinone were judged environ- seed, with several harvests a year, they require mentally safe and effective. Other herbicides such year-round crop-control efforts. as dicamba, imazapyr, picloram, and triclopyr CROP-CONTROL POLICIES (DRUGS) 375 were also tested and found to be more toxic but less tion of nearly 30 percent of Thailand’s 10,500 effective. Use of herbicides on poppy and mari- acres (4,200 ha) of opium, about half of Colom- juana has been tested and thoroughly documented. bia’s 6,000 acres (2,500 ha) of opium, approxi- Concise environmental reviews (measuring impact mately 10 percent of Bolivia’s 131,000 acres on environment) and environmental-impact state- (53,000 ha) of coca, and a little less than half of ments (measuring health consequences for con- Jamaica’s 4,500 acres (1,800 ha) of cannabis. sumers who use the drug product after it has been sprayed with herbicide) have been filed for 2,4-D, CROP-ERADICATION DIFFICULTIES glyphosate, and paraquat use on poppy and mari- juana fields. Conceptual, political, and technical arguments are often raised against drug-crop eradication. Op- ponents of eradication believe that the reduction of CROP-ERADICATION SUCCESSES foreign supplies of illicit drugs is probably not In Mexico, Colombia, Belize, Myanmar (for- achievable, or short-term at best; they say that even merly Burma), Bolivia, Jamaica, and Thailand, if eradication had a longer-term impact in the croperadication efforts continue to have varying source country, it would not have a meaningful degrees of success in reducing illicit crop cultiva- effect on levels of illicit-drug consumption in the tion. In the mid-1970s, Mexico began an aerial United States, where the consumer would simply herbicidal-eradication program on both opium and switch to other available drugs. Moreover, some marijuana and reduced the cultivation of these il- fear that inordinate environmental damage will re- licit crops significantly. In 1991, Mexico reportedly sult from herbicide use. Others question whether a destroyed some 16,000 of its 25,000 acres (6,500 global policy of crop control is feasible politically, of its 10,000 hectares) of opium and 27,000 of its because many growing areas are far beyond gov- 71,500 acres (11,000 of its 29,000 hectares) of ernment control, and even when there is govern- cannabis. In the early 1980s, the Colombian gov- ment jurisdiction, crop eradication becomes im- ernment used glyphosate in the north to eradicate practical because the grower can continually shift most of its marijuana there. In the early 1990s, areas of cultivation. Instituting effective eradica- Colombia planned to use the same herbicide on tion efforts in some source countries, such as Peru, newly discovered opium in the Cauca and Huila might also drive political insurgents (who co-locate departments. In 1987, the U.S. government sup- with the drug traffickers) into threatening alliances ported the government of Belize in an aerial mari- that would undermine the central govenment even juana-eradication program, which resulted in a 90 further. Finally, some question the value of supply- percent decline in cannabis production. reduction efforts at the source altogether, since In the 1987–1988 growing season, Myanmar world production and supply of illicit drugs vastly sprayed the herbicide 2,4-D from fixed-wing agri- exceed world demand. If the worldwide supply cultural-spray aricraft to destroy about 31,000 were reduced dramatically, it would not be felt in acres (12,500 ha) of opium poppy. This program the United States until the supply had dried up came to a halt late in 1988 when the government throughout the rest of the world, because U.S. con- moved its limited military resources to attack sumers often pay higher prices than those in any mounting antigovernment protests. The political other market; moreover, U.S. dollars are the pre- balance also changed abruptly when Myanmar’s ferred narco-currency (Perl, 1988). ruling military eliminated the opium-eradication program, abolished bureau rights, and accommo- CROP-SUBSTITUTION EFFORTS dated certain trafficking insurgents (the Wa and Kokang Chinese components of the now-defunct Crop substitution—the replacement of opium, Burmese Communist Party, who were lighting one coca, or marijuana production with a legal agricul- of Burma’s principal enemies, Khung Sa and his tural commodity—can never be successful by itself, Shan United Army). because of the immense profits from illicit-drug In addition to these aerial herbicidal-eradication cultivation. A more broadly defined income-re- efforts, manual eradication of crops continued in placement approach (which may include an agri- 1991 in a number of countries, to include destruc- cultural crop-substitution component), however, 376 CROP-CONTROL POLICIES (DRUGS) coupled with strong law enforcement, may succeed CROP-SUBSTITUTION DIFFICULTIES in convincing drug growers to stop planting the Several inherent difficulties exist with crop-sub- illicit crop. stitution approaches. In the Malakand District of Pakistan’s North- West Frontier Province, the U.S.—Pakistani efforts 1. Many of the growing regions are remote inhospi- in the early 1980s to implement a fully integrated, table areas, outside central government control. rural development project, which provided roads, 2. In a free-market economy, no legitimate crop water, electrification, and agricultural substitutes can compete with either coca or opium as an (e.g., peanuts, apples), resulted in a net reduction income-producing agricultural commodity. in opium poppy production. Providing project sup- Even if there were competitive substitutes, with port for the 300,000 inhabitants of the district the immense profits from the drug trade, the drug traffickers could continue to raise the price enabled local residents to earn an income from an to compete for willing cultivators. extensive road-building and infrastructure devel- 3. Much of the land in the growing zones cannot opment program, thus making cultivation of the produce legitimate agricultural products suffi- opium poppy unnecessary. A side benefit of the cient to support the farming population. development efforts was the creation of valuable 4. The presence of political insurgents and threat infrastructures to raise the standard of living of violence in some of the growing areas (Peru, throughout the region and encourage the nomadic Myanmar, Afghanistan) create an unfavorable populations to establish roots and achieve more climate for crop substitution. stable living conditions. 5. There are difficulties in finding international The Highland Village Project in northern Thai- markets to accept the substitute crop; for exam- land has provided similar benefits to the culturally ple, in Bolivia’s Chapare region, oranges and diverse, opium-producing hill tribes. This resulted coffee are viable agricultural products, but the in decreased opium cultivation consistently in the international coffee cartel and U.S. citrus grow- early 1990s. In Laos, the Houaphanh project near ers do not allow Bolivian products to compete the remote border region with Vietnam began in for shares of existing markets. 1990 to provide area development incentives (of 6. In some regions, such as Peru’s Upper Huallaga improved water and roads and medical and educa- Valley and Bolivia’s Chapare, the vast majority tional benefits) for growers who opted to cease of coca cultivators are not farmers and know planting opium. In the Western Hemisphere, a nothing about agriculture. Many were unem- principal component of the Andean Strategy to ployed urban dwellers and laborers who moved eliminate illicit coca in Peru and Bolivia has an to the coca-growing regions to seeka viable liv- economic-assistance element that provides hard- ing after the collapse of the tin market in the late 1970s and early 1980s in Bolivia. In the long currency earnings, trade incentives, and local run, regional development efforts in the urban project assistance to entice the growers away from areas may be required to attract the cultivators coca cultivation. Some funds have already been backto their places of origin. expended on agro-research (discovering viable 7. Successful crop substitution takes years of agro- crops), infrastructure development, extension research, infrastructure development, training, training, and rudimentary marketing. and marketing; it may take too long for subsis- In the broadest sense of the term, crop substitu- tence-crop and/or cash-crop producers to make tion worked rather effectively in Turkey in the a living. In Pakistan’s Malakand project, it took early 1970s when a government cash subsidy per- more than five years to develop the agricultural mitted the farmers to harvest the poppy before the component. Some argue that in the absence of plant ripened to produce the opium gum. In this strong law enforcement and control, crop sub- way, the traditional cooking and ceremonial uses of stitution becomes only an additional income poppy could be maintained through the poppy generator, not a true substitute. The growers straw process, as it is called, but the seed pod would will accept the substitute and continue to culti- not be available for the illicit opium gum. vate the illicit-drug crop. CULTS AND DRUG USE 377

8. Corruption and powerful interest groups in the CROSS-DEPENDENCE See Addiction: growing areas pose serious impediments to any Concepts and Definitions; Tolerance and Physical crop-control efforts. Dependence

(SEE ALSO: Foreign Policy and Drugs; Golden Tri- angle; International Drug Supply Systems) CROSS-TOLERANCE See Addiction: Con- cepts and Definitions; Tolerance and Physical De- pendence

BIBLIOGRAPHY

BUREAU OF INTERNATIONAL NARCOTICS MATTERS, U.S. DE- CULTS AND DRUG USE The relationship PARTMENT OF STATE. (1990). International cocaine between cults and drug use is complex and contra- strategy: Report to the Congress. Washington, DC: dictory. Traditionally, cults are groups that diverge Author. from major religions or that form new philosophi- cal/religious systems, often around a charismatic BUREAU OF INTERNATIONAL NARCOTICS MATTERS, U.S. DE- leader. Consequently, at any given time, it may be PARTMENT OF STATE. (1990). International narcotics difficult to distinguish a cult from a newly formed control strategy report (INCSR). Washington, DC: religion. Some cults last and become new religions; Author. some remain cults, some die. The line is hard to LABATT-ANDERSON (1990). Environmental assessment of draw and open to interpretation, even by social the use of herbicides to eradicate illicit coca overseas scientists and the clergy who specialize in this field. (Revised) Washington, DC: U.S. Department of State. MORALES, E. (1989). Cocaine: white gold rush in Peru. BACKGROUND Tucson: University of Arizona Press. MUSTO, D. (1973). The American disease. New Haven & Historically, some cults and cultlike groups have London: Yale University Press. sponsored the use of drugs as an integral aspect of ritual. In ancient Greece, for example, the use of NADELMANN, E. A. (1988). U.S. drug policy: A bad ex- ergot (genus Claviceps), a fungus that grows on port. Foreign Policy, 70, 83–108. grains and causes hallucinations, appears to have OFFICE OF NATIONAL DRUG CONTROL POLICY. (1992). played a significant role in the rituals of the National Drug Control Strategy, 1992. Washington, Eleusinian mysteries, celebrated in worship of the DC: Author. goddesses Demeter and her daughter Persephone. PERL, R. F. (1989). Congress and international narcotics As poets noted, ‘‘I have seen the truth within the control. CRS Report for Congress. Washington, DC: kernel of wheat’’—a foreshadowing of the Coun- The Library of Congress. tercultural Revolution/Love Generation, when a REUTER, P. (1985). Eternal hope: America’s quest for purified ergot derivative (LYSERGIC ACID DI- narcotics control. The Public Interest, 79, 79–95. ETHYLAMIDE, LSD) offered a similar experience. VAN WERT, J. (1988). The U.S. State Department’s nar- Indeed, the word lysergic means ‘‘dissolving ergot.’’ cotics control policy in the Americas. Journal of Inter- In Islam, alcohol is forbidden, but medieval Is- american Studies and World Affairs, 30(2 & 3), 1– lamic sects were formed to use HASHISH (a form of 18. Cannabis sativa, MARIJUANA). It came into use in WALKER, W. O., III. (1981, 1989). Drug control in the the Islamic Middle East only centuries after the Americas. Albuquerque: University of New Mexico Prophet Mohammed (lived about 570 to 632) and his followers founded the Moslem religion; hashish Press. was allegedly used to offer a taste of the paradise to WHITE, P. T. (1985). The poppy—for good and evil. come. National Geographic, 167 (2), 143–189. In pre-Columbian America, drugs of a wide WHITE, P. T. (1989). Coca—an ancient herb turns variety were utilized in religious rituals; the Native deadly. National Geographic, 175 (1), 6–51. American Church still continues to use the JAMES VAN WERT HALLUCINOGENS peyote and mescaline (both de- 378 CULTS AND DRUG USE

This juxtaposition had been anticipated by some earlier poets, such as William Blake (1757–1827), Charles Baudelaire (1821–1867), and Arthur Rimbaud (1854–1891), by the illustrator Aubrey Beardsley (1872–1898), and by cult figures such as Aleister Crowley (born Edward Alexander Crowley, 1875–1947). By combining aspects of their own experimentation with hallucinogenic drugs with elements of Transcendental Meditation/ Mahareshi (movements based on Buddhism) in their song ‘‘Lucy in the Sky with Diamonds’’ (1967), the much adored singing group called the Beatles (the members born between 1940 and More than 900 members of the People’s Temple 1943, active as a group from 1960 to 1969) both died by mass suicide/murder on November 18, mirrored and promoted the use of hallucinogens as 1979, in Jonestown, Guyana. The leader, Jim providing a readily accessible transcendental expe- Jones, had lured many people into the cult by rience—although in Buddhism the goal of all exis- claiming he would cure their drug abuse tence is the state of complete redemption (nirvana, ᭧ problems. ( Bettmann/CORBIS) a state achieved by righteous living, not by drugs). Unlike Aldous Huxley (1894–1963), who com- rived from the small cactus Lophophora wil- bined an interest in Vedanta (an orthodox system liamsii). Recent court decisions have protected and of Hindu philosophy) and the use of mescaline, the reaffirmed the right of this church to use these Beatles and their alleged mentor, the Mahareshi drugs in religious ceremonies. As Preston and Mohesh Yogi, proclaimed the desirability of en- Hammerschlag (1983) have noted, this use of hal- lightening the masses rather than restricting en- lucinogens is rigidly controlled—part of a tran- lightenment to a righteous educated elite. scendent experience, accompanied by rituals of pu- In literary works of that era, such as Armistead rification, and not lending itself to use on a Maupin’s Tales of the City (1978), characters rou- promiscuous basis. tinely advocate and use mind-altering substances (especially marijuana) without any apparent ap- TWENTIETH CENTURY preciation of their darker potential, which was con- sistent with the general attitude toward TOBACCO The 1960s and 1970s were characterized by an and alcohol use at that time as well. In addition, extraordinary youth movement of baby-boomers there was no special appreciation that drug use, in with an intense interest in the cultic and the oc- and of itself, might encourage cult affiliation, yet cult—and by a popularization of drug use within this was very much the time of the rapid growth of mainstream American society. Some of this interest cults among youth in the United States. was fueled by the philosophies and practices of The relationship of such cults to drug use is Asia, especially Southeast Asia, where the Vietnam paradoxical. Deutsch (1983) has noted that pro- War was being fought; some was inspired by the longed drug use may encourage this type of cult Shangri-La nature of the lands of the Himalayas, affiliation, and many cult groups offer themselves where Buddhism was practiced in secluded monas- to the public and to vulnerable persons as quasi- teries and nirvana was sought. As the ‘‘Greening of therapeutic contexts where the person will be able America’’ proceeded through these two decades, to transcend the need for drugs. This aspect of cult- mind-altering joined ALCOHOL and NICOTINE, be- appeal turned thousands of lost and confused free coming available on the street, and were no longer spirits and flower-children into vacant-eyed smil- confined to the disenfranchised or marginal. There ing cultists who signed over to the cult all their was an increasing juxtaposition of the so-called worldly goods—to spend their days wandering the transcendent religious experience (the mind-ex- streets, airports, and bus or train stations, seeking panding experience) with drug use that often be- donations for their cult by shaking bells and came drug abuse. tambourines or by offering flowers to passing CUSTOMS SERVICE, U.S. 379 strangers. Rigorous training programs, called come independent members of mainstream society. ‘‘brainwashing’’ by parents of the lost children and Often times program staff really help individual by other skeptics, were fashioned to strip cultists of members overcome drug problems and other prob- free will and substitute nodding acquiescence. lems. Yet other times, a false resolution of these problems comes through fusion with an authoritar- THE PEOPLE’S TEMPLE ian and charismatic leader who will ostensibly pro- vide the continuity and structure for which the One charismatic cult leader was the Reverend substance abuser hungers. Jim Jones, leader of the People’s Temple. His claim of curing drug abuse was only one of the lures. SUMMARY After moving around the United States for a while, he brought his followers to an isolated spot in South Drugs and other mind-altering substances have America, where one of the former substance abus- formed an integral part of some cultic/religious rit- ers mixed for them a massive batch of poisoned uals from very ancient times. In the mid-to-late Kool-Aid for the cult’s final event—a basically un- twentieth century, the structure provided by groups explained mass suicide. that mobilize intense religious or quasi-religious feelings has sometimes enabled vulnerable individ- SCIENTOLOGY uals to transcend their personal difficulties. How- ever, the very intensity of the substance user’s ob- The People’s Temple was not unique— ject hunger may enable the transformation of organizations such as Narcanon (that is, narcotics otherwise viable or valuable organizations into anonymous) have stated that their treatment of cults or cultlike groups. substance abusers reflects the dianetics-based teachings of L. Ron Hubbard (born Lafayette Ron- (SEE ALSO: Religion and drug use) ald Hubbard, 1911–1986), an American science- fiction writer, whose Scientology movement ex- panded in the 1950s when he moved to England BIBLIOGRAPHY (he was subsequently banned from re-entering En- DEUTSCH, A. (1983). Psychiatric perspectives on an gland in 1968). Scientology is a quasi-philosophi- Eastern-style cult. In David A. Halperin (Ed.), Psy- cal system that claims to improve mental and phys- chodynamic perspectives on religion, sect, and cult. ical well-being as followers advance within the cult, Littleton, MA: James Wright-PSG. by undertaking (and paying well for) a series of PRESTON, R., & HAMMERSCHLAG, C. (1983). The Native courses. American Church. In David A. Halperin (Ed.), Psy- chodynamic perspectives on religion, sect, and cult. TWELVE-STEP PROGRAMS Littleton, MA: James Wright-PSG. REBHUN, J. (1983). The drug rehabilitation program: Intense religious commitment is a significant as- Cults in formation? In David A. Halperin (Ed.), Psy- pect of much of the twelve-step recovery move- chodynamic perspectives on religion, sect, and cult. ment. Accordingly, there is concern that this level Littleton, MA: James Wright-PSG. of commitment to a program can lead to a kind of REICH, C. A. (1970). The greening of America. New York: cult affiliation. ALCOHOLICS ANONYMOUS (AA), the Random House. oldest, most constructive, and most respected of the WASSON, R. G., HOFMANN,A.&RUCK, C. A. P. (1978). TWELVE-STEP programs, is not considered a cult. The road to Eleusis: Unveiling the secret of the myster- Still, Rebhun (1983) and many others have noted ies. New York: Harcourt, Brace, Jovanovich. the danger that drug-treatment programs can turn into cults such as SYNANON. Synanon was not DAVID A. HALPERIN unique; the history of residential drug-treatment REVISED BY JAMES T. MCDONOUGH,JR. centers includes a number of authoritarian and hi- erarchical organizations. Recovering substance- abusers often find it very difficult to leave the CUSTOMS SERVICE, U.S. See U.S. Gov- protection of the THERAPEUTIC COMMUNITY to be- ernment Agencies: U.S. Customs Service D

DARE See Volume 4, Appendix II, Drug DELIRIUM Delirium has been defined in Abuse Resistance Education (DARE) Regional many ways. Some use the term to refer to an acute, Training Centers hyperactive, confusional state. Psychiatrists define it more broadly to describe clinical states charac- terized by a reduced level of consciousness, an in- ability by the affected individual to sustain or shift DARP See Drug Abuse Reporting Program attention appropriately, disorganized thinking, dis- orientation to time, place, or person, and memory impairment. In addressing the affected individual, DAWN See Drug Abuse Warning Network questions need to be repeated, the individual may perseverate in responses, and speech may be ram- bling or incoherent. Additional features include an altered sleep-wake cycle, sensory misperceptions, DAYTOP VILLAGE See Treatment Pro- disturbances in the pace of psychological and mo- grams/Centers/Organizations: An Historical Per- tor activity, and varying mood states (e.g., apathy, spective euphoria). Sensory misperceptions—usually visual ones—may include illusions (e.g., specks on the floor are thought to be insects) or hallucinations (one ‘‘sees’’ a relative in the room when there is See U.S. Government: The Organization DEA actually no one there). Delusions may be present of U.S. Drug Policy (e.g., the person is convinced that medical staff are secret government agents). The individual may re- spond emotionally (e.g., with anxiety) and behav- DECRIMINALIZATION See Marihuana iorally (e.g., attack those viewed as threatening) to Commission: Recommendations on the context of the delusion. There may be elevated Decriminalization; Policy Alternatives blood pressure, a rapid heartbeat, and sweating and dilated pupils. The onset of such a clinical state is relatively rapid (taking an hour to days), the symptoms fluctuate throughout the course of DELINQUENCY AND DRUG ABUSE See illness, and the duration is usually brief (about one Conduct Disorder and Drug Use; Crime and Drugs; week). It is important to note that the altered level Gangs and Drugs of consciousness exists on a continuum. Hy-

381 382 DELIRIUM TREMENS (DTS) pervigilance can progress to confusion and tion in drinking. The course of illness is generally drowsiness. short, lasting, in most cases, two to three days. The The factors that may cause delirium are numer- disorder becomes significantly more life threaten- ous. They can include head trauma, infections ing if there is concurrent physical illness, such as (e.g., meningitis), metabolic disorders, liver and liver failure, infection, or trauma. kidney disease, postsurgical states, and psychoac- Clinical signs and symptoms are the same ones tive substance intoxication and withdrawal. The that are characteristic of a delirium and include common underlying functional disturbance in de- disorientation, fluctuating levels of consciousness, lirium is diffuse impairment of brain-cell metabo- vivid hallucinations, delusions, agitation, fever, el- lism and stability. These changes can frequently be evated blood pressure, rapid pulse, sweating, and seen on an electroencephalogram (EEG). Delirium tremor. The delirium may at times be preceded by a can occur at any age but is more common in the withdrawal seizure. Close monitoring and medical very young and the very old. It is most often seen in treatment in a hospital setting are required. hospital settings. The treatment of delirium con- sists of maintaining critical bodily functions (i.e., (SEE ALSO: Withdrawal: Alcohol ) cardiac and respiratory functions and hydration), correcting the precipitating problem, and manag- BIBLIOGRAPHY ing the psychological and behavioral symptoms. GOODWIN, D. W. (1989). Alcoholism. In H. I. Kaplan & B. J. Sadock (Eds.), Comprehensive textbookof psy- (SEE ALSO: Delirium Tremens; Withdrawal: Alco- chiatry, 5th ed., vol. 1. Baltimore: Williams & Wil- hol ) kins. PLUM, F., & POSNER, J. B. (1980). The diagnosis of stu- BIBLIOGRAPHY por and coma, 3rd ed. Philadelphia: Davis.

AMERICAN PSYCHIATRIC ASSOCIATION. (1987). Diagnostic MYROSLAVA ROMACH and statistical manual of mental disorders-3rd edi- KAREN PARKER tion-revised. Washington, DC: Author. HORVATH, T. B., ET AL. (1989). Organic mental syn- dromes & disorders. In H. I. Kaplan & B. J. Sadock DEMEROL See Meperidine (Eds.), Comprehensive textbookof psychiatry , 5th ed., vol. 1. Baltimore: Williams & Wilkins. LISHMAN, W. A. (1987). Organic psychiatry, 2nd ed. DEPENDENCE See Addiction: Concepts London: Blackwell. and Definitions; Disease Concept of Alcoholism and PLUM, F., & POSNER, J. B. (1980). The diagnosis of stu- Drug Abuse por and coma, 3rd ed. Philadelphia: Davis. MYROSLAVA ROMACH KAREN PARKER DEPRESSANTS See Drug Types

DELIRIUM TREMENS (DTS) This DEPRESSION The term depression has clinical disorder is a DELIRIUM that occurs after been used to refer both to an emotional state and a abrupt cessation of, or reduction in, ALCOHOL con- group of psychiatric disorders. As an emotional sumption in an individual who has been a heavy state, it is also known by various comparable terms: drinker for many years. It represents the most se- dejection, despair, sadness, despondency, lowering vere form of the alcohol WITHDRAWAL state and is of spirits. Cognitions (perceptions and judgments) not very common. It is associated, however, with a of a negative nature often accompany depressed significant mortality rate of those who develop it mood. (10–15%), if left untreated. Most people experience brief periods of de- Typically, the delirium sets in forty-eight to sev- pressed or despondent mood, often in response to a enty-two hours after the last drink or after reduc- disappointing life event. Each individual utilizes DESIGNER DRUGS 383

different COPING skills and relies on available social (SEE ALSO: Causes of Substance Abuse; Complica- supports to deal with such episodes, which gener- tions: Mental Disorders) ally pass within hours to days. When a dysphoric mood becomes more severe, is BIBLIOGRAPHY persistent, and impairs functioning, a major de- pression as a clinical syndrome has developed. GRUENBERG, A. M., & GOLDSTEIN, R. D. (1997). Depres- sive disorders. In A. Tasman, G. Kay, & J. A. Lieber- Concurrent clinical features include a loss of inter- man (Eds.), Psychiatry, 1st ed. Philadelphia, PA: est or pleasure in usual activities, a sense of hope- W. B. Saunders Company. lessness, poor or alternatively increased sleep, loss KELLER,M.B.(ED.) (1988). Unipolar Depression. In of appetite or overeating with resultant changes in A. J. Frances & R. E. Hales (Eds.), American Psychi- weight, fatigue, anxiety, restlessness, obsessive atric Press review of psychiatry (Vol. 7). Washington thinking, difficulty concentrating, irritability, feel- DC: American Psychiatric Press. ings of worthlessness, recurring thoughts of death, KESSLER, R. C., ET AL. (1994). Lifetime and 12-month and suicidal ideation or an actual attempt to end prevalence of DSM-III-R psychiatric disorders in the one’s life. Suicidal disturbances are of serious con- United States. Archives of General Psychiatry, 51,8– cern; approximately 66 percent of depressed pa- 19. tients contemplate suicide, and it is estimated that MYROSLAVA ROMACH 10 to 15 percent succeed. In some cases, psychotic KAREN PARKER features such as hallucinations and delusions may develop. Depression is one of the most common psychiat- ric disorders seen in adults. The lifetime prevalence DESIGNER DRUGS Designer drugs are of major depressive disorder (using DSM-III-R cri- synthesized chemical analogues of known, danger- teria) in the United States is estimated to be 12.7 ous drugs; they are designed to produce pharmaco- percent in men and 21.3 percent in women. Some logical effects similar to the drugs they mimic. In individuals suffer from chronically depressed mood the pharmaceutical industry, the development of of a less intense nature than that experienced in a new drugs often utilizes principles of basic chemis- try, so that the structure of a drug molecule may be major depressive episode; this is referred to as slightly altered to change its pharmacological activ- dysthymia. A depressive syndrome may occur as ity. For therapeutic purposes, these strategies have part of manic-depressive illness, and depression as had a long and successful history; for medical phar- a symptom (i.e., a depressed mood) can be found in maceutics, many useful new drugs or modifications many other psychiatric disorders. of older drugs have resulted in improved health Depression should be distinguished from the care. The principle of structure-activity relation- normal despair of bereavement and from the vari- ships has been applied to many medically approved ous medical disorders (e.g., Parkinson’s disease) drugs in the marketplace, especially in the search and chemical agents (e.g., alcohol or drugs for for painkillers—nonaddicting opioid analgesics. heart conditions) that can produce symptoms of The clandestine production of new street drugs depressed mood. The cause of depression is un- is, however, intended to avoid federal regulation known. Biological factors (e.g., dysregulation of and control. This practice can often result in the neurotransmitter systems), genetic factors, and appearance of unknown substances, with wide- psychosocial factors (e.g., life events, learned be- ranging degrees of purity, which have the potential haviors, and cognitions) have been proposed, and it to cause dangerous toxicity and serious health con- is likely that all interact to varying extents. Depres- sequences for the unwitting drug user (the quality sion is a treatable (but not really curable) illness in of personnel involved in clandestine drug synthesis the vast majority of people. Treatment consists of a can range from cookbook amateurs to highly number of modalities, depending on the type and skilled chemists). The most publicized case regard- severity of the depression. PSYCHOTHERAPY, anti- ing the tragic consequences associated with the depressant medications, and electroconvulsive manufacture and use of designer drugs on the street therapy are the main interventions used. involves MPTP (1-methyl, 4-phenyl, 1,2,3,6-tetra- 384 DESIGNER DRUGS hydropyridine), a substance that was later found to cause a Parkinsonian syndrome in humans. A controlled substance that has served as a tem- plate for the design of new look-alike OPIOID drugs is MEPERIDINE (Demerol). A slight change in its chemical structure yields the drug known as MPPP (1-methyl-4-propionoxy-4-phenylpyridine), a meperidine look-alike drug, which is known on the streets as synthetic heroin. In California in 1982, four young drug abusers developed Parkinsonian symptoms after the illicit intravenous use of street HEROIN. The analysis of their remaining drug sam- ples revealed the presence of both MPPP and MPTP. The dealer involved in this illicit synthesis and sale of MPPP was a bad chemist, since MPTP represents a side product formed through the inad- equate control of the temperature and/or acidity of the chemical reaction. Another opioid that has resulted in serious health hazards on the street is fentanyl (Sub- limaze), a potent and extremely fast-acting NAR- The production of many substances such as COTIC ANALGESIC (painkiller) with a high ABUSE methamphetamine, PCP, MDMA and LIABILITY. This drug has also served as a template methcathinone requires little sophisticated for many look-alike drugs that come out of clan- equipment or knowledge of chemistry. Many destine chemical laboratories. Very slight modifi- clandestine labs are small enough to fit on a cations in the chemical structure of fentanyl can kitchen table. (Drug Enforcement Administration) result in analogues such as para-flouro-, 3-methyl-, or alpha-methyl-fentanyl—with, respectively rela- tive potencies 100, 900, and 1,100 times that of and other cardiovascular effects, all of which are MORPHINE. During the 1980s, the Drug Enforce- suggestive of excessive central nervous system stim- ment Administration (DEA) has reported a steady ulation. Following chronic administration in ani- increase in deaths from drug overdoses associated mals, MDA has been demonstrated to produce a with fentanyl-like designer drugs. Not every ‘‘de- degeneration of serotonergic nerve terminals in signer’’ drug is actually thought up by chemists in rats, implying that MDA might induce chronic neu- illegal labs; some were actually synthesized for le- gitimate medical uses but were never marketed. rological damage in humans as well. This also sug- HALLUCINOGENIC drugs, such as LSD or gests that extreme caution should be exercised re- MESCALINE, rarely cause death—except as ACCI- garding the manufacture and use of MDA, MDMA, DENTS related to drug-induced mental aberrations. and related drugs—although a few psychothera- Adverse reactions to typical hallucinogens are usu- pists claim that MDMA is a useful adjunct in the ally treated by support, reassurance, and a quiet treatment of some patients. environment. Hallucinogenic designer drugs, how- The widespread illicit manufacture and use of ever, include such substituted AMPHETAMINE designer drugs with unknown chronic toxicity (‘‘speed’’) analogues as methylenedioxy- could result in millions of people experimenting amphetamine (MDA), methylenedioxymetham- with the drug before the toxic effect was recog- phetamine (MDMA or ‘‘Ecstasy’’), and methy- nized; this could potentially produce an epidemic of lenedioxyethamphetamine (MDEA or ‘‘Eve’’). Both neurodegenerative disorders. acute and chronic toxicity have been reported fol- lowing the administration of these drugs. Acute toxicity is usually manifested as restlessness, agita- (SEE ALSO: Complications; Controlled Substances tion, sweating, high blood pressure, tachycardia, Act of 1970; MDMA; MPTP) DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA 385

BIBLIOGRAPHY fortable transition to a drug-free state. Detoxifica- tion is generally the first step in the process of BARNETT,G.,&RAPAKA, R. S. (1989). Designer drugs: treatment for rehabilitation. An overview. In K. K. Redda, C. A. Walker, & G. Barnett (Eds.), Cocaine, marijuana, designer drugs: Chemistry, pharmacology, and behavior (pp. 163– (SEE ALSO: Addiction: Concepts and Definitions; 174). Boca Raton, FL: CRC Press. Clonidine; Treatment Types: Overview; Treatment Types: Nonmedical Detoxification; Withdrawal: DOWLING, G. P., MCDONOUGH, E. T., III. & BOST,R.O. (1987). ‘‘Eve’’ and ‘‘ecstasy’’: A report of five deaths Alcohol ) associated with the use of MDEA and MDMA. Journal JOHN T. SULLIVAN of the American Medical Association, 257, 1615. NICHOLS, D. E. (1989). Substituted amphetamine con- trolled substance analogues. In K. K. Redda, C. A. DETOXIFICATION: NONMEDICAL See Walker, & G. Barnett (Eds.), Cocaine, marijuana, Treatment Types designer drugs: Chemistry, pharmacology, and be- havior (pp. 175–185). Boca Raton, FL: CRC Press. NICK E. GOEDERS DEXTROAMPHETAMINE This is the d-isomer of AMPHETAMINE. It is classified as a PSY- CHOMOTOR STIMULANT drug and is three to four DESOXYN See Methamphetamine times as potent as the l-isomer in eliciting central nervous system (CNS) excitatory effects. It is also more potent than the l-isomer in its ANORECTIC DETOXIFICATION: AS ASPECT OF (appetite suppressant) activity, but slightly less po- TREATMENT Detoxification is the term com- tent in its cardiovascular actions. It is prescribed in monly used to describe the process or set of proce- the treatment of narcolepsy and OBESITY, although dures involved in readjusting a drug- or alcohol- care must be taken in such prescribing because of dependent person to a lower or absent tissue level of the substantial ABUSE LIABILITY. the substance (drug) of dependence. With chronic High-dose chronic use of dextroamphetamine (long-term) use of many drugs, there is adaptation can lead to the development of a toxic psychosis as within the nervous system. Readaptation of the well as to other physiological and behavioral prob- nervous system to the absence of a particular sub- lems. This toxicity became a problem in the United stance can cause a WITHDRAWAL syndrome (as a States in the 1960s, when substantial amounts of manifestation of PHYSICAL DEPENDENCE). The pa- the drug were being taken for nonmedical reasons. tient would reasonably be expected to have symp- Although still abused by some, dextroamphetamine toms (what they tell the health-care provider) and is no longer the stimulant of choice for most psy- exhibit signs (what the observer sees) of a with- chomotor stimulant abusers. drawal syndrome. The detoxification process usually occurs in a (SEE ALSO: Amphetamine Epidemics; Cocaine) supportive environment, which might be a hospi- MARIAN W. FISCHMAN tal or clinic, but not always; it might also involve the use of medications (other drugs) in order to control or suppress symptoms and signs of with- drawal, but not always. The level of care and the DIAGNOSIS OF DRUG ABUSE: DIAG- use of medications depends on the substance of NOSTIC CRITERIA Diagnosis is the process of abuse and the level of physical dependence (sever- identifying and labeling specific disease conditions. ity of withdrawal syndrome), complications, or The signs and symptoms used to classify a sick potential for complications. The more severe com- person as having a disease are called diagnostic plications are seen most frequently in association criteria. Diagnostic criteria and classification sys- with alcohol or sedative-hypnotic withdrawal. The tems are useful for making clinical decisions, esti- goal of detoxification is to provide a safe and com- mating disease prevalence, understanding the 386 DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA causes of disease, and facilitating scientific commu- CLASSIFICATION SYSTEMS nication. ALCOHOLISM and drug ADDICTION have been Diagnostic classification provides the treating variously defined as medical diseases, mental disor- clinician with a basis for retrieving information ders, social problems, and behavioral conditions. In about a patient’s probable symptoms, the likely some cases, they are considered the symptom of an course of an illness, and the biological or psycho- underlying mental disorder (Babor, 1992). Some of logical process that underlies the disorder. For ex- these definitions permit the classification of alco- ample, the DIAGNOSTIC AND STATISTICAL MANUAL holism and drug dependence within standard no- (DSM) of the American Psychiatric Association menclatures such as the International Classifica- (1987) is a classification of mental disorders that tion of Diseases and the Diagnostic and Statistical provides the clinician with a systematic description Manual of Mental Disorders. The recent revisions of each disorder in terms of essential features, age of both of these diagnostic systems has resulted in a of onset, probable course, predisposing factors, as- high degree of compatibility between the classifica- sociated features and differential diagnosis. Mental tion criteria used in the United States and those health professionals can use this system to diagnose used internationally. Both systems now diagnose substance use disorders in terms of the following dependence according to the elements first pro- categories: acute INTOXICATION,ABUSE,DEPEN- posed by Edwards and Gross (1976). They also DENCE,WITHDRAWAL,DELIRIUM, and other disor- include a residual category (harmful alcohol use ders. In contrast to screening, diagnosis typically [ICD-10]; alcohol abuse [DSM-III-R]) that allows involves a broader evaluation of signs, symptoms, classification of psychological, social, and medical and laboratory data as these relate to the patient’s consequences directly related to substance use. illness. The purpose of diagnosis is to provide the Some diagnostic classification systems are used clinician with a logical basis for planning TREAT- primarily for epidemiological and clinical research. MENT and estimating prognosis. These include the Feighner Criteria (Feighner et Another purpose of classification is the collection al., 1972) and the Research Diagnostic Criteria of statistical information on a national and interna- (Robins, 1981). Other classifications are intended tional scale. The primary purpose of the INTERNA- primarily for clinical care (DSM-III-R; see Ameri- TIONAL CLASSIFICATIONOF DISEASES (ICD), for ex- can Psychiatric Association, 1987) or statistical re- ample, is the enumeration of morbidity and porting (ICD-10; see World Health Organization, mortality data for public health planning (World 1992). Health Organization, 1992). In addition, a good classification will facilitate communication among HISTORY TAKING scientists and provide the basic concepts needed for theory development. Both ICD and DSM have been Obtaining accurate information from patients used extensively to classify persons for scientific with alcohol and drug problems is often difficult research. Classification provides a common frame because of the stigma associated with substance of reference in communicating scientific findings. abuse and the fear of legal consequences. At times Diagnosis also may serve a variety of adminis- they want help for the medical complications of trative purposes. When a patient is suspected of substance use (such as injuries, or depression) but having a substance use disorder, diagnostic proce- are ambivalent about giving up alcohol or drug use dures are needed to exclude ‘‘false positives’’ (i.e., entirely. It is often the case that these patients are people who appear to have the disorder but who evasive and attempt to conceal or minimize the really do not) and borderline cases. Insurance reim- extent of their alcohol or drug use. Acquiring accu- bursement for medical treatment increasingly de- rate information about the presence, severity, dura- mands that a formal diagnosis be confirmed ac- tion and effects of alcohol and drug use therefore cording to standard procedures or criteria. The requires a considerable amount of clinical skill. need for uniform reporting of statistical data, as The medical model for history taking is the most well as the generation of prevalence estimates for widely used approach to diagnostic evaluation. epidemiological research, often requires a diagnos- This consists of identifying the chief complaint, tic classification of the patient. evaluating the present illness, reviewing past his- DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA 387 tory, conducting a review of biological systems also about physical conditions and psychiatric dis- (e.g., gastrointestinal, cardiovascular), asking orders that are commonly associated with sub- about family history of similar disorders, and dis- stance abuse. A second type of diagnostic interview cussing the patient’s psychological and social func- is exemplified by the STRUCTURED CLINICAL INTER- tioning. A history of the present illness begins with VIEW for DSM-III-R (SCID), which is designed for questions on use of alcohol, drugs, and TOBACCO. use by mental health professionals (Spitzer et al., The questions should cover PRESCRIPTION DRUGS as 1992). The SCID assesses thirty-three of the more well as illicit drugs, with additional elaboration of commonly occurring psychiatric disorders de- the kind of drugs, the amount used, and the mode scribed in DSM-III-R. Among these are depression, of administration (e.g., smoking, injection). Ques- schizophrenia, and the substance use disorders. A tions about alcohol use should refer specifically to similar clinical interview, which has been designed the amount and frequency of use of major beverage for international use, is the Schedules for Clinical types (wine, spirits, BEER). A thorough physical ex- Assessment in Neuropsychiatry (SCAN; see Wing et amination is important because each substance has al., 1990). The SCID and SCANinterviews allow specific pathological effects on certain organs and the experienced clinician to tailor questions to fit body systems. For example, alcohol affects the the patient’s understanding, to ask additional ques- liver, stomach, and cardiovascular system. Drugs tions that clarify ambiguities, to challenge incon- often produce abnormalities in ‘‘vital signs’’ such sistencies, and to make clinical judgments about as temperature, pulse, and blood pressure. A men- the seriousness of symptoms. They are both mod- tal status examination frequently gives evidence of eled on the standard medical history practiced by substance use disorders because of poor personal many mental health professionals. Questions about hygiene, inappropriate affect (sad, euphoric, irri- the chief complaint, past episodes of psychiatric table, ANXIOUS), illogical or delusional thought disturbance, treatment history, and current func- processes, and memory problems. The physical ex- tioning all contribute to a thorough and orderly amination can be supplemented by laboratory psychiatric history that is extremely useful for diag- tests, which sometimes aid in early diagnosis before nosing substance use disorders. severe or irreversible damage has taken place. Lab- In recent years there has been interest in re- oratory tests are useful in two ways (1) alcohol and searching and developing a system of self-reporting drugs can be measured directly in blood, urine, and to aid in the diagnosing of drug use severity. There exhaled air; (2) biochemical and psychological has been resistance to this kind of diagnostic tool functions known to be affected by substance use because of clinical suspicion that individuals with can be assessed. Many drugs can be detected in the substance-use disorders often are not capable of urine for twelve to forty-eight hours after their con- reporting their symptoms accurately. The result of sumption. An estimate of BLOOD ALCOHOL which is a reliance on clinicians or trained inter- CONCENTRATION (BAC) can be made directly by viewers over self-reporting, paper/pencil measures blood test or indirectly by means of a breath or to determine a patient’s drug use severity. How- saliva test. Elevated gamma glutamyl transpepti- ever, patient-reported data on outcomes and effec- dase (GGTP), a liver enzyme, is a sensitive indica- tiveness of substance abuse treatments is becoming tor of chronic, heavy alcohol intake. an increasing necessity. Additionally, according to In addition to the physical examination and lab- a recent investigation of methodological studies, oratory tests, a variety of diagnostic interview pro- self-report measures appear to be neither inher- cedures have been developed to provide objective, ently reliable nor unreliable. Certainly the informa- empirically based, reliable diagnoses of substance tion reported can be imprecise because of memory use disorders in various clinical populations. One loss and under- or overreporting, among other vari- type, exemplified by the DIAGNOSTIC INTERVIEW ables. Also a variety of conditions can render self- SCHEDULE (DIS; see Robins et al., 1981) and the report measurements susceptible to measurement Composite International Diagnostic Interview error and systematic response bias but there is no (CIDI; see Robins et al., 1988), is highly structured empirical evidence to definitively show that self- and requires a minimum of clinical judgment by reported data is more problematic than interviewer the interviewer. These interviews provide informa- formats. Research has shown that format can cre- tion not only about substance use disorders, but ate systematic bias but this can be accounted for by 388 DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA combining the data from alternate forms (Heithoff sufficient to result in a diagnosis of harmful use. & Wiseman, 1996). The key issue in the definition of this term is the distinction between perceptions of adverse effects DIAGNOSIS OF ABUSE AND (e.g., wife complaining about husband’s drinking) HARMFUL USE and actual health consequences (e.g., trauma due to accidents during drug intoxication). Since the A major diagnostic category that has received purpose of ICD is to classify diseases, injuries, and increasing attention in research and clinical prac- causes of death, harmful use is defined as a pattern tice is substance abuse in contrast to dependence. of use already causing damage to health. This category permits the classification of mal- Harmful patterns of use are often criticized by adaptive patterns of alcohol or drug use that do not others and sometimes legally prohibited by govern- meet criteria for dependence. The diagnosis of ments. The fact that alcohol or drug intoxication is abuse is designed primarily for persons who have disapproved by another person or by the user’s recently begun to experience ALCOHOL or drug culture is not in itself evidence of harmful use— problems, and for chronic users whose substance- unless socially negative consequences have actually related consequences develop in the absence of occurred at dosage levels that also result in psycho- marked dependence symptoms. Examples of situa- logical and physical consequences. This is the tions in which this category would be appropriate major difference that distinguishes ICD-10’s harm- include (1) a pregnant woman who keeps drinking ful use from DSM-IV’s substance abuse—the latter alcohol even though her physician has told her that category includes social consequences in the diag- it could be responsible for FETAL damage; (2) a nosis of abuse. college student whose weekend binges result in missed classes, poor grades, and alcohol-related THE DEPENDENCE traffic ACCIDENTS; (3) a middle-aged beer drinker SYNDROME CONCEPT regularly consuming a six-pack each day who de- velops high blood pressure and fatty liver in the The diagnosis of substance use disorders in absence of alcohol-dependence symptoms, and ICD-10 and DSM-IV is based on the concept of a (4) an occasional MARIJUANA smoker who has an dependence syndrome, which is distinguished from accidental injury while intoxicated. disabilities caused by substance use (Edwards, In the latest version of the Diagnostic and Statis- Arif, & Hodgson, 1981). An important diagnostic tical Manual (DSM IV; see American Psychiatric issue is the extent to which dependence is suffi- Association, 1994), substance abuse is defined as a ciently distinct from abuse or harmful use to be maladaptive pattern of alcohol or drug use leading considered a separate condition. In DSM-IV, sub- to clinically significant impairment or distress, as stance abuse is a residual category that allows the manifested by one or more of the symptoms listed clinician to classify clinically meaningful aspects of in Table 1. For comparative purposes, the table a patient’s behavior when that behavior is not also lists the criteria for harmful use in ICD-10 and clearly associated with a dependence syndrome. In for alcohol abuse in DSM-III-R. To assure that the ICD-10, harmful substance use implies identifiable diagnosis is based on clinically meaningful symp- substance-induced medical or psychiatric conse- toms rather than the results of an occasional excess, quences that occur in the absence of a dependence the duration criterion specifies how long the symp- syndrome. In both classification systems, depen- toms must be present to qualify for a diagnosis. dence is conceived as an underlying condition that In ICD-10, the term harmful use refers to a has much greater clinical significance because of its pattern of using one or more PSYCHOACTIVE sub- implications for understanding etiology, predicting stances that causes damage to health. The damage course, and planning treatment. This will become may be (1) physical (physiological)—such as fatty clear in the following discussion of the assumptions liver, pancreatitis from alcohol, or hepatitis from behind the dependence-syndrome concept. needle-injected drugs; or (2) mental (psychologi- The dependence syndrome is seen as an interre- cal)—such as depression related to heavy drinking lated cluster of cognitive, behavioral, and physio- or drug use. Adverse social consequences often ac- logical symptoms. Table 2 summarizes the criteria company substance use, but are not in themselves used to diagnose dependence in ICD-10, DSM- DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA 389

III-R, and DSM-IV. A diagnosis of dependence in dependence syndrome elements in relation to the all systems is made if three or more of the criteria criteria for DSM-III-R, DSM-IV, and ICD-10. The have been experienced at some time in the previous same elements apply to the diagnosis of depen- twelve months. dence on all psychoactive substances, including al- The dependence syndrome may be present for a cohol, marijuana, opiates, cocaine, sedatives, ph- specific substance (e.g., tobacco, alcohol, or encycledine, other hallucinogens, and tobacco. The diazepam), for a class of substances (e.g., opioid elements represent biological, psychological (cog- drugs), or for a wider range of various substances. nitive), and behavioral processes. This helps to ex- A diagnosis of dependence does not necessarily plain the linkages and interrelationships that ac- imply the presence of physical, psychological, or count for the coherence of signs and symptoms. social consequences, although some form of harm is The co-occurrence of signs and symptoms is the usually present. There are some differences among essential feature of a syndrome. If three or more these classification systems, but the criteria are very criteria do occur repeatedly during the same pe- similar, making it unlikely that a patient diagnosed riod, it is likely that dependence is responsible for in one system would be diagnosed differently in the the amount, frequency, and pattern of the person’s other. substance use. The syndrome concept implicit in the diagnosis Salience. Salience means that drinking or of alcohol and drug dependence in ICD and DSM is drug use is given a higher priority than other activi- a way of describing the nature and severity of ties in spite of its negative consequences. This is addiction (Babor, 1992). Table 2 describes four reflected in the emergence of substance use as the 390 DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA

TABLE 2 ICD and DSM Diagnostic Criteria for Dependence (labeled according to diagnostic level-physiological, cognitive, and behavioral-and underlying dependence elements)

Dependence Diagnostic ICD-10 DSM-III-R DSM-IV Element Level Symptoms Symptoms Symptoms

Salience Cognitive, Progressive neglect of al- Important social, occupa- Important social, occupa- behavioral ternative activities tional, or recrea- tional, or recrea- in favor of substance tional activities tional activities use given up given up Behavioral Persistence with sub- Continued use despite Continued use despite stance use despite social, psychological, psychological or harmful conse- or physical problems physical problems quences Behavioral, Great amount of time de- physiolog- voted to substance ical use, intoxication, or withdrawal; failure to fulfill major role obligations Impaired Behavioral, A strong desire or sense Persistent desire or one control cognitive of compulsion to or more unsuccess- drink or use drugs ful efforts to cut down or control substance use Behavioral Evidence of impaired Substance often taken in Substance often taken in capacity to control larger amounts or larger amounts or substance use in over longer period over a longer period terms of its onset, than the person than intended termination, or intended Any unsuccessful effort levels of use or a persistent desire to cut down or con- trol substance use Tolerance Biological, Increased doses of sub- Marked tolerance; need Either (a) increased behavioral stance are required for markedly in- amounts needed to to achieve effects creased amounts of achieve desired ef- originally produced substance to achieve feet; or (b) markedly by lower doses intoxication or de- diminished effect sired effect or mark- with continued use edly diminished effect with contin- ued use of the same amount Withdrawal Behavioral, A physiological with- Characteristic withdrawal Either (a) characteristic and biological, drawal state symptoms withdrawal syn- with- cognitive Use to relieve or avoid Substance often taken to drome for sub- drawal withdrawal symp- relieve or avoid stance; or (b) the relief toms and subjective withdrawal symp- same substance awareness that this toms taken to relieve or strategy is effective avoid symptoms DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA 391 preferred activity from a set of available alternative ered present if the drinker has repeatedly failed to activities. In addition, the individual does not re- abstain or has only been able to control drinking spond well to the normal processes of social control. with the help of treatment, mutual-help groups, or For example, when drinking to intoxication goes removal to a controlled environment (e.g., prison). against the tacit social rules governing the time, In addition to an inability to abstain, impaired place, or amount typically expected by the user’s control is also reflected in the failure to regulate the family or friends, this may indicate increased sa- amount of alcohol or drug consumed on a given lience. occasion. The cocaine addict vows to snort only a A characteristic of salience is that drinking or small amount but then continues until the entire drug use persists in spite of its negative conse- supply is used up. For the alcoholic, impaired con- quences. This implies that substance use has be- trol includes inability to prevent spontaneous onset come the preferred activity in the person’s life. One of drinking bouts as well as failure to stop drinking indication of this is the amount of time or effort before intoxication. This behavior should be distin- devoted to obtaining, using or recovering from sub- guished from situations in which the drinker’s stance use. For example, people who spend a great ‘‘control’’ over the onset or amount of drinking is deal of time at parties, bars, or business lunches regulated by social or cultural factors, such as oc- give evidence of the increased salience of drinking cur during college beer parties or fiesta drinking over nondrinking activities. occasions. One way to judge the degree of impaired Chronic drinking and drug intoxication interfere control is to determine whether the drinker or drug with the person’s ability to conform to tacit social user has made repeated attempts to limit the quan- rules governing daily activities, such as keeping tity of substance use by making rules or imposing appointments, caring for children, or performing a limits on access to alcohol or drugs. The more these job properly, that are typically expected by the attempts have failed, the more the impaired control person’s reference group. Substance use also results is present. in mental and medical consequences. Thus, a key Tolerance. TOLERANCE is a decrease in re- aspect of the dependence syndrome is the persis- sponse to a psychoactive substance that occurs with tence of substance use in spite of social, psychologi- continued use. For example, increased doses of cal, or physical harm, such as loss of employment, heroin are required to achieve effects originally marital problems, depressive symptoms, accidents, produced by lower doses. Tolerance may be physi- and liver disease. This indicates that substance use cal, behavioral, or psychological. Physical toler- is given a higher priority than other activities, in ance is a change in cellular functioning. The effects spite of its negative consequences. of a dependence-producing substance are reduced, One explanation for the salience of drug and even though the cells normally affected by the sub- alcohol-seeking behavior despite negative conse- stance are subjected to the same concentration. A quences is the relative reinforcement value of im- clear example is the finding that alcoholics can mediate and long-term consequences. For many al- drink amounts of alcohol (e.g., a quart of vodka) coholics and drug abusers, the immediate positive that would be sufficient to incapacitate or kill reinforcing effects of the substance, such as eu- nontolerant drinkers. Tolerance may also develop phoria or stimulation, far outweigh the delayed at the psychological and behavioral levels, indepen- negative consequences, which may occur either in- dent of the biological adaptation that takes place. frequently or inconsistently. Psychological tolerance occurs when the marijuana Impaired Control. The main characteristic of smoker or heroin user no longer experiences a impaired control is the lack of success in limiting ‘‘high’’ after the initial dose of the substance. Be- the amount or frequency of substance use. For havioral tolerance is a change in the effect of a example, the alcoholic wants to stop drinking, but substance because the person has learned to com- repeated attempts have been unsuccessful. Typi- pensate for the impairment caused by a substance. cally, rules and other stratagems are used to avoid Some alcoholics, for example, can operate ma- alcohol entirely or to limit the frequency of drink- chinery at moderate doses of alcohol without im- ing. Resumption of heavy drinking after receiving pairment. professional help for a drinking problem is evi- Withdrawal Signs and Symptoms. A with- dence of lack of success. The symptom is consid- drawal state is a group of symptoms occurring after 392 DIAGNOSIS OF DRUG ABUSE: DIAGNOSTIC CRITERIA

cessation of substance use. It usually occurs after ness that this strategy is effective are cardinal repeated, and usually prolonged drinking or drug symptoms of dependence. Morning drinking to re- use. Onset and course of the withdrawal symptoms lieve nausea or the ‘‘shakes’’ is one of the most are related to type of substance and dose being used common manifestations of physical dependence in immediately prior to abstinence. Table 3 lists some alcoholics. common withdrawal symptoms associated with Other Features of Dependence. To be labeled de- different psychoactive substances. Some drugs, pendence, symptoms must have persisted for at such as Cannabis (MARIJUANA) and HALLUCINO- least one month or must have occurred repeatedly GENS do not typically produce a withdrawal syn- (two or more times) over a longer period of time. drome after cessation of use. The patient does not need to be using the substance Alcohol withdrawal symptoms follow the cessa- continually to have recurrent or persistent prob- tion or reduction of prolonged heavy drinking lems. Some symptoms (e.g., the desire to cut down) within hours. These include tremors, hyperactive may occur repeatedly whether the person is using reflexes, rapid heartbeat, hypertension, general the substance or not. malaise, nausea, and vomiting. Seizures and con- Many patients with a history of dependence ex- vulsions may occur, particularly in people with a perience rapid reinstatement of the syndrome fol- preexisting seizure disorder. Patients may have lowing resumption of substance use after a period HALLUCINATIONS, illusions, or vivid nightmares. of abstinence. Rapid reinstatement is a powerful Sleep is usually disturbed. In addition to physical diagnostic indicator of dependence. It points to the withdrawal symptoms, anxiety and depression are impairment of control over substance use, the rapid also common. Some chronic drinkers never have a development of tolerance, and (frequently) physi- long enough period of abstinence to permit with- cal withdrawal symptoms. drawal to occur. Patients who receive OPIATES or other drugs for The use of a substance with the intention of PAIN relief following surgery (or for a malignant relieving withdrawal symptoms and with an aware- disease like cancer) sometimes show signs of a DIAGNOSTIC AND STATISTICAL MANUAL (DSM) 393

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History, rationale drinking or drug use is resumed after a period of and description. Archives of General Psychiatry, detoxification. 49(8), 624–629. TARTER,R.E.&KIRISCI, L. (1997). The drug use screen- (SEE ALSO: Addiction: Concepts and Definitions; ing inventory for adults: Psychometric structure and Alcoholism: Origin of the Term; Causes of Sub- discriminative survey. American Journal of Drug and stance Abuse; Disease Concept of Alcoholism and Alcohol Abuse, 23, no. 2, 207–220. Drug Abuse; Tolerance and Physical Dependence; WING, J. K., ET AL. (1990). SCAN: Schedules for clinical Wikler’s Pharmacologic Theory of Drug Addiction) assessment in neuropsychiatry. Archives of General Psychiatry, 47, 589–593. BIBLIOGRAPHY WINTERS, K. C., LATIMER,W.&STINCHFIELD,R.D. (1999). The DSM-IV criteria for adolescent alcohol AMERICAN PSYCHIATRIC ASSOCIATION. (1994). Diagnostic and cannabis use disorders. Journal of Studies on Al- and statistical manual of mental disorders-4th edi- cohol, 60, issue 3, 337. tion. Washington, DC: Author. WORLD HEALTH ORGANIZATION. (1992). The ICD-10 AMERICAN PYSCHIATRIC ASSOCIATION. (1987). Diagnostic classification of mental and behavioural disorders: and statistical manual of mental disorders-3rd edi- Clinical descriptions and diagnostic guidelines. Ge- tion-revised. Washington, D.C.: Author. neva: Author. BABOR, T. F. (1992). Nosological considerations in the THOMAS F. BABOR diagnosis of substance use disorders. In M. Glantz & R. Pickens (Eds.), Vulnerability to drug abuse. Wash- REVISED BY CHRIS LOPEZ ington DC: American Psychological Association. EDWARDS, G., ARIF, A., & HODGSON, R. (1981). Nomen- clature and classification of drug- and alcohol-related DIAGNOSTIC AND STATISTICAL MAN- problems: A WHO memorandum. Bulletin of the UAL (DSM) The Diagnostic and Statistical World Health Organization, 59(2), 225–242. Manual of Mental Disorders is the most widely ac- EDWARDS, G., & GROSS, M. M. (1976). Alcohol depen- cepted diagnostic system in the United States. First dence: Provisional description of a clinical syndrome. published by the American Psychaiatric Associa- British Medical Journal, 1, 1058–1061. tion (APA) in 1952, the DSM is used by medical FEIGHNER, J., ET AL. (1972). Diagnostic criteria for use in professionals, insurance companies, and the court psychiatric research. Archives of General Psychiatry, system to diagnose and define mental illnesses and 26, 57–63. disorders, including substance abuse and depen- HEITHOFF,K.A.&WISEMAN, E. J. (1996). Reliability of dence. In fact, the diagnosis code assigned to a case paper-pencil assessment of drug use severity. Ameri- often determines insurance reimbursement for can Journal of Drug and Alcohol Abuse, 22, no. 1, treatment. The book is also an important indicator 109–123. of societal mores: until 1973 homosexuality was ROBINS, L. (1981). The diagnosis of alcoholism after defined as a mental disorder. DSM III. In R. E. Meyer ct al., Evaluation of the The first tabulation of mental illness in the alcoholic: Implications for research, theory and treat- United States appeared in the 1840 census, when ment. NIAAA Research Monograph no. 5, DHHS the category ‘‘idiots’’ and the category ‘‘insane’’ Publication no. (ADM) 81–1033. Washington, DC: were first counted. By the 1880 census, seven types U.S. Government Printing Office. of mental illness were recognized, including epi- 394 DIAGNOSTIC AND STATISTICAL MANUAL (DSM) lepsy. In 1917 the American Medico-Psychological often persist into adult life. Axis III refers to physi- Association (now the APA), in conjunction with the cal disorders or conditions that are potentially rele- National Commission on Mental Hygiene, further vant to the understanding or management of the enlarged its categories of mental illness. This patient. Axis IV rates the severity of psychosocial broader list, while certainly of greater clinical use, stressors that have occurred in the year preceding was still chiefly designed to count the numbers and the current evaluation and that may have contrib- types of patients in mental hospitals. Several years uted to the patient’s symptoms. Axis V is a global after this tabulation, the newly renamed APA re- assessment of psychological, social and occupa- leased a compendium of nationally recognized psy- tional functioning, which should be taken into ac- chiatric terms—most of which applied to psychotic disorders and severe neurological impairments— count in treatment planning. that would become part of the American Medical For the first time DSM-III listed substance use Association’s standard classified nomenclature of disorders as a separate diagnosis category, distin- disease. guishing them from personality disorders, which After the end of World War II, the Veterans they had previously been considered. In addition, Administration (VA) added many more diagnoses the term dependence replaced the more generic to the APA inventory, incorporating the various alcoholism or addiction, and was distinguished psychological manifestations exhibited by ser- from abuse by the presence of the symptoms of vicemen. This expanded compilation proved to be TOLERANCE or WITHDRAWAL. Alcohol and drug influential, for shortly after its publication the abuse were assigned to separate subcategories, per- World Health Organization (WHO) published the mitting a greater differentiation and range of sever- sixth edition of its International Classification of ity for each. Diseases (ICD), which for the first time included Another important change to the substance use information on mental disorders, much of it based disorders section in DSM-III (Rounsaville, Spitzer, on by the VA classifications. & Williams, 1986) was the adoption of a new de- The first edition of the DSM (DSM-I), published in 1952, was little more than a pamphlet. Its im- pendence syndrome concept (Edwards, Arif, & portance, however, lay in its description and defini- Hodgson, 1981), in which dependence was defined tion of the approximately 100 diagnostic categories as an interrelated cluster of psychological symp- then recognized by clinicians. DSM-I, like its suc- toms: a strong desire or CRAVING for the substance; cessor, DSM-II, was heavily influenced by the sev- physiological signs, especially tolerance and with- enth and eighth editions of ICD. In fact, until the drawal; and behavioral indicators, particularly us- publication of of DSM-III, the American system for ing the substance to relieve withdrawal discomfort. classifying psychiatric disorders was virtually iden- Significantly, the medical and social consequences tical to the ICD. of both acute intoxication and chronic substance During the 1970s, however, researchers affili- use, such as ACCIDENTS and liver damage are not ated with the Washington University School of among the primary diagnostic criteria of depen- Medicine (Feighner et al., 1972) developed the ‘‘re- dence. They do, however, play a prominent role in search diagnostic’’ approach to psychiatric diagno- defining the substance abuse category. sis, which emphasized clearly formulated and ob- After the publication of a revised third edition in servable signs and symptoms that could be used for 1987 (DSM-III-R), a fourth edition (DSM-IV) was both research and clinical practice. DSM-III, pub- lished in 1980, incorporated this approach, adding published in 1994. This version contained further clear diagnostic standards and objective descrip- changes in the diagnosis of substance-related disor- tions of symptoms and behaviors. ders that were designed to assure compatibility be- DSM-III also introduced a multiaxial system for tween DSM and ICD. Both publications now define diagnostic evaluation to ensure that all relevant substance dependence as a maladaptive pattern of clinical information was considered. Axis I de- substance use leading to clinically significant im- scribes syndromes, such as major DEPRESSION, pairment or distress, as manifested by three or SCHIZOPHRENIA, and substance use disorders. Axis more of the following symptoms occurring in the II covers childhood and personality disorders that same twelve-month period: DIAGNOSTIC INTERVIEW SCHEDULE (DIS) 395

Tolerance—the need for markedly increased problems: A WHO memorandum. Bulletin of the amounts of the substance to achieve in- World Health Organization, 59, 225–242. toxication or the desired effect FEIGHNER, J., ET AL. (1972). Diagnostic criteria for use in Withdrawal—behavioral changes that occur psychiatric research. Archives of General Psychiatry, when blood or tissue levels of the sub- 26, 57–63. stance decline after a period of prolonged ROUNSAVILLE, B. J., SPITZER, R. L., & WILLIAMS,J.B. or heavy use; often accompanied by use of (1986). Proposed changes in DSM-III substance use the substance to relieve withdrawal disorders: description and rationale. American Jour- symptoms. nal of Psychiatry, 143, 463–468. Increased use—taking the substance in larger THOMAS F. BABOR amounts or over a longer period. REVISED BY AMY LOERCH STRUMOLO Unsuccessful attempts to cut down or control substance use. Much time spent in activities related to pro- DIAGNOSTIC INTERVIEW SCHEDULE curing or using the substance. (DIS) Developed in the late 1970s for use in Ignoring or reducing important social, occupa- large-scale studies of the prevalence of mental dis- tional, or recreational activities because orders in the U.S. population (Regier et al., 1984), of substance use. the Diagnostic Interview Schedule (DIS) is a highly Continued use despite physical or psychologi- structured psychiatric interview that carefully cal problems caused by the substance. specifies the questions that the interviewer must Patients can become dependent on any of the ask to make a DIAGNOSIS. Another version is the following: ALCOHOL,TOBACCO,SEDATIVES– DISC, or Diagnostic Interview Schedule for Chil- HYPNOTICS–ANXIOLYTICS,CANNABIS (MARIJUANA), dren. Unlike the DIS, this version allows the STIMULANTS,OPIOIDS,COCAINE,HALLUCINOGENS, re-ordering of questions or sections. Because the PCP (PHENCYCLIDINE), or a combination of drugs, DIS requires a minimum of clinical judgment, it which is known as POLYSUBSTANCE ABUSE. The can be administered by nonprofessional or most important factor in determining dependence, nonclinician interviewers who have received a week according to the DSM-IV, is not simply abusing of intensive training. In addition to alcohol and alcohol or drugs, but the patient’s refusal to stop other substance-use disorders, the DIS provides di- using the substance(s) despite recognizing the seri- agnostic information about DEPRESSION, ous problems this causes. SCHIZOPHRENIA, and ANXIETY disorders; eating dis- orders; ANTI-SOCIAL PERSONALITY; and a variety of (SEE ALSO: Addiction: Concepts and Definitions; other psychiatric conditions. The DIS has been the Alcoholism: Origin of the Term; Disease Concept of subject of a number of validation studies showing Alcoholism and Drug Abuse) that nonclinician interviewers diagnose patients as accurately as trained clinicians using criteria from DSM-III (DIAGNOSTIC AND STATISTICAL MANUAL of Mental Disorders, third edition). With the Ameri- BIBLIOGRAPHY can Psychiatric Association’s publication of the re- AMERICAN PSYCHIATRIC ASSOCIATION. (1994). Diagnostic vised versions of DSM, major changes were made to and statistical manual of mental disorders-4th edi- the DIS as well. tion. Washington, DC: Author. In June 2000 a study of 349 individuals who AMERICAN PSYCHIATRIC ASSOCIATION. (1987). Diagnostic were given the DIS was published, then examined and statistical manual of mental disorders-3rd edi- by psychiatrists using the Schedules for Clinical tion-revised. Washington, DC: Author. Assessment in Neuropsychiatry (SCAN). The DIS AMERICAN PSYCHIATRIC ASSOCIATION. (1980). Diagnostic missed many cases of major depressive disorders and statistical manual of mental disorders-3rd edi- (as determined by SCAN), but there was corre- tion. Washington DC: Author. lation in the symptom groups. The researchers con- EDWARDS, G., ARIF, A., & HODGSON, R. (1981). Nomen- cluded that DIS may be too conservative with risk clature and classification of drug- and alcohol-related factors. 396 DIAGNOSTIC INTERVIEW SCHEDULE (DIS)

The DIS was first used in The Epidemiologic patients are asked if they have had difficulty ab- Catchment Area (ECA) study, which was a survey staining from drugs (‘‘Have you ever tried to cut of mental disorders in the United States. This sur- down on any of these drugs but found you vey’s results led to worldwide testing, which in turn couldn’t?’’); experienced WITHDRAWAL symptoms led to comparative analyses among the nations. (‘‘Has stopping or cutting down on any of these The DIS also has been widely used in research on drugs made you sick?’’); or experienced other substance-use disorders (Helzer & Canino, 1992), physical complications (‘‘Did you have any health in part because it can be administered by problems like an accidental OVERDOSE, a persistent nonclinician interviewers in population surveys. In- cough, a seizure [fit], an infection, a cut, sprain, terviewers read questions aloud to the subject ex- burn, or other injury as a result of taking any of actly as they are written in the interview booklet. these drugs?’’). The DIS can be scored manually or No deviation from the written format is allowed, by computer to obtain specific drug and alcohol except to repeat questions that may have been mis- diagnoses in DSM-III-R. understood. A set of standard probes is used to In 1994, the American Psychiatric Association determine whether a given symptom was caused by released the fourth edition of the Diagnostic and the effects of physical illness. The interviewer also Statistical Manual of Mental Disorders (DSM-IV). asks for the age of onset and the recency of most This version is applicable to both children and symptoms. adults, which has made it an integral part of school A series of thirty questions constitutes the ALCO- and child psychology, especially when dealing with HOL DEPENDENCE/abuse section of the DIS. The attention deficit hyperactivity disorder (ADHD). section begins with questions about alcohol con- The DSM-IV functions as a way of organizing and sumption and intoxication (e.g., ‘‘Have you ever recognizing cognitive and personality disorders, as gone on binges or benders where you kept drinking well as addictive and disruptive behaviors. The for a couple of days or more without sobering DSM-IV was also used in the late 1990s (in con- up?’’). Additional questions are asked to diagnose the symptoms of dependence (e.g., ‘‘Did you ever junction with part of the DIS) to help determine get tolerant to alcohol, that is, you needed to drink substance abuse treatment needs for prisoners and a lot more in order to get an effect, or found that to screen veterans for post-traumatic stress disor- you could no longer get high on the amount you der (PTSD). used to drink?’’). A third type of question pertains to the symptoms of alcohol abuse (e.g., ‘‘Have you (SEE ALSO: Addiction: Concepts and Definitions; ever had trouble driving because of drinking—like Diagnosis of Drug Abuse; Disease Concept of Alco- having an ACCIDENT or being arrested for drunk holism and Drug Abuse) driving?’’). The drug dependence section of the DIS (version BIBLIOGRAPHY III-B) consists of twenty-four questions that con- form to the DSM-III-R criteria for drug use disor- AMERICAN PSYCHIATRIC ASSOCIATION. (1987). Diagnostic ders. This section begins by asking if the patient and statistical manual of mental disorders-3rd edi- has used any of the following types of drugs ‘‘to get tion-revised. Washington, DC: Author. high or for other mental effects’’: MARIJUANA, BELL, C. C., ET AL. (1999). DSM-IV (Evaluation). JAMA, STIMULANTS (e.g., AMPHETAMINES), SEDATIVES The Journal of the American Medical Association, (e.g., BARBITURATES), prescribed drugs (e.g., 282, 387. TRANQUILIZERS), COCAINE,HEROIN, other OPIATES, BRESLAU,N.,ET AL. (1999). Short screening scale for PSYCHEDELICS, PCP, INHALANTS, and other drugs DSM-IV posttraumatic stress disorder. American not previously specified. If the person has used any Journal of Psychiatry, 156, 908. of these substances more than five times, additional EATON, W. W., ET AL. (2000). A Comparison of Self- questions are asked to evaluate the mode of inges- Report and Clinical Diagnostic Interviews for Depres- tion for each drug (e.g., by mouth, smoking, snort- sion: Diagnostic Interview Schedule and Schedules for ing, or injecting). Clinical Assessment in Neuropsychiatry in the Balti- The remaining questions ask about DSM-III-R more Epidemiologic Catchment Area Follow-Up. Ar- symptoms of dependence and abuse. For example, chives of General Psychiatry, 57, 217. DIMETHYLTRYPTAMINE (DMT) 397

EDELBROCK, C., ET AL. (1999). Interviewing as Commu- nication: An Alternative Way of Administering the Diagnostic Interview Schedule for Children. Journal of Abnormal Child Psychiatry, 27, 447. HELZER, J. E., & CANINO,G.J.(EDS.). (1992). Alcohol- ism in North America, Europe, and Asia. New York: Oxford University Press. JENSEN, P. S., & EDELBROCK, C. (1999). Subject and Interview Characteristics Affecting Reliability of the Diagnostic Interview Schedule for Children. Journal Figure 1 of Abnormal Child Psychiatry, 27, 413. Dihydromorphine LEUZZI, R. A., & SPANDORFER, J. (2000). Some individu- als never outgrow ADHD, says DSM-IV. Internal Medicine, 21, 44. similar to that of morphine. These include consti- LO, C. C., & STEPHENS, R. C. (2000). Drugs and Pris- pation and respiratory depression. Chronic use will oners: Treatment Needs on Entering Prison. American produce TOLERANCE AND PHYSICAL DEPENDENCE. Journal of Drug and Alcohol Abuse, 26, 229. NIGG, J. T. (1999). The ADHD Response-Inhibition Defi- (SEE ALSO: Addiction: Concepts and Definitions; cit as Measured by the Stop Task: Replication with Opiates/Opioids; Opioids: Complications and DSM-IV Combined Type, Extension, and Qualifica- Withdrawal ) tion. Journal of Abnormal Child Psychology, 27, 393. REGIER, D. A., ET AL. (1984). The NIMH Epidemiologic BIBLIOGRAPHY Catchment Area (ECA) program: Historical context, major objectives and study population characteristics. REISINE, T., & PASTERNAK, G. (1996) Opioid analgesics Archives of General Psychiatry, 41, 934–941. and antagonists. In J. G. Hardman et al. (Eds.), The ROBINS, L., ET AL. (1989). NIMH diagnostic interview Pharmacological Basis of Therapeutics, 9th ed. (pp. schedule, version III, revised (DIS-III-R). St. Louis: 521–555). New York: McGraw-Hill. Washington University. GAVRIL W. PASTERNAK ROBINS,L.N.,ET AL. (1982). Validity of the diagnostic interview schedule. version II: DSM-III diagnoses. Psychological Medicine, 12, 855–870. DILAUDID See Hydromorphone THOMAS F. BABOR REVISED BY REBECCA MARLOW-FERGUSON DIMETHYLTRYPTAMINE (DMT) This drug is a member of the HALLUCINOGENIC sub- stances known as indoleamines. These are com- See Benzodiazepines DIAZEPAM pounds that are structurally similar to the neuro- transmitter SEROTONIN. Although found in certain plants and, according to some evidence, can be DIET PILL See Amphetamine; Anoretic formed in the brain, DMT is synthesized for use. Its effects are similar to those produced by LYSERGIC ACID DIETHYLAMIDE (LSD), but unlike LSD, DMT DIHYDROMORPHINE Dihydromorphine is inactive after oral administration. It must be is a semisynthetic OPIOID ANALGESIC (painkiller), injected, sniffed, or smoked. derived from MORPHINE. Structurally, it is very DMT has a rapid onset, usually within one min- similar to morphine—the only difference being the ute, but the effects last for a much shorter period reduction of the double bond between positions 7 than those produced by LSD—with the user feeling and 8 in morphine to a single bond. Although ‘‘normal’’ within thirty to sixty minutes. This is slightly more potent than morphine in relieving because DMT is very rapidly destroyed by the en- PAIN, it is not widely used clinically. At standard zyme monoamine oxidase, which metabolizes analgesic doses, it has a side-effect profile very structurally related compounds, such as serotonin. 398 DIS

controversy since then, and has itself been chal- lenged by other conceptual models. Because this article is concerned primarily with the disease con- cept, the other models will be mentioned only briefly. Among the first to propose that excessive alcohol Figure 1 use might be a disorder, rather than willful or sinful DMT behavior, were the physicians Benjamin Rush, in the United States, and Thomas Trotter, in Great The dose amount of DMT is critical, since larger Britain. Both Rush and Trotter believed that some doses produce slightly longer, much more intense, individuals developed a pernicious ‘‘habit’’ of and sometimes very uncomfortable ‘‘trips’’ than do drinking and that it was necessary to undo the lower doses. The sudden and rapid onset of a period habit to restore those individuals to health. Words of altered perceptions that soon terminates is also such as habit and disease were used to convey in- disconcerting to some users. DMT was known terwoven notions. Trotter saw ‘‘the habit of drunk- briefly as the ‘‘businessman’s LSD’’—one could enness’’ as ‘‘a disease of the will,’’ while Rush saw have a PSYCHEDELIC experience during the lunch drunkenness as a disease in which alcohol was the hour and be back at work in the afternoon. It has, causal agent, loss of control over drinking behavior however, in fact never been a widely available, the characteristic symptom, and total abstinence steadily obtainable, or popular drug on the street. the only effective cure. In 1849, a Swedish physi- cian, Magnus Huss, introduced the term alcoholism (SEE ALSO: DOM; MDMA) [‘‘alcoholismus’’] to designate not only the disorder of excessive use but an entire syndrome, including BIBLIOGRAPHY the multiple somatic consequences of excessive use. Late-nineteenth-century physicians, although HOLLISTER, L. E. (1978). Psychotomimetic drugs in not the first to see habitual use of other drugs (such man. Handbookof Psychopharmacology, 11 , 389– as OPIATES,TOBACCO,COFFEE) as disorders, are 424. credited with stressing the idea that each was but a STRASSMAN, R. J., & QUALLS, C. R. (in press). Dose-re- subtype of a more generic disorder of inebriety. sponse study of N,N-Dimethyltryptamine in hu- However, they also minimized Trotter’s and Rush’s mans. I. neuroendocrine, autonomic and cardiovascu- notions of learned behavior as a central feature of a lar effects. Archives of General Pyschiatry. generic disorder of inebriety and emphasized in- DANIEL X. FREEDMAN stead the idea of a disorder rooted in acquired or R. N. PECHNICK inherited biological malfunction or VULNERABIL- ITY. This more biologically based view of inebriety was used in Britain and the United States by advo- cates of publicly funded treatment facilities— DIS See Diagnostic Interview Schedule inebriate asylums. Many temperance leaders also supported the establishment of treatment facilities. However, while physicians advocated treatment, DISEASE CONCEPT OF ALCOHOLISM temperance leaders, still convinced that alcohol it- AND DRUG ABUSE Throughout most of re- self was the root of the problem, pushed for its corded history, excessive use of ALCOHOL was control and, eventually, for its prohibition. viewed as a willful act leading to intoxication and In the United States, the ratification in 1920 of other sinful behaviors. The Bible warns against the Eighteenth Amendment, which prohibited the drunkenness; Islam bans alcohol use entirely. Since production, sale, and distribution of alcohol, tem- the early nineteenth century, the moral perspective porarily dampened scientific inquiry into the na- has competed with a conceptualization of excessive ture of alcoholism. But concern about the problem- use of alcohol as a disease or disorder, not necessar- atic and excessive use of other drugs, such as ily a moral failing. The disease (or disorder) con- OPIOIDS,COCAINE, and BARBITURATES, continued cept has, in turn, been evolving with considerable to stimulate writings both in the United States and DISEASE CONCEPT OF ALCOHOLISM AND DRUG ABUSE 399 abroad. Was excessive drug use a disease, a moral the ‘‘classic’’ disease model to distinguish it from failure, or something else—perhaps something in later perspectives of a disorder or syndrome more between? powerfully influenced by learning and social By the mid-twentieth century, the rise of factors. ALCOHOLICS ANONYMOUS (AA), the publications of Alcohol researcher and theorist Thomas Babor E. M. Jellinek, and the establishment of the Yale has pointed out that when definitions specify alco- Center for Alcohol Studies revived interest in ex- hol addiction or dependence as a disease entity, it ploring the nature of ALCOHOLISM. In the early can be argued more convincingly that ‘‘dependence 1960s, the idea reemerged that, for certain ‘‘vul- is an organically based entity which produces a nerable’’ people, alcohol use leads to physical ad- characteristic set of signs and symptoms . . . and diction—a true disease. increases the probability of repetitive drinking behavior.’’ EARLY MODELS OF THE The American Psychiatric Association included DISEASE CONCEPT alcoholism in the first edition (1952) of the DIAGNOSTIC AND STATISTICAL MANUAL of Mental Central to the disease concept of alcoholism put Disorders. In the second edition (DSM-II), pub- forward by Jellinek were the roles of TOLERANCE lished in 1968, the group followed a precedent set AND PHYSICAL DEPENDENCE, usually considered by the World Health Organization’s INTERNA- hallmarks of ADDICTION. Tolerance indicates that TIONAL CLASSIFICATIONOF DISEASES (ICD-8) and increased doses of a drug are required to produce included three subcategories of alcohol-related dis- effects previously attained at lower doses. Physical orders: alcohol addiction, episodic excessive drink- dependence refers to the occurrence of WITH- ing, and habitual excessive drinking. Both of these DRAWAL symptoms following cessation of alcohol or publications included alcoholism among the per- other drug use. Although Jellinek recognized that sonality disorders and certain other nonpsychotic alcohol problems could occur without alcohol ad- disorders, implying that the alcohol use was either diction, addiction to alcohol moved to the center of secondary to an underlying personality problem or scientific focus. a response to extreme internal distress. This view of Despite being couched in the language of sci- excessive drug use as a symptom of some other ence, the reemergence of the disease concept of psychiatric disorder is sometimes referred to as the alcoholism was not a result of new scientific find- symptomatic model. According to this concept, ings. Jellinek believed it was necessary to see alco- drug or alcohol dependence is not really a disorder holism as a disease in order to increase the avail- in and of itself. ability of services for alcoholics within established Meanwhile, from the late 1950s and throughout medical facilities. He also recognized that efforts to the 1960s, the Expert Committee on Addiction- prevent alcoholism would still have to address the Producing Drugs of the WORLD HEALTH ORGANIZA- complex cultural, demographic, political and eco- TION (WHO) continued to formulate and refine def- nomic issues contributing to the problem. Although initions of addiction and HABITUATION that could he sometimes appeared to take a broad view of the facilitate WHO’s responsibility (required by inter- disease concept of alcoholism, he reserved the dis- national treaties) for control of NARCOTICS, co- ease category for those individuals manifesting tol- caine, and CANNABIS. In the 1950s, the presence of erance, withdrawal symptoms, and either ‘‘loss of physical dependence was emphasized in the defini- control’’ or ‘‘inability to abstain’’ from alcohol. tion of drug dependence, and the WHO Expert These individuals could not drink in moderation; Committee was still concerned with differentiating with continued drinking, their disease was progres- between psychic dependence and physical depen- sive. Others who drank merely in response to psy- dence. At one level, the concept of psychic depen- chological stress (‘‘alpha alcoholism’’) and those dence was compatible with the psychodynamic who sustained toxic consequences from alcohol but view that these disorders were a response to psychic were not physically dependent (‘‘beta alcoholism’’) distress (such as negative mood states). According did not qualify for his more explicit and restrictive to the psychodynamic model, excessive alcohol or definition of disease. Jellinek’s view of alcoholism drug consumption was merely a response to under- as a progressive disease is sometimes referred to as lying psychopathology. This model was also consis- 400 DISEASE CONCEPT OF ALCOHOLISM AND DRUG ABUSE tent with Jellinek’s view of one of the ‘‘species’’ of underlying personality problem. These statements alcoholism, in which individuals drink to relieve come close to being current definitions of the classic emotional pain (alpha alcoholism). In 1969, the disease model. committee abandoned the effort to differentiate habits from addictions and adopted terminology PROBLEM DRINKING AS A first proposed by Nathan Eddy and colleagues in DISTINCT DIMENSION 1965, in which the term drug dependence desig- nates ‘‘those syndromes in which drugs come to The importance of what can now be called the control behavior.’’ The committee recognized that classic ‘‘disease model’’ of alcoholism as a primary dependencies on different classes of drugs (such as focus for health programs was challenged in 1977 alcohol, opiates, cocaine) can differ significantly by a report of a WHO Expert Committee on alco- and that withdrawal symptoms are not always hol-related disabilities. This report stressed that present or necessary aspects of dependence (see not everyone who develops a disability related to Table 1). alcohol use exhibits alcohol dependence or addic- In 1972, alcoholism was included in a listing of tion, nor would such an individual necessarily de- diagnostic criteria for use in psychiatric research velop a dependence in the future. The report as- published by Feighner and coworkers. The defining serted that some alcohol-related disabilities criteria for alcoholism included withdrawal symp- represent a dimension of problem drinking distinct toms, loss of control, severe medical consequences, from the disease of alcoholism or alcohol depen- and social problems. In the same year the NA- dence syndrome. This perspective provided support TIONAL COUNCIL ON ALCOHOLISM also outlined cri- teria for diagnosing alcoholism, which emphasized for policies aimed at reducing overall alcohol con- tolerance and physical dependence and incorpo- sumption, not just at promoting abstinence among rated certain concepts developed by ALCOHOLICS vulnerable individuals. The report described the al- ANONYMOUS. This definition, and one issued jointly cohol dependence syndrome itself as a learned phe- with the American Medical Society on Alcoholism nomenon, not a disease state, which is either pres- in 1976 (see Table 1), represented an attempt to ent or absent, but ‘‘a condition which exists in emphasize the seriousness of the disorder, the expe- degrees of severity.’’ It is important to recognize rience of clinicians and of recovering alcoholics, that this syndrome perspective does not take a posi- and the view that alcoholism is a primary or inde- tion on whether alcoholism should be considered a pendent disorder, not merely a manifestation of an disease. DISEASE CONCEPT OF ALCOHOLISM AND DRUG ABUSE 401

The concept of dependence as a syndrome is of severity, rather than as a discrete category. quite similar to that put forward in 1965 by drug- Third, dependence should be differentiated from abuse researcher Jerome Jaffe, who viewed addic- alcohol-related disabilities. Both dependence and tion as standing at one end of a continuum of in- disabilities exist in degrees, rather than on an all- volvement in drug use: ‘‘In most instances it will or-none basis. There is some evidence that people not be possible to state with precision at what point with more severe degrees of alcohol dependence [along the continuum] compulsive use should be who seek treatment have a different clinical course considered addiction,’’ Jaffe observed. He empha- from those with less severe dependence. sized that ‘‘the term addiction cannot be used inter- By the late 1970s, the American Psychiatric changeably with physical dependence. It is possible Association’s Diagnostic and Statistical Manual, to be physically dependent on drugs without being 3rd edition (DSM-III), moved away from more de- addicted and . . . to be addicted without being scriptive and psychodynamic orientation toward a physically dependent.’’ In this view, the behavioral nomenclature in which specific diagnostic criteria disorder, not physical dependence, is the syndrome. were laid out for specific syndromes. In the case of Jaffe defined addiction as ‘‘a behavioral pattern of alcohol and drug dependence, the original drafts of drug use, characterized by overwhelming involve- DSM-III considered inclusion of a dependence syn- ment with the use of a drug (compulsive use), the drome that varied in degree of severity and in securing of its supply, and a high tendency to which tolerance and physical dependence were im- relapse after withdrawal.’’ This proposed generic portant, but not essential, criteria for diagnosis. At notion of dependence is applicable to STIMULANTS the last moment, however, it was decided that and HALLUCINOGENS (for which physical depen- tolerance and physical dependence were both nec- dence is not a significant factor), as well as to essary and sufficient for a diagnosis of drug depen- alcohol, opiates, and SEDATIVE-HYPNOTIC drugs dence; the presence of other criteria listed were by (for which physical dependence is a factor). The themselves insufficient without tolerance and phys- Diagnostic and Statistical Manual of Mental Disor- ical dependence. Nevertheless, by distinguishing ders, 3rd edition, revised (DSM-III-R), published drug (or alcohol) dependence from drug (or alco- by the American Psychiatric Association more than hol) abuse, DSM-III recognized the two-dimen- twenty years later, in 1987, also used such a generic sional conceptualization previously put forth in the definition. WHO report of 1977 and in ICD-9. In 1980, during the short interval between the publication of DSM-III and the beginning of work FROM PSYCHIC AND PHYSICAL on DSM-III-R, a WHO working group met to fur- DEPENDENCE TO ther refine terminology. One result of the meeting DEPENDENCE SYNDROME was the publication of a WHO memorandum on The changing perspectives on the general con- nomenclature and classification of drug- and alco- cept of drug dependence, given momentum by the hol-related problems that endorsed the concept 1977 WHO report on alcohol and by other re- that drug dependence is a syndrome that exists in search, were ultimately reflected in changes in the degrees and that can be inferred from the way in definitions and other positions of the World Health which drug use takes priority over a drug user’s Organization and in its 1980 International Classifi- once-held VALUES. The criteria for making this in- cation of Diseases, 9th edition (ICD-9). With its ference included many of those mentioned by Ed- publication, the concept of an alcohol dependence wards and Gross in their 1976 paper and some that syndrome formally emerged at an international had been developed for DSM-III. The WHO memo- level. The ICD-9 concept of dependence was based randum, while recognizing the importance of toler- on a 1976 proposal by researchers Griffith Ed- ance and physical dependence, did not view these wards and Milton Gross, who defined seven charac- phenomena as always essential and required. It en- teristics of the alcohol dependence syndrome and dorsed again the two-dimensional perspective— proposed that there are certain implicit assump- not all drug or alcohol problems are manifestations tions to the syndrome: First, it is a symptom com- of dependence; and harmful or hazardous use can plex involving both biological processes and learn- occur independently of the decreased flexibility and ing. Second, it should be defined along a continuum constricted choice that are the hallmarks of the 402 DISEASE CONCEPT OF ALCOHOLISM AND DRUG ABUSE dependence syndrome. This perspective was un- At the same time, at the international level, the derscored by pointing out that the presence of framers of ICD-10 continued the evolution begun physical dependence per se (as in the case of pa- in ICD-9 and adhered closely to the concepts of tients taking drugs for pain) was not in itself suffi- dependence outlined in the 1977 WHO report and cient for the diagnosis of dependence. The memo- 1981 WHO memorandum. Published in 1992, randum also presented a model of dependence ICD-10 includes a generic model of drug depen- emphasizing that the dependence phenomenon is dence with similar criteria for alcohol, tobacco, not a property of the individual but resides in the opioids, and other drugs that affect the brain. Like relationships among the elements in the model— DSM-IV, ICD-10 presents a number of criteria social, psychological, and biological. This view has (six) for determining the presence of the alcohol (or been called the biopsychosocial model. drug) dependence syndrome; at least three of these must be present for the clinician to judge that the CRITERIA FOR DIAGNOSIS OF A syndrome exists to some degree. GENERIC DEPENDENCE DISORDER ICD-10 does not include a diagnostic category of The American Psychiatric Association’s DSM- alcohol or drug abuse but instead includes a cate- III-R, published in 1987, built on both DSM-III and gory of harmful use—a pattern of use that is the WHO memorandum. It presented nine criteria causing damage to mental or physical health. Un- for diagnosing a generic dependence syndrome, ap- like DSM-IV, which defines drug or alcohol (sub- plied to a wide variety of drugs. The user must have stance) abuse as ‘‘a maladaptive pattern of use’’ experienced at least three criteria in order for the causing significant impairment or distress and in- practitioner to consider any degree of dependence terpersonal, family, and legal problems (e.g., ar- to be present. Neither tolerance nor physical depen- rests), ICD-10 does not consider such patterns of dence was a required criterion. The presence of use and consequences necessarily to be evidence of more than three criteria would indicate a more harmful use. severe degree of dependence. Drug abuse was a ICD-10 and DSM-IV share important character- residual category used for designating drug-related istics that represent a further evolution in under- problems when dependence was not present. standing drug and alcohol dependence syndromes. The DSM-III-R conceptualization of dependence In contrast to some disease-oriented defintions that was controversial. Because for many years physical see alcoholism as uniformly progressive, in ICD-10 dependence and tolerance had been considered evi- and DSM-IV the course of the disorder is not one of dence of ‘‘true disease,’’ many clinicians believed uniform progression or predictable cure, but there that changing these criteria from the necessary and are a variety of significant states of remission. For required status they had had in DSM-III was a example, DSM-IV distinguishes early remission mistake that erroneously broadened the category of drug dependence. Much of the focus in the develop- (within the first 12 months) from sustained remis- ment of DSM-IV, published in 1994, was on how to sion (at least 12 months); within each of these it restore the primacy of these phenomena in the di- differentiates full remission from partial remission agnosis of drug and alcohol dependence. DSM-IV (i.e., all criteria for dependence have not been met, defines seven generic criteria for alcohol and other although at least one has been met intermittently or drug dependence. Three are required for a diagno- continuously). DSM-IV also recognizes the circum- sis of alcohol or other drug dependence. Although stances supporting remission and allows for dis- tolerance and withdrawal are listed first, they are tinctions such as remission while the user is in a not required—but the clinician must specify controlled environment (where substances are whether either is present. highly restricted) or remission from drug of depen- Despite these concerns, there was little argument dence when the user is maintained on a similar about the importance of psychological and socio- agonist. The categorization of states of remission logical factors in the development and perpetuation (abstinence) in ICD-10 is somewhat similar, al- of the syndrome—that is, there was still consensus though the distinction between early and sustained about the biopsychosocial model. remission is not made. DISEASE CONCEPT OF ALCOHOLISM AND DRUG ABUSE 403

CHALLENGES TO THE dent alcoholics had to remain abstinent in order to DISEASE CONCEPT maintain improvement. Several studies appeared to confirm that severely dependent alcoholics might The classic disease model of alcoholism and be different from those who were less dependent. drug dependence has served as a challenge to some Some researchers, such as Hodgson, reported that behavioral researchers and social scientists; they small doses of alcohol had a ‘‘priming’’ effect (i.e., have raised a number of questions about biologi- stimulated a strong urge to drink more), the magni- cally based theories of such behaviors. Critics of the tude of which correlated with the severity of alcohol disease concept point to studies showing that some dependence. Other researchers criticized the meth- former alcoholics could apparently return to nor- odology used in previous studies. (For references, mal drinking. Such findings challenged the concept see Meyer, 1992.) of alcoholism as a progressive disease. The concept These findings help to explain why, beginning in of inevitable ‘‘loss of control’’ over drinking was the late 1970s, the classic disease concept was be- also challenged by Merry’s study (1966) in which ing reexamined and redefined as a symptom com- alcoholics were given drinks containing either plex called ‘‘dependence’’ or ‘‘dependence syn- vodka or a placebo (no alcohol) on alternate days drome.’’ However, this shift has not satisfied some and reported having no more desire to drink after critics who object to any conceptualization that consuming the vodka than after the placebo. The comes close to viewing compulsive alcohol or other results suggested that if ‘‘loss of control’’ did occur drug use as a disease or disorder. The debate over in alcoholics, it was not triggered as a biological the disease concept continues to be more heated in response to alcohol but rather as a learned response the alcohol field than in other areas of addictive with associated EXPECTANCIES concerning drinking disorders, such as compulsive use of opioids. In the behavior. Researchers Nancy Mello and Jack Men- early 1990s, however, an analogous and equally delson also reported, in 1971, that alcoholics did heated debate has developed about the conceptual- not manifest ‘‘loss of control’’ in their drinking ization of tobacco smoking. behavior and did not drink to avoid withdrawal While health professionals throughout the world symptoms. The work of Mello and Mendelson and now generally agree that some forms of drug and of other researchers led to the conclusion that alcohol use should be seen as disorders (at least for drinking behavior could be shaped like any other record-keeping and some public policy purposes), operant in a behavioral paradigm. Other research- dissent from this view persists. The most compel- ers challenged the notion of alcoholism as a distinct ling arguments against the disease concept have entity (with clear differentiations between alcohol- come from social and behavioral scientists. This ics and nonalcoholics), as well as the concepts of may be partly because behavioral clinicians tend to inevitable progression to loss of control and of work with less seriously impaired individuals, while alcoholism as a permanent and irreversible condi- physicians usually deal with people whose depen- tion precluding the possibility of moderate drink- dence has become more severe; and also because ing. (For these and other references, see Meyer, the physician’s primary-care office may be where 1992.) early identification of substance-abuse problems These findings by behavioral researchers in the and effective behavioral interventions is most likely laboratory had counterparts in large surveys of to take place. drinking practices conducted by the RAND Corpo- ration. Evidence in the general population indi- ALTERNATIVE MODELS cated that some alcoholics might be able to drink moderately without relapsing to excessive drinking. Swedish researcher Lars Lindstro¨m’s summary These and other such challenges to the disease of current perspectives on the nature of alcoholism concept of alcoholism sharpened the debate and is equally applicable to the divergent views about clarified the construct. Efforts to replicate some of other forms of excessive and/or compulsive drug these earlier studies sometimes led to conflicting use. Each of these models attempts to explain why results, calling into question the conclusions they people use alcohol or drugs, why use escalates to had drawn or leading to refinements. RAND Corpo- excessive and/or harmful levels, why some people ration found at later follow-up that severely depen- continue drug use despite the harmful conse- 404 DISEASE CONCEPT OF ALCOHOLISM AND DRUG ABUSE quences, how and why they stop using drugs, and service for specific patients. Instead, these pro- why they relapse after a period of abstinence. The grams emphasize the experience and knowledge perspectives include the moral model, which holds that staff derive from the recovery process built on that individuals have choice and are accountable TWELVE-STEP mutual-help principles. There are for their behavior; the disease model (both the no patients—only participants—and the role of classic and its variants); the symptomatic model, staff is to manage the environment. Yet social which views excessive drug or alcohol use as a models, in emphasizing the critical role that people symptom of underlying psychiatric disorder; the ‘‘in recovery’’ play in the helping process, are em- learning model (drug addiction and alcoholism are ploying a term—recovery—that is itself derived learned behaviors); the social model, which empha- from the classic disease concept, which views alco- sizes the primacy of environmental factors, such as holism as a permanent disease state for which the availability, social controls, interpersonal relation- only cure is total abstinence and the twelve-step AA ships; and the biopsychosocial model, which at- program as the best route to such abstinence. tempts (in several variants) to synthesize elements of other models, taking into account biology, vul- PERSISTENCE OF THE nerability, psychopathology, and cultural, social, MORAL PERSPECTIVE economic, and pharmacological factors. The de- pendence syndrome model is probably best viewed Despite the preponderance of medical opinion as a variant of the biopsychosocial model. that some drug and alcohol users have a disorder— Lindstro¨m points out that these models are now a diminished capacity to choose freely whether or rarely encountered in pure form: each commonly not to use a particular substance—the moral incorporates elements from other perspectives. models retain some vitality. In 1882, when the Furthermore, proponents of a particular model disease concept was first gaining momentum, the may, in practice, give greater emphasis to the cen- Reverend J. E. Todd wrote an essay entitled tral features of another. For example, ALCOHOLICS ‘‘Drunkenness a Vice, Not a Disease.’’ In the late ANONYMOUS (AA) generally espouses the disease 1980s, the disease concept critics Fingarette and model. Yet because AA holds people accountable Peele put forth almost precisely the same thesis. for the consequences of their drug use and empha- Peele has argued that the disease concept excul- sizes the central role of spiritual alienation in the pates the individual from responsibility, runs coun- perpetuation of alcoholism, AA’s approach may ter to scientific facts, and is perpetuated for the also be seen as a variant of the moral model. benefit of the treatment industry. However, his the- Although the term disease concept is often used sis has been criticized for using the classic disease synonymously with biological or medical model, model as a ‘‘straw man’’ because it does not take these terms do not always convey the same ideas, into account the more recent adoption of the bio- especially with respect to implications for treat- psychosocial model. ment. For example, the medical model of treatment Some sociologists in the United States have is frequently contrasted with the social or social noted that the term alcoholic is still commonly used recovery model, now widely used and advocated in as a synonym for drunkard rather than as a desig- California. Medical-model programs are generally nation for someone with an illness or disorder. The characterized not only by a philosophy about the word addict is similarly used in a pejorative way, problem but also by hospital-based detoxification, even when it is used more loosely to refer to a wide often pharmacologically assisted, and outpatient range of relatively benign behaviors, such as run- components in which there are formal treatment ning or watching television. In the minds of most plans. Attention is paid to careful record keeping people, the concept of alcoholism or drug addiction and professional credentials of the treatment staff. as a disorder or disease can coexist quite comforta- Physicians retain medical and legal responsibility bly with the concept of drunkenness or drug use as for the overall program. In contrast, social-model a vice. Since the nature of drug dependence is so recovery programs reject the involvement of profes- closely linked to questions about the nature of free sional staff and many of the activities of the medi- will and human volition—issues that have fasci- cal model, such as the data gathering, licensing, nated philosophers and scientists through the and record keeping that link funding to units of ages—it is likely that the disease concept of addic- DISTILLATION 405

tion will continue to be debated for a long time to JAFFE, J. H. (1992). Current concepts of addiction. In come. C. P. O’Brien & J. H. Jaffe (Eds.), Addictive states. New York: Raven Press. (SEE ALSO: Addiction: Concepts and Definitions; JAFFE, J. H. (1965). Drug addiction and drug abuse. In Alcoholism; Causes of Substance Abuse; Tolerance L. S. Goodman & A. Gilman (Eds.), The pharmaco- and Physical Dependence; Treatment, History of, logical basis of therapeutics, 3rd ed. New York: Mac- in the United States) millan. JELLINEK, E. M. (1960). The disease concept of alcohol- BIBLIOGRAPHY ism. New Brunswick, NJ: Hillhouse Press. KELLER, M., & DORIA, J. (1991). On defining alcoholism. AMERICAN PSYCHIATRIC ASSOCIATION. (1952). Diagnostic Alcohol Health and Research World, 15(4), 253– and statistical manual of mental disorders; DSM-II 259. (1968); DSM-III (1978); DSM-III-R (1987); DSM-IV LINDSTRO¨ M, L. (1992). Managing alcoholism. New York: (1994). Washington, DC: Author. Oxford University Press. BABOR, T. F., ET AL. (1986). Issues in the definition of MELLO,N.K.,&MENDELSON, J. H. (1971). Drinking diagnosis of alcoholism: Implications for a reformula- patterns during work: Contingent and noncontingent tion. Progress in Neuropsychopharmacology and Bio- alcohol acquisition. In Public Health Service HSM logical Psychiatry, 10, 113–128. 719045, Recent advances in alcoholism. Washington, EDDY, N. B., ET AL. (1965). Drug dependence: Its signifi- DC: U.S. Government Printing Office. cance and characteristics. Bulletin of the World MERRY, J. (1966). The loss of control myth. Lancet, 1, Health Organization, 32, 721–733. 1257–1258. EDWARDS, G. (1992). Problems and dependence: The MEYER, R. (1992). The concept of disease in alcoholism history of two dimensions. In M. Lader et al. (Eds.), and drug addiction. In Drugs and alcohol against life The nature of alcohol and drug-related problems. (Dolentium hominum, no. 19). Vatican City: Vatican New York: Oxford University Press. Press. EDWARDS, G., & GROSS, M. M. (1976). Alcohol depen- PEELE, S. (1989). Diseasing of America. Boston: Hough- dence: Provisional description of a clinical syndrome. ton Mifflin. British Medical Journal, 1, 1058–1061. ROOM, R. (1983). Sociology and the disease concept of EDWARDS, G., ET AL. (1981). Nomenclature and classifi- alcoholism. In R. G. Smart et al. (Eds.), Research cation of drug- and alcohol-related problems: A WHO advances in alcohol and drug problems, vol. 7. New memorandum. Bulletin of the World Health Organi- York: Plenum. zation, 50, 225–242. SCHUCKIT, M. S., ET AL. (1991). Evolution of the DSM EDWARDS, G., ET AL.(EDS.). (1977). Alcohol-related dis- diagnostic criteria for alcoholism. Alcohol Health and abilities. Geneva: World Health Organization. Research World, 15(4), 278–283. FEIGHNER, J. P., ET AL. (1972). Diagnostic criteria for use WIKLER, A. (1980). Opioid dependence: Mechanisms in psychiatric research. Archives of General Psychia- and treatment. New York: Plenum. try, 26, 57–63. WORLD HEALTH ORGANIZATION. (1992). The ICD-10 FINGARETTE, H. (1988). Heavy drinking: The myth of classification of mental and behavioural disorders: alcoholism as a disease. Berkeley: University of Cali- Clinical descriptions and diagnostic guidelines. Ge- fornia Press. neva: Author. FLAVIN, D. K., & MORSE, R. M. (1991). What is alcohol- WORLD HEALTH ORGANIZATION. (1978). Mental disor- ism: Current definitions and diagnostic criteria and ders: Glossary and guide to their classification (in their implications for treatment. Alcohol Health and accordance with 9th revision of the International Research World, 15(4), 266–271. Classification of Diseases). Geneva: Author. GRANT, B. F., & TOWLE, L. H. (1991). A comparison of diagnostic criteria: DSM-III-R, proposed DSM-IV, and JEROME H. JAFFE proposed ICD-10. Alcohol Health and Research ROGER E. MEYER World, 15(4), 284–292. HODGSON, R., ET AL. (1979). Alcohol dependence and the priming effect. Behavioral Research Therapy, 17, DISTILLATION Distillation is the process 379–387. of purifying liquid compounds on the basis of dif- 406 DISTILLED SPIRITS, TYPES OF ferent boiling points or the process of separating most commonly used plants are sugarcane, liquids from compounds that do not vaporize. Since potatoes, sugar beets, corn, rye, rice, and barley; the actual process causes liquids to precipitate in a various fruits such as grapes, peaches, and apples wet mist or drops that concentrate and drip, the are also used. Flavors may be added to provide word derives from the Latin de (from, down, away) distinctive character. ,stillare (to drip). All distilled spirits begin as a colorless liquid ם In the simplest form of distillation, saltwater can pure ethyl alcohol (as it was called by 1869)— be purified to yield freshwater by steam distillation, C2H6O. This had been called aqua vitae (Latin, leaving a residue of salt. Distillation is also the water of life) by medieval alchemists; today it is process by which alcohol (ethanol, also called ethyl often called grain alcohol, and the amount con- alcohol) as liquors or spirits, are separated from tained in distilled spirits ranges from 30 to 100 fermenting mashes of grains, fruits, or vegetables. percent (60 to 200 proof)—the rest being mainly When this process is used to distill alcohol, it is water. Examples of distilled spirits include brandy, based on the following: Ethyl alcohol (C2H6O) has a lower boiling point than does water (78.5ЊC ver- whiskey, rum, gin, and vodka. Brandy was called sus 100ЊC), so alcohol vapors rise first into the brandewijn by the Dutch of the 1600s—burned, or condenser, where cool water circulates around the distilled, wine. It was originally produced as a outside of the condenser, causing the alcohol va- means of saving space on trade ships, to increase pors to return to liquid form and drop into the the value of a cargo. The intent was to add water to collection flask. The purity of the distillate can be the condensate to turn it back into wine, but cus- increased by repeating the process several times. tomers soon preferred the strong brandy to the acidic wines it replaced. Cognac is a special brandy About 800 A.D., the process of distillation was evolved by the Arabian alchemist Jabir (or Geber) produced in the district around the Charente river ibn Hayyah. He may also have named the distillate towns of Cognac and Jarnac, in France, where wine alcohol, since the word derives from an Arabic root, is usually distilled twice, then put into oak barrels al-kuhul, which refers to powdered antimony to age. The spirits draw color and flavor (tannins) from the wood during the required five-year aging (kohl) used as an eye cosmetic in the Mediterra- process. nean region; with time and use it came to mean any Beer and wine were the most popular drinks of finely ground substance, then the ‘‘essence,’’ and the New World colonists. By the mid-1700s, whis- eventually, the essence of wine—its spirit, or alco- key (from uisce beathadh in Irish Gaelic; uisge hol. It came into English from Old Spanish, from beatha in Scots Gaelic) was introduced into the the Arabic spoken by the Moors of the Iberian American colonies by Scottish and Irish settlers to peninsula during their rule there (750–1492 A.D.). Pennsylvania. Whiskey is distilled off grains— usually corn or rye, but millet, sorghum, and barley (SEE ALSO: Beers and Brews; Distilled Spirits, are also used. Traditional American whiskeys are Types of; Fermentation) bourbons (named after Bourbon county in Ken- tucky), which are made from a sour mash of rye BIBLIOGRAPHY and corn. Bourbons typically contain 40 to 50 percent ethyl alcohol (called 80 to 100 proof, dou- LUCI´A, S. P. (1963). Alcohol and civilization. New York: bled by the liquor industry). Canadian whiskey is McGraw-Hill. very similar to bourbon and to rye whiskey, while SCOTT E. LUKAS Irish whiskey is dry (has less sugars), with a dis- tinctive austere flavor gained by filtration. All these whiskeys lack the smoky taste of Scotch whiskeys, DISTILLED SPIRITS, TYPES OF Dis- which get their unique flavor by using malt that tilled spirits (or, simply, spirits or liquors) are the had been heated over peat fires. By using less malt ALCOHOL-containing fluids (ethanol, also called and by aging for only a few years in used sherry ethyl alcohol) obtained via DISTILLATION of fer- casks (traditionally), a light flavor is produced; by mented juices from plants. These juices include using more malt and long aging, heavy peaty wines, distillates of which are termed brandies. The smoky flavors are produced. Today, some scotches DISTILLED SPIRITS, TYPES OF 407

Figure 1 Simple Distillation Apparatus Figure 1 andSimple other Distillation whiskeys are blended to achieve uniform the thick syrup separated from raw sugar during tasteApparatus from batch to batch. crystal sugar manufacture. Caribbean colonists The distillation of fermented sugarcane grew sugarcane and shipped barrels of molasses to (Saccarum officinarum) results in rum. Of all dis- New England. New Englanders shipped back bar- tilled spirits, rum best retains the natural taste of its rels of rum. Both substances were originally ballast base, because (1) the step of turning starch into for the barrels, which were made from New En- sugar is unnecessary; (2) it can be distilled at a gland’s local forests to hold the sugar shipped from lower proof; (3) chemical treatment is minimized; the Caribbean to the mother country, England. and (4) maturing can be done with used casks. The Gin is a clear distillate of a grain (or beer) base amount of added (sugar-based) caramel gives rum that is then reprocessed; juniper berries and other its distinctive flavor and color—which can vary herbs are added to give it its traditional taste. from clear to amber to mahogany. The New En- Vodka is also clear liquor, often the same as gin gland colonists made rum from molasses, which is without the juniper flavor. Traditional vodkas, 408 DISTILLED SPIRITS COUNCIL

made in Russia, Ukraine, Poland, and other East- very high proofs, to avoid state and federal con- ern European countries, are made from grain or trols or taxation. The term firewater was used potatoes at a very high proof; typical ranges are 65 along the American frontier after about 1815, to to 95 proof, or about 33 to 43 percent ethyl alcohol. indicate any strong alcoholic beverage; this was of- Vodka has no special taste or aroma, although ten traded, given, or sold to Native Americans, some are slightly flavored with immersed grasses, causing cultural disruptions and social problems herbs, flowers, or fruits. The Scandinavian aquavit that continue even today. These include a high is clear, like vodka, distilled from either grain or rate of ALCOHOLISM and children born with FETAL potatoes, and flavored with caraway seed; it is simi- ALCOHOL SYNDROME. lar to Germany’s ku¨ mmelvasser (ku¨ mmel means caraway in German). When any clear liquor is (SEE ALSO: Alcohol: History of Drinking; Beer and added to fruit syrups, the product is called a cordial Brews) or a liqueur. Swiss kirschwasser is, however, a clear high-proof cherry-based brandy (Kirsche means cherry in German); and slivovitz is a clear high- BIBLIOGRAPHY proof Slavic plum-based brandy. BRANDER, M. (1905). The original scotch. New York: The raw grain alcohol distilled in the American Clarkson N. Potter. South and in Appalachia has been called white LUCI´A, S. P. (1963). Alcohol and civilization. New York: lightning since the early 1900s; this is also known McGraw-Hill. as moonshine, corn whiskey, or corn liquor— illegally produced in private nonlicensed stills, in SCOTT E. LUKAS

DISTILLED SPIRITS COUNCIL In 1974, the Distilled Spirits Council of the United States, Inc. (DISCUS) was formed by the merger of three organizations—the industrywide Licensed Beverage Industries, Inc. (LBI), the Distilled Spirits Institute (DSI), and the Bourbon Institute. DIS- CUS, headquartered in Washington, DC, is sup- ported by the distilled spirits producers, repre- senting 90 percent of the liquor sold in the United States. In all major respects DISCUS is a trade association representing producers and marketers of distilled spirits sold in the United States. DISTILLED SPIRITS COUNCIL 409

DISCUS’s primary functions are to maintain levels), whose membership includes nine other as- legislative relations with state and federal govern- sociations. LBIC has supported varied prevention ments (lobbying); to conduct or support economic groups and specialists in conducting medical and and statistical research; to promote export and public education programs devoted to alcoholism standards of identity for American-made liquors; to as a treatable illness; FETAL ALCOHOL SYNDROME maintain a voluntary code of ADVERTISING prac- (FAS); teenage drinking; and drunk driving. The tices; and to represent the distilling industry on consortium has conducted the nationwide Friends social issues of concern, such as teenage drinking, Don’t Let Friends Drive Drunk campaign. DRUNK DRIVING, and other forms of ALCOHOL DISCUS member companies are the principal abuse. State government relations activities are supporters of the Century Council, a nonprofit or- conducted by DISCUS regional representatives. ganization dedicated to reducing alcohol abuse As a trade association, DISCUS seeks to inform across the United States. Through public/private the public about the importance of distilled spirits partnerships, Century Council investigates, funds, to the U.S. economy. By 1999, the distilled spirits and implements innovative approaches to address industry generated $95 billion in U.S. economic the problems of drunk driving and underage drink- activity annually and over 1.3 million people were ing. employed in the United States through the manu- In 1994, DISCUS developed and initiated the facture, distribution, and sale of distilled spirits. Drunk Driving Prevention Act (DDPA), model leg- Jobs within the distilled spirits industry account for islation that strengthens drunk driving laws. Its more than $28 billion in U.S. wages. provisions, many of which are being considered As had its predecessor LBI, DISCUS has sup- and adopted by state legislatures around the coun- ported programs of alcohol abuse PREVENTION and try, include mandatory alcohol and drug education research conducted by independent groups and ex- for drivers; a ban of open containers in motor vehi- perts in education, traffic safety, and alcoholism. cles; Administrative License Revocation (ALR) au- These projects have included the Grand Rapids, thorizing a police officer to confiscate the license of Michigan, study of drunk driving (1961–1965) any driver who either fails a chemical test or refuses and the research led by Harburg and Gomburg to submit to it; zero tolerance for drivers under age (1978–1984) on how drinking may affect the off- 21; mandatory license revocation for persons under spring of different types of drinkers. age 21 who attempt to purchase, consume, or mis- In addition to supporting the Harvard Medical represent their age for the purpose of buying or School course for DIAGNOSIS and TREATMENT of consuming beverage alcohol; and mandatory alco- alcoholism, now adopted by eighty medical schools, hol and drug testing in fatal crashes. DISCUS has provided extensive support to national DISCUS has also developed BACCHUS (Boost- organizations in the alcoholism field since 1970. Its ing Alcohol Consciousness Concerning Health of approach is based on the knowledge that alcohol- University Students). BACCHUS is a college-based ism is an identifiable illness and can respond to peer education program to reduce alcohol abuse. Its intervention and treatment. educational materials include Open Doors, a Guide In 1978, DISCUS endorsed the ‘‘responsible de- to Alcohol and Residence Life for Resident Admin- cisions on alcohol’’ approach developed by the Ed- istrators; Community College Guide to Peer Educa- ucation Commission of the States, and in 1982, it tion; Gamma Guide (Greeks Advocating Mature supported the National Association of State Boards Management of Alcohol); Certified Peer Educator of Education in its nationwide project based on this Training Program; and Student Athletes as Peer concept (which includes abstinence). In 1980, DIS- Educators. CUS cooperated with the U.S. Department of DISCUS has discouraged drinking by underage Health and Human Services and other sponsors in youth; encouraged adults who choose to drink to do supporting the Friends of the Family parenting ed- so responsibly; and emphasized significant distinc- ucation program. tions between normal social drinking and alcohol In 1979, DISCUS became a charter member of abuse. the Licensed Beverage Information Council The organization’s economic research includes (LBIC), an industrywide consortium (beer, wine, annual compilations of ‘‘apparent consumption’’ and spirits at the producer, wholesaler, and retailer data (i.e., distilled spirits entering channels of 410 DISULFIRAM trade) and an assessment of the liquor industry’s the late 1990s, DISCUS began publicizing the contributions to the economy. Total U.S. distilled health benefits of alcohol consumption. It noted a spirits consumption has declined in recent years, a growing body of scientific evidence reporting that fact noted by DISCUS as one of the many refuta- moderate beverage alcohol consumption may re- tions of the ‘‘control of alcohol availability’’ hy- duce the risk of cardiovascular disease, the leading pothesis. cause of death in the United States. This potential The DISCUS Code of Good Practice provides for benefit is equally available from moderate con- self-regulation of advertising practices by distillers. sumption of any form of beverage alcohol— An unusually high degree of compliance has been distilled spirits, beer, or wine. However, DISCUS achieved even with nonmembers. The code was does not promote the use of alcohol consumption applied to radio in 1936, when that was a major for health reasons. medium; it has voluntarily excluded the use of television as an advertising medium by distillers (SEE ALSO: Advertising and the Alcohol Industry; since 1947. Contrary to a widely held impression, Alcohol: History of Drinking; Legal Regulation of spirits advertising on television is not prohibited by Drugs and Alcohol; Minimum Drinking Age Laws; law. Prevention; Social Costs of Alcohol and Drug Distilled spirits have been the most heavily taxed Abuse; Tax Laws and Alcohol ) consumer commodity in the United States. DISCUS and its predecessors have claimed over the years BIBLIOGRAPHY that such taxes are discriminatory and excessive, and they do not reduce chronic alcohol-abuse prob- BORKENSTEIN, R. F. (1965). The role of the drinking lems. DISCUS has consistently argued that the tax driver in traffic accidents. Project of the Department structure imposed on distilled spirits is unjust be- of Police Administration, Indiana University, initiated cause the government taxes spirits at a higher rate November 10, 1961. than beer and wine. It contends that standard ser- DISTILLED SPIRITS COUNCIL OF THE UNITED STATES (DIS- vings of beer, wine, and distilled spirits contain the CUS) (2000). www.discus.health.org/. same amount of alcohol, yet the federal tax rate on HARBURG, E., & GOMBERG, E. (1984). Alcohol use/absti- distilled spirits is almost three times the rate on nence among men and women in a small town setting. wine and over two times the rate on beer. Project of the University of Michigan, initiated No- In 1999, DISCUS continued to lobby Congress vember 1, 1978. for a reduction in excise taxes. DISCUS pointed out PAUL F. GAVAGHAN that more than half of the price that consumers REVISED BY FREDERICK K. GRITTNER spend on a typical bottle of distilled spirits is taxes. Federal, state, and local governments receive more than $18 billion per year in tax revenue from the beverage alcohol industry and tax revenues from DISULFIRAM The registered trademark the distilled spirits industry alone account for more name for disulfiram is Antabuse—it is the most than $7.5 billion. DISCUS pointed out that federal, commonly used medication for the treatment of state and local governments combined realize four- ALCOHOLISM and the only one of two medications teen times more in spirits tax revenues than the (the other being naltrexone) approved for this use distillers make in profits. However, Congress has in the United States, as of 2000. It is not intended remained unresponsive to the attempt by DISCUS as a substitute for the counseling alcoholics receive to reduce excise taxes. while in treatment; it is meant to be an aid in As a long-standing policy, DISCUS and its mem- keeping alcoholics sober, so that they may benefit bers do not encourage people to start drinking or to from counseling. Although disulfiram has been in drink too much. DISCUS’s review of the research clinical use since the late 1940s, only since the literature indicates that there is no scientific evi- 1980s has its efficacy been studied by appropriate dence that brand advertising either influences or scientific methodology. shapes those behaviors. The marketing purpose of Disulfiram is used to deter drinking by causing product advertising is to build consumer accep- an unpleasant reaction if a medicated person tance of specific brands, according to DISCUS. In drinks ALCOHOL (ethanol). This reaction is called DISULFIRAM 411 the disulfiram–ethanol reaction (DER); the symp- the drug by the U.S. Food and Drug Administration toms include flushing, dizziness, rapid heartbeat, (FDA), a number of additional studies of naltrex- nausea, vomiting, and headache. The DER is of one have been published. In addition, a large num- varying severity, and the degree of severity often ber of studies are underway, with support from the depends on the dose of disulfiram being taken plus National Institute on Alcohol Abuse & Alcoholism the amount of alcohol that was consumed. A DER (NIAAA). Although, most studies of naltrexone can cause hypotension (low blood pressure) and have shown it to be helpful for relapse prevention, can be so severe that death occurrs, although with not all studies have been positive. adjusted dosage regimens this is very rare. Disulfiram blocks the action of several of the ADMINISTRATION AND DOSAGE body’s enzymes, including aldehyde dehydroge- nase (ALDH). The inhibition of ALDH is responsi- Disulfiram should be administered only by a ble for the DER; this occurs because ethanol physician and is given by mouth in tablet form. It (drinking alcohol) is metabolized in the liver to should never be given until the patient has ab- acetaldehyde. Acetaldehyde, in turn, is converted stained from alcohol for at least 12 hours, and to acetic acid, which is catabolized to water and preferably for 48 hours. The dose is usually 250 or carbon dioxide. 500 milligrams daily. Some patients report not Aldehyde dehydrogenase is the enzyme that fa- experiencing a DER with smaller doses, so larger cilitates the catabolism of acetaldehyde to acetate doses may be required. Clinical experience indi- acid. When the action of ALDH is inhibited by cates, however, that doses larger than 500 milli- disulfiram, acetaldehyde is not converted to acetate grams are accompanied by a greater risk of serious but accumulates in the blood. Most of the symp- side effects. A problem that limits the effectiveness toms of the DER are due to the increased circulat- of disulfiram is that patients frequently stop taking ing acetaldehyde. Since the inhibition of ALDH by the medication. To prevent this, disulfiram tablets disulfiram is irreversible, a person taking di- sometimes have been implanted just below the skin sulfiram cannot stop taking it one day and begin of the abdominal wall. This technique, however, drinking the next—several days (usually 4 to 7) has been shown to be ineffective (Johnsen et al., must go by, because this is the amount of time 1987) because the absorption of the implanted di- necessary for the body to produce new enzyme. sulfiram is erratic and poor, resulting in very low blood levels of disulfiram and a weak or no DER. OTHER MEDICATIONS Patients should take disulfiram only under care- ful medical and nursing supervision. They should Certain other medications cause a mild DER, be warned that as long as they are taking the drug, including such antibiotics as metronidazole ingesting alcohol in any form will make them sick (Flagyl). A medication available in Canada but not and may endanger their life. Patients should be in the United States is citrated CALCIUM CARBIMIDE taught to recognize and avoid disguised forms of (Temposil), which inhibits ALDH in a mixed re- alcohol such as cough syrups, mouthwashes, some versible–irreversible fashion. When citrated cal- sauces, fermented vinegar, and even aftershave lo- cium carbimide is discontinued, 80 percent of tion or rubbing alcohol. In addition, patients ALDH activity is restored within 24 hours. Hence, should be taught to recognize the signs of disturbed one can drink alcohol as soon as a day after liver function (jaundiced eyeballs or skin, nausea or stopping the use of citrated calcium carbimide pain in the upper right quadrant of the abdomen, without having a reaction. dark urine, clay-colored stool) and report them at In addition to disulfiram, there are other medi- once to their doctor. cations with different mechanisms of action that are now approved for use in helping recovering SIDE EFFECTS alcoholics maintain sobriety. The most promising of these newer drugs is naltrexone hydrochloride The use of disulfiram may be accompanied by (ReVia), an opioid agonist that was found in 1992 side effects. The most common one is drowsiness; to reduce the incidence of relapse in alcoholics in for this reason, the medication is usually taken at outpatient treatment programs. Since approval of bedtime. Timing is usually sufficient to take care of 412 DIVERSION

this problem, but if not, the medication may have HARDMAN,J.G.,&LIMBIRD, L. E. (Eds.) (1996). Good- to be discontinued, especially for those who drive or man and Gilman’s the pharmacological basis of ther- work in hazardous environments. Idiosyncratic apeutics, 9th ed. New York: McGraw-Hill. liver toxicity can occur from taking disulfiram. For JOHNSEN, J., ET AL. (1987). A double-blind placebo con- this reason, liver function must be monitored trolled study of male alcoholics given a subcutaneous closely during the first several months of treatment, disulfiram implantation. British Journal of Addiction, and if blood tests indicate possible liver damage, 82, 607–613. disulfiram must be discontinued immediately. WILSON, B. A., SHANNON, M. T., & STANG, C. L. (Eds.) A 1986 Swedish study found that disulfiram en- (1995). Nurses drug guide, 3rd ed. Norwalk, CT: hances the absorption and toxicity of lead in rats. Appleton & Lange. Recovering alcoholics who must work in environ- RICHARD K. FULLER ments containing lead or lead products are advised RAYE Z. LITTEN not to use disulfiram to maintain sobriety. REVISED BY REBECCA J. FREY In addition, serious psychotic reactions and de- pressive episodes have occurred in patients taking disulfiram. In a multisite study of 605 men, admis- DIVERSION See Treatment Alternatives to sions for psychiatric problems were uncommon; as Street Crime many admissions of this type occurred in men tak- ing the placebo or not receiving disulfiram as in those receiving a 250-milligram dose (Branchey et DMT See Dimethyltryptamine al., 1987). The risk of serious psychoses or of major affective illnesses occurring appears to be worse with higher doses. DOGS IN DRUG DETECTION In 1970, the U.S.CUSTOMS SERVICE faced a shrinking inspec- INTERACTIONS WITH OTHER DRUGS tional staff, a flood of illegal NARCOTICS, and an Disulfiram should not be given to patients who increasing load of vehicles and passengers entering are taking metronidazole (Flagyl) or paraldehyde the United States. In that same year a manager in (Paral), as these drugs will produce a DER. Pa- the U.S. Customs Service thought that dogs could tients taking isoniazid (INH, Laniazid) may de- be used to detect illegal narcotics. The manager’s velop neurological symptoms if given disulfiram. name has been lost in the corporate history of the Lastly, disulfiram may increase the blood levels Customs Service, yet years later not only are dogs and toxicity of warfarin (Coumadin), barbiturates, used to detect narcotics but also currency, wea- and phenytoin (Dilantin). pons, explosives, fruits, and meats. Dogs could be trained to detect anything that produces an odor. (SEE ALSO: Naltrexone; Relapse; Treatment: Alco- Although the idea of narcotic detector dogs origi- hol; Treatment Types: Aversion Therapy) nated in the U.S. Customs Service, Customs’ man- agers had to go to the U.S. Air Force for the techni- cal expertise—not in narcotic detection, because it BIBLIOGRAPHY did not exist, but dog training in general. The air BRANCHEY, L., ET AL. (1987). Psychiatric complications force loaned the Customs Service five instructors to following disulfiram treatment. American Journal of develop the program. Those instructors, using the Psychiatry, 144, 1310–1312. age-old method of trial and error, developed a FULLER, R. K., ET AL. (1986). Disulfiram treatment of training method for narcotic detection that was still alcoholism: A Veterans Administration cooperative used in the 1990s. Through the years, several key study. Journal of the American Medical Association, aspects of the training program were identified and 256, 1449–1455. became the basis for a very successful program— FULLER, R. K., LEE, K. K., & GORDIS, E. (1988). Validity dog selection; development of a conditioned re- of self-report in alcoholism research: Results of a Vet- sponse; and odor integrity. erans Administration cooperative study. Alcoholism: It became evident that to make the training pro- Clinical and Experimental Research, 12, 201–205. gram successful the instructors had to start with a DOGS INDRUG DETECTION 413

into them over the centuries. In addition, these breeds predominated in the dog shelters and hu- mane societies used by U.S. Customs as the pri- mary source for its dog procurement, which has not only benefited the Customs’ program but the local dog shelters too. Local shelters must by law destroy stray dogs after a certain time period if no one selects or adopts the dog. The Customs’ instructors select dogs scheduled to be put to sleep. The Customs’ training method is based on the natural behavior of these retriever breeds of dogs. By using a dog’s natural behavior, the instructors An airport security officer guides a dog along a can adjust certain aspects of their training program row of luggage, checking for narcotics. In the to deal with the individual personality of each dog. United States, the Customs Service’s Canine Although each dog that entered the training pro- Enforcement Program has accounted for more gram possessed the same basic qualifications, each than 120,000 drug seizures. (᭧ Galen Rowell/ then displayed them in varying degrees of intensity CORBIS) because of personality differences. During the training process, the other aspect of dog that displayed certain natural traits. Those the program that ensured success has been main- traits were retrieval motivation and self-confi- taining the integrity of the narcotic odor. During dence. The instructors soon realized that a dog the development of the training program there were displaying a natural desire to retrieve was the eas- several incidents when the detector dog would re- iest to condition for response to the narcotic odor. spond to nondrug odors. In those incidents a com- They used the retrieval method just as the Russian mon factor was identified: The nondrug odor was physiologist Ivan Pavlov (1849–1936) used a bell: present in the training program. To the dog, the In Pavlov’s experiments, he had observed that dogs materials that were used in the scent-association salivate when food is placed in their mouths. He process (a process by which the dog identifies the would give the dogs food while providing another narcotic odor with the tug-of-war game) combined stimulus such as a bell ringing. After a few repeti- with the drug odor represented a completely differ- tions, the dogs would salivate when they heard the ent odor picture (a combination of odors that the bell ring—even without the food being present. dog associates with a positive reward). This situa- The dogs had learned to associate the bell ringing tion became apparent when the drug was separated with food. This response was called a conditioned from the other materials; the dog would not re- response. spond to it alone or would display a considerable The Customs’ instructors used a similar method amount of confusion when confronted with it. This to create a conditioned response to a drug odor. A problem was eliminated by ensuring that all mate- dog was subjected to a series of retrieval exercises rials used in the training process smelled like the with a specific drug’s odor. After each retrieval, the specific drug in question. dog played a game of tug-of-war with its handler In summary, the key factors in narcotic detec- and would receive physical praise. The dog soon tor-dog training is (1) dog selection; (2) develop- associated the specific drug odor with the game and ment of a conditioned response; and (3) the integ- the physical praise. rity of the narcotic odor. This information is a very Using the dogs’ natural desire to retrieve as a small segment of the overall training methodology. selection criterion limited the number of breeds Further information about this type of dog training that could be considered for this type of training. It can be obtained through the U.S. Customs Service’s was obvious that most of the sporting breeds fit this Office of Canine Enforcement Programs, Washing- criterion—golden retrievers; Labrador retrievers; ton, D.C. German short-hair retrievers; and mixed breeds of these types. They have had the retrieval drive bred (SEE ALSO: Drug Interdiction) 414 DOLOPHINE

BIBLIOGRAPHY in the hope of producing a shorter, less-intense trip than LSD, which, it was thought, might be more U.S. CUSTOMS SERVICE (1978). Detector dog training useful and manageable in producing a period of manual. Washington, DC: U.S. Government Printing insight and self-reflection in psychotherapy. This Office. hope was never achieved. CARL A. NEWCOMBE (SEE ALSO: Designer Drugs; Dimethyltryptamine)

DOLOPHINE See Methadone BIBLIOGRAPHY

SHULGIN, A., & SHULGIN, A. (1991). PIHKAL: A chemical love story. Berkeley, CA: Transform Press. DOM This drug’s street name is STP. During DANIEL X. FREEDMAN the hippie drug culture of the VIETNAM war period, R. N. PECHNICK its name referred to ‘‘serenity, tranquility, and peace.’’ This was also a taunt and a spoof, since the initials were the same as a widely available oil additive that made an automobile engine run DOPAMINE Dopamine (DA) is a catechol- smoothly. The drug DOM is a member of a family amine according to its chemical structure and a of HALLUCINOGENIC substances based on molecular neurotransmitter of special importance for drug additions to phenethylamine. This is a group of addiction. DA is a decarboxylated form of dopa (an compounds that have structural similarities to the amino acid) found especially in the basal ganglia. catecholamine-type NEUROTRANSMITTERS, such as Chemically known as 3,4 dihydroxyphenyl- NOREPINEPHRINE, epinephrine, and DOPAMINE. ethylamine, DA arises from dihydroxphenylacetic While our bodies make these catecholamines from acid (dopa) by the action of the enzyme dopa de- dietary amino acids, they do not make the chemical carboxylase. Dopamine-containing NEURONS substitutions that produce a PSYCHEDELIC com- (nerve cells) are widespread in the brain and the pound. MESCALINE is the best and longest known of body. Small interneurons are found in the auto- this family of HALLUCINOGENS. nomic ganglia, retina, hypothalamus, and medulla. DOM is a synthesized compound that produces Long axon neurons are found in two extensive cir- effects similar to mescaline and LYSERGIC ACID DI- cuits: (1) the nigrostriatal pathway links the sub- ETHYLAMIDE (LSD), but the effects of DOM can last stantia nigra neurons to the basal ganglia neurons for fourteen to twenty hours, much longer than and regulates locomotor events; (2) the mesocor- those of LSD. In addition, the effects of DOM have tical and mesolimbic circuits arise in the ventral a very slow onset. Some of the initial street users of tegmental area and project to the neocortex, limbic DOM had previous experience with LSD, a drug cortices, nucleus accumbens, and amygdala, where with a much more rapid onset. When the typical they regulate emotional events, including several LSD-type effects were not found soon after taking forms of drug addiction, reinforcement, or reward. DOM, some users took more drug, which led to a DA is also found in minute amounts in other cate- very intense and long-lasting psychedelic experi- cholamine neurons as a precursor to norepineph- ence. Ironically, DOM was originally manufactured rine. The DA transporter, which transports DA from outside the nerve terminal to inside the nerve terminal, functions to retrieve released DA and help terminate its action at receptors. The transporter is the target of psychostimulant drugs that produce their effects, at least in part, by blocking the trans- porter and preventing its removal from receptors. A consistent observation, for example, is the efflux of DA from nerve terminal regions in the nucleus ac- Figure1 cumbens in response to giving animals a psycho- DOM stimulant such as cocaine or amphetamine. DA is DOSE-RESPONSE RELATIONSHIP 415 also thought to be involved in schizophrenia and Often, however, the response (ordinate) is plot- psychosis since DA-receptor-blocking drugs are ted against the logarithm of the drug concentration clinically useful antipsychotic agents. Another dis- (abscissa) to transform the dose-response relation- ease, in which DA is lost due to the degeneration of ship into a sigmoidal curve. This transformation DA-containing neurons, is Parkinson’s disease, makes it easier to compare different dose-response which can be treated by replacing DA with its pre- curves—since the scale of the drug concentration cursor, dopa. axis is expanded at low concentrations where the effect is rapidly changing, while compressing the FLOYD BLOOM scale at higher doses where the effect is changing more slowly (see Figure 2). Finally, there are two basic types of dose-re- DOPE/DOPE FIEND See Slang and Jargon sponse relationships. A graded dose-response curve plots the degree of a given response against the concentration of the drug as described above. The second type of dose-response curve is the quantal DORIDEN See Glutethimide dose-effect curve. In this case, a given quantal ef- fect is chosen (e.g., a certain degree of cough sup- pression), and the concentration of the drug is plot- DOSE-RESPONSE RELATIONSHIP The ted against the percentage of a specific population relationship between the dose (amount) of a drug in which the drug produces the effect. The median and the response observed can often be extremely effective dose (ED50 or the dose at which 50% of complex, depending on a variety of factors includ- the individuals exhibit the specified quantal effect) ing the absorption, metabolism, and elimination of and the median lethal dose (LD50 or the dose at the drug; the site of action of the drug in the body; which death is produced in 50% of the experimen- and the presence of other drugs or disease. In gen- tal animals in preclinical studies) can be estimated eral, however, at relatively low doses, the response from quantal dose-effect curves. With this type of to a drug generally increases in direct proportion to curve, the relative effectiveness of various drugs for increases in the dose. At higher doses of the drug, producing a desired or undesired effect, as well as the amount of change in response to an increase in the relative safety between various drugs, can be determined. The ratio of the LD50 to the ED50 for the dose gradually decreases until a dose is reached a given effect indicates the therapeutic index of a that produces no further increase in the observed drug for that effect and suggests how selective the response (i.e., a plateau). The relationship between drug is in producing its desired effects. In clinical the concentration of the drug and the observed studies, the concentration of the drug required to effect can therefore be graphically represented as a produce toxic effects can be compared to the con- hyperbolic curve (see Figure 1).

Figure 1 Figure 2 Representative Dose-Effect Curve, with Its Four Representative Dose-Effect Curve, Showing a Characteristics Median Effective Dose (ED50) 416 DOVER’S POWDER centration required for a specific therapeutic effect and fame. On one of his voyages he found the in the population to estimate the clinical therapeu- shipwrecked Alexander Selkirk, who, on being re- tic index. turned to London, created a sensation and was to become the inspiration for Daniel Defoe’s Robinson (SEE ALSO: Drug Metabolism) Crusoe. Dover retired from his merchant sailing career a wealthy man, but poor investments led BIBLIOGRAPHY him to resume his medical career first in Glouces- tershire and later in London. GILMAN, A. G., ET AL.(EDS.). (1990). Goodman and In 1732, probably to attract patients to his new Gilman’s the pharmacological basis of therapeutics, practice in London, Dover published An Ancient 8th ed. New York: Pergamon. Physician’s Legacy to His Country, one of the earli- NICK E. GOEDERS est medical treatises written for the general public. The book listed forty-two ailments with successful treatments used by Dover, and included the testi- monial letters of many ‘‘cured’’ patients. The book DOVER’S POWDER Dover’s Powder, de- enjoyed popular success and was reprinted eight veloped and described by the British physician times, the last in 1771, nearly thirty years after his Thomas Dover in 1732, was one of the more popu- death. One remedy described in the book, the use of lar and enduring of the opium-based medications mercury, earned him the nickname during his life- that were widely used in the United States and time of the Quicksilver Doctor, but the formula for Europe prior to the twentieth century. The medica- Dover’s Powder, which appears unchanged in all tion combined OPIUM with what we know today as eight editions, has proven to be his most enduring ipecac (ipecacuanha), a substance that induces legacy. Appearing on page 18 of the original edition vomiting. The result was a pain-reducing potion as a treatment for gout, the directions read: that might induce a sense of euphoria but could not be ingested in large quantities because of its emetic Take Opium one ounce, Salt-Petre and Tartar properties. Taken as a nonprescription medicine by vitriolated each four ounces, Ipecacuana one the general public for over 200 years, it was also ounce, Liquorish one ounce. Put the Salt Petre and prescribed by physicians for home and hospital use. Tartar into a red hot mortar, stirring them with a Versions of the preparation are still listed in phar- spoon until they have done flaming. Then powder maceutical formularies in which ‘‘Dover’s Powder’’ them very fine; after that slice your opium, grind commonly denotes any opium-based mixture that them into powder, and then mix the other powders includes ipecacuanha. The wide use of Dover’s with these. Dose from forty to sixty or seventy Powder declined in the early 1900s largely because grains in a glass of white wine Posset going to bed, of the addiction that resulted from the prolonged covering up warm and drinking a quart or three pints of the Posset—Drink while sweating. use of OPIATES, because of the introduction of other nonaddicting ANALGESICS (painkillers), mainly as- Dover’s familiarity with opium most probably pirin, and because of laws regulating sales of opium resulted from his association with Thomas Syden- products. ham and thereby his acquaintance with the benefits Thomas Dover (1662–1742) studied medicine of laudanum (an alcoholic tincture of opium). Do- at Oxford University in the 1680s. He claimed to ver’s ingenious use of opium with ipecacuanha have served an apprenticeship with Dr. Thomas seems to have been original. His unique formula, Sydenham, the illustrious seventeenth-century Pulvis Ipecacuanha Compositus, with its specificity practitioner and teacher, who originated the for- of ingredients, produced a relatively reliable and mula for LAUDANUM, another early and popular consistent potion in an era when there was no opium-based medicine. Dover practiced medicine regulation of medications and little standardization for over fifty years, although during his lifetime he in their preparation. Medications could be pur- was more famous for his exploits as an adventurer chased at apothecary shops with or without doc- and privateer. His involvement in the early slave tors’ prescriptions or at back-street stores that sold trade and in the plundering of Spanish settlements drugs along with food, clothing, and other necessi- off the coast of South America brought him fortune ties of life. The major issue at the time in the use of DOVER’S POWDER 417 opiate-based medications was not that they con- not until the end of the century—as a result of tained what we now know to be a NARCOTIC, but better education of physicians and pharmacists, whether the consistency of the formula or the mis- advances in diagnosis and therapeutics, and a use by the patient caused overdoses of what could growing understanding of the nature of addic- be poisonous ingredients. Dover’s Powder provided tion—that opium-based medications were sup- a stable product that, because of the ipecacuanha, planted by other curative treatments and by non- could not be taken in excess at any one time. The addictive salicylate analgesics such as aspirin. powder came to be trusted by the general public Opium-based medicines used today, such as MOR- and widely prescribed by physicians. It was consid- PHINE and CODEINE, are government-regulated and ered such a safe remedy that it was even prescribed can be purchased legally only by prescription. for children. Dover’s Powder in its original form is now an Although Dover originated his powder as treat- obsolete medication. It should be recognized for its ment for gout, it was used throughout the eigh- place in the history of pharmacology as a relatively teenth and nineteenth centuries along with many reputable medicine used from 1732 until the other opium-based patent and official preparations 1930s, an era in which opium-based medications by large numbers of people for a wide variety of were one of the few remedies that brought relief to disorders. Opium, used as a healing plant for over suffering patients. Many of these medications came 6,000 years, was an ingredient in countless formu- to be misused by both patients and physicians who las that were openly available and credited with had little understanding of addiction and few op- curing the most common disorders of the time. tions for PAIN relief. Thomas Dover, seen as an Mixed in a tincture, it was found in laudanum; in a adventurer and opportunist by many during his camphorated formula it became PAREGORIC; and it lifetime, developed a preparation that allowed pa- was also included in preparations for lozenges, tients to use a narcotic while limiting its ingestion. plasters, enemas, liniments, and other general More precise knowledge of the healing as well as the medications. Opium-based medicines were used for many dis- addictive properties of narcotics allows modern orders, including insomnia, diarrhea, bronchitis, physicians and pharmacologists to deal specifically tuberculosis, chronic headache, insanity, menstrual with the dosage of narcotic medications. Neverthe- disorders, pain, malaria, syphilis, and smallpox. less, Dover’s Powder, an ingenious and effective Often both physicians and patients mistook its nar- solution to a thorny problem, became a household cotic properties, which relieved pain and created a name long after its originator’s medical career had sense of well-being, as curative rather than pallia- ended and his medical treatise had been published. tive, and little was understood of the darker side of opiate medications—the destructive nature of ad- (SEE ALSO: Addiction: Concepts and Definitions; diction—until well into the nineteenth century. By Britain, Drug Use in; Disease Concept of Alcohol- this time, it was common for middle- and upper- ism and Drug Abuse; Opioids and Opioid Control: class people, especially women and those with History) chronic diseases, to be addicted to opiates that were frequently seen in innocuous health elixirs or in BIBLIOGRAPHY remedies that had been originally prescribed by physicians. Widespread prescribing by physicians BERRIDGE,V.,&EDWARDS, G. (1981). Opium and the and easy availability of the opiate medications people: Opiate use in nineteenth century England. made addiction a frequent result of medical London: Allen Lane. therapeutics. BOYES, J. H. (1931). Dover’s Powder and Robinson Cru- By the middle of the nineteenth century, the soe. New England Journal of Medicine, 204, 440– issue of opium addiction began to appear with 443. more frequency in the medical literature, and in COURTWRIGHT, D. T. (1982). Darkparadise: Opiate ad- both the United States and England there were diction in America before 1940. Cambridge, MA: Har- pressures to regulate both the pharmacy trade and vard University Press. the use of narcotic medications, especially the pat- DUKE, M. (1985). Thomas Dover—physician, pirate and ent medicines containing opiates. Even then, it was powder, as seen through the looking glass of the 20th- 418 DRAMSHOP LIABILITY LAWS

century physician. Connecticut Medicine, 49, 179– (SEE ALSO: Alcohol: History of Drinking; Driving, 182. Alcohol, and Drugs; Driving Under the Influence; OSLER, W. (1896). Thomas Dover, M. B. (of Dover’s Drug Interactions and Alcohol; DrunkDriving; Le- Powder), physician and buccaneer. Bulletin of the gal Regulation of Drugs and Alcohol; Mothers Johns Hopkins Hospital, 7,1–6. Against DrunkDriving; Students Against Destruc- tive Decisions) VERNER STILLNER

BIBLIOGRAPHY

DRAMSHOP LIABILITY LAWS Dram- EDWARDS G., ET AL. (1994). Alcohol policy and the public shops are taverns, saloons, bars, and drinking es- good. Oxford: Oxford University Press. tablishments. All states impose fines and other pun- MOORE, M. H. and GERSTEIN, D. (ed). (1981). Alcohol ishments when alcohol is sold to ‘‘visibly intoxi- and public policy: Beyond the shadow of prohibition. cated’’ customers or ‘‘habitual drunkards.’’ Washington, D.C.: National Academy Press. Although historically these laws aimed to preserve MOSHER, J. M. (1987). Liquor liability law. New York: public order and morality, today they are perceived Matthew-Bender. primarily as tools to curtail drunk driving. Their WAGENAAR, A. C. and HOLDER, H. D. (1991). Effects of effectiveness is a direct function of compliance and alcoholic beverage server liability on traffic crash in- juries. Alcoholism: Clinical and Experimental Re- enforcement. Although compliance has rarely been search 15, 942–947. studied, one study in Michigan found that an in- crease in police enforcement (through visits and CHRISTOPHER B. ANTHONY warnings) resulted in a three-fold increase in the REVISED BY RICHARD J. BONNIE rates of service refusal to intoxicated patrons. In addition, service intervention training has been vol- untarily implemented in many states and is re- DRIVING, ALCOHOL, AND DRUGS quired by law in some. Although the evidence is Injuries, especially from motor vehicle collisions, mixed, recent research indicates that sustained are the leading cause of death for individuals under server training can reduce the risk of drunk driv- age 44. The presence of alcohol is the factor most ing. frequently associated with fatalities in vehicles, In addition to these statutory penalties, more drownings, falls, and fire (U.S. Department of than half the states also impose tort liability on Health and Human Services, 1987). In the first tavern keepers for injuries caused by intoxicated report to Congress on traffic safety and alcohol patrons. Liability in such situations serves both (U.S. Department of Transportation, 1968), it was compensatory and deterrent purposes. Although it concluded that more than 50 percent of fatal traffic collisions and 33 percent of serious injury traffic is difficult to isolate the effects of the threat of collisions were alcohol-related. so-called ‘‘dramshop tort liability’’ or server behav- Although the association between alcohol con- ior, one study attributed a decline in traffic crash sumption and traffic accidents had been recognized injuries in Texas to the filing of two major liability by the beginning of the twentieth century, the mag- suits in that state (Wagenaar & Holder, 1991). nitude of the problem did not capture public atten- Courts in a few states have extended the dramshop tion until the 1970s. Public tolerance of DRIVING principle to private ‘‘social hosts’’ who fail to take UNDER THE INFLUENCE of alcohol decreased adequate precautions to prevent obviously intoxi- sharply—a shift in attitude that, combined with cated guests from getting behind the wheel. increased legal countermeasures, resulted in a sig- Whether or not the threat of liability for servers nificant decline in alcohol-related fatalities from a of alcohol exerts a clear-cut deterrent effect, it is high of 57 percent in 1982 to 38 percent in 1998. clear that dramshop liability serves an important Voas et al. (1998) compared the relative fre- pedagogical effect and, together with other legal quency of driving under the influence of alcohol in and cultural factors, helps to shape social norms three U.S. nationwide surveys, done in 1973, 1986, against driving while intoxicated. and 1996 on weekend nights. Drivers were stopped DRIVING, ALCOHOL, AND DRUGS 419 at random and asked to provide breath samples for Moskowitz and Robinson (1988) reviewed 177 alcohol testing. The blood alcohol concentration experimental studies of alcohol’s effects on driving- (BAC) levels were compared for the three surveys related behaviors that met criteria of scientific as a function of time, day, gender, age, ethnicity, merit. The behavior found to be most affected by geographical region, etc. Across nearly all popula- alcohol was divided attention, with impairment tion subgroups, the presence of alcohol in night- even seen at alcohol levels below 0.02 percent time weekend drivers dropped from 36 percent in (20mg/100mL). Divided-attention tasks involve 1973 to 26 percent in 1986 to 17 percent in 1996. simultaneously monitoring and responding to more However, although the percent of decline for driv- than one source of information, which is character- ers with BACs below 0.10 percent was 54 percent istic of many complex man-machine interactions from 1973 to 1996, there was only a 45 percent such as driving and flying. While operating a vehi- decline in drivers with over 0.10 percent BAC. De- cle, drivers under the influence of alcohol fre- spite this significant drop in the number of alcohol quently fail to detect significant potential threats in impaired drivers in the last two and a half decades, the environment. alcohol still remains the single largest factor in Similarly, studies have indicated that informa- traffic fatalities and serious injuries. tion processing and perception are affected at low Epidemiological studies have compared the BAC BAC levels. Tracking, which is analogous to car levels in collision-involved drivers with those of control functions such as maintaining heading and randomly selected drivers passing the collision site lane position, has been shown to be impaired at low at similar times. These studies have demonstrated BACs when performed simultaneously with other that the probability of a crash increases with any functions in divided-attention situations, but less impaired when the tracking task is performed by departure from zero BAC and increases exponen- itself. Similarly, complex reaction-time tasks in- tially with increasing BAC levels. By the time BAC volving several competing stimuli and responses levels exceed 0.2 grams alcohol per deciliter of are impaired at low BACs, whereas simple reaction blood (200 mg/100 mL.), the probability of a colli- time requiring little information processing was sion increases more than 100 times (i.e., 10.000%). more resistant to the effects of alcohol. Most areas of human behavior are impaired Studies of psychomotor skills performance in eventually by increasing alcohol levels. However, driving simulators and closed-course driving stud- the examination of alcohol-related collision data ies have shown considerable variation in the BAC from governmental investigations and police colli- levels at which impairment appears. These varia- sion reports suggests that information-processing tions are likely explained by the differences in in- errors are common in the majority of alcohol-re- formation-processing requirements among these lated traffic collisions. Information-processing defi- varied tasks. The review concluded that no mini- cits include impairment of attention, visual search, mum threshold for alcohol’s impairment of com- and perception. The second largest category of hu- plex human-machine tasks exists. Any reliable man factor errors involves judgment, such as speed measure of alcohol in the human system produces selection. Failure to control a car because of de- some impairment. creasing motor skills remains a distant third crash Other areas that have been suggested as leading category, despite the popular assumption that links to alcohol-related accidents, such as poor judgment driving impairment with the appearance of intoxi- and violent and aggressive behavior, have been in- cation and motor incapacitation. frequently examined by researchers—mainly be- The results observed in epidemiological survey cause of the difficulty of developing laboratory studies are supported by numerous experimental techniques to measure them. studies in which driver behavior was examined un- The low BAC levels at which laboratory studies der controlled conditions. Such laboratory studies have indicated significant impairment and epide- either examine one or two behaviors relevant to miological studies have shown increased crash fre- driving at a time or in more complex studies of quency are below the levels at which the majority of driving-related behavior use driving simulators the population would exhibit symptoms of intoxi- and a closed-course driving situation that preserve cation such as slurred speech and unsteady gait. the safety of the driver. Thus, the absence of signs of intoxication is not 420 DRIVING, ALCOHOL, AND DRUGS evidence that a driver is capable of operating a ence of the drug rather than the level of motor vehicle or other machinery safely. concentration. Moskowitz and Fiorentino (2000) updated One technique to circumvent control-group Moskowitz and Robinson’s 1988 report with a re- problems has been to assign responsibility or non- view of an additional 112 studies published from responsibility to crash-involved drivers and then 1981 to 1997. Although the main conclusions of correlate the presence of drugs with the frequency the 1988 report remained confirmed, the most re- of crash responsibility. Within the constraints of cent publications more frequently report impair- these epidemiological studies, researchers have of- ments at very low alcohol levels, reflecting im- ten concluded that tranquilizers, antihistamines, provements in the sensitivity and reliability of and antidepressants are overrepresented in crash- scientific investigation. Moreover, new behavioral involved drivers. areas are being explored, such as the tendency to Terhune and colleagues (1992) examined the fall asleep at the wheel, which increases signifi- presence of drugs in blood specimens from 1,882 cantly at low BAC levels. fatally injured drivers. Drugs, both illicit and pre- scription, were found in 18 percent of the fatalities. MARIJUANA was found in 6.7 percent, COCAINE in OTHER DRUGS 5.3 percent, tranquilizers in 2.9 percent, and AM- The major involvement of alcohol in traffic acci- PHETAMINES in 1.9 percent of these fatally injured dents and other injuries is well documented. What drivers. conclusions can we draw about the role of drugs When crash responsibility was assigned and cor- other than alcohol in traffic safety? Although labo- related with drug use, the small number of individ- ratory studies on the effects of many drugs and uals in each separate drug classification made sta- alcohol are similar in demonstrating the impair- tistical significance difficult to obtain despite the ment of performance skills, there are difficulties in fact that several drug categories were associated executing epidemiological studies on the effects of with increased crash responsibility. Crash-respon- drugs in driving. For example, few non-crash-in- sibility rates did increase significantly as the num- volved drivers volunteer to provide blood samples ber of drugs in the driver increased. Many drug so their drug levels might be compared with those users used several drugs simultaneously and these drivers had the highest collision rates. Alcohol was in blood samples obtained from collision victims. found in 52 percent of the fatalities, with more than Although several studies have been completed in 90 percent of the drivers with BACs over 0.08 per- hospitals with drug levels in trauma patients in- cent considered responsible for the crash. volved in driving collisions with blood samples The most frequently used illicit drug in the from volunteers who were in the hospital for other United States of America for the last half-century is reasons, serious questions arise regarding the rep- marijuana and epidemiological studies have dem- resentativeness of the control group. onstrated that is the most frequent drug consumed Another problem in relating drug use to vehicle by drivers. Bates and Blakely (1999) have reviewed crashes has been difficulty of evaluating the behav- the epidemiological literature for marijuana’s role ioral significance of drug blood levels. Unlike alco- in motor vehicle crashes. They concluded that there hol, where levels in venous blood samples or breath is no evidence marijuana alone increased either samples are essentially equivalent to those from fatal or serious injury crashes. However, the evi- blood in the brain, the site of drug action, for nearly dence is inconclusive whether the presence of mari- all other drugs have a complex relationship be- juana in combination with alcohol increases fa- tween blood plasma level and the degree of result- talities or serious injuries over that produced by ing behavioral impairment. Many drugs remain alcohol alone. Nor was it possible to determine present in the plasma for weeks beyond any period whether marijuana increases the rate of less serious in which behavioral effects may be observed. In vehicle crashes. other cases, drug levels in plasma drop extremely In contrast to the lack of scientific information rapidly and become difficult to detect while behav- available from epidemiological sources about the ioral impairment remains. Thus, most epidemio- role of drugs in causing collisions, numerous exper- logical studies of drugs and driving report the pres- imental research has been performed to evaluate DRIVING, ALCOHOL, AND DRUGS 421 the effects of drugs on skills performance. Regula- erance to some of these side effects, which may tory agencies in many countries have frequently explain why epidemiological studies have not found required an evaluation of the side effects of pre- differences in crash rates between NARCOTIC users scription drugs on skills performance. Also, numer- and control groups. Moreover, patients maintained ous governments have supported studies of the ef- on a stabilized dosage of METHADONE, a synthe- fects of illicit and abused drugs on skills sized narcotic, have shown little evidence of im- performance in the laboratory. pairment in a wide variety of experimental and Thus, the evaluation of the effects of drugs on epidemiological studies. driving and other human-machine interactions has depended primarily on experimental studies where Another category of drug that shows evidence of changes in behavior can be observed as a function impairing skills performance in laboratory studies of differences in administered doses and the time is the antihistamines, many of which produce im- after administration. However, no other drug has pairment of performance accompanied by com- been evaluated in as extensive a range of behaviors plaints of drowsiness and lack of alertness. Again, as has alcohol. Nevertheless, many drugs have been recent pharmacological advancements have pro- studied with respect to some important variables duced antihistamine drugs, like loratadine required for driving. (Claritin), which maintain antihistamine actions The emphasis in these drug studies has tended to but have difficulty crossing the blood-brain barrier be on the evaluation of vision, attention, vigilance, and thus produce little impairment. and psychomotor skills. Driving-simulator studies Of all illicit drugs, marijuana has had the largest have also been done on occasion. The psychomotor number of experimental studies performed to ex- skill most often examined has been some form of tracking. amine its effects. Many of these studies indicate Reviewing this literature presents considerable that marijuana impairs coordination, tracking, difficulties since there are so many differences be- perception, and vigilance, as well as performance in tween classes of drugs, as well as between individ- driving simulators and on-the-road studies. ual drugs within the same drug classification. For Although there has been concern over increased example, many minor tranquilizers, especially driver use of STIMULANTS, such as amphatamines BENZODIAZEPINES, have been shown to impair at- and cocaine, there is little experimental evidence tention and tracking in a wide variety of studies. demonstrating driving impairment by these drugs. However, recently introduced tranquilizers, such as On the contrary, most studies of these stimulants, buspirone, exhibit little evidence of impairment. as well as of CAFFEINE, indicate an improvement in Conclusions about impairments in a drug cate- skills performance. However, with the chronic gory are likely to change because of the pressures (long-term) use of stimulants, an increased dose exerted by the drug regulatory agencies on drug companies to develop medicines that do not impair must be taken as tolerance develops. Thus, the dose skills performance. For example, hypnotics often levels examined in the laboratory may not reflect exhibit residual skills impairment the day following those found among drivers. Second, after the stim- use. New drugs have been introduced whose dura- ulation phase, a subsequent depressed phase occurs tion of effects is shorter so there will be less residual (the ‘‘crash’’) with increased drowsiness and lack impairment after awakening. of alertness. The stimulant drugs have not been Another class of psychoactive drugs, the well studied in relation to driving and should be. ANTIDEPRESSANTS, especially amitriptyline, have Further study is needed—both for acute (one-time) been long known to impair performance in a vari- use and chronic use. ety of skills. Again, recently introduced types of antidepressants do not produce the same degree of impairment. (SEE ALSO: Dramshop Liability Laws: DrunkDriv- Although narcotic ANALGESICS derived from ing; Minimum Drinking Age Laws; Mothers Against OPIUM (OPIATES) have been shown experimentally DrunkDriving; Psychomotor Effects of Alcohol and to lead to decreased alertness, there have been Drugs; Social Class of Alcohol and Drug Abuse; reports that chronic use produces considerable tol- Students Against Destructive Decisions). 422 DRIVING UNDER THE INFLUENCE (DUI)

BIBLIOGRAPHY

BATES,M.N.&BLAKELY, T. A. (1999). Role of cannabis in motor vehicle crashes. Epidemiological Reviews, 21(2), 222-232. MOSKOWITZ, H., & FIORENTINO, D. (2000). A review of the literature on the effects of low doses of alcohol on driving-related skills. Report no. DOT HS 809 028. U.S. Department of Transportation, Washington, DC. MOSKOWITZ, H., & ROBINSON, C. D. (1988). Effects of low doses of alcohol on driving-related skills: A review of the evidence. Report No. DOT HS 807 280. U.S. Department of Transportation, Washington, DC. TERHUNE, K. W., ET AL. (1992). The incidence and role Four of the 40 officers at a roadblockin Cary, of drugs in fatally injured drivers. Report no. DOT North Carolina, stop cars to checkfor drunk 808 065. U.S. Department of Transportation, Wash- drivers on December 13, 1997. During the ington DC. Saturday night sweep, officers statewide charged U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. 69 people with DWI and seized six cars. (1987). Sixth special report to the U.S. Congress on (AP Photo/Karen Tam) alcohol and health. Rockville, MD: Author. U.S. DEPARTMENT OF TRANSPORTATION. (1968). Alcohol Traffic Safety Administration (NHTSA) estimates and highway safety: A report to the Congress. Wash- that in 1998, alcohol was involved in 39 percent of ington, DC: U.S. Government Printing Office. all fatal crashes (almost 16,000 fatalities) and 7 VOAS, R. B., ET AL. (1998). Drinking and driving in the percent of all crashes. NHTSA estimates that three United States: The 1996 national roadside survey. out of ten Americans will be involved in an alcohol- Accident, Analysis & Prevention, 30(2), 267-275. related crash sometime during their lives. HERBERT MOSKOWITZ (SEE ALSO: Breathalyzer; Dramshop Liability Laws; Driving, Alcohol, and Drugs; Drug Interac- DRIVING UNDER THE INFLUENCE tions and Alcohol; DrunkDriving; Mothers Against (DUI) DRIVING UNDER THE INFLUENCE is a term DrunkDriving; Students Against Destructive Deci- that refers to the operation of a motor vehicle after sions) consuming alcohol and being affected by it in some way. It may be used as a legal term denoting a lesser BIBLIOGRAPHY offense than DRIVING WHILE INTOXICATED (DWI). AMERICAN MEDICAL ASSOCIATION COUNCIL ON SCIENTIFIC Specific blood-alcohol concentration (BAC) limits AFFAIRS. (1986). Alcohol and the driver. Journal of are associated with a DUI offense. These vary the American Medical Association, 255(4), 522–527. among states and countries but are often between NATIONAL HIGHWAY SAFETY ADMINISTRATION. (1998). Al- .05 percent and .10 percent (50 milligrams per cohol fact sheet. Washington, D.C. deciliter [mg/dl] and 100 mg/dl). In the United States, most states place the limit at .010 percent to MYROSLAVA ROMACH be classified as driving under the influence. Some KAREN PARKER states have reduced the legal limit to 0.08 percent, REVISED BY FREDERICK K. GRITTNER but Congress rejected legislation in 1998 that would have required all states to lower the drunken driving arrest threshold to .08 percent. DROPOUTS AND SUBSTANCE USE There is a strong correlation between a BAC The Monitoring the Future project (HIGH SCHOOL greater than 0.05 percent and risk of serious injury SENIOR SURVEY) and other studies of school-age or death while operating a motor vehicle. After the youths have helped us to understand the substance- BAC reaches .08 percent or more, the probability of use patterns of ADOLESCENTS who remain in and a crash climbs rapidly. The National Highway graduate from high school. In contrast, not nearly DROPOUTS AND SUBSTANCE USE 423 as much is known about the substance use of those school are other signs that help to predict who will who become high school dropouts. Nonetheless, by drop out before completing high school. This pro- putting together evidence from a variety of sources, vides some evidence that sometimes there can be an including the NATIONAL HOUSEHOLD SURVEY ON underlying common cause in earlier stages of DRUG ABUSE and the Epidemiologic Catchment growth and development and that it is essential to Area surveys sponsored by the U.S. government, it consider these earlier stages in observing a link is possible to say that high school dropouts are between later substance use and dropping out of much more likely to have started using TOBACCO, school. ALCOHOL, and other drugs, as compared with their Working along these lines, Judith Brook and her peers who remained in school. There also is some research team have looked into school grades and evidence that dropping out of high school is associ- poor school achievement with the idea that stu- ated with an increased risk of adult-onset alcohol- dents who did not do well in elementary school dependence syndromes, even among persons whose might be at greater risk for later drug use, in the dropping out could not have been caused by the same way that not doing well in school was a sign of consequences of starting to drink during the ado- greater risk for dropping out. Her research group lescent years. Whether this conclusion also holds also sought to determine whether later improve- for adult-onset DEPENDENCE on other drugs such as ments in academic performance might modify the COCAINE or MARIJUANA is not yet clear but is under risk profiles of low achievers in primary school. study. In studying a large sample of school-age youth In trying to understand how it might happen from primary school through high school, this team that dropouts are more likely to be substance users, of researchers has found a moderately strong link- the possibility should be considered that substance age between early poor school achievement and use has caused some people to drop out of school, as later drug use, but also discovered that the linkage well as the possibility that some schools suspend or was substantially weaker when low achievers in expel students for smoking tobacco, drinking alco- primary school did much better in later school hol, or using other drugs. By themselves, these cir- years. This type of developmental evidence is im- cumstances could be enough to explain why high portant and needs to be replicated by others before school dropouts are more likely to have taken illicit strong conclusions can be drawn. It does suggest drugs or started underage smoking or drinking. that it might be possible to use achievement- In addition, when students drop out before grad- strengthening programs not only to reduce school uating from high school, they often begin spending dropout rates but also to reduce rates and levels of more time with older youths and adults, some of teenage drug use. whom serve as role models for substance use and Several research groups are carrying out rigor- who may give the dropouts cigarettes or offer them ous field experiments to see whether intervention opportunities to try alcohol or other drugs for the programs directed at entire classrooms of first- and first time. As a result, not only is there the possibil- second-graders might change their risks for later ity that substance use may lead to dropping out, drug use, conduct problems, and dropout rates. but it is also possible that dropping out may lead to These very early interventions are not drug-educa- substance use. tion classes. The first- and second-grade teachers More complicated possibilities must also be are working with the students to help promote their taken into account. A developmental perspective learning and school achievement in new ways and makes it possible to imagine that the greater fre- to help them behave themselves and adapt better to quency of substance use among high school drop- the rules of the elementary school classroom. outs might have its origins in the earlier years of Other research groups are trying to reduce drop- childhood, so that it is not a simple matter of sub- out rates and substance use by targeting the more stance use leading to dropping out, or dropping out vulnerable or higher-risk elementary school and leading to substance use. For example, it has been middle school students, and giving them and their found that youngsters who frequently broke rules, FAMILIES special programs to promote learning and got into fights, and had trouble adapting to elemen- a sense of mastery over schoolwork; sometimes this tary school were more likely to become heavy drug is being done in connection with social-influences users ten or more years later. CONDUCT problems at intervention programs. In contrast with interven- 424 DRUG

tions directed at all students in the first- and sec- DRYFOOS, J. D. (1991). Adolescents at risk. New York: ond-grade classrooms, these involve ‘‘pull-out’’ Oxford University Press. programs for the specially targeted higher-risk GALLO, J. J., ROYALL, D. R., & ANTHONY, J. C. (1993). students. Risk factors for the onset of depression in middle age Future research will provide more definitive evi- and later life. Social Psychiatry and Psychiatric Epi- dence on the underlying mechanisms that account demiology, 28(3), 101–108. for observed associations between dropping out of HAWKINS, J. D., VON CLEVE E., & CATALANO, R. F., JR. high school and substance use, as well as for the (1991). Reducing early childhood aggression. Results newer suspected associations between dropping out of a primary prevention program. Journal of Ameri- of school and the risk for adult-onset alcohol-de- can Child and Adolescent Psychology, 30(2), 208– pendence syndromes (Crum et al., 1993). If the 217. intervention programs are found to reduce dropout JOHNSTON, L. D., O’MALLEY, P. M., & BACHMAN,J.G. rates and also levels of alcohol, tobacco, and other (1992). National survey results on drug use from the drug involvement, this will provide some powerful Monitoring the Future Study, 1975–1992 (vol. 1). evidence on the causal significance of the early Rockville, MD: National Institute on Drug Abuse. developmental antecedents and will help to explain KELLAM, S. G., ET AL. (1994). The course and malleabil- why dropouts are more likely to be drug users. ity of aggressive behavior from early first grade into In the meantime, the broad range of unfortunate middle school: Results of a developmental epidemio- effects of dropping out of school makes it important logically-based preventive trial. Journal of Child Psy- to sustain and increase the vigor of stay-in-school chology, Psychiatry and Allied Disciplines, 35(2), programs as well as outreach programs for youths 259–281. who are chronically absent from school or who ac- WERTHAMER-LARSSON, L. A. (1994). Methodological is- tually have dropped out before graduation. These sues in school-based services research. Special sec- programs may help the individual youths, their tion: Mental health services research on children, ado- families, and society in many ways; they may not lescents and their families. Journal of Clinical Child only confer benefits in relation to schooling and Psychology, 23(2), 121–132. better preparation for adult life, but also reduce the ERIC O. JOHNSON amount of substance use in the teenage years, pre- vent the occurrence of alcohol and drug problems in adulthood, and possibly prevent other psychiat- DRUG As a therapeutic agent, a drug is any ric disorders such as major DEPRESSION. substance, other than food, used in the prevention, diagnosis, alleviation, treatment, or cure of disease. (SEE ALSO: Attention Deficit Disorder; Coping and It is also a general term for any substance, stimulat- Drug Use; Education and Prevention; Epidemiology ing or depressing, that can be habituating. Accord- of Drug Abuse; Vulnerability As Cause of Substance ing to the U.S. Food, Drug, and Cosmetic Act, a Abuse) drug is (1) a substance recognized in an official pharmacopoeia or formulary; (2) a substance in- tended for use in the diagnosis, cure, mitigation, BIBLIOGRAPHY treatment, or prevention of disease; (3) a substance BROOKS, J. S., ET AL. (1988). Personality, family and other than food intended to affect the structure or ecological influences on adolescent drug use. A devel- function of the body; (4) a substance intended for opmental analysis. Journal of Chemical Dependency use as a component of a medicine but not a device Treatment, 1, 123–162. or a component, part, or accessory of a device. CRUM, R. M., HELZER, J. E., & ANTHONY, J. C. (1993). Pharmacologists consider a drug to be any mole- Level of education and alcohol abuse and dependence cule that, when introduced into the body, affects in adulthood: A further inquiry. American Journal of living processes through interactions at the molecu- Public Health, 83(6), 830–837. lar level. Hormones can be considered to be drugs, DISHION, T. J., REID, J. B., & PATTERSON, G. R. (1988). whether they are administered from outside the Empirical guidelines for a family intervention for body or their release is stimulated endogenously. adolescent drug use. Journal of Chemical Dependency Although drug molecules vary in size, the molecu- Treatment, 1(2), 189–224. lar weight of most drugs falls within the range of DRUG ABUSE REPORTING PROGRAM (DARP) 425

100–1,000, since to be a drug it must be absorbed drug abusers entering them in the early 1970s; and distributed to a target organ. Efficient absorp- (2) describing during-treatment performance mea- tion and distribution may be more difficult when sures and how they related to differences in treat- drugs have a molecular weight greater than 1,000. ments and clients; (3) describing post-treatment The drug’s molecular shape is also important, since outcomes and how they related to differences in most drugs interact with specific RECEPTORS to pro- treatments and clients; and (4) describing impor- duce their biological effects. The shape of the re- tant elements of long-term addiction careers. ceptor determines which drug molecules are capa- The DARP data system contained records on ble of binding. The shape of the drug molecule almost 44,000 admissions to fifty-two federally must be complementary to that of the receptor to supported treatment agencies from 1969 to 1973— produce an optimal fit and, therefore, a physiologi- the years during which the current community cal response. treatment delivery system first emerged in the Within this general definition, most POISONS United States. The study population consisted of would be considered to be drugs. Although water clients from major TREATMENT modalities— and oxygen technically fit this general definition METHADONE MAINTENANCE PROGRAMS,THERAPEU- and are used therapeutically and discussed in phar- TIC COMMUNITY, outpatient drug-free, and macology textbooks, they are rarely considered to DETOXIFICATION—as well as a comparison intake- be drugs. Efforts have been made to develop a more only group. restricted definition, but because so many mole- cules and substances can affect living tissue, it is THE EFFECTIVENESS OF difficult to draw a sharp line. DRUG-ABUSE TREATMENT

(SEE ALSO: Inhalants; Plants, Drugs from; Vita- Initial research in this 20-year project focused mins) on ways of measuring characteristics of treatments, clients, and behavioral outcomes (see Sells & Asso- ciates, 1975). It was found that drug use and crimi- BIBLIOGRAPHY nal activities decreased significantly during treat- HARDMAN, J. G., ET AL.(EDS.). (1996). The pharmaco- ment, including outpatient as well as residential logical basis of theraupeutics, 9th ed. New York: programs. More important, the effects continued Mcgraw-Hill. after treatment was ended. A sample of 6,402 cli- STEDMAN’S MEDICAL DICTIONARY. (1992). 27th ed. Balti- ents located across the United States were selected more, MD: Lippincott, Williams, & Wilkins. for follow-up an average of three years after leaving NICK E. GOEDERS DARP treatment (and 83% were located). Metha- done maintenance, therapeutic communities, and outpatient drug-free programs were associated DRUG ABUSE See Addiction: Concepts and with more favorable outcomes among opioid ad- Definitions dicts than outpatient detoxification and intake- only comparison groups; however, only clients who remained in treatment three months or longer DRUG ABUSE REPORTING PROGRAM showed significant improvements after treatment. (DARP) The Drug Abuse Reporting Program Numerous studies of these data helped establish began in 1969 as a comprehensive data system that that treatment ‘‘works’’ and that the longer clients included intake and during-treatment information stay in treatment, the better they function after on individuals entering drug treatment programs treatment (see Simpson & Sells, 1982). funded by the U.S. government. Over time, it was the basis for carrying out the first national evalu- LONG-TERM OPIOID ation study of community-based treatment pro- ADDICTION CAREERS grams. It was conducted at Texas Christian Univer- sity over a period of twenty years and included four To study long-term addiction careers, a sample distinct phases of research: (1) describing major of 697 daily OPIOID (primarily HEROIN) users were treatment modalities and the characteristics of followed up with again, at twelve years after enter- 426 DRUG ABUSE TREATMENT OUTCOME STUDIES (DATOS)

ing treatment (and 80% were located). It was BIBLIOGRAPHY found that about 25 percent of the sample was still SELLS, S. B., ET AL. (1975). The DARP research program addicted to daily opioid use in year twelve. Length and data system. American Journal of Drug and Alco- of addiction (defined as the time between first and hol Abuse, 2, 1–136. last daily opioid use) ranged from one to thirty-four SIMPSON,D.D.,&SELLS, S. B. (1990). Opioid addiction years. Of the total sample, 50 percent was addicted and treatment: A 12-year follow-up. Malabar, FL: nine-and-a-half years or longer, yet 59 percent Krieger. never had a period of continuous daily use that SIMPSON,D.D.,&SELLS, S. B. (1982). Effectiveness of exceeded two years. Only 27 percent reported con- treatment for drug abuse: An overview of the DARP tinuous addiction periods that lasted more than research program. Advances in Alcohol and Sub- three years. stance Abuse, 2(1), 7–29. Three-fourths of the addicts studied had experi- DWAYNE SIMPSON enced at least one ‘‘relapse’’ to daily opioid use after they had temporarily quit. Among those who had ever temporarily quit daily opioid use at least once, DRUG ABUSE TREATMENT OUTCOME 85 percent had done so while in a drug-abuse treat- STUDIES (DATOS) This family of studies is ment, 78 percent had quit while in a jail or prison, designed to provide comprehensive information on 69 percent had temporarily quit ‘‘on their own’’ continuing and new questions about the effective- ness of the drug-abuse treatment that is available (without treatment), and 41 percent had quit while in a variety of publicly funded and private pro- in a hospital for medical treatment. The most fre- grams. These data update and augment the infor- quent reasons cited for quitting addiction the last mation available from earlier national studies, such time involved psychological and emotional prob- as the DRUG ABUSE REPORTING PROGRAM (DARP) lems. Ex-addicts reported they had ‘‘become tired of study, which began in the late 1960s, and the the hustle’’ (rated as being important by 83% of the TREATMENT OUTCOME PROSPECTIVE STUDY sample) and needed a change after ‘‘hitting bottom’’ (TOPS) of clients entering treatment in the 1970s. (considered important by 80%). Other reasons cited The work was sponsored by the NATIONAL INSTI- as being important were ‘‘personal or special’’ TUTE ON DRUG ABUSE (NIDA) and conducted by the events such as a marriage or the death of a friend National Development and Research Institute, (64%), fear of being sent to jail (56%), and the need Texas Christian University, and the University of to meet family responsibilities (54%) (See Simpson California, Los Angeles. The major objective of DATOS is to examine the & Sells, 1990, for further details). effectiveness of drug-abuse treatment by conduct- ing a multisite, prospective clinical and epidemio- SUMMARY logical longitudinal study of drug-abuse treatment. Effectiveness was examined by using data from The DARP findings have been widely used to 10,010 client interviews conducted from 1991 to support continued public funding of drug-abuse 1993 at entry to treatment each three months, dur- treatments and to influence federal drug policy in ing treatment, and one year after leaving treat- the United States. Other similar national treatment ment. Interviews of clients at admission were sup- evaluation studies have been planned and under- plemented with comprehensive clinical assessments taken at the beginning of each decade since the of psychological, social, and physical impairments 1970s. Current research efforts focus on increasing in addition to drug and alcohol dependence. Treat- understanding of the particular elements of treat- ment outcomes were compared for clients who en- ment that are most effective and how they can be tered treatment with varied patterns of drug abuse and levels of psychosocial impairment. improved. A secondary objective was to investigate the pro- cess of drug-abuse treatment. A detailed examina- (SEE ALSO: Drug Abuse Treatment Outcome Stud- tion was being conducted of the treatments and ies; Narcotic Addict Rehabilitation Act) services available and provided to each client, how DRUG ABUSE TREATMENT OUTCOME STUDIES (DATOS) 427 these treatments and services are delivered to the of education, more of them are married, fewer are client, and how the client responds to treatment in fully employed, and a lower percentage of them terms of cognitive and behavioral changes. report that they have considered or attempted sui- The study population includes 1,540 clients cide. A higher proportion of the clients on METHA- from twenty-nine outpatient methadone programs; DONE are entering treatment for the first time, and 2,774 clients from twenty-one long-term residen- the proportion of criminal-justice referrals is higher tial or THERAPEUTIC COMMUNITY programs; 2,574 in long-term residential and outpatient drug-free clients from thirty-two outpatient drug-free pro- programs than they are in short-term inpatient grams; and 3,122 clients from fourteen short-term, programs. inpatient, or chemical dependency programs. In In all types of programs, cocaine abuse predomi- addition, treatment programs from DATOS were nated in the early 1990s, compared to heroin abuse compared with those for TOPS a decade earlier and in the past, but the cocaine use was usually com- for DARP two decades earlier in order to determine bined with extensive use of ALCOHOL. Multiple how drug-abuse treatment programs have changed abuse of psychotherapeutic agents has decreased, and what the changes imply for the provision of so less than 10 percent of clients report that they effective treatment approaches and services. regularly use these agents as opposed to treatment The DATOS research builds and expands the services. Outpatient programs have fewer early knowledge generated from previous research on the dropouts, but this may reflect better screening and effectiveness of treatment. Several events, however, longer, more extensive intake processes. The influ- have necessitated a continuing nationally based ence of cost-containment measures and managed multisite study of drug-abuse treatment and treat- care became evident with shortened durations of ment effectiveness. Major changes have occurred in treatment for short-term inpatients. Short-term in- the nation’s drug-abusing population and treat- patient programs also admit more public sector ment system. The OMNIBUS Recommendation Act patients than in the 1980s. Early analyses from the of 1981 shifted the administration of treatment DATOS indicate that rates of drug use toward the programs from the federal government to the start of outpatient treatment are two to three times states. The AIDS epidemic has intensified interest in higher than those that were found in TOPS. drug-abuse treatment as a strategy to reduce expo- The early results of DATOS also show that cli- sure to the HUMAN IMMUNODEFICIENCY VIRUS ents entering drug treatment are a diverse group (HIV), which causes AIDS. COCAINE use rather who have multiple problems. Two-thirds of the cli- than OPIOID use was the major drug problem of the late 1980s and early 1990s. Efforts to contain ents are men, and approximately half have previ- health-care costs may dramatically transform both ously been in treatment. Those who have health the public and private treatment systems. It has insurance that covers treatment are, by far, in the therefore become necessary to update information minority. Although the clients entering short-term so as to reexamine what we have learned about inpatient chemical-dependency programs appear treatment effectiveness, and so as to augment the to have a higher rate of private insurance coverage types of data that are available for exploring new (40 percent) than any other classification of clients, issues about the nature, effectiveness, and costs of their rate is considerably lower than that observed treatment approaches. The research based on among the same type of clients in the 1980s. De- DATOS has been organized into four areas: pending on the type of treatment, 25 to 50 percent (1) treatment selection, access, and utilization, of clients reported predatory criminal activity in (2) treatment engagement and retention, the previous year, and less than 20 percent were (3) addiction and treatment, and (4) applications fully employed. The clients have a variety of health and policy development. Details of these studies problems, and many report significant psychiatric can be found in the following references as well as impairment. Few have received mental health ser- at the URL http://www.DATOS.org. vices, however, and about one in every three clients The initial comparison of data from the DATOS report that they use emergency rooms as their pri- and from the TOPS shows the following about the mary health-care provider. Taken together, these clients in DATOS: They are older, a greater per- data indicate that most clients have deficits in centage of them are women, they have more years many areas of their lives and have multiple needs in 428 DRUG ABUSE TREATMENT OUTCOME STUDIES (DATOS) addition to those directly related to their drug ing treatment, and one year after leaving treat- abuse (e.g., medical services and vocational needs). ment. Treatment outcome will also be assessed by Patterns of drug use vary markedly by type of using such measures as changes in the use of the treatment in DATOS clients. Although cocaine is primary problem drug; the use of other drugs; anti- the most frequently cited drug of abuse, most cli- social, delinquent, or criminal behavior; school at- ents abuse multiple drugs and exhibit complex pat- tendance and achievement; vocational training and terns of drug use. Frequent alcohol use is also employment; family and social functioning; and common among many of the clients, as is weekly treatment retention. A secondary objective of use of marijuana. Multiple abuse of psychothera- DATOS–Adolescent is to investigate the drug- peutic agents is reported by less than 10 percent of abuse treatment that adolescents receive. A sample clients. of thirty long-term residential, outpatient drug- Drug-treatment programs are focusing on pro- free, and short-term inpatient programs will be viding drug-counseling services to meet the multi- used to accomplish these objectives. The proposed ple problems of clients, but fewer specialized ser- sample design will include three thousand clients. vices, such as medical or psychological services, are The Early Retrospective Study of Cocaine Treat- being provided to meet clients’ other needs. Only a ment Outcomes is an accelerated retrospective third to a half of clients who report a need for study of clients with a primary diagnosis of cocaine medical services are receiving them, and the situa- dependence who had been admitted to DATOS– tion is much worse in regard to psychological, fam- Adult programs prior to or in the early stages of ily, legal, employment, and financial services. Less DATOS. The research will provide data about out- than 10 percent of clients who report a need actu- comes for cocaine abusers during the first year of ally receive the service while they are in methadone treatment, describe the treatment received by these and outpatient drug-free programs. The percent- clients through a study of treatment process, and age of clients who receive specialized services other establish a client data base for future follow-up than drug counseling (e.g., medical or psychologi- studies. A sample of 2,000 records for cocaine- cal attention) has declined dramatically since the abusing clients discharged from residential, hospi- mid-1980s. The impact of cost-containment mea- tal-based, and outpatient nonmethadone programs sures and managed care is evident in the shorter will be abstracted to obtain baseline data. A sample stays of clients, particularly those enrolled in short- of 1,200 face-to-face, follow-up interviews will be term inpatient programs. completed, after twelve months of treatment, with Limited information on treatment outcomes has the discharged clients whose records were reviewed provided a mixed indication of the outcomes of during the record-abstraction phase of the project. treatment. The combination of more severe impair- Data analyses of the project will be targeted at ment and less extensive services suggests the poten- describing the posttreatment outcomes for cocaine tial for poorer outcomes. On the positive side, cli- abusers by detailing their treatment experiences ents in treatment are being retained in treatment. and investigating their posttreatment experiences. However, compared to earlier findings, findings This description will include the type, intensity, from the early 1990s indicated that a higher per- and duration of services received and an examina- centage of clients were actively using drugs during tion of the interrelationships between client and the first months of treatment. treatment characteristics and posttreatment out- Two other studies have been included under the comes. Along with cocaine use, other outcomes that DATOS program of research. The Drug Abuse will be considered include the use of drugs other Treatment Outcome Study–Adolescent (DATOS– than cocaine, economic functioning, illegal activi- Adolescent) research study is designed to examine ties, and psychological status. Analytic methods the effectiveness of drug-abuse treatment for ado- will include univariate and descriptive statistics as lescents through a multisite prospective longitudi- well as multivariate methods. The collection of fol- nal study of youth entering treatment programs low-up data for this retrospective study will be that focus on adolescents. Effectiveness will be ex- conducted simultaneously with the collection of amined by using interview data from youth under data for the twelve-month follow-up of DATOS cli- eighteen supplemented by interviews with parents ents. A close coordination with the DATOS–Adult or guardians conducted at entry to treatment, dur- is designed to permit comparison across studies. DRUG ABUSE WARNING NETWORK (DAWN) 429

(SEE ALSO: Drug Abuse Reporting Program; Metha- the data. In addition, analysis of the data requires done Maintenance Programs; Opioid Dependence; familiarity with the types of cases reportable to Treatment, History of in the United States; Treat- DAWN. For example, the emergency-room system ment: Outcome Prospective Study; Treatment contains data not only on OVERDOSE cases, but on Types) individuals seeking DETOXIFICATION in an emer- gency room or those suffering from chronic effects BIBLIOGRAPHY of drug use—situations that do not necessarily re- quire emergency treatment. Therefore, DAWN SIMPSON,D.D.,&BROWN, B. S. (Eds.) (1999). Special cases may reflect other phenomena than medical issue: Treatment processes and outcome studies from consequences (e.g., changes in nonhospital medical DATOS. Drug and Alcohol Dependence, 57(2), 81– treatment availability). 174. SIMPSON,D.D.,&CURRY, S. J. (Eds.) (1997). Special HISTORY issue: Drug abuse treatment outcome study (DATOS). Psychology of Addictive Behavior, 11(4), 211–337. DAWNwas created in 1972 by the U.S. Depart- SIMPSON,D.D.,&JOE, G. W., FLETCHER, B. W., ET AL. ment of Justice, DRUG ENFORCEMENT ADMINISTRA- (1999). A national evaluation of treatment outcomes TION (DEA), as a surveillance system for new drugs for cocaine dependence. Archives of General Psychia- of abuse. Since 1980, the DAWNsystem has been try, 56, 507–514. managed by the NATIONAL INSTITUTE ON DRUG ABUSE (NIDA) and, more recently, the Office of ROBERT HUBBARD Applied Studies of the SUBSTANCE ABUSE AND MEN- REVISED BY DWAYNE SIMPSON TAL HEALTH S ERVICES A DMINISTRATION (SAMHSA), which currently oversees it. The Emergency-Room System. At its outset, DRUG ABUSE WARNING NETWORK the DAWNemergency-room system consisted of a (DAWN) This is a voluntary national data col- sample of hospitals in twenty-one metropolitan lection system that gathers information on sub- areas and a panel of hospitals representative of the stance abuse that results in visits to hospital emer- nation as a whole. In subsequent years, however, gency departments (ED) in the contiguous United changes in hospital participation led to a sample States. Hospitals tracked in the DAWNsystem in- that was no longer representative of all hospital clude nonfederal, short-stay, general hospitals that EDs in the coterminous United States. Thus, data have twenty-four-hour ED—representative of the collected by the DAWNsystem before 1988 mea- coterminous United States as a whole—plus a sam- sure drug-related cases only for those hospitals in- ple of hospitals in twenty-one major metropolitan cluded in the sample; actual estimates of the num- areas. The system also collects data on drug-related ber of drug deaths and hospital emergencies in the deaths from a nonrandom sample of medical exam- metropolitan areas or across the nation are not iners. Such data are published annually in separate available for those years (1972–1987). The pri- reports titled DAWNMedical Examiner Data. mary utility of the data prior to 1988, then, is for The data collected by the DAWNsystem repre- examining trends in drug emergencies and deaths sent one of the most widely used national indicators in the participating hospitals over time, rather than of drug abuse—frequently used by researchers and deriving estimates of actual numbers of cases in the policymakers to determine the nature and extent of United States. medical consequences of drug use nationally and in DAWNdata have been collected from a repre- the participating metropolitan areas. Although the sentative sample of eligible hospitals in the co- data are widely used to monitor patterns and trends terminous United States. It includes an oversampl- of drug abuse, DAWNshould be used with caution. ing from twenty-one metropolitan areas and a The DAWNdata represent information only on in- National Panel of hospitals sampled from locations dividuals who enter an emergency room because of outside of these areas. This sample design corrects their drug use. Therefore, the data reflect only the the limitations of the pre-1988 sample. It also al- most serious cases of drug abuse. Consequences of lows for inferences about the actual number of drug use that are less severe are not represented in drug-abuse episodes in the contiguous United 430 DRUG ABUSE WARNING NETWORK (DAWN)

States and for the separate DAWNmetropolitan males and females occurred in about equal num- areas. bers. Dependence (37% of episodes) and suicide DATA COLLECTION (32%) were the most frequently cited motives for drug use. When analyzed by reason for contact in In each participating facility, a reporter, usually the emergency room, the data show that overdose a member of the hospital ED or medical records (OD) was the most frequently cited reason for the staff, is assigned to conduct data collection. The majority of episodes (42%), while the remainder of reporter reviews records for each case appropriate episodes were due to another cause. for inclusion in the DAWNsystem and records de- In 1999, the largest number of episodes mographic information and information about the (196,277, or 35% of all episodes) were due to use circumstances of the episode, including the date of ALCOHOL in combination with other drugs. The and time of the ED visit and the reason the person other drugs mentioned most frequently were CO- came to the ED. For each drug mentioned, the CAINE (168,763, or 30%), HEROIN/MORPHINE DAWNreport includes the form in which the drug (84,409, or 15%), amphetamine (11,954, or 2%), was acquired, its source, and its route of adminis- and methamphetamine/speed (10,447, or 2%). In tration. Only one reason for taking substances is 1999, marijuana/hashish mentions exceeded her- recorded. A report for each case is then submitted oin/morphine mentions, changing a rank ordering to SAMHSA for data entry. of illicit drug mentions that had been constant since The following criteria are used in determining 1990. whether a case is reportable to DAWN. For each Long-term Trends, 1990–1999. The number of record, the patient must be between six and ninety- drug-related episodes rose 49 percent from 1990 to seven years of age and must meet all of the follow- 1999, from 371,208 to 554,932. Although males ing criteria: consistently outnumber females in illicit drug men- 1. The patient was treated in the hospital’s emer- tions, their long-term patterns of growth are simi- gency department. lar. From 1990 to 1999, mentions of cocaine and 2. The patient’s presenting problem(s) had been heroin/morphine more than doubled for both males induced by or related to drug use, regardless of and females. ED mentions of marijuana/hashish in whether the drug ingestion occurred minutes or 1999 were five and six times their 1990 levels for hours before the visit. males and females, respectively. Mentions of the 3. The case involved the nonmedical use of a legal four major illicit drugs increased from 1990 to drug or any use of an illegal drug. 1999 as follows: marijuana/hashish (15,706 to 4. The patient’s reason for taking the substance(s) 87,150, or 455%), methamphetamine/speed included one of the following: (1) DEPENDENCE, (5,236 to 10,447, or 100%), heroin/morphine (2) SUICIDE attempt or gesture, or (3) psychic (33,884 to 84,409, or 149%), and cocaine (80,355 effects. to 168,763, or 110%). Emergencies for those over age thirty-five rose significantly over the time pe- DAWNcases do not include accidental ingestion riod (124%), while the number of episodes for or inhalation of a substance, nor do they include those twenty-five and under increased less than 20 adverse reactions to prescription or over-the-coun- percent. ter drugs. Up to four substances can be reported for Among adolescents age twelve to seventeen, any drug-abuse death or emergency-room case. Al- mentions of marijuana/hashish increased 489 per- cohol is reportable only when it is used in combina- tion with a reportable substance. cent (from 2,170 to 12,784) between 1990 and 1999. This is increase is significant, considering that the number of total drug-related episodes TRENDS IN DRUG-RELATED among patients in this age group increased only 7 EMERGENCIES AND DEATHS percent (from 49,109 to 52,783) between 1990 Drug-related Episodes in 1999. In 1999, there were and 1999. In addition, the long-term trends for an estimated 554,932 drug-related ED episodes in methamphetamine/speed, cocaine, and heroin/ the coterminous United States. Episodes from morphine among youth aged twelve to seventeen DRUG COURTS 431 show increasing use among individuals in this of cocaine and, later, crack cocaine, particularly in group. America’s cities, translated into a new challenge for the criminal justice system that was already at its (SEE ALSO: Abuse Liability of Drugs; Complica- limits. The volume of court cases exploded, pushing tions; Drug Interactions and Alcohol; Epidemiology the judicial process to its limits and threatening of Drug Abuse; National Household Survey on traditional modes of managing the criminal Drug Abuse) caseload. Worse, the huge wave of arrests of drug offenders beginning in and accelerating during the BIBLIOGRAPHY 1980s found a correctional system of local jails and state prisons in many locations in the nation that COLLIVER, J. D. (1991). Characteristics and implications were already chronically overcrowded. With little of the new DAWNemergency room sample. In Epide- room in prisons for the new arrestees, institutional miologic trends in drug abuse, Community Epidemiol- crowding was exacerbated and the processing of ogy Workgroup Proceedings, July. Rockville, MD: Na- criminal cases was slowed, causing backlogs in the tional Institute on Drug Abuse. courts and a wide range of problems for the justice NATIONAL INSTITUTE ON DRUG ABUSE. (1991). Statistical system as a whole. series: Annual emergency room data, 1991. Data from In Miami, at the gateway of major drug traf- the Drug Abuse Warning Network. Series I, Number ficking routes from South America, the drug crisis 11-A. Rockville, MD: Author. was particularly acute. A study had shown that NATIONAL INSTITUTE ON DRUG ABUSE. (1991). Statistical approximately 90 percent of felony defendants en- Series: Annual medical examiner data, 1991. Data tering the judicial process in Miami (Metropolitan from the Drug Abuse Warning Network. Series I, Dade County) tested positively for drugs (excluding Number 11-B. Rockville, MD: Author. alcohol) at the time of their arrest. With historical hindsight, the innovation of the Miami Drug Court CLARE MUNDELL by its justice leaders (including its chief judge, Ger- REVISED BY PATRICIA OHLENROTH ald Wetherington, its prosecutor, Janet Reno, its public defender, Bennet Brummer, and its control drug control administrator, Timothy Murray) DRUG ADDICTION See Addiction: Con- seems obvious and common-sensical. The court cepts and Definitions; Disease Concept of Alcohol- system and government leaders reasoned that, if ism and Drug Abuse Dade County could not arrest and punish its way out of the drug problem, perhaps it should try pro- viding treatment as a reasonable alternative to DRUG CARTEL See Colombia as Drug prosecution and confinement. Source The first drug court in the United States went into operation in Miami under the supervision of Judge Stanley Goldstein, the nation’s first drug DRUG CONTROLS See Controls: Sched- court judge, in the summer of 1989. Since the uled Drugs/Drug Schedules, U.S. breakthrough efforts of the Miami justice leaders, by all measures, the growth of treatment drug courts in the United States has been extraordinary, with upwards of 400 courts reportedly in operation DRUG COUNSELOR See Professional Cre- in the year 2000 and others in some stage of plan- dentialing ning or preparation. The drug court model has also been adapted in other countries, from Canada and Australia to Great Britain and Ireland. DRUG COURTS Drug courts emerged as a Taken at its most challenging and as envisioned method for responding to America’s drug problems by its most ardent proponents, the drug court at a time when health, treatment and justice sys- model potentially represents the first stages of a tems were overwhelmed by the drug epidemics of fundamental paradigm shift in justice away from a the 1980s. The dramatic increase in the availability predominantly punitive orientation (a.k.a. ‘‘justice 432 DRUG COURTS as usual’’) toward an approach that seeks to con- drug treatment would be available.) For many dec- front and meliorate the problems associated with ades, drug treatment has also been available as a persons who appear in the criminal caseload. The condition of diversion for less serious offenses but challenges implicit in this approach are fundamen- has not demonstrated significant impact. From a tal and draw into the criminal court setting exper- judicial perspective, however, the court’s typical tise from health and behavioral sciences as well as involvement in substance abuse treatment was to linkages with a variety of social services in relation- order or ‘‘refer’’ offenders ‘‘out’’ to treatment, ships and configurations that produce a new mix of when such treatment was recommended by proba- values, aspirations and methods to guide the judi- tion staff at the pre-sentence stage. The judge in cial process. To their proponents, drug courts rep- such cases would have little other involvement in resent a major and promising departure from what the treatment process, except to set treatment as a had become an unrewarding routine of processing, condition of probation, and, later, hear allegations punishing and re-punishing drug offenders to little of noncompliance at revocation hearings. By keep- avail. Instead, the drug court model takes on ‘‘root ing a judicial distance from the treatment process, causes’’ of crime more easily ignored or viewed as judges deferred to the expertise and practices of someone else’s responsibility. treatment providers and probation agencies whose The foundation of the drug court model lies in its responsibilities were to manage and monitor the underlying values, philosophical outlook, and the treatment process. central role it assigns to the judge, as it incorporates Drug courts were ‘‘invented’’ to reinvent a help- a mix of values with a decided shift toward treat- ing justice role, similar to the one formerly played ment and restoration of offenders to the commu- by probation services, but this time entrusted to the nity. The mix also includes deterrent and desert power, authority, symbolism and centrality of the values that realistically circumscribe the arena of criminal court judge and occurring at an earlier the drug court modality: it is transacted in a crimi- stage. Many early drug courts consciously excluded nal (usually felony) courtroom. The therapeutic probation departments from their drug court de- activities associated with the treatment-oriented sign, although there were some notable exceptions drug court occur in a ‘‘theater in the square,’’ the (e.g., Maricopa County, Baltimore, and Oakland). square representing not only the architectural fea- While early drug courts ultimately found top-notch tures of the physical courtroom but also the bound- treatment providers willing to craft customized ap- aries imposed by the criminal process. Led and proaches to fit the needs of the drug courts, under closely supervised by the drug court judge, the drug former practices, treatment providers operated un- court operates in the context of the criminal process der their own rules and discretion in determining and, therefore, differs notably from substance eligibility, level of care and termination, which re- abuse treatment that might be provided to addicted flected a different professional orientation and view citizens in civilian contexts outside of the justice of how substance abusers should be treated. system. Within those judge-enforced boundaries Previously there was little judicial input into the marking the criminal process, however, the drug content of treatment programs and little two-way court model has innovated a new working relation- communication between the court and the treat- ship between the criminal court and health, treat- ment provider, except when the program needed to ment and related services that adapts the criminal notify the court of an individual’s completion of process to the needs of treatment and an under- treatment or failure to comply with the require- standing of addiction. The drug court seeks to re- ments of the treatment process. Judges delegated solve the apparently contradictory aims of the typi- the responsibility for treatment and supervision to cally punitive justice process and the more probation and treatment providers. Under the supportive treatment process. ‘‘refer-out’’ model, treatment providers controlled Until recently, the likelihood that an offender admission screening (some resisted accepting crim- identified as having a serious drug problem would inal justice clients), the level of care to be provided be placed in treatment was poor and depended on (the mix and location of services, from outpatient being convicted and, usually, sentenced to proba- to inpatient and including ancillary services), and tion. (Only in rare settings would a sentence to the termination process. Typically, treatment pro- incarceration include the realistic possibility that viders could discharge an ‘‘uncooperative’’ client DRUG COURTS 433 that was having a difficult time fulfilling the condi- ture and content of the treatment delivered to sub- tions of the program. stance abusing offenders, the methods employed in The drug court innovation sought to build the the drug courts to encourage positive and discour- new approach based on a ‘‘hands-on’’ and engaged age negative behavior by participants (including judicial role, a strong supervisory and case man- the use of sanctions and rewards), the productivity agement approach (initially not necessarily involv- of the courts (in terms of measurable outcomes ing probation), agreed upon, acceptable and rele- such as reduced substance abuse and criminal be- vant treatment services, and a more connected havior), and the extent of system-wide support in relationship with treatment providers in a court- and outside criminal justice and health systems. treatment process in which the judge controlled the Although there are common elements shared by admission and termination criteria. Thus, by de- most drug courts, proliferation of the drug court sign under the drug court model, the drug court model is not explained by the wholesale adoption of treatment program could not, on its own, reject a fixed, ‘‘cookie-cutter’’ approach in the many ju- difficult criminal justice clients accepted into the risdictions across the nation. The original Miami drug court and could not, without judicial ap- model evolved in its successive adaptations in other proval, terminate participants when they had failed settings, and was itself transformed in substance to comply with treatment program requirements. and procedure as the basic model traveled across Within these general elements of the treatment- the United States and to locations abroad. The drug oriented philosophy, the central judicial role and court methodology has been adapted to grapple new criminal court-treatment relationship, drug with other problems associated with court popula- courts are characterized by other distinguishing el- tions, including community issues, domestic vio- ements. The Drug Court Program Office of the U.S. lence and mental health and has directly and indi- Department of Justice sponsored an initiative by rectly spawned a variety of related innovations, so the National Association of Drug Court Profes- that one can now speak of ‘‘problem-solving’’ or sionals (NADCP) to identify key components of ‘‘problem-oriented’’ courts to refer to a more ac- drug courts. The ten components identified by tive, ‘‘hands-on’’ judicial and justice-system phi- NADCP, adopted as a standard by the Justice De- losophy. partment in reviewing grant applications, include The rapidly growing volume of drug courts (as integration of treatment and case processing; a well as of other ‘‘problem-solving’’ courts) suggests non-adversarial approach which also respects due that nationally the drug court experiment struck a process and public safety; early identification and fundamental chord of dissatisfaction with tradi- enrollment of participants; provision of a con- tional justice machinery that seemed only to punish tinuum of treatment services; drug testing; court and process. A number of states (California, New responses to performance in treatment; hands-on York, Louisiana, Ohio, Florida), large counties judicial supervision of treatment; monitoring and (Los Angeles County, Clark County, Nevada), and evaluation; continuing interdisciplinary education; large urban centers (Miami; Brooklyn; Buffalo; and, forging partnerships between the court and Portland, Oregon; Seattle) have incorporated drug other criminal justice, health, social service agen- courts into their administrative and budgetary cies and the community. planning processes because their growing numbers Prior to the NADCP practitioner-oriented pro- raise questions for court systems as a whole about cess to identify key components of drug courts for priorities, resources, effective management, and the purposes of constructing standards, a working performance standards. typology of drug courts identified eight critical di- mensions of the drug court innovation mainly for BIBLIOGRAPHY the purposes of evaluation. These include the target problems drug courts were designed to address, GOLDKAMP, J. S. (1994). Justice and treatment innova- specific criminal justice target populations they tion: The drug court movement: A working paper of sought to enroll in treatment, mechanisms em- the first National Drug Court Conference. Philadel- ployed to identify and evaluate court treatment phia: Crime and Justice Research Institute. candidates, the ways in which they involved modi- GOLDKAMP, J. S. (1999a). The origins of the treatment fications to the traditional court process, the struc- drug court in Miami. In C. TERRY (Ed.), The early 434 DRUG ENFORCEMENT ADMINISTRATION

drug courts: Case studies in judicial innovation. Bev- be important, because this can lead to changes in erly Hills, Sage Publications. the plasma levels of the drug, which can influence GOLDKAMP, J. S. (1999b). Challenges for research and the amount of drug that reaches the brain. innovation: When is a drug court not a drug court? In The distribution of a drug throughout the body C. TERRY (Ed.), Judicial change and drug treatment can be affected by changes in the binding of the courts: Case studies in innovation. Newbury Park: drug to proteins in the bloodstream or by dis- Sage Publications. placing the drug from tissue binding sites, both of GOLDKAMP, J. S. (2000). The drug court response: Issues which can affect the plasma concentration of the and implications for justice change. Albany Law Re- drug and potentially affect the amount of drug that view, 63, 923–961. reaches the brain. Drug metabolism can be either GOLDKAMP, J. S., WHITE, M. D., and ROBINSON, Jennifer. stimulated or inhibited, resulting in decreased or (2000). Retrospective evaluation of two pioneering increased plasma concentrations of the drug, re- drug courts: Phase I findings from Clark County, spectively. The stimulation (induction) of drug- Nevada, and Multnomah County, Oregon. An interim metabolizing enzymes in the liver can be produced report of the national evaluation of drug courts. Phil- by drugs such as the BARBITURATES, but a week or adelphia: Crime and Justice Research Institute. more is often required before maximal effects on HORA, P. F., SCHMA, W. G., and ROSENTHAL,J.T.A. drug metabolism are observed. As drug metabolism (1999). Therapeutic jurisprudence and the drug court increases, the amount of drug available to enter the movement: Revolutionizing the criminal justice sys- brain decreases. tem’s response to drug abuse and crime in America. The inhibition of drug metabolism often occurs Notre Dame Law Review, 74, 439–537. much more rapidly than the stimulation, usually as NATIONAL ASSOCIATIONOF DRUG COURT PROFESSIONALS. soon as a sufficient concentration of the metabolic (1997). Defining drug courts: The key components. inhibitor is achieved, which results in increased Washington: U.S. Department of Justice, Office of plasma and brain concentrations of the drug. The Justice Programs, Drug Courts Program Office. renal (kidney) excretion of drugs that are weak JOHN S. GOLDKAMP acids or weak bases can be influenced by drugs that alter urinary pH to change the reabsorption of the drug from urine into the kidney. The active secre- tion of the drug into the urine can also be affected. DRUG ENFORCEMENT ADMINISTRA- Both processes can ultimately affect the plasma and TION See U.S. Government subsequent brain concentrations of the drug. Phar- macodynamic mechanisms can either enhance or reduce the response of a given drug. For example, if DRUG-FREE SCHOOLS See Parents two drugs are agonists for the same receptor site— Movement; Prevention Movement DIAZEPAM (Valium) and CHLORDIAZEPOXIDE (Li- brium) for BENZODIAZEPINE receptor-binding sites—then an additive biological response is likely DRUG INTERACTION AND THE BRAIN to occur unless a maximum response is already When two or more drugs are taken at the same time present. If, however, an AGONIST competes with an complex interactions may occur. Drugs can interact ANTAGONIST for the same binding site (e.g., see to change biological functions within the body MORPHINE and NALOXONE in OPIOIDS, discussed through PHARMACOKINETIC or PHARMACODYNAMIC below), then a decreased biological response is mechanisms or through their combined toxic ef- likely. fects. Changes in the pharmacokinetic properties of Enhanced or diminished biological responses a drug can include changes in absorption, distribu- can be observed even if the drugs do not interact tion, metabolism, and excretion of the drug, and with the same receptor-binding sites. In this case, each of these can affect blood and plasma concen- the net effect is the sum of the pharmacological trations and, ultimately, brain levels of the drug. properties of the drugs. For example, if two drugs Although a change in the speed at which a drug share a similar biological response (e.g., central reaches the bloodstream is rarely clinically rele- nervous system depression) even though they pro- vant, a change in the amount of drug absorbed can duce their effects at different sites, then the concur- DRUG INTERACTION AND THE BRAIN 435

rent ingestion of both drugs can result in an en- ANTIDEPRESSANTS, antianxiety drugs, or with an hanced depression of the central nervous system ANALGESIC agent (such as morphine) can result in (see the ALCOHOL [ethanol] and Valium discussion serious and potentially fatal drug interactions below). Finally, the concurrent ingestion of two or through a potentiation of the depressant effects of more drugs, each with toxic effects on the same these drugs on the central nervous system. Since organ system, can increase the chance for extensive the 1960s, a significant number of musicians, ac- organ damage. tors, and other high-profile personalities have ei- ther accidentally or intentionally overdosed from a DEPRESSANTS combination of alcohol and other central nervous system depressants. A few notable examples in- Alcohol (Ethanol) and Valium. Reactions clude actress Marilyn Monroe, musicians Jimi Hen- that are additive (combined) or synergistic (coop- drix, Janis Joplin, Jim Morrison, Keith Moon, and erative effects greater than the sum of the indepen- John Bonham. dent effects of the drugs taken alone) are common side effects that result from the consumption of two or more drugs with similar pharmacological prop- STIMULANTS erties. For example, although alcohol (ethanol) is Stimulants and Toxic Effects. Synergistic considered by many to be a stimulant drug be- toxic effects are also often obscured with other cause, typically, it releases an individual’s latent classes of drugs. For example, the concurrent inges- behavioral inhibitions (i.e., it produces disinhibi- tion of central nervous system stimulants (e.g., AM- tion), alcohol actually produces a powerful depres- PHETAMINE,COCAINE,CAFFEINE) can also produce sion of the central nervous system similar to that additive side effects, especially with respect to toxic seen with general anesthetics. The subsequent im- reactions involving the heart and cardiovascular pairment of muscular coordination and judgment system. These toxic reactions are often manifested associated with alcohol intoxication can be en- as an irregular heartbeat, stroke, heart attack, or hanced by the concurrent administration of other even death. Drugs with apparently different mech- central nervous system depressants. Often, Valium anisms of action can result in dangerous and unex- or Librium (benzodiazepines that are considered pected synergistic side effects with fatal conse- relatively safe drugs) may be purposely ingested quences. For example, some amphetamine and along with ethanol in an attempt to ‘‘feel drunk’’ cocaine users often attempt to self-medicate their faster or more easily. Since ethanol actually in- feelings of ‘‘overamp,’’ or the excessive STIMULANT creases the absorption of benzodiazepines, and also high resulting from prolonged central nervous sys- enhances the depression of the central nervous sys- tem stimulation, through the concurrent adminis- tem, the potential toxic side effects of the two drugs are augmented. Ethanol is often a common contrib- tration of central nervous system depressants such utor to benzodiazepine-induced coma as well as to as alcohol, barbiturates, or heroin (i.e., a benzodiazepine-related deaths, demonstrating that ‘‘speedball’’). The rationale behind this potentially interactions of these drugs with alcohol can be dangerous practice is that a few beers, a Quaalude, especially serious. Furthermore, the combination of or perhaps a shot of heroin will help the individual alcohol with the SEDATIVE-HYPNOTIC BARBITU- ‘‘mellow out’’ for a while before inducing a stimu- RATES (e.g., pentobarbital, secobarbital) can also lant high again. High doses of cocaine or amphet- produce a severe depression of the central nervous amine can, however, result in respiratory depres- system, with decreased respiration. The intentional sion from actions on the medullary respiratory ingestion of ethanol and secobarbital (or Valium) is center. Therefore, the concurrent ingestion of a a relatively common means of SUICIDE. central nervous system stimulant (e.g., cocaine) Alcohol (Ethanol) and Opioids. Alcohol can with a depressant (e.g., heroin) can result in in- also enhance the respiratory depression, sedation, creased toxicity or death from the enhanced respi- and hypotensive effects of MORPHINE and related ratory depression produced by the combination of opioid drugs. Therefore, the concurrent ingestion of the two drugs. The most well-known casualty from the legal and socially acceptable drug ethanol with this type of pharmacological practice was comedian other sedatives, hypnotics, anticonvulsants, John Belushi. 436 DRUG INTERACTION AND THE BRAIN

CLINICAL USES mation on whether or not the coma is the result of an opioid overdose. The antagonist competes with The principles of drug interactions can be used the agonist (usually heroin or morphine) for the clinically for the treatment of acute INTOXICATION opioid-receptor sites, displacing the agonist from and for WITHDRAWAL—by transforming, reducing, the binding sites to reverse the symptoms of an or blocking the pharmacological properties and/or overdose effectively and rapidly. Continued nalox- the toxic effects of drugs used and abused for one therapy and supportive treatment are often still nonmedical purposes. Although these interactions necessary. often involve a competition with the abused drug If, however, naloxone is administered to an indi- for similar central nervous system RECEPTOR sites, vidual dependent on opioids but not in a coma, a other mechanisms are also clinically relevant. severe withdrawal syndrome develops within a few Disulfiram and Alcohol (Ethanol). One such minutes and peaks after about thirty minutes. De- nonreceptor-mediated interaction involves DI- pending on the individual, such precipitated with- SULFIRAM (Antabuse) and ethanol (alcohol). Since drawal can be more severe than that following the an ethanol-receptor site has not yet been conclu- abrupt withdrawal of the opioid-receptor agonist sively identified, specific receptor agonists and an- (e.g., heroin). In the former instance, the binding of tagonists are not yet available for the treatment of the agonist to opioid receptors is suddenly inhibited ethanol intoxication, withdrawal, and abstinence by the presence of the antagonist (e.g., naloxone); (as they are for opioids). Disulfiram is sometimes even relatively large doses of the agonist (e.g., her- used in the treatment of chronic ALCOHOLISM, al- oin) cannot effectively overcome the binding of the though the drug does not cure alcoholism; rather, it antagonist. Quite the contrary, respiratory depres- interacts with ethanol in such a way that it helps to sion can develop if higher doses of the agonist are strengthen an individual’s desire to stop drinking. administered. Therefore, opioid-receptor antago- Although disulfiram by itself is relatively nontoxic, nists are not recommended for the pharmacological it significantly alters the intermediate metabolism treatment of opioid withdrawal. Rather, longer act- of ethanol, resulting in a five- to tenfold increase in ing, less potent, opioid receptor-agonists, such as plasma acetaldehyde concentrations. This acetal- METHADONE, are more commonly prescribed. dehyde syndrome results in vasodilatation (dilation Methadone. The symptoms associated with metha- of blood vessels), headache, difficulty breathing, done withdrawal are milder, although more pro- nausea, vomiting, sweating, faintness, weakness, tracted, than those observed with morphine or her- and vertigo. All of these reactions are obviously oin. Therefore, methadone therapy can be unpleasant, especially at the same time, thus well gradually discontinued in some heroin-dependent worth avoiding. The acetaldehyde syndrome there- people. If the patient refuses to withdraw from fore helps to persuade alcoholics to remain absti- methadone, the person can be maintained on meth- nent, since they realize that they cannot drink etha- adone relatively indefinitely. TOLERANCE develops nol for at least three or four days after taking to some of the pharmacological effects of metha- disulfiram. The consumption of even small or mod- done, including any reinforcing or rewarding ef- erate amounts of ethanol following disulfiram fects (e.g., the euphoria or ‘‘high’’). Therefore, the pretreatment can result in extremely unpleasant patient cannot attain the same magnitude of eu- drug interactions through the acetaldehyde syn- phoria with continued methadone therapy, al- drome. though the symptoms associated with opioid with- Opioids. Drug interactions involving opioids drawal will be prevented or attenuated. Cross- (morphine-like drugs) and opioid receptors are tolerance also develops to other opioid drugs, so the classic examples of how knowledge of the molecu- patient will not feel the same high if heroin is again lar mechanisms of the actions of a class of drugs used on the street. can assist in the treatment of acute intoxication, This type of maintenance program makes those withdrawal, and/or abstinence. Naloxone, the opi- who are heroin dependent more likely to accept oid-receptor antagonist, can be used as a diagnostic other psychiatric or rehabilitative therapy. It also aid in emergency rooms. In the case of a comatose reduces the possibility that methadone patients will patient with unknown medical history, the intrave- continue to seek heroin or morphine outside the nous administration of naloxone can provide infor- clinic. In this way, the principles of drug interac- DRUG INTERACTIONS AND ALCOHOL 437 tions involving opioid receptors in the central ner- sues, biotransformation (metabolism), and excre- vous system have helped to stabilize TREATMENT tion. Pharmacokinetic interactions refer to the abil- strategies for opioid withdrawal and abstinence. ity of alcohol to alter the plasma and tissue concentration of the drug and/or the drug metabo- (SEE ALSO: Accidents and Injuries; Complications; lites, such that the effective concentration of the Neurological; Drug Abuse Warning Network) drug at its target site of action is significantly de- creased or increased. Pharmacodynamics are con- BIBLIOGRAPHY cerned with the biochemical and physiological ef- fects of drugs and their mechanisms of action. CLONINGER, C. R., DINWIDDIE, S. H., & REICH, T. (1989). Pharmacodynamic interactions refer to the com- Epidemiology and genetics of alcoholism. Annual Re- bined actions of alcohol and the drug at the target view of Psychiatry 8, 331–346. site of action, for example, binding to enzyme, CREGLER, L. L. (1989). Adverse consequences of cocaine receptor, carrier, or macromolecules. Phar- abuse. Journal of the National Medical Association macodynamic interactions may occur with or with- 81, 27–38. out a pharmacokinetic component. For many drugs GRIFFIN, J. P. & D’ARCY, P. F. (1997). Manual of adverse acting on the central nervous system that exhibit drug interactions, Fifth Edition. Oxford: Elsevier Sci- cross-tolerance (a similar tolerance level) with al- ence. cohol, pharmacodynamic interactions with alcohol KARALLIEDDE,L.&HENRY,J.(EDS.)(1998). Handbook are especially important. of drug interactions. New York: Oxford University Most drugs are metabolized in the liver by an Press, Inc. enzyme system usually designated as the cyto- KORSTEN, M. A., & LIEBER, C. S. (1985). Medical chrome P450 mixed-function oxidase system, and complications of alcoholism. In J. H. Mendelson & the liver is the principal site of many alcohol-drug N. K. Mello (Eds.), The diagnosis and treatment of pharmacokinetic interactions. Two major factors— alcoholism, pp. 21–64. New York: McGraw-Hill. blood flow to the liver and the activity of drug- LIEBOWITZ, N. R., KRANZLER,H.R.&MEYER,R.E. metabolizing enzymes—strongly influence the (1990). Pharmacological approaches to alcoholism overall metabolism of drugs. Biotransformation of treatment. Alcohol Health & Research World, 14, drugs that are actively metabolized by liver en- 144–153. zymes mainly depends on the rate of delivery of the REDMOND, D. E., JR., & KRYSTAL, J. H. (1984). Multiple drug to the liver. These may be flow-limited drugs, mechanisms of withdrawal from opioid drugs. Annual where the liver can transform as much drug as it Review of Neuroscience 7, 443–478. receives, or capacity-limited drugs, which have a SANDS, B. F., KNAPP,C.M.&DOMENIC, A. (1993). Medi- low liver-extraction ratio—their clearance (re- cal consequences of alcohol-drug interactions. Alcohol moval from the blood) primarily depends on the Health & Research World, 17, 316–320. rate of their metabolism by the liver. There are a number of factors other than the NICK E. GOEDERS drugs themselves that influence the speed and in- REVISED BY JILL LECTKA tensity of alcohol/drug interactions in the human body. These include the patient’s sex, weight, age, and race; the presence or absence of food in the DRUG INTERACTIONS AND ALCOHOL stomach; and history of alcohol intake. For exam- The term alcohol-drug interaction refers to the ple, the levels of alcohol dehydrogenase (ADH), a possibility that alcohol may alter the intensity of stomach enzyme that oxidizes alcohol to acetalde- the pharmacological effect of a drug, so that the hyde, are lower in women than in men; lower in overall actions of the combination of alcohol plus Asians than in Western Caucasians; and lower in drug are additive, potentiated, or antagonistic. alcoholics than in nonalcoholics. Elderly persons Such interactions can be divided into two broad are at greater risk of alcohol/drug interactions than categories—PHARMACOKINETIC and PHAR- younger adults, because they usually take more MACODYNAMIC. Pharmacokinetics are concerned prescription medications, are more likely to have a with the extent and rate of absorption of the drugs, serious illness, and show age-related changes in the their distribution within the body, binding to tis- absorption and clearance of certain medications. 438 DRUG INTERACTIONS AND ALCOHOL

With regard to stomach contents, food generally may contribute to either increased sensitivity or the slows the rate of alcohol absorption. Consequently, tolerance observed with alcohol-drug interactions. medications that increase the rate of gastric empty- Alcohol can affect drug pharmacokinetics by ing, such as erythromycin (Eryc, Ilotycin) or altering drug absorption from the alimentary tract. cisapride (Propulsid), enhance the rate of alcohol For example, diazepam (Valium) absorption is en- metabolism. hanced by the effects of alcohol on gastric empty- ing. Alcohol placed in the stomach at concentra- ALCOHOL-DRUG INTERACTIONS tions of 1 percent to 10 percent increases the absorption of pentobarbital, PHENOBARBITAL, and Alcohol-drug interactions are complex. The con- theophylline, whereas drugs such as DISULFIRAM sequences of using alcohol and drugs together vary and CAFFEINE decrease alcohol absorption by with the dosage of the drug; the amount of alcohol decreasing gastric emptying. Cimetidine consumed; the mode of administering the drug (Tagamet)—a drug used to treat stomach ulcers— (oral, intravenous, intramuscular, etc.); and the increases blood alcohol concentrations by inhibit- nature of the drug (anticonvulsant, vasodilator, ing ADH in the stomach and first-pass metabolism analgesic, etc.). The alcohol may alter the effects of of alcohol. Binding of a drug to plasma proteins will the drug; the drug may change the effects of alco- change the effective therapeutic level of the drug, hol; or both may occur. because when the drug is linked to the proteins, it is Alcohol-drug interactions are most important not available to act on the tissue. Alcohol itself and with drugs that have a steep DOSE-RESPONSE alcohol-induced liver disease cause a decreased CURVE and a small therapeutic ratio—so that small synthesis and release of such plasma proteins as quantitative changes at the target site of action lead albumin. The resulting hypoproteinemia can result to significant changes in drug action. In alcoholics, in decreased plasma-protein binding of such drugs changes in susceptibility to drugs are due to as quinidine (Quinidex), dapsone (DDS), changes in their rates of metabolism (pharmacoki- triamterene (Dyrenium), and fluorescein (Fluo- netics) and the adaptive and synergistic effects on rescite). Alcohol may also directly displace drugs their organs, such as the central nervous system from plasma proteins. (pharmacodynamics). The clinical interactions of The effects of alcohol on blood flow in the liver alcohol and drugs often appear paradoxical: Sensi- are controversial, although most recent reports sug- tivity to many drugs, especially sedatives and tran- gest an increase; this could be significant with re- quilizers, is strikingly increased when alcohol is spect to metabolism of flow-limited drugs. At present at the same time; however, alcoholics, when higher concentrations, alcohol can act as an organic abstinent, are tolerant to many drugs. These acute solvent and ‘‘fluidize’’ cellular membranes, which and chronic actions of alcohol have been attrib- may increase the uptake or diffusion of drugs into uted, respectively, to additive and adaptive re- the cell. sponses in the central nervous system (phar- macodynamic interactions). METABOLISM It is now recognized that alcohol can also inter- act with the cytochrome P450 drug-metabolizing Many alcohol-drug interactions occur at the system, binding to P450, being oxidized to acetal- level of actual metabolism. Ethanol (ethyl alco- dehyde by P450, increasing the content of P450, hol—common in wines and liquors) will compete and inducing (causing an increase in the activity with such other alcohols as METHANOL (methyl al- of) a unique isozyme of P450. Inhibition of drug cohol—called wood alcohol) or ethylene glycol oxidation when alcohol is present at the active site (antifreeze), for oxidation via alcohol dehydroge- of P450 is due to displacement of the drug by nase. In fact, treatment against poisoning by meth- alcohol and competition for metabolism; this in- anol or ethylene glycol involves the administration creases the half-life and circulating concentration of ethanol—as the competitive inhibitor—or the of drugs. Induction of P450 by chronic-alcohol addition of inhibitors of alcohol dehydrogenase treatment can result in the increased metabolism of such as pyrazole or 4-methylpyrazole. drugs, as long as alcohol is not present to compete As discussed above, the presence of alcohol will for oxidation. These pharmacokinetic interactions inhibit the oxidation of drugs by cytochrome P450. DRUG INTERACTIONS AND ALCOHOL 439

Alcohol has been shown to inhibit oxidation of such were increased in the presence of beer and wine, so representative drugs as aniline, pentobarbital the combination of alcohol plus diazepam pro- (Nembutal), benzphetamine (Didrex), benzpyrene, duced impaired tracking skills, increased nystag- aminopyrine, ethylmorphine, METHADONE, mus (nodding off), and impaired oculomotor (eye) meprobamate (Equanil, Miltown), phenytoin coordination, as compared to diazepam alone. (Dilantin), propranolol (Inderal), caffeine, tolbuta- Therapeutic doses of the tranquilizers diazepam or mide (Orinase), warfarin (Coumadin), phenothi- chlordiazepoxide (Librium) plus alcohol have been azine, BENZODIAZEPINE,CHLORDIAZEPOXIDE, consistently shown to produce impairment of many amitriptyline (Elavil), chlormethiazole, chlorpro- mental and psychomotor skills; EEG (electroen- mazine (Thorazine), isoniazid (INH), imipramine cephalogram) abnormalities could still be detected (Tofranil), dextropropoxyphene, triazolam sixteen hours after administration of fluorazepam (Halcion), industrial solvents, and acetaminophen in the presence of alcohol to volunteers. Alcohol (Tylenol). As this partial list indicates, oxidation of also decreases the rates of elimination of several many classes of drugs can be inhibited in the pres- benzodiazepines in humans. Phenothiazines and ence of alcohol; these include HYPNOTICS,OPIOIDS, alcohol compete for metabolism by P450, resulting psychotropic drugs, anticonvulsants, vasodilators, in the decreased clearance of chlorpromazine antidiabetics, anticoagulants, ANALGESICS, and an- (Thorazine), for example, and enhanced sedative tibacterials. Chronic consumption of alcohol in- effects, impaired coordination, and a severe poten- duces the P450 drug-metabolizing system, which tially fatal respiratory depression. Alcohol inhibits could increase oxidation of drugs in sober or absti- the metabolism of BARBITURATES, prolonging the nent alcoholics. Among the drugs that may be more time and increasing the concentration of these rapidly metabolized in abstinent alcoholics are eth- drugs in the bloodstream, so that central nervous oxycoumarin, ethylmorphine, aminopyrine, anti- system interactions are intensified. In humans, al- pyrine, pentobarbital, meprobamate, methadone, cohol doubles the half-life of pentobarbital; this is theophylline (Bronkodyl, Theo-Dur), tolbutamide, associated with a 10 to 50 percent lower concentra- propranolol, rifamycin, warfarin, acetaminophen, tion of barbiturate sufficient to cause death by res- phenytoin, deoxycline, and ethanol itself. An im- piratory depression, as compared to the lethal dose portant consequence of this ability of chronic etha- in the absence of alcohol. Striking pharmacokinetic nol intake to increase drug-clearance rates is that and pharmacodynamic interactions occur between the effective therapeutic level of a drug will be alcohol and the hypnotic drug CHLORAL HY- different in an abstaining alcoholic than it is in a DRATE—the so-called Mickey Finn or knockout nondrinker. This metabolic drug tolerance can per- drops. Alcohol inhibition of MORPHINE metabolism sist for several days to weeks after alcohol WITH- increases morphine accumulation, potentiates cen- DRAWAL. tral nervous system actions, and increases the prob- ability of death. PHARMACODYNAMIC IMPLICATIONS OTHER CONSEQUENCES These alcohol-drug pharmacokinetic interac- tions can have major pharmacodynamic implica- Pharmacokinetic interactions between alcohol tions. Some examples include the following: The and drugs also have important toxicological and concurrent administration of alcohol plus am- carcinogenic consequences. The metabolism of cer- itriptyline (Elavil) to healthy volunteers resulted in tain drugs produces reactive metabolites; these are an increase in the plasma-free concentration of much more toxic than the parent compound. The amitriptyline, since the alcohol inhibited drug induction of P450, especially the P4502E1 isozyme clearance. Other pharmacodynamic interactions by alcohol, results in the increased activation of between alcohol and amitriptyline include de- drugs and SOLVENTS to toxic reactive intermedi- creased driving skills (and other psychomotor ates—such as carbon tetrachloride, acetamino- skills), greater than additive loss of righting reflex, phen, benzene, halothane, enflurane, COCAINE, and unexpected blackouts, and even death. Laisi et al. isoniazid. In a similar manner, procarcinogens— (1979) showed that plasma levels of the tranquil- such as aflatoxins, nitrosamines, and aniline izer DIAZEPAM (Valium—an antianxiety drug) dyes—are activated to carcinogenic metabolites af- 440 DRUG INTERDICTION ter alcohol induction of P4502E1. Since P4202E1 seize them, together with the transport and/or per- is localized largely in the perivenous zone of the sons that carry them on their way from the produc- liver cell, the increased activation of these toxins ing country to the importing country; many of the (and alcohol itself) after induction by alcohol may SEIZURES occur just as the drugs are brought across explain the preferential perivenous toxicity of sev- the border. The principal drugs subject to U.S. eral hepatotoxins, carcinogens, and alcohol itself. interdiction are COCAINE and MARIJUANA, both of which are imported primarily from Latin America. (SEE ALSO: Complications; Drug Interaction and The United States, uniquely among modern the Brain; Drug Metabolism; Psychomotor Effects nations, has made interdiction a significant part of of Alcohol and Drugs) its effort to control the supply of drugs, at least for cocaine and marijuana, since about 1975. In addi- BIBLIOGRAPHY tion to other federal agencies, it has involved the military in this effort. Though interdictors have BEERS, M. H., & BERKOW, R. (Eds.) (1999). The Merck seized large quantities of drugs, there are still nu- manual of diagnosis and therapy, 17th ed. merous questions about the effectiveness of the Whitehouse Station, NJ: Merck Research Laborato- program as a method of reducing the use of drugs, ries. particularly cocaine. DEITRICH, R. A., & PETERSEN, D. R. (1981). Interaction of ethanol with other drugs. In B. Tabakoff, P. B. GOALS Sutker, and C. L. Randall (Eds.). Medical and social aspects of alcohol abuse. New York; Plenum Press. Interdiction has two general goals. The primary HARDMAN,J.G.,&LIMBIRD, L. E. (Eds.) (1996). Good- one is to reduce the consumption of specific drugs man and Gilman’s the pharmacological basis of ther- within the nation by making it more expensive and apeutics, 9th ed. New York: McGraw-Hill. risky for smugglers to conduct their business. Drug LAISI, U., ET AL. (1979). Pharmacokinetic and phar- seizures raise costs by increasing the amount that macodynamic interactions of diazepam with different has to be shipped in order to ensure that a given alcoholic beverages. European Journal of Clinical quantity will reach the market. Additionally, an Pharmacology, 16, 263–270. effective interdiction program will, among other LEARY, A., & MACDONALD, T. (2000). Interactions be- things, raise the probability that a courier is ar- tween alcohol and drugs. Edinburgh, UK: Royal Col- rested, thereby increasing the price smugglers have lege of Physicians of Edinburgh. to pay to those who undertake the task. These LIEBER, C. S. (1990). Interaction of ethanol with drugs, higher fees raise smugglers’ costs of doing business hepatotoxic agents, carcinogens and vitamins. Alcohol and thus the price they must charge their cus- and Alcholism, 25, 157–176. tomers, the importers. Finally, the increased costs lead to a higher retail price and serve to lower con- LIEBER, C. S. (1982). Medical disorders of alcoholism: Pathogenesis and treatment. Philadelphia: W. B. sumption of the drug. Saunders. At one time it was thought that interdiction could impose a physical limit on the quantity of MEDICAL ECONOMICS COMPANY. (1999). Physicians’ desk reference, 53rd edition. Montvale, NJ: Author. drugs available in this country. With a fixed supply available in the producing nations, each kilogram RUBIN, E., & LIEBER, C. S. (1971). Alcoholism, alcohol seized on its way to the United States would be one and drugs. Science, 172, 1097–1102. less kilogram available for consumption here. How- WILSON, B. A., SHANNON, M. T., & STANG, C. L. (Eds.) ever, this has not proven to be the case. It is now (1995). Nurses drug guide, 3rd ed. Norwalk, CT: generally accepted that production is expandable Appleton & Lange. and that increased seizures can be compensated for ARTHUR I. CEDERBAUM with increases in production, although farmers may REVISED BY REBECCA J. FREY have to receive higher prices to provide greater production. A second, more modest, general goal is to in- DRUG INTERDICTION The interdiction crease the difficulty of smuggling itself and to pro- of illicit drugs into the United States is the effort to vide suitable punishment. Smugglers, or at least the DRUG INTERDICTION 441

has led to a sharp rise in the share of the U.S. marijuana market served by domestic producers.

TECHNIQUES The techniques of interdiction inevitably mirror those of smugglers. Drugs enter the United States by air, land, and sea, by private vessel and com- mercial carrier. Interdiction must, if it is to have any substantial effect on the drug trade, act against all the modes of smuggling; otherwise smugglers will rely on the mode that is not subject to in- terdiction. Interdiction has three separate elements: moni- toring, detection and sorting, and pursuit and ap- prehension. For example, U.S. COAST GUARD ships supported by an extensive radar system patrol the Caribbean, which constitutes the major thorough- fare for smuggling from Latin America. The Coast Guard patrol vessels attempt to see, either directly or through radar, all ships moving along certain routes. This constitutes the monitoring activity. In one method of smuggling heroin, couriers swallow heroin-filled latex balloons before The interdictors must then sort, from all that traf- boarding commercial airlines. (Drug Enforcement fic, the relatively small number that are carrying Administration) illegal drugs. Finally, they must pursue the smug- glers that have been detected, arrest the personnel, and seize the drugs and the ship itself. The in- principals in smuggling organizations, are among terdiction system is as weak as its weakest compo- the most highly rewarded participants in the drug nent; for example, a system that has good pursuit trades. There is support for programs that conspic- capacities but is unable to sort smugglers from in- uously make their lives less easy and that subject nocents effectively will waste much of that pursuit capacity in chasing nonsmugglers. Similarly, good them to the risks of punishment. detection will lead to few captures without effective Three illegal drugs have traditionally dominated monitoring capabilities. imports: cocaine, HEROIN, and marijuana. Heroin The Coast Guard and Customs Service share is subject to only modest interdiction efforts be- primary responsibility for marine and air in- cause it is usually smuggled in conventional com- terdiction. The Coast Guard patrols more distant mercial cargo, or it is carried on (or within) the routes, with Customs having a greater role in the person of the smugglers who travel by commercial U.S. coastal zone. Both agencies also conduct in- traffic; seizures are made only in the course of terdiction against private planes, with Customs routine inspection of cargo and traffic. It is esti- having primary responsibility over the Mexican mated that ten tons of heroin are smuggled into the land border, a major trafficking area. The DEA United States each year, and seizures of more than expanded its air surveillance, having a fleet of ten kilograms are rare. The Drug Enforcement Ad- ninety-five aircraft in 2000. The Border Patrol, a ministration (DEA) reported that a total of 667 unit of the Immigration and Naturalization Service, kilograms of heroin had been seized in 1999, about has primary responsibility for the interdiction of the same amount seized in 1990. Cocaine and mar- drugs carried in cars or on persons crossing the land ijuana have been the primary targets of in- border. In the late 1990s, new technology, such as terdiction, although an effective program of in- x-ray machines that examine commercial vehicles, terdiction against Colombian maritime smuggling was installed at border stations in the Southwest. 442 DRUG INTERDICTION

Both Customs and the Border Patrol make many Florida, the other in Alameda, California. These seizures and arrests in the course of routine inspec- task forces coordinate transit zone activities, in- tion. For example, Customs may find a shipment of cluding the U.S.-Mexico land border and air and cocaine concealed inside a cargo container being maritime traffic along the borders and sea coasts. unloaded in the Miami port; the Border Patrol, in The U.S. Interdiction Coordinator is the Comman- the course of pursing illegal immigrants, might find dant of the U.S. Coast Guard. a ‘‘mule’’ (a person) carrying a backpack full of cocaine or heroin. Drugs are shipped in an amazing EVALUATION TECHNIQUES array of forms; for example, suspended in frozen fruit pulp being imported from Ecuador or in hol- Evaluation of the effectiveness of interdiction lowed lumber from Brazil. has been a vexed issue ever since the activity be- came prominent in the late 1970s. Very large quantities of drugs, particularly of cocaine, have MILITARY INVOLVEMENT been seized, but the size if such seizures has been For a variety of reasons, there was pressure cited both as evidence of success and of failure. It throughout the 1980s to increase the extent of mili- has been questioned whether more cocaine is being tary involvement in drug interdiction. The drug seized because interdictors are getting better at problem was viewed as a national crisis with an their job or because more cocaine is being shipped. important international element. The military was At a minimum, it would be desirable to express seen as having unique capabilities, both of equip- seizures as a fraction of total shipments (consump- ment and of training, to protect the borders. tion plus seizures), but, unfortunately, estimates of The military had been ambivalent about enter- consumption lack any systematic basis. Even ex- ing the drug interdiction arena to any significant pressed as a fraction of shipments, seizures are degree, seeing it as potentially corrupting and an clearly an inadequate measure of the effectiveness inappropriate diversion from its primary mission. of interdiction, since the program imposes two With the collapse of its principal strategic enemy, other costs on smugglers—namely, seizure of assets the Soviet Union, the U.S. military has become (e.g., boats, planes, real estate, and financial hold- more willing to play a major interdiction role. This ings) and the arrest and imprisonment of smugg- has been reflected in large increases to the military ling agents (e.g., crew members on ships, pilots, budgets to handle these new responsibilities. Cur- and couriers for financial transactions). rent law prohibits arrests by military personnel. Reuter et al. (1988) suggest that the most appro- Accordingly, military participation has been con- priate measure is a price increase in the smuggling fined to detection and monitoring rather than pur- sector of drug distribution. Effective interdiction suit and apprehension. should raise smugglers’ costs; the increase will be The U.S. Navy provides a number of ships for reflected in the difference between the price at interdiction patrols in both the Caribbean and the which smugglers purchase drugs in the producer Pacific, combining training with a useful mission. country (export price) and that at which they sell it The military runs the integrated radar and commu- in the importing country (import price). However, nication system that links the Customs Service, the the process cannot serve as an operational criterion Coast Guard, the Border Patrol, and other agencies. for any individual component of interdiction, since There have been no reports of significant problems prices are set in a national market serviced by all of corruption associated with the military role in modes and routes of smuggling. Anderberg (1992) drug interdiction, but relations between the mili- concluded that the available data supported only tary and the civilian law-enforcement agencies with inappropriate and/or inadequate measures of ef- primary jurisdiction have sometimes been strained, fectiveness, while any more cogent measure re- the result largely of differences in organizational quires data that are not available and are not likely cultures. to be readily obtained. With the proliferation of U.S. government units One negative consequence of interdiction identi- involved in interdiction, the need arose for coordi- fied by Reuter et al. (1988) has received little atten- nated command. The government has two Joint tion. By seizing drugs on their way from the source Inter-Agency Task Forces, one based in Key West, country, interdiction may actually increase export DRUG LAWS: FINANCIAL ANALYSIS IN ENFORCEMENT 443 demand for those drugs. As noted earlier, more Moreover, it is difficult to make smuggling very stringent interdiction has two effects; it raises risky when the nation is determined also to main- prices and thus reduces final demand in the United tain the free flow of commerce and traffic. Hun- States, but it also increases the amount that must dreds of millions of people enter the country each be shipped to meet a given consumption (because year; cargo imports also amount to hundreds of of a higher replacement rate). It appears that, millions of tons. Only a few hundred tons of cocaine based on reasonable assumptions about the cost need to be concealed in that mountain of goods and structure of the cocaine trade, the second effect has only a few thousand of those who enter need be in proven greater than the first. the smuggling business to ensure an adequate and modestly priced supply of cocaine. THE EFFECTIVENESS Interdiction has accounted for a significant por- OF INTERDICTION tion of federal government expenditures on drug control. By the end of the 1990s, many critics of the Interdiction clearly has had some important interdiction effort argued that these resources consequences for the drug trade in the United should be put into drug treatment programs and States. In contrast to the 1970s, little marijuana is other programs that could reduce the demand for now imported from Colombia, though that nation illegal drugs. Nevertheless, the U.S. government remains a low-cost producer. Successful in- has remained committed to interdiction operations. terdiction, particularly against marine traffic from Colombia, has imposed such high costs on Colum- (SEE ALSO: Border Management; Dogs in Drug De- bian imports that now both Mexican and U.S. pro- tection; Foreign Policy and Drugs; International ducers have come to dominate the U.S. market. Drug Supply Systems; Operation Intercept; U.S. Interdiction against Mexican-produced drugs is Government: The Organization of U.S. Drug Pol- more difficult and thus the import price of Mexican icy) marijuana is less than that of Colombian. For cocaine there is much less evidence of suc- BIBLIOGRAPHY cess, though interdictors have certainly forced changes in modes of smuggling. In the early 1980s ANDERBERG, M. (1992). Measures of effectiveness in drug much of the cocaine was brought up by private interdiction. Santa Monica, CA: The Rand Corpora- plane directly from Colombia, but now most of it tion. enters either by transshipment through MEXICO or OFFICE OF NATIONAL DRUG CONTROL POLICY. (1991). by commercial cargo. However, though interdictors What America’s users spend on illicit drugs. Washing- now seize a large share of all shipments, they have ton, D.C.: U.S. Government Printing Office. not managed to prevent a massive decline in the OFFICE OF NATIONAL DRUG CONTROL POLICY. (2000). landed price of the drug. Street prices of cocaine National Drug Control Strategy: 2000 Annual Re- and heroin have dropped dramatically since the port. Washington, D.C.: U.S. Government Printing early 1980s. Office. The reasons for this limited success are not hard REUTER, P., CRAWFORD,G.,&CAVE, J. (1988). Sealing to find. Smugglers defray the risks of getting caught the borders: The effects of increased military partici- by carrying across very large quantities, so that the pation in drug interdiction. Santa Monica, CA: The risks per unit smuggled are low. A pilot who Rand Corporation. charges 250,000 dollars for the risks (imprison- PETER REUTER ment, suffering injury or death in the course of REVISED BY FREDERICK K. GRITTNER landing) involved in bringing across a shipment of 250 kilograms is asking for only one dollar per gram, less than 1 percent of the retail price. Even if DRUG LAWS: FINANCIAL ANALYSIS interdictors make smuggling much more risky, so IN ENFORCEMENT The application of finan- that the pilot doubles the demand to 500,000 dol- cial investigative techniques to sophisticated forms lars, the higher fee still adds only another 1 percent of CRIME began decades ago in campaigns to bring to the retail price. underworld bosses to justice. They were charged 444 DRUG LAWS, PROSECUTIONOF not with the underlying offenses of bootlegging or proceeds of those transactions was welcome evi- extortion, but for reaping financial windfalls from dence. For one thing, it could tie their target to the activities that either were not federal offenses at the drug or other transactions that other evidence time or that prosecutors just could not prove. Be- showed they had planned or approved. Drug traf- ginning with the federal tax case against Al Capone fickers and other racketeers who never touch drugs in 1931, Treasury investigators had to find ways do touch, or otherwise control, the money that was around both the lack of federal laws proscribing exchanged for the drugs. Hundreds of criminals racketeering activity and the difficulties in catching have been sent to prison on the basis of financial underworld bosses for their offenses. The approach analyses tying large sums in question to the defen- was creative but simple: Internal Revenue agents dants and alleged criminal transactions. gathered evidence to prove that the racketeers As organized crime began to wane in national spent more income than they reported on their tax prominence in the 1970s, its place was quickly returns. The differential between what was re- taken by an amalgam of homegrown and foreign- ported and what the government alleged they based drug traffickers. Often just as smart and earned would establish that their target received insulated as Mafia bosses, drug traffickers were substantial amounts of unreported income. In an surprised to find themselves equally vulnerable to underworld without pay stubs and annual wage cases built on financial evidence. Passage of a num- statements, how did the government know what ber of federal drug reform laws (in 1970, 1978, the racketeers earned? To tax investigators, it was 1984, 1986, and 1988) added the remedy of asset simple: Show how much the person spent—or at forfeiture to the government’s arsenal of weapons. least the portion of income spent that could be In order to show that their targets acquired assets substantiated. with tainted funds that rendered them forfeitable, As Prohibition gave way to different forms of investigators resorted to the same financial investi- industrial racketeering, syndicated gambling, and gative techniques that had helped build criminal drug trafficking, federal agents grew more frus- tax cases against the same kinds of underworld trated over their poor showing against criminals leaders. who were developing increased sophistication. In- In the mid-1990s, virtually all federal enforce- vestigators turned more and more to financial anal- ment agencies provide some type of basic training ysis as an alternative. They reasoned that what in financial investigation, and several—such as the worked against Al Capone and his cohorts would Drug Enforcement Administration, Federal Bureau probably work against other high-profile racke- of Investigation, and Internal Revenue Service— teers too insulated by their underlings to be impli- have highly specialized programs at their acade- cated in syndicate transactions. mies. DEA and FBI, expert investigators and finan- Proving that individuals—whether they were cial analysts support major drug-trafficking cases Mafia bosses or Colombian drug importers— by providing evidence of unexplained income to received more income than they could substantiate prove the drug charges, and to tie the money to was easier said than done. Typically, there were no drug activity for the purpose of forfeiture. records that acted as a smoking gun by pointing directly to one large unreported sum of yearly in- (SEE ALSO: International Drug Supply Systems; come. Rather, evidence of unreported income was Money Laundering) gathered from a variety of sources and was traced to documented purchases that left a paper trail of CLIFFORD L. KARCHMER deposit slips, bank statements, advices, credit card REVISED BY FREDERICK K. GRITTNER receipts, and mortgages. As investigators soon came to find out, moreover, financial analyses fre- quently turned up large amounts of money in the DRUG LAWS, PROSECUTION OF Drug possession of people who recently had approved arrests in the United States involve a wide variety of plans for a lucrative drug deal or some other illegal controlled substances, including MARIJUANA,CO- transaction. CAINE,HEROIN,PHENCYCLIDINE (PCP), and others, For investigators struggling to tie drug traf- and a number of different charges, including pos- fickers to crimes they only planned, finding the session, dealing (selling), and conspiracy to sell. DRUG LAWS, PROSECUTIONOF 445

After arrest, the prosecutor, or district attorney, are filed by defense attorneys to determine whether exercises the discretion to choose among this broad the search that turned up the drugs was conducted range of legal options in deciding whether to bring in a legal manner. Rulings by the U.S. Supreme a charge and for what activity. Court provide wider latitude to officers who have Drug offenses can violate either federal or state secured a search warrant. laws. Since the majority of arrests are made by local Another important factor involves the level of law-enforcement officials, most defendants are cooperation provided by the defendant. The district charged in state courts. The cases received by fed- attorney often accepts a more lenient agreement for eral prosecutors, called U.S. attorneys, from such defendants who assist law-enforcement officers federal enforcement agencies as the Federal Bureau and/or testify in court concerning who sold them of Investigation (FBI) or the DRUG ENFORCEMENT the drugs they possessed or resold. These plea ADMINISTRATION (DEA), frequently involve more agreements allow the police to target other of- complex matters. However, the volume of federal fenders and also relieve the pressure on the courts. drug prosecutions rose in the 1990s, as tougher Plea bargaining does, however, raise serious ques- federal drug laws and sentencing provisions led tions in the public’s mind about the dangers of state prosecutors to refer these cases to federal ju- leniency; it raises other questions, among defen- risdiction. In addition, federal prosecutors have dants and their attorneys, about equity and fair- used the Racketeer Influenced and Corrupt Organi- ness. Additionally, narcotic officers and prosecu- zations Act (RICO) to prosecute drug traffickers tors often disagree about the outcome or the and to confiscate property used in drug enterprises. handling of a case. These differences are often me- The federalization of drug crimes has had a diated by task forces in which prosecutors with profound impact on the work of the federal courts specialized drug experience are assigned to work and the budget of the federal prison system. with a select group of narcotics officers. In determining what charges should be filed Generally less than 10 percent of drug cases go against the offender, the prosecutor looks to many to trial. In a trial the police officer is a witness in the factors: the criminal history of the defendant, the case brought by the prosecutor. By questioning the seriousness of the drug involved, and the quality of officer, the prosecutor, as lawyer for the state, the evidence. Most states give the district attorney elicits evidence designed to show that the defendant the discretion to charge an enhanced-penalty crime possessed or sold drugs. for a repeat offender. Ultimately the judge determines the actual sen- The vast majority of the cases lead to guilty tence. However, federal and state sentencing guide- pleas, through some form of plea bargaining be- lines limit the judge’s discretion. Many drug crimes tween the prosecutor and the defense attorney. In carry with them mandatory minimum sentences. these agreements, which must be approved by the But commonly in a plea agreement or after trial, the court, the defendant pleads guilty, often in return prosecutor can modify the severity of the sentence for a fine, court-ordered counseling, or a lessened by reducing the charge or by recommending that prison term. Repeat offenders face tougher agree- the court reduce the sentence. Across the country, ments. and even within large counties, great differences In deciding what plea to accept, prosecutors occur in sentencing and in sanction recommenda- consider many of the same factors they did when tions. they brought the original charges. A critical factor Participants in the criminal justice system recog- is the quality of the evidence. Many drug cases are nized that drug-related crimes should be addressed very easy to prove, because the defendant pur- in different ways. The emergence of drug courts in chased or sold the drugs directly to a police officer the 1990s signaled a new way of prosecuting drug or because a search warrant leads to the discovery offenders. Drug courts seek to reduce drug use and of drugs in an area controlled by the defendant. associated criminal behavior by retaining drug-in- District attorneys face much more difficult chal- volved offenders in treatment. Drug courts divert lenges in convicting suspects involved in compli- drug offenders from jail or prison and refer them to cated conspiracy charges such as those associated community treatment. Defendants who complete with the shipment or distribution of drugs. In many the program either have their charges dismissed or drug prosecutions, motions to suppress evidence probation sentences reduced. A 1994 federal law 446 DRUG METABOLISM authorizes the U.S. Attorney General to make lipid-soluble. This solubility permits them to easily grants to state and local governments to establish cross the membrane barrier. After absorption, or- drug courts. By 1999, 416 drug courts were operat- gans with plentiful blood-flow such as the brain, ing in the United States, with over 270 more in the liver, lungs, and kidneys are first exposed to the planning stages. These courts shift discretion from drug. Only highly lipid-soluble drugs can enter the the prosecutor and place it with the judge, who has brain by crossing the blood-brain barrier. broad discretion in a drug court. Drug concentration at the target organ is an Federal and state prosecutors have also used important index for therapy and generally has an asset forfeiture laws to attack drug traffickers. For- optimal range. The drug level can be raised by feiture laws authorize prosecutors to file civil law- increasing dose, or by more frequent administra- suits asking a court for permission to take property tion, but too high a level could cause toxicity. The from a criminal defendant that was either used in drug level at the target organ can also be lowered the crime or was the fruit of a criminal act. Accord- by elimination through the urine or by metabolic ing to Department of Justice statistics, over 28,000 steps that convert the drug to more water-soluble properties were seized in 1996, with a combined forms. Water-soluble metabolites are eliminated value of $1.264 billion. quickly in the urine. Most drugs given orally are Aside from civil forfeiture, prosecutors have also lipid-soluble enough to be reabsorbed in the kid- used non-criminal statutes and ordinances to at- neys and are eliminated only slowly in small tack drug crimes. For example, prosecutors may amounts in the unchanged form in urine (see Fig- use public nuisance laws, zoning laws and public ure 1). Therefore drug metabolism is an important health laws to remove drug offenders from property factor that controls drug levels in the body, because where drugs are being used and sold. Though the without the metabolic step the drug usually re- legal action is addressed at the landlord or property mains in the body or accumulates if it continues to owner, it has the effect of removing drug users and be taken. Drug metabolism is a biochemical process traffickers from apartments and houses. Increas- and involves enzymes; drugs are metabolized se- ingly, cities are condemning and destroying build- quentially or by parallel pathways to various prod- ings that have been used as crack houses and such. ucts called metabolites. Many enzymes have been identified and some are very specific for drugs or (SEE ALSO: Exclusionary Rule; Mandatory Sentenc- substrates, whereas others have broad or less strin- ing; Rockefeller Drug Law) gent structure requirements (see Table 1). Many factors can modify drug metabolism. Ge- netic factors or inherited deficiency of an enzyme BIBLIOGRAPHY could cause accumulation of certain drugs. In- O’MEARA,KELLY PATRICIA. (August 7,2000). When Feds creased levels and increased toxicity may be caused Say Seize and Desist. Insight on the News. by inhibition of drug metabolism by other concur- WHITE HOUSE OFFICE OF NATIONAL DRUG CONTROL POL- rently administered drugs. Decreased plasma levels ICY. (2000). National Drug Control Strategy: 2000 of drugs after repeated administration have been Annual Report. Washington, D.C.: U.S. Government observed and this is attributed to increased enzyme Printing Office. activity by a process called induction; auto- TONRY, M. (1997). President Clinton, mandatory mini- induction causes the increased metabolism of the mums, and disaffirmative action. Tikkun. Nov-Dec inducing drug and cross-induction refers to the 1997. accelerated metabolism of other drugs. West’s Encyclopedia of American Law. (1997). St. Paul: Westgroup. DRUG-METABOLIZING ENZYMES STEPHEN GOLDSMITH Drug-metabolizing enzymes change the chemi- cal nature of drugs by inserting oxygen, hydrogen, water, or small molecules such as amino acids and DRUG METABOLISM Most drugs are sugar molecules. The resulting metabolites may taken by mouth and, in order to be absorbed thus contain hydroxyl (the univalent group or ion through the stomach and intestine, they need to be OH), or hydrogenated or hydrolysis products, or be DRUG METABOLISM 447 conjugated with sugar or other functional groups. Many cytochrome P450 enzymes have been iso- By far the most commonly occurring metabolic step lated and characterized. With molecular biology is hydroxylation (the addition of oxygen) by the techniques, the genetic code DNA has been identi- enzyme oxygenase—and this will be discussed in fied for many cytochrome P450 enzymes. Among detail. these, two forms of cytochrome P450 are known to be deficient in certain individuals. In the mid- OXIDATION BY CYTOCHROME 1970s, a deficiency of the specific cytochrome P450 P450 MONOOXYGENASE called CYP2D6 was independently reported for sparteine (a labor-inducing or antiarrhythmic Oxygen is vital for living organisms, and enzy- drug) and for debrisoquine (an antihypertensive matic reactions involving this molecule for drug agent). Since then, more than thirty clinically use- metabolism are numerous and well characterized. ful drugs have been shown to be metabolized by Lipid-solubility is an important factor for absorp- this enzyme. The presence of this cytochrome P450 tion across the stomach and intestinal wall, and the in a population is polymorphic, that is, some people insertion of an oxygen atom to lipid-soluble com- lack this enzyme. A simple urine test using dex- pounds results in hydroxylated groups (-OH) that tromethorphan, a cough suppressant, is commonly are more water-soluble than the parent compound. used to identify the enzyme deficiency in a patient. The pioneering work on the oxygenation reaction Another cytochrome P450 deficiency involves me- involved the metabolism of BARBITURATES, a class tabolism of mephenytoin (CYP2C type) but not of centrally acting drugs very popular in the 1950s. many drugs are metabolized by this enzyme. The A long-acting barbiturate, PHENOBARBITAL, very frequency of both deficiencies were first established slowly hydroxylates compared to other barbitu- in Caucasians, and CYP2D6 deficiency was re- rates, such as hexobarbital, pentobarbital, and ported to be 7 percent while CYP2C deficiency was secobarbital. The oxygenation enzymes involved 3 percent. Because of the presence of deficient sub- were named cytochrome P450 after the wavelength jects, the population data do not show a bell- of light they absorbed in a spectrophotometer shaped normal distribution curve but rather a bi- (Peak at 450 nanometers [nm]). Subcellular frac- modal distribution indicating polymorphism. tionation by centrifugation yielded ‘‘microsome’’ pellets which contained the cytochrome P450 ac- ALCOHOL METABOLISM tivity. Cytochrome P450 is most abundant in the liver and, before the full nature of cytochrome ALCOHOL (ethanol) metabolism predominantly P450 was known, the microsomal oxygenase was involves a type of oxidation called dehydrogenation often called mixed function oxidase. Cytochrome (loss of hydrogen) and the subcellular fraction P450 consists of a superfamily of enzymes, with called the mitochondria is the major site. Alcohol is wide and sometimes overlapping substrate specific- metabolized by successive dehydrogenation steps, ities. first producing acetaldehyde and secondly acetic Although phenobarbital is no longer widely used acid. The major organ for alcohol metabolism is the for therapeutic purposes, because of better alterna- liver. In heavy drinkers, however, alcohol induces tives with fewer side effects, it is an excellent in- another enzyme, cytochrome P450, and the pro- ducer of certain forms of cytochrome P450 (e.g., portion of the metabolism by this route compared the CYP2B family). to dehydrogenation becomes significant. Because Other important drugs of abuse that are metab- the amount of alcohol ingested must be relatively olized by cytochrome P450 include BENZODIAZE- large to have pharmacological effects, the amount PINES (tranquilizers such as DIAZEPAM [Valium], of alcohol exceeds the amount of enzyme, resulting CHLORDIAZEPOXIDE, alprazolam, triazolam) and in saturation. Acetaldehyde, in general, is toxic OPIOIDS (CODEINE, oxycodone, dextromethor- because it is reactive and forms a covalent bond phan). The first group of drugs is hydroxylated and with proteins. When the enzyme that metabolizes the second group is metabolized by loss of a carbon acetaldehyde to acetic acid is inhibited by an exter- moiety (dealkylation). The dealkylation reactions nal agent, acetalaldehyde levels increase and pro- are also mediated by cytochrome P450. duce a toxic syndrome. Inhibitions of this enzyme, 448 DRUG POLICY FOUNDATION (DPF)

such as DISULFIRAM (Antabuse), have been used in was very common before the introduction of the the treatment of excessive drinking. child-proof cap for drug containers in the 1960s. The difficulty of treating the salicylate poisoning TRANSFERASES FOR CONJUGATION/ was due to saturable glycine conjugation; the SYNTHETIC REACTIONS higher the dose, the slower was the rate of elimina- tion. Products formed by oxidation (e.g., by cyto- Acetylation is also important for the detoxifica- chrome P450) are often metabolized further with tion of carcinogens containing aromatic amines. small molecules such as glucuronic acid (glucose One form of N-acetyltransferase is polymorphic metabolite) or sulphate. The enzymes involved are (people have different forms of the enzyme). The called transferases. Other conjugation reactions are frequency of slow acetylator types shows a large carried out by transferases linking glutathione with variation ranging from 5 to 10 percent in Oriental reactive metabolic products, acetyl-CoA with an and Inuit (Eskimo) subjects to as high as 50 per- amino group on aromatic rings, and glycine (amino cent in Caucasians and Africans. Drugs affected by acid) with salicylate. this genetic polymorphism are isoniazid (antituber- Glucuronic-acid conjugations are catalyzed by culosis), procainamide (antiarrhythmic), sulfa- various forms of glucuronyl transferases, which ap- methazole (antibiotic), and other amine-containing pear to have broad substrate specificity. Glucuro- compounds. nide conjugates are very water-soluble and likely to be quickly eliminated via the kidneys. The plasma CLINICAL CONSEQUENCES levels of glucuronide conjugates of oxazepam (a benzodiazepine antianxiety agent) are, however, Drug metabolites are often pharmacologically several-fold higher than the parent drug. This can less active than the parent drug. Yet some biotrans- be explained by the relatively rapid process of con- formation products are active—for example CO- jugation reaction in the liver compared to the renal DEINE is relatively inactive but is metabolized to the (kidney) clearance of its conjugate. Because glucu- active drug MORPHINE. Because the liver is the ronidation involves a glucose metabolite, which is major site of drug metabolism, acute or chronic abundant, the transferase would not reach satura- liver diseases would alter drug metabolism, result- tion easily, although sulfo-transferase utilizes the ing in prolonged drug half-lives and effects. sulphate which is of limited supply via foods and can be saturated. For example, ACETAMINOPHEN (SEE ALSO: Complications: Liver (Alcohol); Drug (Tylenol) forms both glucuronide and sulfate con- Interaction and the Brain; Drug Interactions and jugates and the sulfation process can be easily satu- Alcohol ) rated after a few tablets. Glutathione conjugation is very important as a BIBLIOGRAPHY detoxification pathway. Unstable or reactive me- JAKOBY, W. B. (Ed.). (1980). Enzymatic basis of tabolites formed from other metabolic reactions detoxication. New York: Academic Press. may cause toxicity by reacting with so-called KALOW, W. (Ed.). (1992). Pharmacogenetics of drug me- house-keeping enzymes in the body. Glutathione, tabolism. New York: Pergamon. because of its abundance, can react with these me- KATSUNG, B. G. (Ed.). (1992). Basic and clinical phar- tabolites instead and acts as a scavenger; an epox- macology, 5th edition. Norwalk, CT: Appleton & ide whose formation is catalyzed by cytochrome Lange. P450 is detoxified, except in an overdose case, by glutathione transferase. Some epoxide intermedi- TED INABA ary metabolites have been shown to be ultimate REVISED BY MARY CARVLIN carcinogens, and detoxification by gluthione would be beneficial. Glycine is the smallest amino acid and the conju- DRUG POLICY FOUNDATION (DPF) gation with salicylic acid (formed rapidly from as- The Drug Policy Foundation (4455 Connecticut pirin) is the major metabolic pathway for salicy- Avenue, NW, Washington, DC) is a not-for-profit lates. Salicylate poisoning, especially in children, organization established to stimulate debate about DRUG POLICY FOUNDATION (DPF) 449 drug policy in the United States and to oppose the testing when appropriate; and decriminalizing current ‘‘war on drugs’’ approach. It favors shifting marijuana. from policies emphasizing law enforcement and The organization also administers a grant pro- drug prohibition to ones that either legalize drug gram that distributes approximately $1.5 million use entirely or at least medicalize the distribution of every year to drug policy reform efforts both within certain drugs. Founded in 1986 by Arnold the United States and abroad. Since its inception, Trebach, a lawyer and professor at American Uni- the grant program has given over $4 million to 306 versity in Washington, DC, the foundation reports drug policy reform organizations worldwide. TLC– that its membership had grown to more than DPF awards its grants to a wide variety of drug 24,000 by 2000. The Drug Policy Foundation has reform organizations, including those that special- merged with the Lindesmith Center to become the ize in criminal justice, drug policy, harm reduction, Lindesmith Center-Drug Policy Foundation and is medical marijuana, methadone maintenance, and now known by the acronym TLC-DPF. The syringe exchange. TLC–DPF provides three types Lindesmith Center is located in New York City of funding: project, general support, and technical (400 West 59th Street). The Lindesmith Center— assistance. For example, in 1998, Positive Health Drug Policy Foundation’s director is Dr. Ethan Project (PHP), a Manhattan-based harm reduction Nadelmann, who has taught at Harvard and agency, received a grant to design and implement Princeton Universities and lectured throughout the New York City’s first syringe-exchange media cam- world on drug policy and international law enforce- paign. Using a social marketing firm, PHP designed ment. an ad promoting the value and availability of sy- In 2000 the board members included Ira Glas- ringe-exchange services in New York City which was placed inside 1,140 N.Y.C. subway cars for 1 ser, executive director of the American Civil month. The primary goals of the campaign were to Liberties Union; Dr. Jocelyn Elders, former Sur- educate drug users about the importance of HIV geon General of the United States; Nicholas Pas- prevention through syringe exchange and thereby tore, fellow at the Criminal Justice Policy Founda- increase the use of syringe exchange throughout the tion; Hon. Robert W. Sweet, Senior Judge for the city. Southern District of New York and Danny The Lindesmith Center Library, located in New Sugarman, manager of the musical group the Doors York City, is a rapidly growing library housing one and author of several books. of the largest collections on drugs and drug policy The guiding principle of the organization is in the world. It contains over 10,000 books, re- harm reduction, an alternative approach to drug ports, government documents, periodicals, videos, policy and treatment that focuses on minimizing and articles from the U.S. and abroad as well as the adverse effects of both drug use and drug prohi- in-depth collections on drug-related policies in bition. TLC-DPF is deeply involved in educating Canada, Latin America, Great Britain, Germany, Americans and others about alternatives to current the Netherlands, Switzerland, and Australia. The drug policies on issues ranging from marijuana and library also maintains an online library at adolescent drug use to illicit drug addiction, the www.lindesmith.org/library/lib.html. spread of infectious diseases, policing drug markets The Drug Policy Foundation sponsors annual and alternatives to incarceration. It promotes drug conferences, at which speakers discuss their per- policies based on common sense, science, public spectives on current drug policy, and has enlisted in health and human rights. Particular attention is its cause many individuals prominent in public life. focused on analyzing the experiences of foreign For example, the Thirteenth Annual Conference on countries in reducing drug-related harms. International Drug Reform was held in Washing- TLC–DPF’s policy priorities are predicated on ton, D.C. in May 2000. the premise that the current drug war is excessive Aside from advocating public policy, the foun- and ineffective in creating a safer or healthier soci- dation has a legal affairs office that uses the court ety. The policy areas include: improving drug edu- system to promote change. For example, the office cation and prevention, especially for young people; serves as counsel in a federal class action lawsuit on ending civil asset forfeiture; shifting current prac- behalf of California physicians and patients to en- tices away from drug testing toward impairment join the federal government from penalizing doc- 450 DRUG RESPONSE tors who recommend medical marijuana to seri- the various laboratory procedures that are used to ously ill patients. The foundation also serves as a combat these problems will be examined. consultant to county and state agencies in Califor- nia to design procedures by which seriously ill peo- DRUG PROPERTIES: ABSORPTION, ple can safely obtain and use medical marijuana. DISTRIBUTION, AND The organization publishes a bi-monthly news- ELIMINATION PHASES letter. The Drug Policy Letter, and the Drug Policy Foundation Press publishes books and papers that Detection of a drug depends largely on its ab- support viewpoints of the foundation. The DPF sorption, distribution, and elimination properties. also receives support from several other founda- There are various routes of drug administration; tions not ordinarily associated with the advocacy of oral (e.g., drinking ALCOHOL or swallowing pills), drug legalization, such as the John D. and Cather- intravenous (e.g., HEROIN injected into a vein) and ine T. MacArthur Foundation. A major contributor inhalation (e.g., smoking MARIJUANA; snorting CO- since 1992 has been the Open Society Foundation, CAINE; sniffing GLUE). Drugs taken orally are usu- a charitable organization that receives its funding ally the slowest to be absorbed (i.e. the speed at from the financier George Soros. which the drug reaches the brain and other body organs) whereas intravenous and inhalation routes result in the fastest absorption. Once the absorbed (SEE ALSO: Prevention Movement; Policy Alterna- tives) drug enters the blood stream it is rapidly distrib- uted to the various tissues in the body. The amount of drug stored depends on the nature of the drug, BIBLIOGRAPHY the quantity, duration of ingestion, the tissue hold- THE LINDESMITH CENTER-DRUG POLICY FOUNDATION WEB ing the drug and the frequency of use. SITE. (2000). www.dpf.org. Some drugs are fat-soluble and are deposited in fat tissues. For example, 9-TETRAHYDRO- JEROME H. JAFFE CANNABINOL (THC), the active ingredient in mari- REVISED BY FREDERICK K. GRITTNER juana, is highly fat-soluble, resulting in rapid re- ductions in blood levels as the drug is being distrib- uted to the various tissues. Blood levels of 9-THC DRUG RESPONSE See Causes of Sub- peak and start to decline in half the time it takes to stance Abuse: Drug Effects and Biological Re- smoke a marijuana ‘‘joint.’’ Concentrations are sponses known to fall by almost 90 per cent in the first hour. Depending on the amount of drug stored in the fat tissues, detection may be possible in the urine for DRUG TESTING METHODS AND CLIN- many days after last use. There are cases where ICAL INTERPRETATIONS OF TEST RE- marijuana metabolites have been detected for as SULTS As interest increases in employment-re- long as sixty days after last use, since small lated drug testing, the technologies and the amounts from fat go back into blood and appear in interpretive skills of analysts continue to evolve. the urine. Ethanol or ethyl alcohol (the beverage Although recent literature indicates that significant alcohol) is not fat-soluble but is distributed in the refinements and modifications to drug testing tech- total body water. Since blood is mostly made up of nology have been made, the complexity of drug water, the presence of alcohol is easier to detect effects is so great that many problems exist in than fat-soluble drugs like 9-THC. interpretation of the test results. The most frequent The ‘‘absorption’’ and ‘‘distribution’’ phases are problems that confront the toxicology laboratory followed by an ‘‘elimination’’ phase. The liver is the relate to developing technology that can determine major detoxification centre in the body where the how much and when the drug was taken, how long drugs are metabolized as blood circulates through after use the tests are capable of showing positive this organ. The metabolites are then excreted into results, the causes and rates of false positive and the urine through the kidneys. At the same time, false negatives, and how tests can be ‘‘beaten’’ by drugs deposited in fat tissues are also slowly re- employees. These problems will be discussed and leased into the blood stream and metabolized. DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS 451

ever, this process may be speeded up. Therefore, great variation can be found in the half-lives of the same drug. Approximately six half-lives are required to eliminate 99 per cent of any drug. Because co- caine’s half-life is relatively short, averaging one hour, only six hours are needed for elimination of 99 per cent of the drug. On the other hand, co- caine’s metabolites have a longer half-life and can be detected for a considerably longer period of time through urine drug assays. Compared to cocaine, PHENOBARBITAL has a much longer half-life of 80-120 hours, so that at least 480 hours (or 20 days) are required to eliminate 99 per cent of the drug. Since there is much variation in the half-life A laboratory technician tests a urine sample for of different drugs and the absolute amount of drug the presence of drugs, 1986. (᭧ Ed Kashi/CORBIS) present can be very small, it is crucial that the appropriate body fluid for analysis is selected for testing. Drugs vary by their elimination half-life. An Ethanol is absorbed from the stomach by simple elimination half-life is the amount of time needed diffusion. Gastric absorption is fastest when strong for the drug level to fall by 50 percent. Every half- drinks, distilled spirits containing 40 to 50 percent life the drug level falls by 50 percent. Table 1 shows ethanol by volume are consumed. Dilute beverages, the impact of the half-life on the amount of drug such as beer (4-5% ethanol) or wine (11-12% eth- left in the body. At the end of 7 half-lives over 99 anol) are absorbed slowly. Alcohol is absorbed very percent of the drug will be eliminated from the rapidly from the small intestines. The essential ac- body. (See Table 2 for drug half-lives). The half- tion of food is to delay gastric emptying and thus life of a drug is heavily influenced by a variety of slow the absorption process. Typically, studies have factors including the individual’s age, sex, physical shown that peak BAC is reached between 30 min- condition as well as clinical status. A compromised utes and 90 minutes of consumption; earlier on an liver and concurrent presence of another disease or empty stomach and later on a full stomach. Once drug have the potential of enhancing the toxic ef- absorbed, ethanol rapidly diffuses throughout the fects of the drug by slowing down the elimination aqueous compartments of the body, going wherever process. Under different clinical conditions, how- water goes.

TABLE 1 Impact of Half-Life Amount of drug Amount of drug left in the body eliminated Start 100% 100%

End of 1st half-life 50.0% 50.0% End of 2nd half-life 25.0% 75.0% End of 3rd half-life 12.5% 87.5% End of 4th half-life 6.25% 93.75% End of 5th half-life 3.125% 96.87% End of 6th half-life 1.56% 98.44% End of 7th half-life 0.78% 99.22% 452 DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS

TABLE 2 Drug Half-Lives and Approximate Urine Detection Periods* Drug Half-life (t2) Detection period

Methamphetamine 12–34 hours 2–3 days Amphetamine (metabolite of 7–34 hours methamphetamine) Heroin 60–90 minutes In minutes Morphine (metabolite of heroin) 1.3–6.7 hours Opiates positive for 2–4 days (EIA) 6-Mono-acetyl-morphine (MAM) 30 minutes Few hours Phencyclidine (PCP) 7–16 hours 2–3 days Cocaine 0.5–1.5 hours Few hours Benzoylecgonine (metabolite of 5–7 hours 3–5 days cocaine) 9-Tetrahydrocannabinol 14–38 hours 90% fall in 1 hour (blood) 9-Tetrahydrocannabinoic acid Depending on use, (marijuana metabolite in urine) few days to many weeks Benzodiazepines Few hours to days days to weeks, depending on half- life Diazepam 15–40 hours 2 weeks Flunitrazepam (rohypnol) 9–25 hours 0.2% excreted unchanged! Methadone 15–40 hours In chronic patients ~22–24 hours Barbiturate (phenobarbital) 35–120 hours 1–2 weeks after last use Alcohol (ethanol) Blood levels fall by an average of 1.5 12 hours 4–5 mmol/L/hour depending on the (15–18 mg/100 mL)/hour peak blood level. Urine typically positive for an additional 1–2 hour. Gamma-hydroxybutyrate 0.3–1.0 hour Less than 12 hours (GHB)

*The detection period is very much dose-dependent. The larger the dose, the longer the period the drug/metabolite can be detected in the urine

Absorption, distribution into different tissues kinetics, i.e., it is largely independent of alcohol and elimination are dynamic processes and take concentration in the blood and its levels decline place simultaneously. The rate of removal of etha- almost linearly over time. The implication of this is nol from the body is the sum of the rates of excre- that BAC falls at a constant rate over time. In social tion in urine, breath and sweat, and the rate of the drinkers it is from 0.015 to 0.018 percent (15 mg/ metabolism in the liver and other tissues. In hu- 100mL to 18 mg/100mL) per hour and in heavy mans, alcohol metabolism follows a ‘‘zero’’ order drinkers it is typically between 0.018 and 0.025 DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS 453 percent (18mg/100mL to 25mg/100mL) per hour. Clinical Effects. Drugs that manifest abuse In the alcoholic patient, the elimination rate is gen- potential and impair behavior such that job per- erally higher. In forensic calculations, a rate of formance can be affected are prime candidates for 0.015 percent (15mg/100mL) per hour is usually testing or monitoring in the workplace. Alcohol and used. In our studies we have found 0.018 percent cocaine are examples of this. (18mg/100mL) per hour to be the average rate of Analytical Methods. A false positive finding metabolism. The larger the dose of alcohol given, can have a serious impact on the livelihood of the the longer the duration of the measurable blood person being tested. Therefore, special attention alcohol concentration. needs to be paid to the testing methods. Ideally the analytical method should be specific for the drug SELECTION OF DRUGS TO being tested (i.e., no false positive), easy and inex- BE TESTED pensive to perform. Confirmation methods should also be readily available. Availability of technical A number of different criteria can be applied to and scientific expertise to perform the tests is also the drug(s) or category of drugs that should be essential. tested or monitored. Drug availability, clinical ef- Interpretation of the analytical results also needs fects and robustness of the analytical method(s) to be carefully considered as even a normal diet can used for analysis are probably the most important. result in a positive drug identification. For exam- Availability. Prescription patterns of psycho- ple, poppy seed ingestion can result in a true posi- active and other drugs vary from place to place and tive analytical result (OPIATES, like heroin, are de- country to country. Abuse of BENZODIAZEPINE ni- rived from the poppy plant PAPAVER SONIFERUM) trazepam is common in Europe but almost un- but it is a false positive for drug use. Some ethnic known in North America, since it is not sold here. diets may also lead to these confounding problems, The psychoactive chemical CATHINON (cathine), as when food containing poppy seeds is eaten dur- the active ingredient in the leaves of the KHAT ing Ramadan. plant, is chewed in northeast Africa, is not a prob- What should be analyzed? Ideally the analysis lem in North America. CODEINE,anOPIOID avail- should look for the parent drug rather than its able in Canada as OVER-THE-COUNTER prepara- metabolite, although this may not always be possi- tions, is sold only by prescription in the United ble as some drugs are very rapidly metabolized States. (e.g., heroin metabolism to MORPHINE). Sensitivity A wide availability of ‘‘legal’’ STIMULANTS poses of the analytical procedure should be dictated by an interesting problem since they are a common the drugs’ psychoactive pharmacological proper- finding in accident victims. A study carried out by ties. If the drug is shown to be devoid of abuse the U.S. National Transportation Safety Board potential then its detection beyond the time of from October 1987 to September 1988 showed that pharmacological activity, although important in over-the-counter stimulants—such as ephedrine, the clinical management of the patient, does not pseudoephedrine and phenylpropanolamine— necessarily serve a useful purpose for a workplace were commonly found among drivers killed in drug screening programme. heavy truck accidents. Amongst the eight States The guidelines developed by the NATIONAL that participated in this safety study almost all AM- INSTITUTE ON DRUG ABUSE in April 1988, address PHETAMINE use was in the California region. Simi- five ‘‘illegal’’ drugs: marijuana, PHENCYCLIDENE, lar findings are also reported from emergency AMPHETAMINE, cocaine and heroin. Rapid screen- rooms over the past five years as well as from ing methods that allowed for ‘‘mass screening’’ admissions in a trauma unit due to motor-vehicle were available at that time, as were the confirma- accidents. All this suggest that drug use varies not tion methods for these five drugs. Mood altering only from place to place but also region to region substances such as benzodiazepines, BARBITURATES within a given country. and some stimulants such as antihistamines are at Thus, the selection of a drug to be tested and present excluded from these regulations in the monitored, appropriate for one country and place, United States. This is probably due to the wide may not necessarily be appropriate for another availability of these drugs as medications within country. the general population and the technological re- 454 DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS quirements for screening and monitoring of these twenty minutes after drinking but high values for drugs. as long as forty-five minutes have been reported. As of the early 1990s, all existing technologies TYPES OF TESTING: BLOOD, URINE, are limited in terms of determining how much or AND HAIR SPECIMENS when the drug was consumed. Blood and saliva concentrations reflect the cur- Blood and urine are the most commonly used rent blood alcohol concentration, but generally a biological fluids in the analysis for drugs other than blood sample is used in hospitals to access the alcohol. Blood, obtained by an invasive procedure, patient in the casualty wards. In programmes re- is available only in small quantities and drug con- quiring monitoring of alcohol use, urine is probably centration levels in blood are typically low. Urine is the sample of choice. Urine alcohol concentration, the preferred sample of choice as it is available in which represents the average blood alcohol concen- larger volumes, contains the metabolite and re- tration between voiding, has the potential of being quires less invasive procedures in its collection. ‘‘positive’’ while the blood may be ‘‘negative.’’ Both sampling procedures, however, are limited in their ability as they only determine the absolute MEASURING IMPAIRMENT amount of drug present in the fluid being exam- ined. This quantity is dependent upon the amount Except for alcohol, the degree to which a person of the drug used, when it was last used, as well as is influenced or impaired by a drug at the time of the half-life of the drug. the test cannot be determined from test results Recently, hair samples have been used to detect alone. Correlations between positive blood levels drug use. A number of technical problems must be and degree of impairment are usually stronger than correlations between urine levels and degree of im- overcome before hair can be used as a definitive pairment; however, neither blood nor urine tests proof of drug use. Hair treatment and environmen- are sufficiently accurate to indicate impairment tal absorption are but two of the many concerns even at high levels of concentration. Human studies and problems that have been cited. An advisory using marijuana and cocaine have shown that a committee of the Society of Forensic Toxicology ‘‘perceived high’’ is reached after the drug concen- has recently reported that ‘‘The committee con- tration has peaked in the blood. Generally, blood cluded that, because of these deficiencies, results of can only show positive results for a short time after HAIR ANALYSIS alone do not constitute sufficient drug consumption, whereas urine can be positive evidence of drug use for application in the for a few days to weeks after last use. For example, workplace.’’ metabolites of 9-THC (active ingredient in mari- Various body fluids such as sweat, saliva, blood, juana) that are lipid-soluble can be detected in the urine and breath, have been used for alcohol analy- urine from a few days to many weeks, depending on sis. Breath, though not a body fluid, is commonly the drug-habit of the user. Excretion of the drug in used by law enforcement authorities. Although a urine and its concentrations are also affected by number of variables can effect breath/blood ratio, a several factors, such as dilution and pH (acidity) of 2100:1 alveolar breath/blood conversion ratio has the urine. I have seen many cases where a strong, been used and accepted for use with positive urine sample for CANNABINOIDS was found BREATHALYZERS. Breath-testing equipment cali- in the morning, a borderline positive in the after- brated with a blood:breath conversion factor of noon, followed by a strong positive the next morn- 2100 consistently underestimate actual BLOOD ing; I have also seen similar cases with respect to ALCOHOL CONCENTRATIONS (BAC). Accuracy of phenobarbital. breath analysis results is subject to various instru- A positive urine test cannot reveal the form in ments and biological factors. Potential errors in which the drug was originally taken—or when and breath analysis can also be caused by the presence how much was taken. For example, CRACK-co- of residual alcohol in the mouth. Immediately after caine, impure cocaine powder or cocaine paste drinking there is enough alcohol vapour in the (which can be smoked, inhaled, injected or mouth to give artificially high concentrations on chewed) all give the same result in the urine test. breath analysis. Generally this effect disappears The consumption of poppy seeds has been reported DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS 455 to give positive results for opiate use, because some of 40mg/100mL. In Canada there are also two seeds contain traces of opiates and some have been limits: 50mg/100mL and 80mg/100mL. BAC lev- known to be contaminated with OPIUM derivatives. els between 50mg/100mL and 80mg/100mL call Similarly, consumption of herbal COCA tea has re- for suspension of driving privileges but above sulted in positive results for cocaine use. These 80mg/100mL are subject to criminal charges. diverse incidences illustrate the difficulties involved in measuring impairment using urine results. URINE TESTING METHODS The problem of interpreting urine-test results is one of the major bases of concern for restricting Urine is the most commonly used fluid for drug their use in the employment setting. Even the effec- screening. The methods most commonly used in tiveness of preemployment drug-screening tests, toxicology laboratories are: immunoassay, chroma- due to the difficulties in interpretation is being tographic and chromatography coupled with mass questioned. Based on a study of 2,229 pre- employ- spectrometry. These methods vary considerably ment drug screening tests and follow-up, one group with respect to their sensitivity and reliability. of researchers have come to the following conclu- Thin-layer chromatography is least expensive, gas sion ‘‘our findings raise the possibility that a chromatography coupled with mass spectrometry preemployment drug screening may be decreas- (GC/MS), which is considered as nearly perfect or ingly effective in predicting adverse outcomes asso- ‘‘gold standard’’, is the most expensive. Table 2 ciated with marijuana use after the first year of summarizes the various methods. employment’’. They make a similar comment Immunoassays (EIA, EMIT, FPIA, CEDIA about cocaine. and KIMS). Immunoassay methods are used for There is no threshold for alcohol effects on per- preliminary screening (i.e., initial screening). Since formance or motor- vehicle-accident risk. Although these methods are based on an antibody-antigen the effects of alcohol on impairment and crash risk reaction, small amounts of the drug or metabo- appear more dramatically above 80mg/100mL, a lite(s) can be detected. Antibodies specific to a par- review of literature would suggest that impairment ticular drug are produced by injecting laboratory may be observed at levels as low as 15mg/100mL. animals with the drug. These antibodies are then It is not possible to specify a blood alcohol concen- tagged with markers such as an enzyme (enzyme tration level above which all drivers are dangerous immunoassay, EIA), a radio isotope (radioimmu- and below which they are safe or at ‘‘normal’’ risk. noassay, RIA) or a fluorescence (fluorescence polar- An author of a major literature review on the be- ization immunoassay, FPIA) label. Reagents con- havioral effects of alcohol concluded that ‘‘that al- taining these labelled antibodies can then be cohol sensitivity can vary from time to time, person introduced into urine samples, and if the specific to person, and situation to situation, the setting of a drug against which the antibody was made is pres- ‘‘safe’’ BAC will always be arbitrary, being based ent, a reaction will occur. RIA is the oldest immu- on a low, but a non-zero, incidence of effects below noassay method used to detect drugs. The major that level’’ and ‘‘the most striking feature to emerge drawback of this method is that it requires a sepa- from any review of the effects of alcohol on behav- ration step and generates radioactive waste. RIA iour is the marked lack of agreement between au- also requires special equipment to measure radio- thors, amounting, in many instances, to direct con- activity. tradiction. This is especially true for the effects of Typically, immunoassays are designed for a smaller dose.’’ class of drugs. Thus, their specificity (the ability to ‘‘Legal’’ BAC levels differ in different countries. detect the presence of a specific drug) is not very Some even have more than one legal limit over good, since substances that have similar chemical which the driver of a vehicle is considered as ‘‘im- structures will ‘‘cross react’’ and give a false posi- paired’’. Some European countries have 50mg/ tive reaction. For example, the immunoassay 100ml others have 80mg/100ml as their legal lim- method for cannabinoids was developed to detect its. In the United States, the legal limits vary from the carboxylic acid metabolite of 9-THC. Yet, 80mg/100mL to 100mg/100mL in different states, there is a suggestion in the literature that some but employees who are regulated by the U. S. De- nonsteroidal anti-inflammatory drugs, such as partment of Transportation have a BAC legal limit ibuprofen (a nonprescription drug in the U. S. and 456 DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS

Canada) and naproxyn give random or sporadic time and under the right conditions, the single ink false positive results for cannabinoids. Cough- spot would separate into many different com- syrup codeine will also give a positive reaction for pounds (spots) of different colours (blue ink is a the morphine (a metabolic product of heroin use) mixture of many dyes). This process, where a mix- immunoassay and many antihistamines that are ture of substances is separated in a stationary me- available over-the-counter may yield positive reac- dium (filter paper), is called chromatography. The tions for amphetamines. While some reagent man- types of chromatographic processes used in the ufacturers claim to have overcome many of these analysis of drugs include thin-layer, gas, and liquid cross-reactivity problems, confirmation by a non- chromatography as well as a combination of gas or immunoassay method is very important. liquid chromatography with mass spectrometry. Urine test kits, designed to detect drugs, have Of the several chromatographic methods, thin been available in North America for the past few layer Chromatography (TLC) is the one most simi- years. More recently, single and multiple test im- lar to the ink separation example mentioned above. munoassay kits designed for home and on-site test- This method requires extensive sample preparation ing have also been introduced. These kits generally and technical expertise on the part of the analyst, carry a cautionary disclaimer that positive test re- but it is inexpensive and very powerful if used sults must be confirmed by the reference GC/MS properly. With the exception of Cannabis, which method. When used in the non-laboratory environ- requires separate sample preparation, a large num- ment, they are prone to procedural inaccuracies, poor quality control, abuse and misinterpretations. ber of drugs (e.g., cocaine, amphetamine, codeine Therefore, these kits should be used with great and morphine) can be screened at the same time. caution. The risk of labelling a person with a false By combining different TLC systems, a high degree positive is high without the accompanying confir- of specificity can be obtained, although the training matory analysis. Table 3 summarizes the advan- of the analyst is crucial because of the subjectivity tages and disadvantages of immunoassay testing. involved in interpreting the results. To identify pos- Chromatographic methods. Separation of a itive TLC ‘‘spots,’’ the technologist looks for the mixture is the main outcome of the chromato- drugs and or its metabolite pattern, often by spray- graphic method. For illustrative purposes, if one ing with reagents that react to form different colors were to put a drop of ink on a blotting paper and with different drugs. The trained technologist can hold the tip of the paper in water, one would ob- comfortably identify more than forty different serve the water rise in the paper. After a period of drugs.

TABLE 3 Common Drug-Testing Methods

1. Immunoassays Enzyme immunoassay (EIA) Enzyme-multiplied immunoassay technique (EMIT) Fluorescence polarization immunoassay (FPIA) Radio immunoassay (RIA) Kinetic interaction of microparticles in solution (KIMS) Cloned enzyme donor immunoassay (CEDIA) Rapid slide tests (point-of-care testing) 2. Chromatographic Methods Thin-layer chromatography (TLC) Liquid chromatography (HPLC) Gas chromatography (GC) 3. Chromatography/Mass Spectrometry Gas chromatography/mass spectrometry (GC/MS) Liquid chromatography/mass spectrometry (HPLC/MS) DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS 457

Similar to TLC, gas chromatography (GC) re- ogies. GC physically separates (chromatographs or quires extensive sample preparation. In GC, the purifies) the compound, and MS fragments it so sample to be analyzed is introduced via a syringe that a fingerprint of the chemical (drug) can be into a narrow bore (capillary) column which sits in obtained. Although sample preparation is exten- an oven. The column, which typically contains a sive, when the methods are used together the com- liquid adsorbed onto an inert surface, is flushed bination is regarded as the ‘‘gold standard’’ by with a carrier gas such as helium or nitrogen. (GC is most authorities. This combination is sensitive i.e., also sometimes referred to as gas-liquid chroma- can detect low levels, is specific, and can identify all tography (GLC). In a properly set up GC system, a types of drugs in any body fluid. Furthermore, mixture of substances introduced into the carrier assay sensitivity can be enhanced by treating the gas is volatilized, and the individual components of test substance with reagents. When coupled with the mixture migrate through the column at differ- MS, HPLC/MS is the method of choice for sub- ent speeds. Detection takes place at the end of the stances that are difficult to volatilize (e.g. steroids). heated column and is generally a destructive pro- Given the higher costs associated with CG/MS, cess. Very often the substance to be analyzed is urine samples are usually tested in batches for ‘‘derivatized’’ to make it volatile or change its chro- broad classes of drugs by immunoassays and posi- matographic characteristics. tive screens are later subjected to confirmation by In contrast to GC, high pressure liquid chroma- this more expensive technique. tography (HPLC) a liquid under high pressure is Table 4 gives a summary of the advantages and used to flush the column rather than a gas. Typi- disadvantages of each method of chromatographic cally, the column operates at room or slightly above drug testing and Table 5 compares all the methods room temperature. This method is generally used of testing. The initial minimal immunoassay and for substances that are difficult to volatilize (e.g., GC/MS (cut-off) levels for five drugs or classes of STEROIDS) or are heat labile (e.g., benzodiaze- drugs as suggested by the U.S. National Institute of pines). Drug Abuse, are listed in Table 6. Gas chromatography/mass spectrometry(GC/ Procedures for alcohol testing. Since the in- MS) is a combination of two sophisticated technol- troduction of the micro method for alcohol analysis

TABLE 4 Advantages and Disadvantages of Immunoassays

Advantages 1. Screening tests can be done quickly because automation and batch processing are possible. 2. Technologists doing routine clinical chemistry testing can be easily trained. 3. Detection limits are low and can be tailored to meet the program screening requirements. For example, lower detection thresholds can be raised to eliminate positives due to passive inhalation of marijuana smoke. 4. Immunoassays are relatively inexpensive, although the single-test kits can be very expensive when quality assurance and quality control samples are included. 5. Immunoassays do not require a specialized laboratory. Most clinical laboratories have automated instruments to do the procedures. Disadvantages 1. Although the tests are useful for detecting classes of drugs, specificity for individual drugs is weak. 2. Since the antibody is generated from laboratory animals, there can be a lot-to-lot or batch-to-batch variation in the antibody reagents. 3. Results must be confirmed by another nonimmunoassay method. 4. A radioactive isotope is used in RIA that requires compliance with special licensing procedures, use of gamma counters to measure radioactivity, and disposal of the radioactive waste. 5. Only a single drug can be tested for at one time. 458 DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS

TABLE 5 Summary of Chromatographic Methods

Advantages All the chromatographic methods are specific and sensitive and can screen a large number of drugs at the same time. TLC Negligible capital outlay is needed. GC The procedure can be automated. HPLC Of the chromatographic procedures, this has the easiest sample preparation requirements. The procedure can be automated. GC/MS This is the “gold standard” test. Computerized identification of fingerprint patterns makes identification easy. The procedure can be automated. This is currently the preferred method for defense in the legal system. Disadvantages All chromatographic methods are labor-intensive and require highly trained staff. Although the chromatographic methods are specific, confirmation is still desirable. TLC Interpretation is subjective, hence, training and experience in interpretation capabilities of the technologist are crucial. HPLC or GC Equipment costs are high, ranging between $25,000 to $60,000, depending on the type of detector and automation selected (1994 $) GC/MS Equipment costs are the highest, ranging from $120,000 to $2000,000, depending on the the degree of sophistication required (1994 $). Due to the complexity of the instrument, highly trained operators and technologists are required.

TABLE 6 Cut-off Levels for Initial and Confirmatory Testsa Test Initial Test Confirmatory Test

THC metaboliteb 100 ng/mL 15 ng/mL Cocaine metabolitesc 300 ng/mL 150 ng/mL Opiate metabolitesd 2000 ng/mL Morphine 300 ng/mL Codeine 300 ng/mL Phencyclidine (PCP) 25 ng/mL 25 ng/mL Amphetamines 1000 ng/mL Amphetamine 500 ng/mL Methamphetamine 500 ng/mL Alcohol 10 mg/100 mL 10 mg/100 mL aApril 1988, National Institute of Drug Abuse (NIDA) Guidelines, SAMHSA 1998. bTHC metabolite is 11-nor-delta-9 THC carboxylic acid. cCocaine metabolite is benzoylecgonine. d25 ng/mL if immunoassay is specific for free morphine. DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS 459 in blood by Widmark in 1922, many new methods INTERPRETATIONS OF and modifications have been introduced. The distil- TEST RESULTS lation/oxidation methods are generally nonspecific False negatives. A positive or negative result for alcohol (ethanol), whereas biochemical meth- is highly dependent on the sensitivity of the drug ods (spectrophotometric) using alcohol dehydroge- detection method. A false negative occurs when the nase (ADH) obtained from yeast and the gas chro- drug is present but is not found because the detec- matographic method that are currently used are tion limit of the method used is too high or the specific for ethanol. The radiative attenuation en- absolute quantity of the drug in the specimen is ergy technique and those using alcohol oxidase method are non-specific and will detect not only too low. ethanol but also other alcohols. The recently intro- Large amounts of fluids consumed prior to ob- duced alcohol dipstick based on the ADH enzyme taining a sample for analysis can affect detection of system is not only specific for ethanol, but also drugs in urine samples. Under conditions of di- sensitive and does not require instrumentation. It lution, although the absolute amount of drug or can be used for the detection of ethanol in all body metabolite excreted maybe the same over a period fluids and can provide semi-quantitative results in of time, the final concentration per millilitre will be ranges of pharmacological-toxicological interest. reduced and may give a false negative result. Acid- Alcohol dipsticks are being used in a number of ity levels in the urine may also affect the excretion laboratories as a screening device. of the drug into the urine. In some cases elimination Breath can be analyzed by using a variety of is enhanced, whereas in other cases, the drug is instruments. Most of the instruments used today reabsorbed. detect ethanol by using thermal conductivity, col- Several measures can be used to decrease the orimetry, fuel cell, infrared or gas chromatography. likelihood of obtaining a false negative result. First, Typically in most countries, local statutes define sensitivity of the method can be enhanced by ana- the instrument and method that can be used for lyzing for the drugs’ metabolites. Heroin use, for evidenciary purposes. A variety of breathalyser in- example, is determined by the presence of its me- struments ranging in costs from $100 to $1000 are tabolite, morphine. Increasing the specimen vol- available to do the test. These instruments are com- ume used for analysis or treating it with chemicals pact and portable. Canadian law enforcement au- can also make laboratory methods more sensitive. thorities use the breathalyser ‘‘Alert’’ which can Studies have shown that a 5mg dose of Valium᭨ is give a ‘‘pass’’ or ‘‘fail’’ result as a roadside alcohol- usually detected for three to four days; however, screening device. The ‘‘failed’’ person is generally when these improved methods are utilized, sensi- subjected to a ‘‘Borkenstein’’ breathalyser to mea- tivity can be increased, such that, the same dose sure the BAC before any charges are brought. Many can be detected for up to 20 days. One important devices are available to preserve the breath sample drawback of such high sensitivities is, that esti- for later analysis if a breathalyser is not available mates of when the drug was taken are far less immediately. In forensic laboratories, gas chroma- accurate. tography (North America) or biochemical proce- False positives. A false positive occurs when dures (many European countries) are used to ana- results show that the drug is present, when in fact it lyze biological samples. is not. False-positive tests are obtained if an inter- Blood samples that cannot be analyzed soon af- fering drug or substance is present in the biological ter collection should have sodium fluoride (NaF) fluid and it cross-reacts with the reagents. An ex- added as a preservative. Alcohol dehydrogenase ample of this is Daypro (oxaprozin) will give a false (ADH), the enzyme responsible for the oxidation of positive for benzodiazepines. Other substances may alcohol, is also present in the red blood cell and will have a metabolite that will give a positive reaction. slowly metabolise the alcohol, causing its concen- An example of this is Selegiline, an antiparkinson tration to drop if the preservative is not added. drug, which has amphetamine as one of its metabo- Large amounts of alcohol can be produced in-vitro lites. Although this would be analytically a true in the urine samples of diabetic patients if samples positive, it is a false positive from a drug abuse are not processed immediately or properly pre- perspective. As discussed in the previous section on served. immunoassay, an initially positive test based on an 460 DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS

TABLE 7 Comparison of All Testing Methods EMIT RIA TLC GC GC/MS FPIA HPLC

Ease of sample preparation X X X Less highly trained technologists X X required Limited equipment required X X X Low detection limits X X X X X Adjustable lower threshold X X Highly specific and sensitive X X X Computerized identification possible X Screen for several drugs at a time X X X Procedure can be automated X X X X Special atomic energy license X required Confirmation of results required X X X X Interpretation is subjective X immunoassay technique should always be con- specimen inspection by substituting clean urine. firmed with an nonimmunoassay method. A con- For example, a company in Florida sells lyophilized firmed positive finding only implies that the urine (freeze dried) clean urine samples through newspa- sample contains the detected drug and nothing per and magazine advertisements. Hiding condoms more. containing ‘‘clean’’ urine on the body or inside the At times false positives are attributable to in- vagina is another common trick. gested substances such as allergy medications. Some have substituted apple juice and tea in Some authors have suggested that employees sub- samples for analysis. Patients are known to add ject to drug screening refrain from using popular everything from bleach, liquid soap, eye-drops, and over-the-counter medications, such as Alka-Seltzer many other household products, hoping that their Plus and Sudafed, because they have caused false- drug use will be masked. Others may hide a mask- positives. Some natural substances such as herbal ing substance under their fingernails and release it teas and poppy seeds can also give positive re- into the urine specimen. Another method is to poke sponses to screens. These may be analytically true a small hole into the container with a pin so that the positives but need to be distinguished from those sample leaks out by the time it reaches the labora- due to illegal drug use. In some instances, false- tory. positives have been due to mistakes or sabotage of Since addition of table salt (NaCl) or bleach to the chain of custody for urine samples. the urine is a common practice, many laboratories routinely test for Na and Cl in the urine. Liquid soap and crystalline drain cleaners that are strong COMMON ADULTERATION METHODS alkaline products containing sodium hydroxide The method of switching ‘‘clean’’ urine for (NaOH) are also used to adulterate the urine sam- ‘‘dirty’’ urine; resubmitting one’s own or urine that ple. These contaminators can be detected by check- is provided by someone else are the most common ing for high levels of pH in the urine sample. ways to fool the drug screening system. A number In-vivo alkalizing or acidifying the urine pH can of entrepreneurs have attempted to bypass urine- also change the excretion pattern of some drugs DRUG TESTING METHODS AND CLINICAL INTERPRETATIONS OF TEST RESULTS 461 including amphetamines, barbiturates and phency- SUMMARY AND CONCLUSION clidine (PCP). In this paper, major issues related to drug testing Water-loading (drinking large amounts of water are discussed. For example, drug-testing tech- prior to voiding) poses an interesting challenge to niques measure drug presence but are not sophisti- testing laboratories. Specific gravity has been used cated enough to measure impairment from drug to detect dilution; however, the measurement range use. It is also very difficult to determine the route of is limited so it is not yet useful. Creatinine levels on drug administration, quantity, frequency, or when random urine samples appear to be a promising the drug was last taken. method for detection of water-loading. A number Selection of the drug to be tested should depend of adulteration methods are being advertised on the on the local availability of the drug, its abuse po- Internet. Invariably, one of the instructions for tential, and clinical effects, as well as the available adulteration is to drink copious amounts of fluids to analytical technology and expertise in testing and bring about in-vivo dilution or water loading. Some interpretation of the laboratory results. The most Internet sites even sell adulterants that can be sophisticated drug-testing approach, gas chroma- added to the urine. Typically these products either tography in combination with mass spectrometry, try to oxidise the drug present or try to change the is considered as a gold standard and thus utilized in pH of the urine to interfere with the analytical confirmatory testing. Typically GC/MS is preceded method. Most of the laboratories involved in drug by a rapid immunoassay method to eliminate the testing routinely test for the various adulterants. To majority of negative samples. detect resubmitted samples a ‘‘urine fingerprint- Despite the existence of sophisticated drug-test- ing’’ method using dietary components has been ing methods, incorrect test results can still occur. described. These can be due to the presence of interfering Drug users are very resourceful and their inge- substances or adulteration of the urine sample. Pa- nuity should not be underestimated. To reduce the tients have been known to adulterate urine samples opportunities for specimen contamination, some to avoid drug detection. A number of techniques workplaces require that employees provide a urine can be employed to reduce the likelihood of obtain- sample under direct supervision. Another tech- ing erroneous results, as well as detect adulterated nique used to detect any sample adulteration is to urine samples. [Parana ‘‘positive’’ drug finding can have a serious impact on the livelihood of an indi- take the temperature of the sample. In a study, we vidual, therefore the performance of these tests took the temperature of urine samples when taken should adhere to the strictest laboratory standards within one minute of voiding; it falls between of performance. Only qualified and experienced in- 36.5ЊC and 34 degrees Celsius, reflecting the inner dividuals with proper laboratory equipment should body core temperature. It is very difficult to achieve perform these analyses. Standards of laboratory this narrow temperature range by hiding a condom performance must meet local legal and forensic filled with urine under the armpit or adding water requirements. Access to the patient samples as well from a tap or toilet bowl to the urine sample. It is as laboratory records must be restricted in order to important that the temperature of the specimen be prevent tampering of samples and results. To measured immediately after the sample is taken, maintain confidentiality and assure proper inter- since it can drop rapidly. pretation of results, the results must be communi- cated only to the physician reviewing the case/pa- LABORATORY PROCEDURAL AND tient. Chain of custody and all documents SECURITY STANDARDS pertaining to the urine sample must be maintained so that they can be examined in case of a legal It is important that the laboratory drug testing challenge. Laboratory must have a complete record facility has qualified individuals who follow a spe- on quality control. Finally, specific initial and con- cific set of laboratory procedures and meet recom- firmatory testing requirements should be met. mended security standards. BHUSHAN M. KAPUR 462 DRUG TRAFFIC CONTROL

DRUG TRAFFIC CONTROL See Drug In- far-reaching problem—not only because of the vast terdiction numbers of people who suffer and die each year from the toxic effects of these drugs but also be- cause of the financial drain in terms of employee DRUG TRAFFICKING See International absenteeism as well as the staggering increases in Drug Supply Systems annual health-care costs. Prescription drugs are covered next, since more prescriptions are written for diazepam (Valium) and the related benzodazepines each year than for any other drug. DRUG TYPES There are many ways to clas- The illegal drugs are then discussed. Although sify drugs, depending on the purposes for the clas- the illicit use of heroin, cocaine, and other drugs sification. For example, a classification can be remains a major social, legal, financial and health based on the chemical properties of drugs and may problem in the United States today, the proportion actually disregard the effects the drugs have on the of the population physically dependent on these body, or it may be based on legal principles, such as drugs is actually relatively low when compared to legal versus illegal, or prescription versus over-the- the legal drugs listed above. Finally, it is important counter (prescription not needed). For purposes of to take into consideration the fact that individuals discussion and teaching, the various drugs that are often do not restrict their drug use only to drugs used and abused by humans for nonmedical pur- within a single category. Alcoholics typically smoke poses are usually grouped into several major cate- cigarettes and often use benzodiazepines as well. gories, each based on their pharmacological actions Heroin users also smoke and may consume alcohol and their subjective effects. Although the mecha- and other sedatives, as well as CANNABIS and stimu- nisms of action may vary among drugs within a lants in some instances. Multiple-drug use is, there- single category, the general subjective effects of the fore, a relatively common occurrence for those us- drugs are similar. ing legal and/or illegal drugs. The major categories include: (1) ethanol (ALCOHOL); (2) NICOTINE and tobacco: (3) central ETHANOL nervous system depressants (BARBITURATES, BENZODIAZEPINES); (4) central nervous system Although alcohol (ethyl alcohol, called ethanol) stimulants (AMPHETAMINES,COCAINE); has been in use since prehistory and worldwide (5) cannabinoids; (6) OPIODS (MORPHINE,HEROIN, throughout recorded history, it is generally ac- METHADONE); (7) psychedelics (LSD,MESCALINE); cepted that its therapeutic value is extremely lim- (8) INHALANTS (glue, nitrous oxide); ited and that chronic ALCOHOLISM is a major social (9) arylcyclohexylamines (PCP). Some categorizers and medical problem. Perhaps 65 percent of all might put cocaine and the amphetamines into sep- adults in the United States use alcohol occasionally. arate categories and group alcohol and the central Hundreds of thousands of individuals suffer and nervous system depressants together. Some might die each year, however, from complications associ- have a separate category for CAFFEINE; others, one ated with chronic alcoholism—and tens of thou- for ‘‘DESIGNER DRUGS’’ (such as MDMA), and refer sands of innocent individuals are injured or killed to them as entactogens. There might also be a each year in alcohol-related traffic ACCIDENTS. miscellaneous category, where drugs such as BETEL Therefore, alcoholism is a far-reaching problem, NUT,KAVA-KAVA,orNUTMEG would be included. affecting the lives of individuals who consume eth- Drugs from the various categories are described anol as well as those who do not. Although alcohol below in terms of their pharmacology, abuse, is considered by many people to be a stimulant DEPENDENCE, and WITHDRAWAL as well as their drug because it typically releases an individual’s toxicity. The legal and readily available drugs (al- latent behavioral inhibitions (i.e., through disinhi- cohol and tobacco) are described first because the bition), alcohol actually produces a powerful pri- worldwide use and abuse of these drugs is far more mary and continuous depression of the central ner- widespread than all the other categories of abused vous system similar to that seen with general drugs combined. The ill health associated with the anesthetics. In general, the effects of alcohol on the ongoing use of alcohol and tobacco has become a central nervous system are proportional to the DRUG TYPES 463

blood concentrations of the drug. Initially, MEMORY vous system depressant effects may result, in part, and the ability to concentrate decrease, and mood from general changes in the function of ion chan- swings become more evident. As the intoxication nels that occur when ethanol dissolves in lipid (fat) increases, so does the impairment of nervous func- membranes. Other research suggests that alcohol tion until a condition of general anesthesia is may interact with specific receptors—binding sites reached (‘‘passing out’’ or ‘‘sleeping it off’’). There associated with the inhibitory NEUROTRANSMITTER is little margin of safety, however; between an anes- GAMMA-AMINOBUTYRIC ACID (GABA), in a manner thetic close of ethanol and severe respiratory de- somewhat analogous to other central nervous sys- pression (unconsciousness or coma). tem depressants (e.g., benzodiazepines or barbitu- In chronic (long-term) alcoholism, brain dam- rates). Since an ethanol RECEPTOR site has not yet age, memory loss, sleep disturbances, psychoses, been conclusively identified, specific receptor AGO- and increased seizure susceptibility often occur. NISTS and ANTAGONISTS are not yet available for the Chronic alcoholism is also one of the major causes treatment of ethanol intoxication, WITHDRAWAL, of cardiomyopathy (heart disease) in the United and abstinence. The drug DISULFIRAM (Antabuse) States due to ethanol-induced, irreversible damage is sometimes used in the treatment of chronic to the heart muscle. Ethanol also stimulates the ALCOHOLISM, although it does not cure alcoholism. secretion of gastric acid in the stomach and can Rather, disulfiram interacts with ethanol to alter contribute to the production of ulcers of the stom- the intermediate metabolism of ethanol, resulting ach and gastrointestinal system. One of the primary in a five- to tenfold increase in plasma acetaldehyde metabolic products of ethanol is acetaldehyde. In concentrations. Those who drink while on di- chronic alcoholism, acetaldehyde can accumulate sulfiram experience the acetaldehyde syndrome— in the liver, resulting in hepatitis and cirrhosis of vasodilatation, headache, difficulty breathing, the liver. Finally, the long-term use of alcohol can nausea, vomiting, sweating, faintness, weakness, result in a state of PHYSICAL DEPENDENCE. With anti vertigo. Taking the drug helps persuade alco- relatively low levels of dependence, withdrawal holics to remain abstinent, since they realize that from alcohol may be associated with rather minor they cannot drink ethanol for at least three or four problems such as SLEEP disturbances, ANXIETY, days without provoking ill-effects. weakness, and mild tremors. In more severe depen- dence, the alcohol withdrawal syndrome includes NICOTINE AND TOBACCO more pronounced tremors, seizures, and DELIRIUM, as well as a number of other physiological and TOBACCO was first introduced to Europe by the psychological effects. In some cases, this with- crews that accompanied Columbus to the New drawal can be life-threatening. World, and by the middle of the nineteenth cen- Since alcohol has CROSS-TOLERANCE with other tury, tobacco use had become widespread. By the central nervous system (CNS) depressants (i.e., 1990s, almost 30 percent of the adults in the ethanol shares many of the same biological effects United States were still regular tobacco smokers. as other CNS depressants), benzodiazepines or bar- This relatively high use of tobacco continues de- biturates can be substituted for ethanol to success- spite the growing warnings that are based on a fully decrease the severity of the alcohol with- wealth of scientific evidence linking cigarette smok- drawal syndrome. Longer-acting benzodiazepines ing to numerous life-threatening health disorders, and related drugs can be used as an ethanol substi- including lung CANCER and heart disease. The con- tute, and the dose of the benzodiazepine can then stituents of tobacco smoke that most likely contrib- be gradually reduced over time to attenuate or pre- ute to these health problems include carbon mon- vent the occurrence of convulsions and other poten- oxide, NICOTINE, and ‘‘tar.’’ However, nicotine also tially life-threatening toxic reactions generally as- appears to be the primary component of tobacco sociated with alcohol withdrawal. smoke that promotes smoking. In regular cigarette As outlined above, the chronic use of ethanol can smokers, nicotine facilitates memory, reduces ag- result in a wide range of toxic effects on a variety of gression, and decreases weight gain. Each of these organ systems; however, the mechanisms through effects could, by itself, provide a rationale for con- which ethanol produces its varied effects are not tinued tobacco use since most individuals find in- clearly understood. The anesthetic or central ner- creased alertness and memory, decreased irritabil- 464 DRUG TYPES ity, and decreased weight gain to be somewhat barbiturates, benzodiazepines, and related drugs. pleasant or desirable; however, these effects may The shorter-acting barbiturates, such as pentobar- actually be secondary to the primary reinforcing bital (‘‘yellow jackets’’) or SECOBARBITAL (‘‘red effects of nicotine itself. Nicotine is self-adminis- devils’’), are usually preferred to the longer-acting tered by laboratory animals, and in laboratory set- drugs such as phenobarbital. Nonbarbiturates such tings, smokers report that the intravenous injection as MEPROBAMATE,GLUTETHAMIDE, methyprylon, of nicotine produces a pleasant feeling on its own. It METHAQUALONE (Quaalude) and some of the shor- is of interest to note, however, that nicotine is aver- ter-acting benzodiazepines are also abused. Pre- sive to nonsmokers, often resulting in dizziness, sumably, the quicker the onset of action for a par- nausea, and vomiting. TOLERANCE rapidly develops ticular central nervous system depressant, the to these unpleasant effects in tobacco smokers, better the ‘‘high.’’ however. There is no general rule that can be used to Although nicotine obviously binds to nicotinic predict the pattern of use of a central nervous sys- receptors associated with the neurotransmitter tem depressant for a given individual. Often there ACETYLCHOLINE, there is evidence that the rein- is a fine line between appropriate therapy for in- forcing or rewarding properties of nicotine may somnia or ANXIETY and drug dependence. Some result from an activation of ascending limbic neu- individuals exhibit cyclic patterns of use with gross rons, which release the neurotransmitter DOPAMINE intoxication for a few days interspersed with pe- (i.e., the mesocorticolimbic dopaminergic system). riods of abstinence. Other barbiturate or benzodi- Interestingly, this same system has been implicated azepine users maintain a chronic low level of intox- in the reinforcing properties of a variety of drugs, ication without observable signs of impairment including stimulants and opiates. As stated above, because of the development of tolerance to many of tobacco smoking has been associated with a wide the actions of these drugs. When higher doses are variety of serious health effects, including cancer used, however, the intoxication may resemble alco- and heart disease; however, the chances of develop- hol intoxication, with slurred speech, difficulty ing them decrease once smoking is terminated. Al- thinking, memory impairment, sluggish behavior, though some of the smoking-induced damage is and emotional instability. Withdrawal from chron- irreversible, the incidence rates for cancer and ic barbiturate or benzodiazepine use can also be heart disease gradually become more similar be- manifested to varying degrees. In the mildest form, tween smokers and nonsmokers the longer the the individual may only experience mild anxiety or smoker refrains from smoking. However, with- insomnia. With greater degrees of physical depen- drawal from tobacco smoking results in a with- dence, tremors and weakness may also be included. drawal syndrome that varies in intensity from indi- In severe withdrawal, delirium and tonic-clonic vidual to individual and often leads to a relapse of (epileptic) seizures may also be present. This severe smoking. This syndrome consists of cravings for withdrawal syndrome can be life-threatening. The tobacco, irritability, weight gain, difficulty concen- degree of severity of the withdrawal syndrome ap- trating, drowsiness, and sleep disturbances. The re- pears to be related to the pharmacokinetics of the cent introduction of nicotine-containing chewing drug used. Shorter-acting benzodiazepines and gum and transdermal patches have significantly barbiturates produce much more severe cases of helped to facilitate abstinence from smoking in a withdrawal than do the longer-acting drugs. There- number of individuals by delivering nicotine fore, in the case of severe withdrawal symptoms through a relatively less toxic route of administra- associated with the chronic use of a short-acting tion. drug, a longer-acting drug should be substituted. The dose of this drug can be gradually decreased so that the individual experiences a much milder and CENTRAL NERVOUS less threatening withdrawal. SYSTEM DEPRESSANTS Receptor-binding sites for benzodiazepines and In general, the incidence and prevalence of the barbiturates are part of a macromolecular complex nonmedical use of central nervous system depres- associated with chloride ion channels and the in- sants (approximately 6 to 8% of young adults) hibitory neurotransmitter GABA. The interaction exceeds that of the opioids. These drugs include the of these drugs with their distinct binding sites re- DRUG TYPES 465 sults in a facilitation of GABAergic neurotrans- ever, anxiety, irritability, and insomnia may be mission, producing an inhibitory effect on neuronal observed. impulse flow in the central nervous system. In nonlaboratory settings, heavy users of cocaine often take the drug in bouts or binges, only CENTRAL NERVOUS stopping when their supply runs out or they col- lapse from exhaustion. Immediately following the SYSTEM STIMULANTS intravenous administration or inhalation of co- Central nervous system stimulants include caf- caine, the individual experiences an intense plea- feine, cocaine, and amphetamine, although the use surable sensation known as a ‘‘rush’’ or ‘‘flash,’’ and abuse of amphetamines and cocaine represent followed by euphoria. Cocaine rapidly penetrates a much greater health risk, with deviation from into the brain to produce these effects, but then is social norms. rapidly redistributed to other tissues. In many Caffeine. Perhaps 80 percent of the world’s cases, the intense pleasure followed by the rapid population ingests caffeine in the form of TEA, decline in the cocaine-induced elevation of mood is COFFEE,COLA-flavored drinks, and CHOCOLATE.In sufficient for the individual to begin to immediately the central nervous system, caffeine decreases seek out and use more of the drug to prolong these drowsiness and fatigue and produces a more rapid pleasurable effects. Following the intranasal ad- and clearer flow of thought. With higher doses, ministration of cocaine, the pleasure is less intense however, nervousness, restlessness, insomnia, and and the decline in brain concentrations of the drug tremors may result. Cardiac and gastrointestinal progresses much more slowly, so that the craving disturbances may also be observed. Tolerance typi- for more of the drug is less pronounced. Cocaine and amphetamine appear to produce their reinforc- cally develops to the anxiety and dysphoria experi- ing or pleasurable effects through interactions with enced by some individuals. Some degree of PHYSI- the neurotransmitter dopamine, especially in CAL DEPENDENCE has, however, been associated limbic and cortical regions of the brain (i.e., within with the chronic consumption of caffeine. The most the mesocorticolimbic dopaminergic system). Both characteristic symptom of caffeine withdrawal is a cocaine and amphetamine block the reabsorption long throbbing headache, although fatigue, leth- of dopamine into the NEURONS, where it was re- argy, and some degree of anxiety are also common. leased, thereby prolonging the action of dopamine In general, the long-term consequences of chronic in the synapse—the space between nerve cells. Am- caffeine consumption are relatively minor. phetamine can also cause the direct release of dopamine from nerve cells and can inhibit the me- COCAINE AND AMPHETAMINE tabolism of the neurotransmitter. It is important to note, however, that every drug that augments the The problems associated with chronic cocaine action of dopamine does not produce pleasurable or and amphetamine use and withdrawal are much rewarding subjective effects. more serious than those associated with caffeine. The toxicity associated with cocaine or amphet- By the mid-1980s, more than 20 million people amine use can be quite severe; it is often unrelated had used cocaine in the United States. With the to the duration of use or to preexisting medical recent introduction of cocaine in the free alkaloid conditions in the individual. This potential for seri- base (‘‘FREEBASE’’ or ‘‘CRACK’’) form, there has ous toxic side effects is amplified by the fact that been a significant increase in cocaine-related medi- tolerance usually develops to the subjective feelings cal, economic, social, and legal problems. In the of the cocaine-induced rush and euphoria, but not free-base form, cocaine can be smoked, resulting in to some of the other central nervous system effects blood levels and brain concentrations of the drug of the drug (especially seizure susceptibility). Some that compare to those observed when the drug is of the more minor toxic reactions include dizziness, injected intravenously. In non-user subjects in a confusion, nausea, headache, sweating, and mild laboratory setting, the administration of cocaine or tremors. These symptoms are experienced by virtu- amphetamine produces an elevation of mood, an ally all cocaine and amphetamine users to some increase in energy and alertness, and a decrease in degree, as a result of stimulation of the sympathetic fatigue and boredom. In some individuals, how- nervous system. More serious reactions are also fre- 466 DRUG TYPES quently observed. These serious toxic effects can is similarly impaired, often much longer than the include irregular heartbeats, convulsions and sei- persistence of subjective effects. With higher doses, zures, heart attacks, liver failure, kidney failure, paranoia, hallucinations, and anxiety or panic may heart failure, respiratory depression, stroke, coma, be manifested. and death. The effects on the heart and cardiovas- Chronic marijuana users sometimes exhibit cular system can sometimes be treated with alpha what is called the AMOTIVATIONAL SYNDROME— and beta noradrenergic-receptor antagonists or which consists of apathy, impairment of judgment, calcium channel blockers, although even prompt and a loss of interest in personal appearance and medical attention is not always successful. The con- the pursuit of conventional goals. However, it is not vulsions can sometimes be controlled with clear whether this syndrome results from the use of diazepam (Valium); ventilation (oxygen) may be marijuana alone or from other factors. Although required for the respiratory depression. In addition this is seldom severe, 9-THC also produces a dose- to the effects described above for cocaine, amphet- related increase in heart rate. Tolerance does de- amine has been reported to produce direct and velop to the effects of marijuana, and in some coun- irreversible neuronal damage to dopaminergic neu- tries, regular users of HASHISH (a concentrated rons. A similar effect for cocaine has not yet been resin containing increased amounts of 9-THC) identified. consume quantities of the drug that would be toxic Psychiatric abnormalities resulting from chronic to most marijuana users in the United States. The central nervous system stimulant abuse can include withdrawal associated with the cessation of mari- anxiety, DEPRESSION,HALLUCINATIONS, and, in juana smoking is relatively mild—consisting of ir- some cases, a paranoid psychosis that is virtually ritability, restlessness, nervousness, insomnia, indistinguishable from a paranoid SCHIZOPHRENIC weight loss, chills, and increased body temperature. psychosis. A withdrawal syndrome is also observed following the abrupt cessation of chronic cocaine or OPIOIDS amphetamine use. This syndrome begins with ex- haustion during the ‘‘crash’’ phase and is followed The use of opioids in the United States is much by prolonged periods of anxiety, depression, an- less prevalent than reported for the other drugs hedonia (loss of pleasure), hyperphagia (gluttony), discussed above. For example, as of the 1990s, less and high craving for the drug. This craving may than 0.5 percent of young adults have reported persist for several weeks, depending on the individ- trying heroin at some time during their lives. There ual. The administration of dopaminergic agonists are three basic patterns of opioid use and depen- or tricyclic ANTIDEPRESSANTS may have some util- dence in the United States. The first group consti- ity in decreasing the severity of the withdrawal tutes the smallest percentage of opioid users— symptoms. those who initially began using morphinelike drugs medically, for the relief of PAIN. The second group began using illegal drugs through experimentation CANNABINOIDS and then progressed to chronic use and depen- Marijuana is probably still the most commonly dence. The third group represents physically ad- used illicit drug in the United States, with about 55 dicted individuals who eventually switched to oral percent of young adults reporting some experience METHADONE, obtained through organized treat- with the drug during their lifetimes. The active ment centers. Interestingly, the incidence of opioid ingredient in MARIJUANA is delta9-TETRAHY- addiction is greater among physicians, nurses, and DROCANNABINOL (9-THC), which exerts its most related health-care professionals (who have access prominent effects on the central nervous system to these drugs) than in any group with a compara- and the cardiovascular system. A marijuana ciga- ble educational background. In many instances rette that contains approximately 2 percent of the (but not all), those addicted either to heroin (usu- active ingredient can produce an increase in feel- ally purchased illegally on the street) or to metha- ings of well-being, euphoria, and relaxation when done (usually from treatment centers) are able to smoked; however, short-term memory can be im- hold jobs and raise a family. Opioids reduce pain, paired as is the ability to carry out goal-directed aggression, and sexual drives, so the use of these behavior. The ability to drive or operate machinery drugs is unlikely to induce crime. Those who can- DRUG TYPES 467 not afford opioids, those who like the ‘‘drug life,’’ ate-receptor agonists such as methadone are more and those who are unable or unwilling to hold a job, commonly prescribed. The symptoms associated resort to crime to support their drug habits. with methadone withdrawal are milder, although Opioid drugs produce their pharmacological ef- more protracted, than those observed with mor- fects by binding to opiate RECEPTORS. The eu- phine or heroin. Therefore, methadone therapy can phoria associated with the use of opioids results be gradually discontinued in some heroin-depen- from interactions of these drugs with the mu-opiate dent individuals. If the patient is unwilling or un- receptor, possibly resulting in the stimulation of able to withdraw from methadone, the individual mesocorticolimbic dopaminergic neuronal activity. can be maintained on methadone indefinitely. The rapid intravenous injection of morphine (or heroin, which is converted to morphine once it PSYCHEDELICS enters the brain) results in a warm flushing of the skin and sensations in the lower abdomen that are Psychedelics include drugs related to the in- often described as being similar in intensity and dolealkylamines, such as lysergic acid diethylamide quality to sexual orgasm. This initial rush (‘‘kick’’ (LSD), PSILOCYBIN, psilocin, DIMETHYL- or ‘‘thrill’’) lasts for about 45 seconds and is fol- TRYPTAMINE (DMT) and diethyltryptamine (DET), lowed by a high—described as a state of dreamy to the phenylethylamines, such as mescaline, or to indifference. Depending on the individual and the the phenylisopropylamines, such as 2,5-dime- social circumstances, good health and productive thoxy-4-methylamphetamine (DOM or ‘‘STP’’) as work are not incompatible with the regular use of well as 3,4-methylene-dioxyamphetamine (MDA) opioids. Tolerance can develop to the ANALGESIC, and 3,4-methylene-dioxymethamphetamine respiratory depressant, sedative, and reinforcing (MDMA or ‘‘ecstasy’’). The feature that distinguishes properties of opioids, but the degree and extent of these psychedelic agents from other classes of drugs tolerance depends largely on the pattern of use. is their capacity to reliably induce states of altered Desired analgesia can often be maintained through perception, thought, and feeling. There is a height- the intermittent use of morphine. Tolerance devel- ened awareness of sensory input accompanied by ops more rapidly with more continuous opioid ad- an enhanced sense of clarity, but a diminished ministration. control over what is experienced. The effects of The abrupt discontinuation of opioid use can LSD and related psychedelic drugs appear to be lead to a withdrawal syndrome that varies in degree mediated through a subclass of receptors associated and severity depending on the individual as well as with the inhibitory neurotransmitter serotonin (i.e., the particular opioid used. Watery eyes (lacrima- serotonin 5HT2 receptors). Immediately after the tion), a runny nose (rhinorrhea), yawning and administration of LSD, somatic symptoms such as sweating occur within twelve hours from the last dizziness, weakness and nausea are present, al- dose of the opioid. As the syndrome progresses, though euphoric effects usually predominate. dilated pupils, anorexia, gooseflesh (‘‘cold tur- Within two to three hours, visual perceptions be- key’’), restlessness, irritability, and tremor can de- come distorted; colors are heard and sounds may be velop. As the syndrome intensifies, weakness and seen. Vivid visual hallucinations are also often depression are pronounced, and nausea, vomiting, present. Many times this loss of control is diarrhea, and intestinal spasms are common. Mus- disconcerting to the individual, resulting in the cle cramps and spasms, including involuntary kick- need for structure—in the form of experienced ing movements (‘‘kicking the habit’’), are also companions during the ‘‘trip.’’ The entire syn- characteristic of opioid withdrawal; however, sei- drome begins to clear after about twelve hours. zures do not occur and the withdrawal syndrome is Little evidence exists for long-term changes in rarely life-threatening. Without treatment, the personality, beliefs, values, or behavior produced morphine-induced withdrawal syndrome usually by the drug. Tolerance rapidly develops to the be- runs its course within seven to ten days. Opiate- havioral effects of LSD after three or four daily receptor antagonists (e.g., NALOXONE) are con- doses of the drug. In general, however, the psyche- traindicated in opioid withdrawal, since these delic drugs do not give rise to patterns of continued drugs can precipitate a more severe withdrawal on use over extended periods. The use of these drugs is their own. Rather, longer-acting, less potent, opi- generally restricted to the occasional trip. With- 468 DRUG TYPES drawal phenomena are not observed after the tion may also occur. In higher doses, anesthesia, abrupt discontinuation of LSD-like drugs, and stupor, convulsions, and coma may appear. The deaths directly related to the pharmacological ef- typical high from a single dose can last four to six fects of LSD are unreported in humans—however, hours and is followed by a prolonged period of fatal ACCIDENTS and SUICIDES have occurred dur- ‘‘coming down.’’ ing periods of LSD intoxication. PCP and related compounds bind with high affinity to a number of distinct sites in the central INHALANTS nervous system, although it is not certain which site(s) is responsible for the primary pharmacologi- The intoxicating and euphorigenic properties of cal effects of these drugs. PCP binds to the sigma nitrous oxide and ethyl ether were well known even site, which also has a high affinity for some selected before their potential as anesthetics was recog- opioids, although the function of the sigma site is nized. Physicians, nurses and other health-care unknown. PCP blocks the cation channel (e.g., ם professionals have been known to inhale anesthetic Ca2 ) that is regulated by N-methyl-D-aspartate gases even though they have access to a wide vari- (NMDA), one type of receptor for excitatory amino ety of other drugs. Adolescents with restricted ac- acid neurotransmitters such as glutamate or aspar- cess to alcohol often resort to ‘‘glue sniffing’’ or the tate. PCP also blocks the reabsorption of the neuro- inhalation of vapors from substances with marked transmitter dopamine into the neurons, where it toxicity, such as gasoline, paint thinners, or other was released, resulting in a prolonged action of the industrial solvents. The alkyl nitrites (butyl, isobu- neurotransmitter, especially within the mesocor- tyl, and amyl) have been used as aphrodisiacs, ticolimbic dopaminergic neuronal system. since the inhalation of these agents is suggested to There appears to be some degree of tolerance to intensify and prolong orgasm. At least 12 percent the effects of PCP, and some chronic users of PCP of young adults have reported some experience with inhalants—however, fatal toxic reactions complain of cravings and difficulties with recent (usually due to cardiac arrhythmias) are often as- memory, thinking, and speech after discontinuing sociated with the inhalation of many of these drugs. the use of the drug. Personality changes can range Inhalation from a plastic bag can result in hypoxia from social withdrawal and isolation to severe anxi- (too little oxygen) as well as an extremely high ety, nervousness, and depression. Although the fre- concentration of vapor. Fluorinated hydrocarbons quency is uncertain, deaths due to direct toxicity, can produce cardiac arrhythmias and ischemia (lo- violent behavior, and accidents have been reported calized anemia). Chlorinated solvents depress heart following the use of PCP. PCP can also produce muscle (myocardial) contractility. Ketones can acute behavioral toxicity—consisting of intoxica- produce pulmonary (lung) hypertension. Neuro- tion, aggression, and confusion, as well as coma, logical impairment can also occur with a variety of convulsions, and psychoses. A PCP-induced psy- solvents. chosis can persist for several weeks following a single dose of the drug. ARYLCYCLOHEXYLAMINES (SEE ALSO: Addiction: Concepts and Definitions; Arylcyclohexylamines include phencyclidine Complications; Epidemiology of Drug Abuse; Na- (PCP or ‘‘angel dust’’) and related drugs that pos- tional Household Survey on Drug Abuse; Treat- sess central nervous system stimulant, central ner- ment) vous system depressant, hallucinogenic, and anal- gesic properties. These drugs (also known as BIBLIOGRAPHY dissociative anesthetics) are well absorbed follow- ing all routes of administration. With even small ANILINE,O.,&PITTS, F. N., JR. (1982). Phencyclidine doses, intoxication is produced, with associated (PCP): A review and perspectives. CRC Critical Re- staggering gait, slurred speech, and numbness in view of Toxicology, 10, 145–177. the extremities. PCP users may also exhibit sweat- BENOWITZ, N. L. (1988). Pharmacologic aspects of ciga- ing, catatonia, and a blank stare as well as hostile rette smoking and nicotine addiction. New England and bizarre behavior. Amnesia during the intoxica- Journal of Medicine, 319, 1318–1330. DRUNK DRIVING 469

BLOOM, F. E. (1989). Neurobiology of alcohol action and vention of the automobile in the 1880s. In 1904, alcoholism. Annual Review of Psychiatry, 8, 347– the Quarterly Journal on Inebriety editorialized 360. that ‘‘the precaution of railroad companies to have CLONINGER, C. R., DUNWIDDIE, S. H., & REICH,T. only total abstainers guide their engines will soon (1989). Epidemiology and genetics of alcoholism. An- extend to the owners of these new motor wagons . . . nual Review of Psychiatry, 8, 331–346. with the increased popularity of these wagons, acci- DEWEY, W. L. (1986). Cannabinoid pharmacology. dents of this kind will multiply rapidly.’’ By 1910, Pharmacology Review, 38, 151–178. drunk driving had already been codified as a mis- FREEDMAN, D. X. (1969). The psychopharmacology of demeanor offense. Moreover, the dangerous mix- hallucinogenic agents. Annual Review of Medicine, ture of alcohol and driving was a key point in the 20, 409–418. Prohibitionists’ argument in favor of the Eigh- GAWIN, F. H., & ELLINWOOD, E. H., JR. (1988). Cocaine teenth Amendment. and other stimulants: Actions, abuse, and treatment. During the 1950s and 1960s, with postwar pros- New England Journal of Medicine, 318, 1173–1182. perity and a developing highway network, both GRIFFITHS, R. R., & WOODSON, P. P. (1988). Caffeine alcohol abuse and traffic safety became serious na- physical dependence: A review of human and labora- tional widespread issues. The Highway Safety Act tory animal studies. Psychopharmacology (Berlin) of 1966 was crucial to mobilizing attention and 94, 437–451. resources in an attack against drunk driving. In HOLLISTER, L. E. (1986). Health aspects of cannabis. effect, it established a federal (not just a state and Pharmacology Review, 38, 1–20. local) jurisdiction by creating the National High- JAFFE, J. H. (1990). Drug addiction and drug abuse. In way Safety Bureau, the precursor of the National A. G. Gilman et al. (Eds.), Goodman and Gilman’s Highway Safety Administration (NHTSA), and it the pharmacological basis of therapeutics, 8th ed. authorized the U.S. Department of Education’s New York: Pergamon. 1968 Report, Alcohol and Highway Safety. This KRANZLER, H. R., & ORROK, B. (1989). The phar- report found that ‘‘the use of alcohol by drivers and macotherapy of alcoholism. Annual Review of Psychi- pedestrians leads to some 25,000 deaths and a total atry, 8, 397–417. of at least 800,000 crashes in the United States NUTT, D., ADINOFF, B., & LINNOILA, M. (1989). Benzodi- each year.’’ The report warned that ‘‘this major azepines in the treatment of alcoholism. Recent Devel- source of human morbidity will continue to plague opments in Alcohol, 7, 283–313. our mechanically powered society until its ramifi- ROBINSON, G. M., SELLERS, E. M., & JANECEK, E. (1981). cations and many present questions have been ex- Barbiturate and hypnosedative withdrawal by a mul- haustively explored and the precise possibilities for tiple oral phenobarbital loading dose technique. Clin- truly effective countermeasures determined.’’ ical and Pharmacological Therapeutics, 30, 71–76. NHTSA became the main sponsor of research and action projects aimed at reducing drunk driv- WOODS, J. H., KATZ, J. L., & WINGER, G. (1987). Abuse liability of benzodiazepines. Pharmacology Review, ing. In 1970, NHTSA launched the Alcohol Safety 39, 251–419. Action Project (ASAP), the first major U.S. initia- tive against drunk driving. The ASAP, established NICK E. GOEDERS in thirty-five communities, sought to achieve a sig- nificant reduction in drunk driving through a mix- ture of intensive countermeasures—including law DRUNK DRIVING Drunk driving results in enforcement, rehabilitation, and education. These one of the most costly social consequences of ALCO- programs were rigorously monitored. Unfortu- HOL abuse. The toll on human life and health nately, despite huge increases in arrests and tens of exacted by drunk drivers can, on its own, make thousands of referrals to drunk-driver schools and alcohol abuse one of the most serious U.S. social rehabilitation programs, a significant decrease in problems. The extent and consequences of drunk drunk driving could not be confirmed, and the driving demonstrate the challenges of harmonizing ASAP was terminated in 1977. a drinking culture with a modern industrial society. The attack on drunk driving did not subside. In The combination of drinking and driving has the late 1970s, there emerged a remarkable grass- been recognized as a serious problem since the in- roots anti-drunk driving movement comprised of 470 DRUNK DRIVING victims, their families, and many other concerned weave in and out of traffic, and cross into lanes of citizens. MOTHERS AGAINST DRUNK DRIVING traffic going in the opposite direction. At the low (MADD), Students Against Driving Drunk end of the continuum are drunk drivers who make (SADD), and REMOVE INTOXICATED DRIVERS (RID) an impaired effort to drive safely; although operat- opened local chapters throughout the United States ing with diminished skill and judgment, they pose and vigorously campaigned for new and tougher less of a risk than the agressive drunk drivers. drunk-driving countermeasures. The crusade The most impressive experimental study of the launched by these groups attracted a great deal of causal role of alcohol in traffic crashes was carried media attention, vaulting drunk driving to the top out during the 1960s by Professor Robert of the nation’s social problems agenda. In 1982, Borkenstein (inventor of the BREATHALYZER) and President Ronald W. Reagan appointed a Presiden- his University of Indiana colleagues. The research- tial Commission on Drunk Driving. Congress ers obtained breath samples from 6,000 accident- linked state highway funds to the states’ passage of involved drivers and, as controls, from 7,500 non- specified anti-drunk driving measures, including a accident-involved drivers. They found that 6.3 per- minimum drinking age of twenty-one. Ultimately, cent of the accident-involved drivers, but fewer every state raised its drinking age accordingly. The than 1 percent of the control drivers, had BACs states passed a deluge of legislation, providing for equal to or greater than 0.1 percent (the prevailing more and better law enforcement and more severe definition of drunk driving in the 1980s). More- criminal penalties of a greater range—including over, each higher BAC level included a dispropor- mandatory jail terms, automatic license forfeiture, tionate number from the accident-involved group. public education, drunk-driver schools, and Thus Borkenstein and his colleagues concluded rehabilitation. that ‘‘BACs above .04% are definitely associated with an increased accident rate. The probability of MAGNITUDE OF THE PROBLEM accident-involvement increases rapidly at BACs above .15%. When drivers with BACs over 0.08% More than 2 million people are arrested each have accidents, they disproportionately involve year for drunk driving. The actual number of of- only the driver’s vehicle, and are more costly in fenses, while unknown and unknowable, must be terms of personal injury and property damage.’’ far greater, since only a fraction of all violators are While most drunk-driving episodes do not result apprehended. A few researchers have mounted in a crash or injuries, the aggregate personal and roadside surveys in which drivers are stopped and property damage perpetrated by drunk drivers is asked to voluntarily provide a breath sample from staggering. A good deal of methodological contro- which the amount of alcohol in the blood can be versy exists about the percentage of the approxi- calculated. While this is the best strategy for deter- mately 45,000 annual traffic fatalities in the United mining the actual amount of drunk driving, there States that can be attributed to drunk drivers. are many problems with this methodology (which NHTSA’s Fatal Accident Reporting System, which roads? what times? how many refusals?). A 1985 has been operating since the mid-1970s, presents Minnesota roadside survey found that of 838 driv- important information about alcohol and traffic fa- ers on the road between 8:00 P.M. and 3:00 A.M. talities but does not attempt to estimate what pro- (prime time for drunk driving), 82.3 percent tested portion of all traffic deaths were caused by drunken negative for any alcohol, 6 percent tested at BLOOD driving. James Fell and Terry Klein, using statisti- ALCOHOL CONCENTRATION (BAC) 0.05–0.09 per- cal modeling techniques, have estimated that ap- cent (included as a lesser Driving While Intoxicated proximately 30 percent of all traffic fatalities can [DWI] offense in some states), and 2.4 percent be attributed to drunk driving; other analyses have tested above the drunk-driving threshold of BAC put this estimate at 50 percent. 0.1 percent. Drunk drivers themselves, often in single-car Drunk drivers do not pose a uniform risk to collisions, comprise a large proportion of those who themselves, their passengers, other motorists, and are killed, giving fatal drunk-driving episodes as pedestrians. The most dangerous of the drunk driv- much resemblance to suicide as to homicide. Nev- ers are the vehicular equivalent of the ‘‘fighting ertheless, each year thousands of innocent pedes- drunk’’; they drive far in excess of the speed limit, trians and motorists are killed by drunk drivers, DRUNK DRIVING 471 and tens of thousands are badly injured. There is exceeds certain levels. When a suspect is arrested also a huge amount of property damage. for drunk driving, he or she is asked to take a deep breath and blow into a machine (the Breathalyzer THE OFFENDER is one model) that measures the amount of alcohol in the breath and converts it into a measure of the It is difficult to find reliable data on which to amount of alcohol in the blood. Pursuant to implied base a profile of the drunk driver. Using arrest data, consent laws, suspects who refuse to provide a we find that the vast majority, 90 percent, of drunk deep-lung breath sample are penalized by loss of drivers are male and white. Despite the common their driver’s license and sometimes by other sanc- belief that teenage drivers are most likely to be tions as well. The evolution of breath-testing equip- drunk, it is the mid-twenties age group that de- ment, including hand-held devices (like the In- serves this notoriety. Since it takes heavy drinking toxilyzer), has greatly eased the identification and (from four to six drinks in two hours, depending on conviction of drunk drivers. Despite folklore to the the drinker’s weight) to reach the prohibited level, contrary, it is extremely rare that suspects who it is unlikely that light drinkers very often commit ‘‘fail’’ the breath test obtain acquittals. Indeed, the drunk-driving offenses. Thus, people who drive conviction rate for drunk driving is well over 90 drunk are likely to be heavy drinkers and alcohol percent. abusers. Nevertheless, light and moderate drinkers In most states, a first drunk-driving offense is a may on occasion drive drunk, perhaps due to a misdemeanor, and a second offense within a speci- binge. Since light and moderate drinkers greatly fied time period (up to ten years in some states) is a outnumber heavy and abusive drinkers, they may felony. In a few states, a first offense is treated as a in fact comprise a substantial proportion of ar- traffic violation, a second offense a misdemeanor, rested drunk drivers. and a third offense a felony. Punishments vary The consensus of studies based on screening from state to state; however, the usual range of tests of drunk drivers is that about 50 percent punishments includes forfeiture of a driver’s license arrested for this offense are alcohol abusers, about for up to 1 year, fines of 500 to 1,000 dollars, and 35 percent are social drinkers, and the remainder incarceration up to 30 days. In the late 1980s, fall in between. While the categories alcohol abuser spurred by the anti-drunk driving citizens’ groups and social drinker are amorphous, a disproportion- and federal financial incentives, several states ately high percentage of those arrested for drunk passed laws mandating at least forty-eight hours of driving are actually heavy drinkers. incarceration for a first DWI offense and a longer The large majority of drunk drivers arrested in time for a second or subsequent offense. Another any given year have not been arrested before. A penalty that has been gaining popularity is the au- well-executed Minnesota study found that only 7 tomatic and immediate forfeiture of the driver’s li- percent of drivers involved in fatal accidents had cense at the police station when the suspect fails or been convicted of drunk driving in the preceding refuses to take the breath test (administrative per se three years; of drunk drivers involved in fatal acci- law). In the early 1990s, and once again in response dents, 13 percent had a DWI conviction in the to federal pressure, states began lowering the pro- previous 3 years, and 25 percent had a license revo- hibited BAC from 0.1 percent to 0.08 percent. cation during the preceding 8 years. The low offi- At least since the early 1970s, the criminal jus- cial rate of recidivism probably means that the tice system’s processing of drunk drivers has been chance of a drunk driver’s being caught is ex- linked to alcohol-treatment programs. In many ju- tremely small. risdictions, all drunk-driving offenders are rou- tinely screened for ALCOHOLISM and alcohol abuse. Alcoholics and abusers may be diverted from pros- THE CRIME OF DRUNK DRIVING ecution to TREATMENT. More likely, however, the The first drunk-driving laws made it an offense judge will require the offender to participate in to drive while intoxicated or to drive under the treatment as a condition of probation or in order influence (DUI) of alcohol. Starting in the 1950s, to obtain a provisional or regular driver’s license. states began to pass per se laws, which made it an In some jurisdictions, the criminal-justice system offense to operate a motor vehicle with a BAC that is the largest source of clients flowing into alcohol- 472 DRUNK DRIVING treatment programs. Thus, enforcement of the based upon probable cause, they were challenged. drunk-driving laws is one of the major ways that In 1990, however, the U.S. Supreme Court upheld alcohol abusers are brought into the alcohol- drunk-driving roadblocks under its administrative treatment matrix. search doctrine (Michigan Dept. of State Police v. In addition to the standard alcohol treatments, Sitz, 110 S. Ct. 2481). The Court ruled that as long the attack on drunk driving has produced one as the roadblocks are situated in a fixed location, unique kind of treatment—the drinking-driver overseen by high-level officials, and operated non- school, which several million people have passed discriminatorily, they do not violate the Fourth through since the mid-1970s. States and localities Amendment. that have such schools often require all drunk driv- ers to attend. New York’s school consists of five DETERRING THE DRINKING DRIVER two-hour sessions and two three-hour sessions. The classes provide information about such matters as Deterrence based on the threat of arrest, convic- the deterioration of driving skills at different BAC tion, and punishment remains the chief strategy in levels, the inability to counteract intoxication with the attack on drunk driving. During the 1980s, coffee or cold showers, and criminal penalties for state and local governments have established doz- drunk driving. People taking these classes are also ens of strike forces and passed hundreds of laws required to fill out the Michigan Alcohol Screening aiming to raise the costs to the offender of driving Test (MAST) to determine whether they are alcohol while intoxicated. In a series of empirical evalua- abusers. tions of police crackdowns and elevated maximum punishments in the United States and abroad, the sociologist H. Laurence Ross found that this type of ENFORCEMENT law-enforcement escalation usually produces a re- Enforcement of drunk-driving laws is the re- duction in drunk driving (as measured by single- sponsibility of local police, county sheriffs, and the vehicle fatalities), but not a long-term reduction. state police or highway patrol. The Fourth Amend- ‘‘No such policies have been scientifically demon- ment to the U.S. Constitution prevents police from strated to work over time under conditions stopping cars at random and requiring drivers to achieved in any jurisdiction . . . the option of take breath tests. Police must have probable cause merely increasing penalties for drinking and driv- to believe that drunk driving or some other offense ing has been strongly discredited by experience to (including traffic offenses) has been, is, or is about date.’’ to be committed. Once a driver has been legiti- While Ross has done far more empirical research mately stopped, the police officer can order the than anybody else on deterring the drunk driver, driver to submit to a field sobriety test, which may his conclusion is not uncontroversial. One criticism consist of walking heel-to-toe, counting back- is that he uses single-vehicle automobile fatalities wards, or performing other tasks that reveal intoxi- to measure the amount of drunk driving; however, cation. If the driver’s performance on the test gives this kind of accident might not be strongly associ- the officer probable cause to believe that the driver ated with the full range of drunk driving, but only is intoxicated, the officer will arrest the driver. At with a narrow group, the most drunken and reck- the station, drivers will be told that they are re- less of drunk driving. Possibly, while law-enforce- quired by the implied-consent law to submit to a ment escalations cannot affect the kind of drunk breath test; refusal to cooperate will lead to license drivers who kill themselves in single-vehicle revocation. crashes, they might be effective in the far more In the 1980s, as states and localities searched for numerous non-fatal drunk-driving episodes that more effective anti-drunk driving strategies, some are engaged in by less pathological alcohol abusers police departments mounted roadblocks at which and sociopathological persons. every car (or every nth car) was briefly stopped and The number of traffic fatalities has fallen from the driver briefly observed and sometimes ques- the late 1980s into the 1990s; drunk-driving tioned. If the officer detected alcohol, the driver was fatalities seem to have fallen more than non-alco- pulled over and required to submit to a breath test. hol-related accidents. There may be reasons for Since these drunk-driving roadblocks were not this other than deterrence, including general re- DRUNK DRIVING 473 ductions in alcohol consumption and abuse and driving involves fixing the defendant’s vehicle so more responsible public attitudes toward sober that it cannot be started until he blows alcohol-free driving—however, a marginal deterrence effect breath into a tube affixed to the vehicle. Such cannot be ruled out. equipment is now available, and several jurisdic- tions have implemented experimental programs. OTHER ANTIDRUNK-DRIVING Other opportunity-blocking strategies include the STRATEGIES twenty-one-year-old drinking age and a spate of In addition to deterrence, states and localities new laws and regulations on bars, taverns, and have implemented many other anti-drunk driving package-goods stores. strategies. Since all these strategies are being used The anti-drunk driving movement has spawned simultaneously, it is impossible to attribute any a large number of educational strategies. These in- reductions to one strategy over another. clude public-service announcements on radio and Some courts have made punitive damages avail- television and educational materials for primary able in drunk-driving cases. This allows the victim and secondary schools. The effects of such pro- of a drunk driver to recover any amount of money a grams are very difficult to evaluate. Rehabilitation jury deems appropriate for punishment. Some strategies for drunk drivers are closely linked to the states permit insurance coverage of punitive dam- matrix of community alcoholism and alcohol-abuse ages, thereby negating whatever deterrent effect services. Drunk drivers are regularly screened for such damages might produce, but not negating a alcohol problems, and those who are identified as windfall for the victim. abusers are typically channeled into treatment In some states, legislatures and courts have ex- through a probationary sentence. panded civil (tort) liability for causing drunk-driv- ing injuries to include commercial hosts and pack- (SEE ALSO: Accidents and Injuries; Addiction: Con- age sellers of alcohol. While these DRAMSHOP LAWS vary from state to state, they essentially make cepts and Definitions; Distilled Spirits Council; purveyors of alcohol to underage or intoxicated Driving, Alcohol, and Drugs; Minimum Drinking persons liable for the injuries caused by such per- Age Laws; Prevention Movement; Psychomotor Ef- sons to themselves or others. A few state courts fects of Alcohol and Drugs; Social Costs of Alcohol have even made social hosts liable for the alcohol- and Drug Abuse) related traffic injuries caused by their guests. An essential strategy for incapacitating drunk BIBLIOGRAPHY drivers is taking away their licenses to drive. Sev- eral studies have shown that drunk drivers who lose GUSFIELD, J. (1981). The culture of public problems: their drivers’ licenses are less likely to have a recur- Drinking—driving and the symbolic order. Chicago: rence than drunk drivers who are fined, sent to jail, University of Chicago Press. or assigned to mandatory treatment programs (ac- JACOBS, J. B. (1989). Drunkdriving: An American di- tually, all these sanctions can be imposed together). lemma. Chicago: University of Chicago Press. Nevertheless, when licenses are suspended or re- LABELL, A. (1992). John Barleycorn must pay: Compen- voked, a good deal of licenseless driving takes sating the victims of drinking drivers. Urbana, IL: place—which is not surprising in a society where University of Illinois Press. people depend on automobiles for their economic MOORE, H., & GERSTEIN,D.(EDS.) (1981). Alcohol and and social lives. Several states also have laws that public policy: Beyond the shadow of prohibition. authorize vehicle impoundment or forfeiture, but Washington, DC: National Academy Press. these sanctions are rarely used, perhaps because of ROSS, H. L. (1992). Confronting drunkdriving . New Ha- the sacred status of the automobile as expensive ven: Yale University Press. private property. ROSS, H. L. (1982). Deterring the drinking driver: Legal Opportunity blocking refers to anti-crime strate- gies that change the environment to reduce the policy and social control. Lexington, MA: Lexington opportunities of committing particular offenses. Books. The best opportunity-blocking strategy for drunk JAMES B. JACOBS 474 DSM

DSM See Diagnostic and Statistical Manual heroin, and they present great abuse liability since they illicit feelings of euphoria and absence of pain. However, there seem to be two opioid systems con- DTS See Delerium Tremens trolling behavior one influencing feelings of RE- WARD (through-endorphins) and one influencing feelings of AVERSION, (through dynorphin). The DUAL DIAGNOSIS See Comorbidity and physiological substrate underlying the effects of dy- Vulnerability; Complications: Mental Disorders norphins is believed to be at the level of the MESOLIMBIC DOPAMINE neurons in the ventral teg- mental area. Dynorphin tonically inhibits the firing DUI/DWI See Driving, Alcohol, and Drugs; of dopamine neurons, thus preventing its release in Driving Under the Influence; Drunk Driving the striatum. Elevations of dopamine levels in the nucleus accumbens are believed to underlie the re- inforcing properties of many PSYCHOSTIMULANT- like drugs, as well as OPIATES. DYNORPHIN Dynorphin is a neuropeptide Due to the ADVERSE feeling associated with transmitter; it is an OPIOID peptide, a member of the endorphin family of peptides. All neurotrans- WITHDRAWAL from many drugs of abuse, the dy- mitters like Dynorphin have receptors. Its greatest norphin system has been implicated in contributing affinity is for the Kappa opioid receptor. Dynor- to this state. Studies have found that there are long- phin’s role in drug abuse was originally anticipated term changes in dynorphin levels in brain areas based on its location in anatomical areas strongly associated with drug abuse, and that these changes associated with the mechanism of action of drugs of also exist during withdrawal. Prenatal exposure to abuse. It is localized in the NUCLEUS ACCUMBENS, cocaine also effects the levels of dynorphin in the AMYGDALA, and VENTRAL TEGMENTAL AREA. brain. These changes are present in both animal Dynorphin induces feelings of dysphoria, or de- and human models of drug abuse. Since drugs spair. This was first documented in animals, and modulate dynorphin systems, we can gain an un- later confirmed in humans. It is surprising because derstanding of how drugs work in the brain by the best known opiate-like drugs are morphine and studying the dynorphin system. ESA&AB-barcode/v1.qx4 10/27/00 4:02 PM Page 1

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