Cocaine: Pharmacology, Effects, and Treatment of Abuse
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Cocaine: Pharmacology, Effects, and Treatment of Abuse U. S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse, and Mental Health Administration Cocaine: Pharmacology, Effects, and Treatment of Abuse Editor: John Grabowski, Ph.D. Division of Clinical Research National Institute on Drug Abuse NIDA Research Monograph 50 1984 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, Maryland 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, D.C. 20402 NIDA Research Monographs are prepared by the research divisions of the National Institute on Drug Abuse and published by its Office of Science The primary objective of the series is to provide critical reviews of research problem areas and techniques, the content of state-of-the-art conferences, and integrative research reviews. Its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community. Editorial Advisors MARTIN W. ADLER, Ph.D. SIDNEY, COHEN M.D. Temple University School of Medicine LosAngeles, California Philadelphia, Pennsylvania SYDNEY ARCHER, Ph.D. MARY L. JACOBSON Rensselaer Polytechnic Institute National Federation of Parents for Troy, New York Drug Free Youth RICHARD BELLEVILLE, Ph.D. Omaha, Nebraska NB Associates, Health Sciences Rockville, Maryland REESE T. JONES, M.D. KARST J. BESTMAN Langley Porter Neuropsychiatric Institute San Francisco, California Alcohol and Drug Problems Association of North America Washington, D.C. DENISE KANDEL, Ph.D. GILBERT J. BOVTIN, Ph.D. College of Physicians and Surgeons of Cornell University Medical College Columbia University New York, New York New York, New York JOSEPH V. BRADY, Ph.D. The John Hopkins University School of HERBERT KLEBER, M.D. Medicine Yale University School of Medicine Baltimore, Maryland New Haven, Connecticut THEODORE J. CICERO, Ph.D. Washington University School of RICHARD RUSSO Medicine New Jersey State Department of Health St. Louis, Missouri Trenton, New Jersey NIDA Research Monograph Series CHARLES R. SCHUSTER, Ph. D. Director, NIDA JEAN PAUL SMITH, Ph.D. Acting Associate Director for Science, NIDA Acting Editor Parklawn Building, 5600 Fishers Lane, RockviIle, Maryland 20857 Cocaine: Pharmacology, Effects, and Treatment of Abuse Dr. John Grabowski, editor of this monograph, was on the staff of the Clinical and Behavioral Pharmacology Branch, Division of Clinical Research, NIDA. He is now affiliated with the Depart- ment of Psychiatry, School of Medicine, Tufts University, Boston, MA 02111. COPYRIGHT STATUS All material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. Library of Congress catalog card number 84-601074 DHHS Publication No. (ADM)87-1326 Alcohol, Drug Abuse, and Mental Health Administration Printed 1984 Reprinted 1987 NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of American Statistics Index, Biosciences Information Service, Chemical Abstracts, Current Contents, Psychological Abstracts, and Psychopharmacology Abstracts. iv Contents Foreword . .vii Cocaine 1984: Introduction and Overview John Grabowski. , . 1 Cocaine: A Growing Public Health Problem Edgar H. Adams and Jack Durell . 9 Neural Mechanisms of the Reinforcing Action of Cocaine Roy A. Wise. 15 The Pharmacology of Cocaine Reese T. Jones. 34 Assessment of the Dependence Potential of Cocaine in Animals Chris E. Johanson. 54 The Behavioral Pharmacology of Cocaine in Humans Marian W. Fischman . 72 Changing Patterns of Cocaine Use: Longitudinal Observations, Consequences, and Treatment Ronald K. Siegel . 92 Cocaine Abuse: A Review of Current and Experimental Treatments Herbert D. Kleber and Frank H. Gawin . .111 List of NIDA Research Monographs . .130 v Foreword Cocaine is currently the drug of greatest national concern, from a public health point of view, and of particularly high interest from the research and scientific point of view. The public health concern derives from the following sources: It has shown the highest continuing rate of increase in DAWN mentions (emergency room visits), overdose deaths, and serious clinical problems, despite a leveling of national prevalence since 1980. Animal studies show it to be one of the most potent reinforcers available. It is the one drug most easily and universally accepted in animal self-administration studies without prior induction training, and is widely used to shape animal behavior for the self-administration of other reinforcing drugs. It has one of the highest reinforcing potentials as measured by breaking point studies, and is the drug which animals, with unlimited access, are most likely to select repeatedly in preference to food and water to the point of death. These preclinical observations and related clinical data lead to the conclusion that the prospect of substantial increases in available supply and decreases in price constitutes a major and growing public health danger. We are still uncertain as to whether the leveling off in overall national prevalence, which as shown by our two major national surveys occurred for cocaine between 1979 and 1982, has continued since then. If so, the increase in medical complications, addiction, and clinical problems described above would represent a higher percentage of a constant total pool of users running into serious problems. This interpretation is consistent with studies showing that an average of 4 to 5 years elapses between first use of cocaine and the need for treatment, and other studies showing that the best predictor of cocaine use is heavy, early marijuana use. The current upsurge in public health related cocaine problems would then be the predictable second stage of the peak of marijuana use which we saw in this country in the late 1970s. An alternative possibility is that greatly increased availability of this most reinforcing illicit drug has broken through powerful cultural and demographic barriers and begun to lead to a substantial increase in the number of users and/or intensified patterns of use. Evidence for this latter alternative may only become evident in future national surveys. vii In any event, while we await further clarification of the exact nature of current trends in cocaine use, there is an urgent need for a rapid increase in information on mechanisms of brain action, treatment methods, health consequences, and prevention strategies. This monograph makes an important contribution towards planning future research by reviewing our knowledge base. Charles R. Schuster, Ph.D. Director National Institute on Drug Abuse viii Cocaine 1984: Introduction and Overview John Grabowski INTRODUCTION Diverse aspects of cocaine pharmacology, use, and effects have been discussed at length in both the lay press and the scientific literature. Research involving cocaine has a long, interesting history which has been described at intervals, and this volume provides a current review of present knowledge concerning the drug. Dramatic increases in use in the past decade, increasing evidence of untoward consequences of use, and resultant public health concerns also set the stage for a timely and thorough review of scientific and clinical issues concerning cocaine. Cocaine is an alkaloidal agent and is derived from the plant Erythroxylon coca and other Erythroxylon species in South America. Its multiple behavioral effects constitute those of the prototypic "stimulant" (with all the caveats pertaining to such loose categorizations). The drug is, thus, viewed in the context of amphetamines, caffeine, khat, and a variety of more recently developed synthetic agents. Cocaine, in the leaf form or as the extracted substance, has been used for different purposes, with varying restrictions, in different cultures. Paralleling the accepted medical and cultural uses has been a history of abuse of the drug. There is, as a result, ample evidence that cocaine abuse can have debilitating physical and behavioral-psychological consequences. Since not all users exhibit these symptoms, however, some have assumed that it is inherently safe. As with all drugs, this is an unwarranted assumption, since definable dose-related hazards exist. Thus, there is considerable interest in delineating the drug's characteristics in terms of abuse. Investigation of this and related drugs is also extremely important because of fundamental scientific issues concerning its neurochemical, pharmacological, and behavioral spectra of action. 1 OVERVIEW OF MONOGRAPH This monograph was developed with emphasis on major areas of scientific and clinical interest. Thus, the topics range from postulated neurochemical mechanisms of action, through analysis of behavioral effects and patterns of use, to review of therapeutic strategies. There has been a dramatic resurgence of cocaine use in the last decade. Adams and Durell address this issue and provide a brief overview of the epidemiological sources by which trends have been followed. In particular, they note substantial increases in medical examiner