DOCUMENT RESUME ED 260 938 SE 045 978 AUTHOR Grabowski, John, Ed. TITLE Cocaine: Pharmacology, Effects, and Treatment of Abuse. National Institute on Drug Abuse Research Monograph 50. INSTITUTION National Inst. on Drug Abuse (DHHS/PHS), Rockville, Md. REPORT NO DHHS-ADM-84-1326 PUB DATE 84 NOTE 143p. AVAILABLE FROMSuperintendent of Documents, U.S. Government Printing Office, Washington, DC 20402. PUB TYPE Collected Works - General (020) EDRS PRICE MF01/PC06 Plus Postage. DESCRIPTORS *Drug Abuse; Drug Addiction; Drug Education; *Drug Rehabilitation; *Drug Use; *Neurology; *Pharmacology; Physiology; Public Health IDENTIFIERS *Cocaine ABSTRACT This monograph consists of eight papers which refer in one way or another to the pharmacology of cocaine. The papers are: (1) Cocaine 1984: Introduction and Overview" (John Grabowski); (2) "Cocaine: A Growing Public Health Problem" (Edgar H. Adams and Jack Durell); (3) "Neural Mechanisms of the Reinforcing Action of Cocaine" (Roy A. Wise);(4) "The Pharmacology of Cocaine" (Reese T. Jones); (5) "Assessment of the Dependence Potential of Cocaine in Animals" (Chris E. Johanson);(6) "The Behavioral Pharmacology of Cocaine in Humans" (Marian W. Fischman); (7) "Changing Patterns of Cocaine Use: Longitudinal Observations, Consequences, and Treatment" (Ronald K. Siegel); and (8) "Cocaine Abuse: A Review of Current and Experimental Treatments" (Herbert D. Kleber and Frank H. Gawin). References, some of them extensive, are included for each paper. A list of National Institute on Drug Abuse (NIDA) research monographs is included. (JN) *********************************************************************** * Reproductions supplied by EDRS are the best that can be made * * from the original document. * *********************************************************************** National Institute on Drug Abuse %No t14 SCOPE OF INTEREST NOTICE The ERIC Fealty has assigned this document for proc ossing up MONOGRAPH SERIESto CD In our judgment, the document rs also of interest to the Clear rnghouses noted to the right Indexing should reflect their special points 01 vied/ w U S OEPARIMENT OF EDUCATION NATIONAL INSTITUTE OF EDUCtil ION I Our AT IONA!Elf SOUR( E5 INFORM h I ION E Efil 44. 444,44444,44r ,r44. IOen r01, the I. rttr.,1rrhls, ,1 Cocaine: tort00,`JAC 11)1,10 ,11, 11i, 111,1, ,1 rtlr,14.0.44 II,lot, 4.4.,41 4r 4, Pharmacology, r4,,E,414,4 ,14,14,,r,1441E, 44.1 NIE Effects, and Treatment of Abuse BES[ COP(iivAILABLE U S DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Servo Alcohol. 01110 Abuse, and Mental Health Adennistration 2 Cocaine: Pharmacology, Effects, and Treatment of Abuse Editor: John Grabowski, Ph.D. Division of Clinical Research National Institute on Drug Abuse N I DA Research Monograph 50 1984 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Aoministration National Institute on Drug Abuse 5600 Fishers Lane Rockville, Maryland 20857 For sale by the Superintendent of Documents, V S Government Printing Office Washington, D.C. 20402 3 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 confer- ences, integrative research reviews and significant original research Its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community Editorial Advisory Board Avram Goldstein, M.D. Addiction Research Foundation Palo Alto, California Jerome Jaffe, M.D. University of Connecticut School of Medicine Farmington. Connecticut Reese T. Jones, M.D. Langley Paler Neuropsychiatric Institute University of California San Francisco. California Jack Mendelson, MD Alcohol and Drug Abuse Research Center Harvard Medical School McLean Hospital Belmont, Massachusetts Helen Now lis, Ph.D. Rochester. New York Lee Robins, Ph.D. Washington University School of Medicine St Louis. Missoun NIDA Research Monograph Series William Po llin, M.D. DIRECTOR, NIDA Jack Durell, M.D. ASSOCIATE DIRECTOR, OFFICE OF SCIENCE, NiDA EDITOR-IN-CHIEF Eleanor W.1Waldrop MANAGING EDITOR Park lawn Building 5600 Fishers Lane. Rockville Maryland 20857 4 Dr. John Grabowski, editor of this monograph, was on the staff of the Behavioral Pharmacology Branch, Division of Clinical Research, NIDA. He is now affiliated with the Department of Psychiatry, School of Medicine, Louisiana State University, Shreveport, Louisiana 71130. COPYRIGHT STATUS All material in this volume except quoted passages from copyrighted sources is inthe 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 ofthe U.S. Department of Health and Human Services. Library of Congress catalog card number 84-601074 DRS publication number (ADM)84-1326 Printed 1984 NIDA Research Monographs are indexed in the Index Medicus.They are selectively included in the coverage of American Statistics Index, BioSciences Information Service, Chemical AbstaT7 trurrent Contents, Psychological Abstracts, and Psychopharmacology AIStr acts. iv 5 Contents Foreword William Pollin 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. 'chanson 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), cverdose 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 meacured 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 clarificationof the exact nature of current trends in cocaine use, there isan urgent need for a rapid increase in information on mechanisms of brain action, treatment methods, health consequences, and preventionstrategies. This monograph makes an important contribution towards planning future research by reviewing our knowledge base. William Pollin, M.D. Director National Institute on Drug Abuse viii 8 Cocaine 1984: Introduction and Overview John Grabowski INTRODUCTION Diverse aspectsof cocaine pharmacology, use, and effects have been discussed at length in both the lay press and the scientific literature. Researchinvolving cocaine has a long, interestinghistory 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 timelyand thorough review of scientific and clinical issues concerning cocaine.