National Institute on Drug Abuse MONOGRAPH SERIES Problems Of Drug Dependence 1979 Proceedings of the 41st Annual Scientific Meeting The Committee on Problems of Drug Dependence, Inc. U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service • Alcohol, Drug Abuse, and Mental Health Administration Problems of Drug Dependence, 1979 Proceedings of the 41st Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Editor: Louis S. Harris, Ph.D. NIDA Research Monograph 27 1979 DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse Division of Research 5600 Fishers Lane Rockville, Maryland 20857 For sale by the Superintendent of Documents. U.S. Government Printing Office Washington, D.C. 20402 Stock No. 017-024-00981-4 The NIDA Research Monograph series is prepared by the Division of Research of the National Institute on Drug Abuse. Its primary objective is to provide critical re- views of research problem areas and techniques, the content of state-of-the-art conferences, 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. College of Physicians and Surgeons Columbia University, New York Reese T. Jones, M.D. Langley Porter Neuropsychiatric institute University of California San Francisco, California William McGlothlin, Ph.D. Department of Psychology. UCLA Los Angeles, California Jack Mendelson, M.D. Alcohol and Drug Abuse Research Center Harvard Medical School McLean Hospital Belmont, Massachusetts Helen Nowlis, Ph.D. Office of Drug Education, DHEW Washington, D.C. Lee Robins, Ph.D. Washington University School of Medicine St. Louis, Missouri NIDA Research Monograph series William Pollin, M.D. DIRECTOR, NIDA Marvin Snyder, Ph.D. DIRECTOR, DIVISION OF RESEARCH, NIDA Robert C. Petersen, Ph.D. EDITOR-IN-CHIEF Eleanor W. Waldrop MANAGING EDITOR Parklawn Building, 5600 Fishers Lane, Rockville, Maryland 20857 Problems of Drug Dependence, 1979 Proceedings of the 41st Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. MEMBERS, COMMITTEE ON PROBLEMS OF DRUG DEPENDENCE, INC. Dr. Joseph Cochin, Chairman Dr. Joseph Brady Dr. Troy Duster Dr. Charles Gorodetzky Dr. Louis Harris Dr. Theresa Harwood Dr. Arthur Jacobson Dr. Jerome Jaffe Dr. Arthur Keats Dr. Harold Kalant Dr. Everette May Dr. Jack Mendelson Dr. John O'Donnell Dr. C. R. Schuster Dr. Henry Swain EXECUTIVE SECRETARY Dr. Leo Hollister MEMBERS, BOARD OF DIRECTORS Dr. E. L. Way, Chairman Am. Soc. Pharmacol. Exptl. Ther. Dr. D. X. Freedman Am. Psychiatric Assn. Dr. K. F. Killam Am. Coll. Neuropsychopharmacol. Dr. Everette May Am. Chemical Society Dr. Edward C. Senay Am. Medical Assn. Dr. Beny J. Primm Natl. Medical Assn. Dr. James Woods Am. Psychological Assn. Dr. Raymond W. Houde Am. Soc. Clin. Pharmacol. Ther. MEMBERS, PROGRAM COMMITTEE Dr. Louis S. Harris, Chairman Dr. Everette L. May Mrs. Linda C. Thornton MEMBERS, COMMITTEE ON ARRANGEMENTS Dr. Martin W. Adler Dr. Alexander L. Beckman Dr. Alan Cowan Dr. Loretta Finnegan Dr. Ellen B. Geller Dr. Alexander Gero Dr. Concetta Harakal Dr. Jeffrey B. Malick Dr. Charles O'Brien Dr. Thaddeus P. Pruss Dr. Charles Puglia Dr. Peter T. Ridley Dr. Frank Robinson Dr. Ronald J. Tallarida Dr. Vernon G. Vernier ACKNOWLEDGMENT The papers in this monograph were presented or read by title at the 41st Annual Scientific Meeting of the Committee on Problems of Drug Dependence, Inc., in Philadelphia, on June 4-6, 1979. The National Institute on Drug Abuse has obtained permission from the copyright holders to print material, as noted, on pages 48-53, 177-183, and 402-408. Further reproduction of this material. without specific permission of the copyright hold- ers is prohibited. All other material except short quoted passages from copyrighted sources is in the public domain and may be reproduced without permis- sion. Citation as to source is appreciated. The United States Government does not endorse or favor any specific commercial product or commodity. Trade or proprietary names appearing in this publication are used only because they are consid- ered essential in the context of the studies re- ported herein. Library of Congress catalog card number 80-600008 DHEW publication number (ADM) 80-901 Printed 1980 NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of Biosciences Information Service, Chemical Abstracts, Psychological Abstracts, and Psycho- pharmacology Abstracts. v CONTRIBUTING FIRMS 1978 - 1979 The following firms have supported the work of the Committee on Problems of Drug Dependence, Inc. through contributions during the previous fiscal year. Abbott Laboratories Bristol Laboratories C. H. Boehringer Sohn Burroughs Wellcome and Company Chemie Linz AG Clin-Midy of America, Inc. Eli Lilly and Company Endo Laboratories, Inc. Hoffman - La Roche, Inc. ICI Americas, Inc. Knoll Pharmaceutical Company Lederle Laboratories McNeil Laboratories Mead Johnson Merck, Sharpe & Dohme Merrell - National Laboratories, Inc. Miles Laboratories, Inc. Pennwalt Corporation Pfizer Central Research Reckitt & Colman Products, Ltd. A. H. Robins Company SISA, Inc. Smith, Kline & French Sterling Drug, Inc. The Upjohn Company USV Pharmaceutical Corporation vi Foreword The National Institute on Drug Abuse is pleased to publish Problems of Drug Dependence, 1979, in its Research Monograph series. These are the proceedings of the 41st annual scientific meeting of the Committee on Problems of Drug Dependence, Inc., which was held in Philadelphia on June 4-6, 1979. The Committee, now incorporated as an independent entity, was for 47 years affiliated with the National Academy of Sciences--National Research Council. Its membership is drawn from all fields of clin- ical medicine, psychiatry, public health, pharmacology, chemistry, and the social sciences. This year, as in previous years, its annual meeting represents a high point in the science activities relevant to drug abuse and neurosciences. The Committee's annual scientific meetings typically present a truly comprehensive assemblage of reports of ongoing research re- lating to all aspects of drug abuse and drug dependence. The pa- pers present contributions to new knowledge of agents involved in drug abuse or significantly affecting the central nervous system: their pharmacological action, biological disposition, abuse poten- tial, safety, tolerance liability, or clinical usefulness, and re- lated experimental and clinical methodology. In addition to papers presented or read by title at the meeting, the proceedings include summaries from a special satellite session on khat and the annual progress reports of NIDA-supported dependence studies of new compounds. To meet space limitations for this volume, many of the papers have been condensed by the authors. The broad range of subjects treated may be easily seen by looking through the detailed index, which gives full accessibility to the contents. vii We believe that this up-to-date review of the field of drug depen- dence will be of value to readers who will bring to it as wide a variety of backgrounds, interests, and concerns as that represented by the Committee on Problems of Drug Dependence itself. William Pollin, M.D. Director National Institute on Drug Abuse viii Contents Foreword William Pollin vii PAPERS PRESENTED AT THE 41ST ANNUAL CPDD MEETING Hooked for Thirty Years: Tales of an Investigator E. L. Way 1 The Prescription of Controlled Substances: What's Right and What's Wrong? S. Cohen 11 Effects of Scheduling on the Economics of Drug Development C. J. Cavallito 17 The Impact of Regulations on the Development of Psychoactive Drugs L. Lasagna 29 The Influence of the Mode of Morphine Administration on Tolerance and Dependence J. Cochin; J. M. Miller; C. E. Rosow; R. Grell; J. L. Poulsen 36 Biosynthesis of the Enkephalins in the Myenteric Plexus of the Guinea-Pig Ileum. Further Analysis of the Interaction of the Enkephalins and Their Analogues With the Opiate Receptors H. W. Kosterlitz; A. T. McKnight; A. D. Corbett; M. G. C. Gillan; S. W. Paterson; L. E. Robson; R. P. Sosa. 48 The Binding of LAAM and its Metabolites to Blood Constituents E. Toro-Goyco; B. R. Martin; L. S. Harris 54 Progress Report From the NIDA Addiction Research Center D. R. Jasinski; E. J. Cone; C. W. Gorodetzky; M. E. Risner; H. E. Shannon; T. P. Su; D. B. Vaupel 61 Drug Dependence Programme of the World Health Organization I. Khan 70 ix Fifty Years of International Control of Dependence- Producing Drugs S. Kaymakcalan 74 A New Synthetic Codeine Substitute: (-)-3-Phenoxy-N- Methylmorphinan E. Mohacsi; W. Leimgruber; H. Baruth 77 Stereospecific and Potent Analgetic Activity for Nantradol-- A Structurally Novel, Cannabinoid-Related Analgetic G. M. Milne; B. K. Koe; M. R. Johnson 84 8ß-Alkyl-N-Cycloalkyl-Dihydro-Codeinones and -Morphinones as Analgesic Narcotic Antagonists M. P. Kotick; D. L. Leland; J. O. Polazzi; R. N. Schut 93 The Pharmacology of TR5109, a New Narcotic Agonist/Antagonist Analgesic J. F. Howes; P. F. Osgood; R. K. Razdan; F. Moreno; A. Castro; J. Villareal 99 Dependence Potential of Loperamide Studied in Rhesus Monkeys T. Yanagita; K. Miyasato; J. Sato 106 Opioid Self-Administration and REM Sleep EEG Power Spectra G. F. Steinfels; G. A. Young; N. Khazan 114 Motor Activity and Learning Ability in Rats Perinatally Exposed to Methadone I. S. Zagon; P. J. McLuughlin 121 Narcotic Drug Discriminations by Rhesus Monkeys and Pigeons J. H. Woods; S. Herling; R. J. Valentino; D. W. Hein; E. H. Coale, Jr. 128 Effects of Closing the Bakersfield Methadone Clinic W. H. McGlothlin; M. D. Anglin 135 An Improved Evaluation Instrument for Substance Abuse Patients: The Addiction Severity Index A. T. McLellan; L. Luborsky; C. P. O'Brien; G. E. Woody 142 Development of Psychiatric Disorders in Drug Abusers: Relation Between Primary Drug and Type of Disorder A. T. McLellan; G.