National Institute on Drug Abuse MONOGRAPH SERIES Problems of Drug Dependence 1984 Proceedings of the 46th Annual Scientific Meeting The Committee on Problems of Drug Dependence, Inc. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration Problems of Drug Dependence, 1984 Proceedings of the 46th Annual Scientific Meeting, The Committee on Problems of Drug Dependence, Inc. Editor: Louis S. Harris, Ph.D. NIDA Research Monograph 55 March 1985 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse Office of Science 5600 Flshers 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 at research problem areas and techniques, the content of state-of-the-art conferences, and integra- tive research reviews. Its dual publication emphasis is rapid and targeted dissem- ination to the scientific and professional community Editorial Advisors Martin W. Adler, Ph.D. Temple University School of Medicine Philadelphia, Pennsylvania Sydney Archer, Ph.D. Rensselaer Polytechnic Institute Troy, New York Richard E. Belleville, Ph.D. NB Associates, Health Sciences Rockville, Maryland Gilbert J. Botvin, Ph.D. Cornell University Medical College New York, New York Joseph V. Brady, Ph.D. The Johns Hopkins University School of Medicine Baltimore, Maryland Theodore J. Cicero, Ph.D. Washington University School of Medicine St Louis, Missouri Sidney Cohen, M.D. Los Angeles, California Reese T. Jones, M.D. Langley Porter Neuropsychiatrlc lnstltute San Francisco, California Denise Kandel, Ph.D. College ot Physicians and Surgeons of Columbia University New York, New York Herbert Kleber, M.D. Yale University School of Medicine New Haven, Connecticut NIDA Research Monograph Series William Pollin, M.D. DIRECTOR, NIDA Jack Durell, M.D. ASSOCIATE DIRECTOR FOR SCIENCE, NIDA EDITOR-IN-CHIEF Eleanor W. Waldrop MANAGING EDITOR Parklawn Building, 5600 Fishers Lane, Rockville, Maryland 20857 Foreword The National Institute on Drug Abuse presents once again to readers of its Research Monograph series the Proceedings of the Annual Scientific Meeting of the Committee on Problems of Drug Dependence, Inc. NIDA and the CPDD share many interests and concerns in developing knowledge that eventually will lessen the destructive effects of dependence-producing substances on individual lives and their costly burden on our society as a whole. As would be expected, the two organizations work closely together. CPDD's Annual Scientific Meetings gather the outstanding investigators from many disciplines to discuss their ongoing projects. Researchers from NIDA's own Addiction Research Center report their findings here. In addition, the work of many other CPDD members and meeting participants receives support through NIDA's grant programs. The CPDD drug testing program to assess the dependence potential and abuse liability of new compounds is also NIDA-supported. Results of these tests, which seek analgesic drugs free of abuse hazard, are included in each year's Proceedings. A symposium on the neuroendocrine effects of substance abuse is featured in Problems of Drug Dependence, 1984. In addition to papers on chemistry and pharmacology, clinical pharmacology, treatment, and epidemiology. It is gratifying to make available to drug abuse professionals and to the public this yearbook of current research on all aspects of the drug abuse field. William Pollin, M.D. Director National Institute on Drug Abuse iii The papers in this monograph were presented or read by title at the 46th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, Inc., in St. Louis, Missouri, June 4-6, 1984. The CPDD, an independent, nonprofit organization, conducts drug testing and evaluations for academic institutions, government, and industry. Louis S. Harris, the editor of the monograph, is chairman of the Department of Pharmacology, Medical College of Virginia, Richmond, Virginia. COPYRIGHT STATUS The figure on page 133 is copyrighted by Ankho International Inc. Its further reproduction is prohibited without specific permission of the copyright holder. The article by Drs. Washton, Gold, and Pottash beginning on page 185 is adapted from material copyrighted by Haworth Press, Inc. The article by the same authors beginning on page 224 is adapted from material copyrighted by Slack, Inc. These articles are used here by permission of the copyright holders. Before reproducing them, readers are advised to determine their copyright status or to secure the permission of the copyright holders. All other 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. The U.S. 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 considered essential in the context of the studies reported herein. DHHS publication number (ADM)85-1393 Printed 1985 NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of the American Statistics Index, Biosciences Information Service, Chemical Abstracts, Current Contents, Psychological Abstracts, and Psychopharmacology Abstracts. iv The Committee on Problems of Drug Dependence, Inc. MEMBERS Leo E. Hollister, Chairman Martin W. Adler Sydney Archer William T. Beaver Richard J. Bonnie Theodore J. Cicero William L. Dewey Marian W. Fischman Roland R. Griffiths Donald R. Jasinski Lloyd D. Johnston Mary Jeanne Kreek William R. Martin Roger E. Meyer Charles P. O'Brien Akira E. Takemori EXECUTIVE SECRETARY Joseph Cochin MEMBERS, BOARD OF DIRECTORS Beny J. Primm, Chairman Natl. Medical Assn. Joseph V. Brady Soc. Behavioral Med. Raymond W. Houde Am. Soc. Clin. Pharmacol. Ther. Keith F. Killam Am. Soc. Pharmacol. Exptl. Ther. Everette L. May Am. Chemical Society Jack H. Mendelson Am. Psychiatric Assn. Lee N. Robins Am. Sociological Assn. Edward C. Senay Am. Medical Assn. E. L. Way Am. Coll. Neuropsychopharmacol. James H. Woods Am. Psychological Assn. v COMMITTEE CHAIRMEN MEMBERS, PROGRAM COMMITTEE Charles W. Gorodetzky Louis S. Harris, Chairman By-Laws Everette L. May Louis S. Harris Joyce H. Pye Scientific Meetings Arthur E. Jacobson MEMBERS, COMMITTEE ON ARRANGEMENTS Drug Testing Program Theodore J. Cicero PERMANENT LIAISON Betty Chester Louis S. Harris Jerome H. Jaffe Arthur E. Jacobson Howard McClain Heinz Sorer Edward C. Tocus CONTRIBUTING FIRMS, 1983-84 The following firms have supported the work of the Committee on Problems of Drug Dependence, Inc., through voluntary contribu- tions during the previous fiscal year. Abbott Laboratories Boehringer Ingelheim International Burroughs Wellcome Company CIBA-GEIGY Clin-Midy of America, Inc. E.I. DuPont de Nemours & Co., Inc. Glaxo Hoechst-Roussel Pharmaceutical, Inc. Hoffman-LaRoche, Inc. ICI Americas, Inc. Key Pharmaceuticals, Inc. Knoll Pharmaceutical Company Lilly Research Laboratories McNeil Pharmaceutical Merck Sharp & Dohme Research Labs Miles Laboratories Ortho Pharmaceutical Corporation Pfizer Central Research Reckitt & Colman Pharmaceuticals Div. A.H. Robins Company Sandoz, Ltd. (Basle) Sandoz, (New Jersey) Schering Corporation Searle Research & Development Smith, Kline & French Laboratories Sterling Drug, Incorporated Syntex The Upjohn Company Wyeth Laboratories vi Contents Foreword William Pollin iii Plenary Session Presentation to Kay Croker of J. Michael Morrison Award for Outstanding Achievement in Science Administration in the Drug Field Martin W. Adler 1 Introduction of Nathan B. Eddy Memorial Award Recipient--1984 Louis S. Harris 2 The Analgesic Connection: The Nathan 8. Eddy Memorial Lecture Raymond W. Houde 4 Symposium Opiate and Opioid Modulation of Reproductive Endocrinology in the Male and Female: Development and Pregestational Aspects Theodore J. Cicero 14 Acute Effects of Marijuana on Pituitary and Gonadal Hormones During the Periovulatory Phase of the Menstrual Cycle Jack H. Mendelson; Nancy K. Mello; Patricia Cristofaro; James Ellingboe; and Richard Benedikt 24 Feminization in Alcoholic Liver Disease: The Role of Ethanol and Alcoholic Liver Disease David H. Van Thiel; Judith S. Gavaler; and Patricia K. Eagon 32 Effects of Delta-9-Tetrahydrocannabinol on Reproductive Neuroendocrine Function in the Female: Animal Studies Lee Tyrey and Laura L. Murphy 42 Progress Reports Progress Report From the NIDA Addiction Research Center (Preclinical Laboratory), Lexington, Kentucky (1984) C. W. Gorodetzky; W. F. Buchwald; E. J. Cone; W. D. Darwin; W. B. Pickworth; M. E. Risner; and L. G. Sharpe 52 vii Progress Report From the NIDA Addiction Research Center Baltimore, Maryland (1984) Donald R. Jasinski; Rolley E. Johnson; John E. Hickey; Charles A. Haertzen; Jack E. Henningfield; and Karen Kumor 59 Progress Report From The Division of Behavioral Biology, The Johns Hopkins University School of Medicine George E. Bigelow; Joseph V. Brady; Roland R. Griffiths; Maxine L. Stitzer; Nancy A. Ator; Stephen T. Higgins; Ira A. Lfebson; and Scott E. Lukas 66 Report From The University