Table Of ContentChemical and Biological Aspects of
Drug Dependence
Chemical
And Biological
Aspects Of
Drug
Dependence
Editors:
S.J. Mulé, Ph.D., Chief
New York State
Narcotic Addiction Control Commission
Testing and Research Laboratory
Brooklyn, New York
Henry Brill, M.D., Director
Pilgrim State Hospital
West Brentwood, New York
published by:
ffirgraras
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CONTRIBUTORS
Dr. R. Aston Dr. Max Fink
Department of Pharmacology & Anesthesiology New York Medical College
Wayne Medical School 5 East 102nd Street
Detroit, Michigan New York, New York 10029
Dr. M. M. Baden Dr. H. F. Fraser
New York University 1131 Merrick Drive
School of Medicine Merrick Place
New York, New York 10016 Lexington, Kentucky 40502
Dr. Henry Brill Dr. Robert George
Pilgrim State Hospital Department of Pharmacology
P.O. Box 22 University of California
West Brentwood, New York 11717 Los Angeles, California 90024
Dr. S. T. Christian Dr. M. Ginsburg
NIMH Addiction Research Center Department of Pharmacology
P.O. Box 2000 Chelsea College of Science & Technology
Lexington, Kentucky 40507 Manresa Road
London, S. W. 3, England
Dr. Doris H. Clouet
New York State Dr. S. Hashimoto
NACC Testing & Research Laboratory N.Y. State Psychiatric Institute
80 Hanson Place 722 West 168th Street
Brooklyn, New York 11217 New York, New York 10032
Dr. B. M. Cox Dr. M. Helpern
Department of Pharmacology New York University
Chelsea College of Science & Technology School of Medicine
Manresa Road New York, New York 10016
London, S. W. 3, England
Dr. Carl C. Hug, Jr.
Dr. W. L. Dewey Dept. of Anesthesiology & Pharmacology
Department of Pharmacology Emory University, School of Medicine
University of North Carolina 69 Butler Street, S. E.
School of Medicine Atlanta, Georgia 30303
Chapel Hill, North Carolina 27514
Dr. Arthur Jacobson
Dr. Seymour Ehrenpreis Section on Medicinal Chemistry
New York State Research Institute National Institutes of Health
for Ne uro chemistry & Drug Addiction Bldg. 4, Room 136
Ward's Island, New York 10035 Bethesda, Maryland 22014
Mr. B. Eisenberg Dr. Reese T. Jones
Department of Neuropathology The Langley Porter Neuropsychiatrie
N.Y. State Psychiatric Institute Institute
722 West 168th Street 401 Parnassus Avenue
New York, New York 10032 San Francisco, California 94122
Dr. H. Kalter Dr. Maurice H. Seevers
Department of Pediatrics Department of Pharmacology
Childrens Hospital Research Foundation University of Michigan
Elland Avenue & Bethesda School of Medicine
Cincinnati, Ohio 45229 Ann Arbor, Michigan 48104
Dr. M. Kaufman Dr. Alexander T. Shulgin
N.Y. State Psychiatric Institute 1483 Shulgin Road
722 West 168th Street Lafayette, California 94549
New York, New York 10032
Dr. Eric J. Simon
Dr. Charles S. Lieber New York University School of Medicine
Mt. Sinai School of Medicine (CUNY) New York, New York 10016
Section of Liver Disease & Nutrition
Veterans Administration Hospital Dr. Charles B. Smith
130 West Kingsbridge Road Department of Pharmacology
Bronx, New York 10468 University of Michigan
School of Medicine
Mr. J. C. Liu Ann Arbor, Michigan 48104
Department of Neuropathology
N.Y. State Psychiatric Institute Dr. Solomon H. Snyder
722 West 168th Street Department of Pharmacology
New York, New York 10032 Johns Hopkins School of Medicine
725 North Wolfe Street
Dr. Peter Lomax Baltimore, Maryland 21205
Department of Pharmacology
University of California Dr. Sheldon Stolman
Los Angeles, California, 90024 Department of Pharmacology
Michigan State University
Dr. Anand L. Misra East Lansing, Michigan 48823
New York State NACC
Testing & Research Laboratory Dr. D. N. Teller
80 Hanson Place New York State Research Institute
Brooklyn, New York 11217 for Neurochemistry & Drug Addiction
Ward's Island, New York 10035
Dr. S. J. Mule, Chief
New York State NACC Dr. E. O'F. Walsh
Testing & Research Laboratory Department of Biochemistry
80 Hanson Place University of Hong Kong
Brooklyn, New York 11217 Hong Kong
Dr. Leon Roizin Dr. Abraham Wilker
Psychiatric Research Center for Advanced Study
N.Y. State Psychiatric Institute in the Behavioral Sciences
722 West 168th Street 202 Junipero Serra Blvd.
New York, New York 10032 Stanford, California 94305
PREFACE
Drug dependence has reached epidemic proportions affecting all strata of our society.
Since the etiology of drug dependence is complex and largely unknown, its treatment and
prevention have proceeded on a "trial and error" basis with mainly disappointing results.
A major alternative would be a task force attack at the cellular level to uncover the
molecular basis for the development of drug dependence. Such knowledge would lead to
rational, effective, and successful programs, to cure and/or prevent drug dependence.
It is the purpose, indeed the objective, of this monograph to provide the scientist with
a reference text that provides the basic knowledge and background information that
currently defines the chemical and biological basis of drug dependence. The approach
being a logical extension of the purpose, the nature of drug dependence and drug abuse
must first be clearly defined and characterized. Since many drugs of various chemical
formulations induce physical and/or psychic dependence, the characteristics of drug
dependence of each pharmacological class of drugs must be described. The importance of
quantitative screening tests and procedures for determining drug dependence in man and
in animals and the abuse potential of the drug must be understood. Certainly a drug may
be defined by its chemical structure as well as by the altered function that follows an
interaction with the endogenous receptor. Therefore, the chemical characteristics of such
a seemingly disparate group of compounds must be defined and, where possible,
correlated with their capacity to induce drug dependence. This relationship may further
be viewed through similarities in receptor activity, disposition, and biotransformation as
well as detection and identification of these drugs in the biological medium. The
foregoing knowledge now allows the presentation of the touchstone of the text, i.e., the
theories related to tolerance development and physical dependence. Since these drugs act
primarily within the central nervous system, it seemed most logical to include in this
section the electrophysiology, neuropathology, teratology, embryolethality, and
mutagenicity of these compounds. Finally, full attention to biochemical mechanisms
associated with such biological strata as enzymes, proteins, nucleic acids, carbohydrates,
neurohumors, lipids, and hormones was explained in relationship to drug dependence.
The monograph appropriately ends with a bonus providing insight into theoretical
biochemical mechanisms related to physical and/or psychic dependence.
The unusually broad nature of the subject matter demanded the expertise that could
only be provided through multiple authorship. The group of "super" contributors
brought such outstanding backgrounds, knowledge, and experience to bear on their
specific chapters that the editorial task was practically reduced to mere proofreading. Of
course, regardless of the effort, it is impossible in a multiauthored text to be fully aware
of omitted data or to eliminate all duplication of information.
Special acknowledgment is made to Ms. Mary Gatsoulis and Earleen Ryan for
cheerfully and effectively attending to the mundane tasks of record keeping, letter and
manuscript typing, filing, and copying. The absence of such effective assistance certainly
would have prevented the final publication of this book.
S. J. Mulé
H. Brill
New York, N. Y.
THE EDITORS
S. J. Mulé, Ph.D., is Chief of the New York State Narcotic Addiction Control Commission Testing
and Research Laboratory, New York.
Dr. Mulé received his B.A. degree in Chemistry in 1954 from College of Wooster, Wooster, Ohio; the
M.S. degree in Biochemistry and Physiology in 1955 from Rutgers University, New Brunswick, New
Jersey; and the Ph.D. degree in Pharmacology in 1961 from the University of Michigan, Ann Arbor,
Michigan. Dr. Mulé subsequently received postdoctoral training in the Departments of Physiological
Chemistry and Pharmacology at the University of Wisconsin. He continued his research at the
Addiction Research Center of the National Institute of Mental Health, Lexington, Kentucky. His
present research concerns the disposition and biotransformation of narcotic analgesics, the detection
and identification of drugs subject to abuse, and the biochemical mechanisms of drug dependence.
Dr. Mulé has published extensively in the scientific literature and is a member of pharmacological,
chemical, and forensic societies.
Henry Brill, M.D., is Director, Pilgrim State Hospital, West Brentwood, Long Island, New York.
Dr. Brill is a graduate of Yale College and Yale School of Medicine. He is a member of Phi Beta
Kappa and Sigma Xi.
As First Deputy Commissioner of the New York State Department of Mental Hygiene, Dr. Brill was
instrumental in developing the state's narcotic addiction program and the alcoholic program from
1954 to 1964. He was formerly Vice Chairman of the New York State Narcotic Addiction Control
Commission. Since 1971 Dr. Brill has been a member of the National Commission on Marihuana and
Drug Abuse.
Dr. Brill is a diplomate or member of numerous professional societies, among which is the Expert
Panel of Drug Dependence of the WHO. He has authored some 50 papers on drug dependence.
