Psychotropic Agents: Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs

518 Pages·1982·14.97 MB·English

by  A. T. Shulgin (auth.)

Handbook of
Experimental Pharmacology
Continuation of Handbuch der experimentellen Pharmakologie
Vol. 551111
Editorial Board
G. V. R Born, London· A. Farah, Rensselaer, New York
H. Herken, Berlin· A. D. Welch, Memphis, Tennessee
Advisory Board
S. Ebashi . E. G. Erdos· V. Erspamer· U. S. von Euler· W. S. Feldberg
G. B. Koelle· O. Krayer· M. Rocha e Silva· J. R. Vane· P. G. Waser
Psychotropic Agents
Part III: Alcohol and Psychotomimetics,
Psychotropic Effects of Central Acting Drugs
Contributors
L. G. Abood' G. K. Aghajanian . J. B. Appel' W O. Boggan
D.A. Buxton' H. Coper' T. L. Chrusciel' J. Ellingboe' C.-J. Estler
D.X. Freedman· H.J. Gartner' S.R. Goldberg· D. T. Greenwood
H. Halbach' H. Heimann' L.E. Hollister· D.M. Kuhn' WR. Martin
R. Mechoulam . N. K. Mello· J. H. Mendelson· D. N. Middlemiss
A. D. Poling· H. E. Shannon' A. T. Shulgin . R. D. Spealman
Editors
F. Hoffmeister· G. Stille
Springer-Verlag Berlin Heidelberg New York 1982
Professor Dr. F. HOFFMEISTER
Bayer AG, Institut fUr Pharmakologie, Aprather Weg 18a, D-5600 Wuppertal 1
Professor Dr. G. STILLE
Institut fUr Arzneimittel des Bundesgesundheitsamtes,
StauffenbergstraBe 13, D-I000 Berlin 30
With 21 Figures
ISBN-13: 978-3-642-67772-4 e-ISBN-13: 978-3-642-67770-0
DOl: 10.1007/978-3-642-67770-0
This work IS subject to copynght. All nghts are reserved, whether the whole or part of the material IS concerned
specifically those of translation, reprintmg, re·use of Illustrations, broadcasting, reproducing by photocopying machine
or similar means, and storage in data banks. "Under § 54 of the German Copyright Law where copies are made for other
than pnvate use a fee IS payable to 'Verwertungsgesellschaft Wort', Munich."
© by Spnnger· Verlag Berhn Heidelberg 1982
Softcover reprint of the hardcover 1st edition 1982
The use of registered names, trademarks, etc. in this publication does not Imply, even in the absence of a specific
statement, that such names are exempt from the relevant protective laws and regulatIOns and therefore free for general use.
Preface
The description of the pharmacology of psychotomimetics, cannabis, and alcohol in
this third volume concludes the discussion on psychotropic agents.
As psychomotor stimulants these groups of psychotropic agents are of little or no
therapeutic relevance, but since they are used in a nonmedical manner, or are even
considered by some groups of the population as social commodities, their behavioral
effects and psychopharmacological properties are not the concern of the pharmacol
ogist alone. The same is true of psychotomimetics, as well as cannabis and its
components. Psychotomimetics have a social history going back many hundreds of
years and are among the most potent psychotropic agents known to man.
The closing description of psychopharmacology also deals with the psychotropic
effects of a number of drugs not primarily considered to be psychotropic. Their
psychotropic effects are either an inherent constituent of their therapeutic profile, as is
the case with opiates, hypnotics, and caffeine, or they may occur indirectly as side
effects or accompanying effects during therapy. This applies to p-adrenoreceptor
antagonists and anticholinergics.
The editors are also aware that a description of psychotropic agents would not
have been complete without discussing the medical, ethical, and legal aspects of the
development, clinical testing, and use of such drugs.
Conscious of the fact that it is almost impossible to describe and discuss
psychopharmacology completely, the editors express the hope that those topics of
major importance have been included. It would not have been possible to compile the
three volumes on psychotropic agents without the cooperation of numerous scientists
from all over the world. Therfore, the editors would like to express their gratitude to all
those who cooperated in making it possible to publish those three volumes.
Wuppertal/Berlin F. HOFFMEISTER' G. STILLE
List of Contributors
Professor Dr. L. G. ABOOD, University of Rochester, Center of Brain Research,
Medical Center, Rochester, NY 14642jUSA
Professor Dr. G. K. AGHAJANIAN, Departments of Psychiatry and Pharmacology,
Yale University School of Medicine and the Connecticut Mental Health Center,
3400 Park Street, New Haven, CT 06508/USA
Professor Dr. J. B. ApPEL, Behavioral Pharmacology Laboratory, Department of
Psychology, University of South Carolina, Columbia, SC 29208jUSA
Professor Dr. W. O. BOGGAN, Department of Psychiatry and Biochemistry, Medical
University of South Carolina, Charleston, SC 29403/USA
Dr. D. A. BUXTON, ICI Imperial Chemical Industries Ltd., Pharmaceuticals Division,
Mereside Alderley Park, GB-Macc1esfield, Ches. SK 104TG
Professor Dr. H. COPER, Institut fUr Neuropsychopharmakologie der Freien Uni
versitiit, Ulmenallee 30, D-lOOO Berlin 19
Professor Dr. T. L. CHRUSCIEL, Institute for Drug Research and Control, 30/34
Chalmska, P-00725 Warsaw
Dr. J. ELLINGBOE, Alcohol and Drug Abuse Research Center, Harvard Medical
School, The McLean Hospital, 115 Mill Street, Belmont, MA 02178jUSA
Professor Dr. C.-J. ESTLER, Institut fUr Pharmakologie und Toxikologie der Uni
versitiit Erlangen-Niirnberg, UniversitiitsstraBe 22, D-8520 Erlangen
Professor Dr. D. X. FREEDMAN, University of Chicago, Department of Psychiatry,
950 East 59th Street, Chicago, IL 60637/USA
Dr. H. J. GARTNER, Psychiatrische Universitiitsklinik, OsianderstraBe 22, D-7400
Tiibingen
Dr. S. R. GOLDBERG, National Institute on Drug Abuse, Addiction Research Center,
P.O. Box 12390, Lexington, KY 40583jUSA
Dr. D. T. GREENWOOD, ICI Imperial Chemical Industries Ltd., Pharmaceuticals
Division, Mereside Alderley Park, GB-Macc1esfield, Ches. SK 104TG
Professor Dr. H. HALBACH, D-8210 Prien, Stetten
Professor Dr. H. HEIMANN, Psychiatrische Universitiitsklinik, OsianderstraBe 22,
D-7400 Tiibingen
VIII List of Contributors
Dr. L. E. HOLLISTER, Stanford University School, Veterans Administration Hospital,
3801 Miranda Avenue, Palo Alto, CA 94304/USA
Dr. D. M. KUHN, Behavioral Pharmacology Laboratory, Department of Psychology,
University of South Carolina, Columbia, SC 29208/USA
Professor Dr. W. R. MARTIN, University of Kentucky, Albert B. Chandler Medical
Center, College of Medicine, Department of Pharmacology, Lexington,
KY 40536/USA
Professor Dr. R. MECHOULAM, The Hebrew University of Jerusalem, Department of
Natural Products, IL-Jerusalem
Professor Dr. N. K. MELLO, Alcohol and Drug Abuse Research Center, Harvard
Medical School, The McLean Hospital, 115 Mill Street, Belmont, MA 021 78jUSA
Dr. J. H. MENDELSON, Alcohol and Drug Abuse Research Center, Harvard Medical
School, The Mclean Hospital, 115 Mill Street, Belmont, MA 92178jUSA
Dr. D. N. MIDDLEMISS, ICI Imperial Chemical Industries Ltd., Pharmaceuticals
Division, Mereside Alderley Park, GB-Macclesfield, Ches. SK 104TG
Professor Dr. A. D. POLING, Western Michigan University, Department of Psychology,
Kalamazoo, MI49008/USA
Dr. H. E. SHANNON, National Institute on Drug Abuse, Addiction Research Center
P.O. Box 12390, Lexington, KY 40583/USA
Dr. A. T. SHULGIN, 1483 Shulgin Road, Lafayette, CA 94549jUSA
Dr. R. D. SPEALMAN, Harvard Medical School, New England Regional Primate
Research Center, Southborough, MA/USA
Contents
Psychotomimetics
CHAPTER 1
Chemistry of Psychotomimetics. A. T. SHULGIN
A. Introduction . . . . . 3
I. Terminology. . . 3
II. Methods of Assay. 4
III. Classification. . . 5
B. Psychotomimetics Structurally Related to Serotonin 6
I. Indoles . . . . . . . . . . . . . . . .. 7
I. Nitrogen-Substituted Tryptamine Derivatives. 7
2. Ring-Substituted Tryptamine Derivatives 7
II. Beta-Carbolines. . . . . . . . . . . 8
III. Ergot-Related Drugs . . . . . . . . 10
I. Synthetic Lysergic Acid Derivatives. 11
2. Natural Lysergic Acid Derivatives . 11
C. Psychotomimetics Structurally Related to Dopamine. 13
I. Phenethylamines . . . . . . . . . . . . . . 13
II. Phenylisopropylamines. . . . . . . . . . . . 14
D. Psychotomimetics Structurally Related to Acetylcholine:
Atropine-Related Drugs . . . . 17
E. Miscellaneous Psychotomimetics 18
I. Ibotenic Acid. . . . . 18
II. Dissociative Anesthetics 20
III. Ibogaine. . 20
IV. Kavakava. 21
V. Marihuana. 21
References. . . . . 23
CHAPTER 2
Pharmacology and Toxicology of Psychotomimetics. L. E. HOLLISTER.
With 2 Figures
A. Introduction . . . . . . . . . . . . 31
B. Definition of a Psychotomimetic Drug . 31
x
Contents
C. Types of Psychotomimetics. . . . . . 31
D. Epidemiologic Aspects. . . . . . . . 32
E. The LSD-Mescaline-Psilocybin Group. 32
I. Chemistry . . . 32
II. Pharmacology . 34
III. Clinical Effects . 35
IV. Adverse Effects. 36
F. Harmine Alkaloids and Piperidyl Benzilates. 37
G. Phencyclidine. 38
I. History ... 38
II. Chemistry .. 39
III. Pharmacology 39
IV. Clinical Effects . 40
V. Overdoses 41
H. Conclusions 42
References. . 42
CHAPTER 3
Psychotomimetics: Behavioral Pharmacology. J. B. APPEL, A. D. POLING,
and D.M.KUHN
A. Introduction . . . . . . . . . . . . . . . . . . . . . . . 45
B. The Behavioral Pharmacology of LSD and Related Compounds . 45
I. Operant (Instrumental) Behavior . . . . . . . . . . . . 45
1. Positive Reinforcement: Schedule-Controlled Behavior. . 45
2. Negative Reinforcement: Escape and Avoidance Behavior 46
II. Respondent (pavlovian) Behavior. 47
1. Appetitive Conditioning. . . . 47
2. Aversive (Defense) Conditioning 47
III. Perceptual Effects. . . . . . . . 48
IV. Tolerance and Related Phenomena 49
1. Tolerance. . . 49
2. Cross-Tolerance . . . . . . . 49
3. Dependence. . . . . . . . . 49
V. Stimulus Properties of Psychotomimetics . 49
1. Discriminative Stimulus Properties . 50
2. Reinforcing Properties . . . . . . 50
3. Unconditioned Stimulus Properties . 51
C. Summary and Conclusions. 51
References. . . . . . . . . . . . . . . . . 52
CHAPTER 4
Biochemical Pharmacology of Psychotomimetics. D. X. FREEDMAN and
W.O.BOGGAN
A. Introduction . 57
B. Effects in Man 59
Contents XI
C. 5-HT and LSD 61
I. The First 60 min 62
II. Beyond 60 min . 63
III. LSD-5 HT Summary 64
D. Other Psychotomimetics . 65
E. LSD and Catecholamines 66
F. Lisuride and LSD. . . . 69
G. Tolerance, Blockade, and Enhancement of LSD Effects 71
H. Adenylate Cyclase. . . 72
I. Stereospecific Binding . 74
1. Conclusion. 76
References .. 77
CHAPTER 5
Neurophysiologic Properties of Psychotomimetics. G. K. AGHAJANIAN.
With 2 Figures
A. Introduction . . . . . . . . . . . . . . . . . . . 89
B. Psychotomimetic Drugs and Related Neurotransmitters 89
I. Psychedelics . . . . . . . . . . . . . 89
I. LSD and the Simple Indoleamines . . 90
2. Mescaline and Methoxyamphetamines. 95
II. Stimulants. . . . . . . . . . . . . . 98
1. Comparison of Amphetamine Isomers on the Activity of NE and
DA Neurons. . . . . . . . . . . . . . . . . . . . . . . . 98
2. Differential Actions of Amphetamine Isomers on Striatal and Non-
striatal DA Systems. . . . . . . . . . . . . . . . . 99
III. Deliriants . . . . . . . . . . . . . . . . . . . . . . 99
1. Antimuscarinic Drugs and Central Cholinergic Pathways. 100
2. Action of Physostigmine in Cholinergic Pathways. . 101
3. Deliriants as a Model for Human Memory Disorders 101
C. General Conclusions. 101
I. Stimulants. . . . 101
II. Deliriants . . . . 102
III. Psychedelic Drugs. 102
References. . . . . . . . 103
CHAPTER 6
Dependence-Producing Liability of LSD and Similar Psychotomimetics.
A. D. POLING and J. B. ApPEL. With I Figure
A. Introduction: Definition of Drug Dependence. . . . . III
B. Discovery of and Effects of LSD . . . . . . . . . . III
C. Problems in Assessing Dependence-Producing Liability. 113
D. Social Factors and the Dependence-Producing Liability of LSD. 114
E. Summary and Conclusions . 115
References. . . . . . . . . . . . . . . . . . . . . . . . . . 115
XII Contents
Cannabis
CHAPTER 7
Chemistry of Cannabis. R. MECHOULAM. With 6 Figures
A. Introduction . . . . . . . . . . 119
B. Naturally Occurring Cannabinoids 120
I. Isolation and Structure 120
II. Chemical Properties. . . . . 122
III. Syntheses . . . . . . . . . 124
C. Structure-Activity Relationships (SARs) 125
D. Cannabinoid Analysis .. 127
E. Cannabinoid Metabolites. 128
F. Concluding Remarks 130
References. . . . . . . . . 131
CHAPTER 8
Pharmacology and Toxicology of Cannabis. H. COPER
A. Introduction . . . . . 135
B. Pharmacokinetic Effects 135
I. Absorption. 135
II. Distribution . . . 136
III. Elimination . . . 137
C. Pharmacodynamic Effects 138
I. In Information-Bearing Macromolecules . 138
II. In Functional Macromolecules 139
III. In Functional Systems. . . . . . . . . 140
1. Neurotransmission . . . . . . . . . 140
2. Cardiovascular and Respiratory Systems. 141
3. Food Consumption and Temperature Regulation. 142
4. Analgetic and Anticonvulsant Effects . . . . . . 143
5. Motor System, Psychomotor Performance Tasks, and EEG 143
D. Aspects of Tolerance . . . . 144
E. Interactions with Other Drugs 147
F. Conclusion. 149
References. . . . . . . . . . . 150
Alcohol
CHAPTER 9
General Pharmacology and Toxicology of Alcohol. T. L. CHRUScIEL
A. Introduction . . . . . 161
B. General Pharmacology. 161
I. Absorption. . . 161