This volume addresses the general problem of drug addiction from several points of view, which are in some ways quite unique and different from other areas of pharmacology. Drug addiction is closely associated with criminal behavior. One of the great and noble edifices of civilization is the philosophic and ethical view that man is perfectible, and some believe that this can be achieved by providing the appropriate circumstance or environment in which man can mature and be educated. Some have postulated that drug abuse is a consequence of an inadequate or pathologic set of socializing experiences or is a consequence of basic conflicts between the values and accepted patterns of behavior of a subculture and that of a larger culture. The degree to which man is malleable and perfectible by social forces is not known nor do we know the true desirability of socializing individuals to the extent that their behavior does not deviate from social norms. Some deviancy is essential for innovation and creativity, and at times there may be difficulties in determining whether an innovator or creator is exhibiting sociopathic behavior or not. This aspect of drug addiction is inherently a matter of social values and ethics.

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Section I Problems of Drug Dependence.- 1 General Problems of Drug Abuse and Drug Dependence.- A. Introduction.- B. Cost of Abuse of Major Drugs (Economic, Social, and Health).- I. Narcotic Analgesics.- II. Sedative/Hypnotics and Minor Tranquilizers (Depressants).- III. Alcohol.- IV. Amphetaminelike Agents (Stimulants).- V. Hallucinogens.- VI. Cannabis, Marihuana, Hashish.- VII. Summary and Conclusions.- C. Legal and Regulatory Approaches to Minimizing Drug Abuse.- I. Forces Influencing Federal Legislation.- II. Summary of Laws of the United States Regulating Drugs of Abuse.- D. Medical Treatment and Research Efforts.- I. National Research Council.- II. The Federal Government.- 1. Treatment.- 2. Research.- III. Medical and Psychiatric Concepts of Addiction.- 1. Psychopathology.- 2. Sociologic Theories.- 3. Tolerance, Dependence, and Conditioning.- 4. Heredity.- E. Conclusions.- Most Usual Abbreviations.- References.- Section II Morphine Dependence.- 1 Neuropharmacology and Neurochemistry of Subjective Effects, Analgesia, Tolerance, and Dependence Produced by Narcotic Analgesics.- A. Introduction.- B. Subjective States and Their Correlates.- I. Introduction.- II. Subjective Effects in Man.- 1. Single Doses.- 2. Effects of Chronic Administration and Withdrawal.- III. Mouse.- IV. Rat.- V. Cat.- VI. Protracted Abstinence.- VII. EEG Effects.- VIII. Discussion and Conclusions.- C. Analgesia and Pain.- I. Introduction.- II. Neuropharmacology of Pain and the Narcotic Analgesics.- 1. Peripheral Nerve and the Myoneural Junction.- 2. Spinal Cord.- a) Segmental and Spinal Cord Reflexes.- ?) Cat.- ?) Dog.- ?) Rat.- b) Spinal Cord Inhibitory Processes.- 3. Supraspinal Influences.- 4. Sensory Pathways.- 5. Discussion and Conclusions.- III. Neurochemical and Neurohumoral Changes Associated with Analgesia.- 1. Introduction.- 2. Acetylcholine.- a) Analgesia.- b) Guinea Pig Ileum and Other Isolated Tissues.- c) Brain ACh Release.- d) Brain ACh Metabolism.- 3. Serotonin.- Analgesia.- 4. NE and E.- a) Analgesia.- b) Interactions with Narcotic Analgesics.- c) Metabolism.- ?) Dopamines ?-Hydroxylase.- ?) Tyrosine Hydroxylase.- ?) Reserpine.- ?) 6-OHDA.- ?) Pyragallol.- ?) Isolated Tissue.- 5. Dopamine (DA).- 6. Other Drugs Which Affect Indole and Catecholamine Metabolism.- 7. Cyclic AMP, Prostaglandins, and Polypeptides.- 8. Discussion and Conclusions.- D. Tolerance and Physical Dependence.- I. Introduction.- II. Definitions.- III. Description of Tolerance and Dependence.- 1. Mouse.- 2. Rat.- 3. Guinea Pig.- 4. Rabbit.- 5. Dog.- 6. Monkey.- 7. Man.- IV. Problems of Quantitating Tolerance and Physical Dependence.- 1. Tolerance.- a) Baseline Problem.- b) The Syndrome Problem.- c) Change in Effect.- d) Quantitation of Tolerance.- 2. Physical Dependence.- a) Baseline Problem.- b) Syndrome Problem.- V. Neurophysiology.- 1. Isolated Tissues.- 2. Spinal Cord and Brain.- VI. Neurochemical and Neurohumoral Changes.- 1. ACh.- 2. E and NE.- a) Adrenal Medulla.- ?) Single Doses (Cat, Dog, Rat, Mouse, Rabbit).- ?) Chronic Administration.- ?) Abstinence (Rat, Dog, Rabbit, Man).- b) Brain.- ?) Single Doses (Cat, Dog, Rat, Mouse).- ?) Chronic Administration (Monkey, Cat, Dog, Rat, Mouse).- ?) Abstinence.- 3. DA.- a) Single Doses (Cat, Monkey, Rabbit, Mouse, Rat).- b) Chronic Administration (Rat, Mouse, Dog, Monkey, Man).- c) Abstinence (Rat, Dog, Mouse).- 4. Serotonin.- a) Single Doses (Cat, Dog, Rat, Mouse).- b) Chronic Administration (Dog, Rat, Mouse, Rabbit, Man).- c) Abstinence.- 5. Proteins, Polypeptides, Cyclic AMP, Prostaglandins, and GABA.- VII. Theories of Tolerance and Physical Dependence.- 1. Neuronal and Neurohumoral Factors.- 2. General Theories.- a) Homeostasis.- b) Learning and Adaptation.- c) Reversible Changes.- d) Persisting Changes.- Single Cells.- VIII. Summary and Conclusions.- Abbreviations.- References.- 2 Assessment of the Abuse Potential of Narcotic Analgesics in Animals.- A. Introduction.- B. Reinforcing Properties.- C. Pharmacologic Equivalence.- I. Autonomic, Somatomotor, and Behavioral Effects in Nondependent and Dependent Animals.- II. Tolerance and Cross-Tolerance.- III. Suppression Studies.- IV. Direct Addiction and Precipitation Studies.- D. Mouse.- I. Pharmacologic Profile.- II. Direct Addiction, Suppression and Precipitated Abstinence Studies.- E. Rat.- I. Pharmacologic Profile.- II. Self-Administration.- III. Suppression Studies.- IV. Direct Addiction and Precipitation Studies.- F. Dog.- I. Pharmacologic Profile.- II. Self-Administration.- III. Suppression Studies.- IV. Direct Addiction and Precipitation Studies.- G. Monkey.- I. Pharmacologic Profile.- II. Self-Administration.- III. Suppression Studies.- IV. Direct Addiction and Precipitation Studies.- Direct Addiction.- H. Critique of Certain Critical Drugs.- I. Meperidine and Ketobemidone.- II. Dextrorphan and Dextromethorphan.- III. Phenazocine, GPA-1657 (Beta-[-]-5-phenyl-9-methyl-2?-hydroxy-2-methyl-6,7-benzomorphan) and GPA-2087 (l-alpha-5,9-diethyl-2?-hydroxy-2-methyl-6,7-benzomorphan; l-etazocine).- IV. Profadol and Propiram.- J. Discussion and Conclusions.- I. Species.- II. Sensitivity of Measures and Experimental Design.- III. Validity of Tests.- 1. Pharmacologic Profile.- 2. Self-Administration.- 3. Suppression Studies.- a) Partial Agonists.- b) Species.- 4. Direct Addiction and Precipitation Studies.- IV. Conclusions.- References.- 3 Assessment of the Abuse Potentiality of Morphinelike Drugs (Methods Used in Man).- A. Introduction.- I. Rationale for Assessment.- II. Origin of Assessment.- 1. Development of Morphine Substitutes.- 2. Protection of the Public Health.- B. Origin of Methods.- I. Physical Dependence.- 1. Substitution Hypothesis.- 2. Experimental Procedures.- II. Euphoria and Subjective Effects.- 1. Initial Definition.- 2. Experimental Procedures.- C. Current Methods.- I. Physical Dependence.- 1. Substitution Tests.- 2. Direct Addiction.- II. Euphoria and Subjective Effects.- D. Narcotic Antagonists.- I. Nalorphine and Cyclazocinelike Antagonists.- II. Antagonists Lacking Agonist Effects (Naloxone).- III. Partial Agonists of the Morphine Type.- E. Validity.- I. Subjective Effects and Euphoria.- II. Physical Dependence.- III. Indication of Abuse Potential.- F. Pentazocine and Related Compounds.- G. Summary and Conclusions.- References.- 4 Psychiatric Treatment of Narcotic Addiction.- A. Introduction.- B. Psychoanalytic Treatment.- C. Institutional Treatment.- D. Community Treatment Efforts.- I. Psychiatrically Oriented Programs.- II. Synanon.- E. Civil Commitment Programs.- F. Conclusions.- References.- 5 Chemotherapy of Narcotic Addiction.- A. Introduction.- B. Diagnosis of Narcotic Addiction.- I. Diagnosis of Psychopathy.- II. Diagnosis of Tolerance an…