Drug Addiction II

Section I Amphetamine and Psychologen Dependence.- 1 General Pharmacology of Amphetamine-Like Drugs.- A. Pharmacokinetics and Metabolism.- A. Structure-Activity Relationships Among the Amphetamines.- I. Effect of Aromatic Substitution.- II. Effect of Length of the Side Chain.- III. Effect of Substitution of the Primary Nitrogen.- IV. Effect of Substitution of the Side Chain.- V. Stereoisomers.- B. Metabolism.- I. Pathways of Metabolism.- 1. Hydroxylation of Amphetamine.- 2. Aliphatic Hydroxylation.- 3. Oxidative Deamination.- 4. N-Dealkylation.- 5. N-Oxidation.- II. Stereoselectivity in Amphetamine Metabolism.- III. Factors Influencing the Metabolism of Amphetamine.- 1. Species.- 2. Urinary pH.- 3. Other Drugs.- 4. Other Factors.- IV. Metabolism of Amphetamine in Dependent Subjects.- C. Pharmacokinetics of Amphetamine.- D. Relationship Between Blood Levels and Effect in Man.- References.- B. Effects of Amphetamine in Animals.- A. Introduction.- B. Effects of Amphetamine on Neuronal Transmission.- I. Biochemical Neuropharmacology.- 1. Adrenergic Transmission.- a) Storage of CA.- b) Uptake of CA.- c) Release of CA.- d) Enzymatic Inactivation of CA.- e) Synthesis of CA.- f) Turnover of CA.- g) Uptake into and Release from Adrenergically Innervated Tissues of Amphetamine Itself.- h) Amphetamine Metabolites and Tissue CA.- i) Summary and Conclusions.- 2. Serotoninergic (5HT) Transmission.- a) Storage of 5HT.- b) Uptake of 5HT into Neurons and Platelets.- c) Release of 5HT.- d) Enzymatic Inactivation of 5HT.- e) Synthesis and Turnover of Brain 5HT.- f) Summary and Conclusions.- 3. Cholinergic Transmission.- 4. Other Putative Transmittors.- 5. Secondary Transmission; Cyclic Adenosine-3?,5?-monophosphate (cAMP).- 6. Summary and Conclusions.- II. Functional Neuropharmacology.- 1. Effects of Amphetamine on Peripheral Noradrenergically Innervated and Other Tissues in Vivo and in Vitro.- a) The Cat Nictitating Membrane and the Rat Inferior Eyelid.- b) The Cat Iris.- c) The Guinea Pig Vas Deferens.- d) The Rabbit and Guinea Pig Intestines.- e) The Guinea Pig Bladder.- f) Other Peripheral Effects of Amphetamine Possibly Mediated via Serotoninergic Mechanisms.- g) On Tachyphylaxis to the Sympathomimetic Effects of Amphetamine and its Metabolites.- h) Summary of Conclusions.- 2. Effect of Amphetamine on Sympathetic Ganglia.- 3. Effects of Amphetamine on the Nerve Impulse Activity of Single Neurons in the Central Nervous System.- a) Brain Stem Reticular Formation.- b) Hypothalamus.- c) Locus Ceruleus.- d) Substantia Nigra.- e) Caudate Nucleus.- f) Raphé Nuclei.- g) Summary and Conclusions.- 4. Functional Effects of Amphetamine Directly Related to Release of DA, NA, and 5HT in the CNS.- a) Amphetamine Induced Turning and Rotation in Rats and Mice after Unilateral Lesions in the Dopamine Neuronal Systems.- b) The Flexor Reflex.- c) The Extensor Reflex.- d) Summary and Conclusions.- 5. General Summary and Conclusions.- C. Pharmacologic Effects of Amphetamine.- I. Behavioral Effects of Amphetamine.- 1. Gross Behavior.- a) Stereotyped Behavior.- b) Motor Activity.- c) Behavior Observed in the Open Field.- d) Exploratory Behavior.- e) Gross Behavior Effects in Birds.- f) General Summary and Conclusions.- 2. Social Behaviors.- a) Social Interaction.- b) Aggressive Behavior.- c) Sexual Behavior.- 3. Conditioned and Operant Behaviors.- a) The Conditioned Avoidance Response.- b) Positively Reinforced Operant Behavior.- c) Intracranial Self-Stimulation.- d) Self-Administration of Amphetamine in Animals.- e) Amphetamine as an Aversive Stimulus.- f) Maze Performance.- g) Conditioned Reflexes.- h) Miscellaneous Behavioral Studies.- 4. Effects of Amphetamine on Learning and Memory.- a) Experiments on Learning and Memory.- b) State-Dependent Learning.- c) Summary and Conclusions.- II. Effects of Amphetamine on Food and Water Intake.- 1. Food Intake.- a) Amphetamine-Induced Anorexia.- b) Effects of Other Drugs on Amphetamine-Induced Anorexia.- c) Effects of Brain Lesions on Amphetamine-Induced Anorexia.- d) Effects of Brain Stimulations on Amphetamine-Induced Anorexia.- e) Effects of Amphetamine on the Electrical Activity of Neurons Within the Hypothalamus.- f) Intracerebral Injections of Amphetamine and Food Intake.- g) Other Factors Affecting Amphetamine-Induced Anorexia.- h) Effects of Chronic Administration of Amphetamine on Food Intake and Body Weight.- i) Summary of Proposed Mechanisms for the Anorexigenic Effect of Amphetamine.- 2. Hoarding Behavior.- 3. Water Intake.- III. Autonomic, Metabolic, and Endocrine Effects of Amphetamine; Amphetamine Toxicity.- 1. Cardiovascular Effects of Amphetamine.- a) Arterial Blood Pressure.- b) Effect of Amphetamine on Pulmonary Circulation.- c) Effect of Amphetamine on Cerebral Circulation.- d) Effects of Surgical Manipulations on the Pressor Response to Amphetamine.- e) Effects of Other Drugs on the Pressor Effect of Amphetamine.- f) Effects of Repeated Doses of Amphetamine on Blood Pressure.- g) Summary and Conclusions.- 2. Respiratory Effects of Amphetamine.- 3. Amphetamine Induced Salivation.- 4. Body Temperature.- a) Amphetamine-Induced Hyperthermia.- b) Effects of Other Drugs on Amphetamine-Induced Hyperthermia.- c) Effects of Brain Lesions on Amphetamine-Induced Hyperthermia.- d) Other Factors Influencing Amphetamine-Induced Hyperthermia.- e) Physiologic Correlates to Amphetamine-Induced Hyperthermia.- f) Biochemical Correlates to Amphetamine-Induced Hyperthermia.- g) Effects of Chronic Amphetamine Administration on the Hyperthermic Response.- h) Amphetamine Induced Hypothermia.- i) Behavior Thermoregulation.- j) Summary of Mechanisms Involved in Amphetamine-Induced Changes in Body Temperature.- 5. Effects of Amphetamine on General Metabolic Processes in Brain and Peripheral Tissues.- a) Oxygen Consumption.- b) Brain Adenosine Nucleotide and Phosphate Metabolism.- c) Carbohydrate Metabolism.- d) Lipid Metabolism.- e) Protein Metabolism.- f) Nucleic Acid Metabolism.- g) Miscellaneous Studies on General Metabolism.- 6. Endocrinologic Effects of Amphetamine.- a) Insulin.- b) ACTH-Corticosteroids.- c) Growth Hormone.- d) Prolactin.- e) Pineal Gland Hormones.- f) Thyroid Hormones.- 7. Toxicity of Amphetamine.- a) Lethality After Amphetamine Administration.- b) Factors of Importance for Amphetamine Induced Toxicity in Aggregated and Isolated Mice and Rats.- c) Effects of Other Drugs on Amphetarnine-Induced Toxicity in Mice and Rats.- d) Chronic Toxicity of Amphetamine.- e) Pathologic-Anatomical Findings in Amphetamine-Intoxicated Animals.- f) On the Cause of Death in Amphetamine Intoxication.- g) Summary and Conclusions.- IV. Miscellaneous Pharmacologic Effects on Amphetamine.- 1. Electroencephalographic Changes Caused by Amphetamine.- 2. Effects of Amphetamine on Seizure Susceptibility.- 3. Sleep and Wakefulness.- 4. Amphetamine-Induced Analgesia.- 5. Effects of Amphetamine on Physical Performance in Animals.- D. Conclusion.- Abbreviations Used.- References.- C. Effects of Amphetamines in Humans.- A. General Considerations.- B. Effects of Single Doses.- I. Mood.- II. Performance.- III. Wakefulness.- IV. Anorexia.- V. Analgesia.- VI. Libido.- VII. EEG.- VIII. Evoked Responses.- IX. REM Sleep.- X. Cerebral Blood Flow.- XI. Auditory Thresholds.- XII. Critical Flicker Frequency.- XIII. Pupil Size.- XIV. Cardiovascular Effects.- XV. Respiration.- XVI. Metabolic Changes.- XVII. Blood Cells.- XVIII. Various Smooth-Muscle Effects.- XIX. Hormones and Neurotransmitters.- C. Effects of Chronic Administration.- I. Mood.- II. Abuse Potential.- III. Performance.- IV. Wakefulness.- V. Anorexia.- VI. Analgesia.- VII. Libido.- VIII. EEG.- IX. REM Sleep.- X. Cerebral Blood Flow, Auditory Thresholds, Critical Flicker Frequency, and Pupil Size.- XI. Cardiovascular Effects.- XII. Metabolic Effects.- XIII. Respiration, Blood Cells, and Smooth-Muscle Effects.- XIV. Hormones and Neurotransmitters.- D. Acute and Subacute Intoxication.- I. Paranoid Psychosis.- II. Stereotyped Behavior.- III. The Choreic Syndrome.- IV. Excitation Syndrome.- V. Dysautonomic Syndrome.- VI. Cerebrovascular Accidents.- E. Blockade of Amphetamine Effects.- References.- 2 Amphetamine Dependence; Clinical Features.- A. Naturally-Occurring Psychostimulants.- I. Khat.- II. Xanthines.- III. Ephedrine.- IV. Absinthe.- V. Cocaine.- B. Exogenous Phenethylamine Congeners.- C. Synthetic Psychostimulants.- I. Amphetamine and Methamphetamine.- II. Other Amphetamine Congeners.- III. Psychodelic Amphetamines.- D. Changing Medical Views on Amphetamine Abuse and Psychotoxicity.- E. Contemporary Medical Indications.- I. Obesity.- II. Narcolepsy.- III. Hyperkinetic Syndromes of Children.- IV. Emotional Depression.- V. Analgesia.- VI. Miscellaneous Applications.- F. Psychotoxicity.- I. Acute Intoxication.- II. Dependency Syndromes.- III. Amphetamine Psychosis.- 1. Clinical Syndrome.- 2. Clinical Features.- 3. Withdrawal, Hospital Course and Treatment.- G. Experimentally Induced Amphetamine Psychoses.- References.- 3 Pharmacology and Classification of LSD-like Hallucinogens.- A. Introduction.- B. Classification of LSD-like Hallucinogens.- I. Problem.- II. Effects of LSD-like Hallucinogens, Mescaline, and Other Hallucinogens.- 1. Man.- a) Behavioral and Subjective Changes.- b) Physiologic Changes.- c) Effects of Related Drugs.- ?) Indoleamines and LSD Derivatives.- ?) ?-Phenethylamines and Amphetamines.- d) Interactions with LSD.- 2. Other Species.- a) Mouse.- b) Rat.- c) Rabbit.- d) Cat.- e) Dog.- f) Monkey.- g) Others.- III. Tolerance and Cross-Tolerance.- 1. Man.- 2. Rat.- 3. Rabbit.- 4. Cat.- 5. Dog.- IV. Criteria for LSD-like Hallucinogens.- Characteristics.- V. Chemical Structures of LSD-like Hallucinogens.- 1. ?-Phenethylamines.- 2. Amphetamines.- 3. Indoleamines.- 4. Lysergic Acid Amides.- C. Mode of Action.- I. Serotonin Antagonist Theory.- II. Serotonin Agonist Theory.- III. Tryptamine Agonist Theory.- IV. Other Brain Amines and Polypeptides.- V. Distribution.- D. Sites of Action.- I. Spinal Cord.- II. Pons Medulla.- 1. Cardiovascular Changes.- 2. Respiration.- 3. Chemoreceptive Trigger Zone.- 4. Tolerance.- III. Mesencephalon.- 1. Effects on the Eye, Optic Tract, and Lateral Geniculate.- 2. Pupils.- IV. Diencephalon-thermal Regulations.- IV. Cortex.- 1. Effects of LSD-like Hallucinogens on Cortical Neurons.- 2. Seizure Activity.- 3. Transcallosal Potentials.- 4. EEG, Cortical Evoked Potentials, and Sleep.- a) Rat.- b) Rabbit.- c) Cat.- d) Monkey.- e) Man.- E. Conclusions and Discussion.- I. Pharmacologic Characteristics of LSD-like Hallucinogens.- II. LSD Hallucinogens - Agonists.- III. Tolerance.- IV. Modes of Action.- V. Mechanisms of Action.- VI. Abuse Potential and Identification of LSD-like Drugs.- Most Usual Abbreviations.- References.- Section II Marihuana Dependence.- 1 Cannabis. Its Chemistry, Pharmacology, and Toxicology.- A. Introduction.- B. Chemistry.- Isolation.- C. Distribution and Fate.- D. Pharmacology.- I. Central Nervous System.- 1. General Effects in Man.- 2. Overt Behavior.- 3. Aggression.- 4. Operant or Conditioned Behavior.- 5. Analgesia.- II. Biogenic Amines.- 1. NE, E, and DA.- 2. 5-HT.- 3. ACh.- III. Cardiovascular and Autonomic Effects.- IV. Endocrine Effects.- V. Cellular Effects.- E. Toxicology.- F. Tolerance.- Physical Dependence.- G. Therapeutic Potential.- References.- Autor Index.