Neuropathology of Drug Addictions and Substance Misuse Volume 1: Foundations of Understanding, Tobacco, Alcohol, Cannabinoids and Opioids

Neuropathology of Drug Addictions and Substance Misuse

Volume 1: Foundations of Understanding, Tobacco, Alcohol, Cannabinoids and Opioids

Editor

Victor R. Preedy

King’s College London, London, UK

Table of Contents

Cover image

Title page

Copyright

List of Contributors

Preface

Acknowledgments

Part I. Setting the Scene: Foundations for Understanding Substance Misuse and Their Effects

Chapter 1. The Nervous System and Addictions: Essentials for Clinicians

Introduction

A Neuroanatomical Compass

General Structure of the Neuroanatomical System

Psychoactive Substances and the Brain

The Neurobehavioral Facets of Addiction: From Recreational Use to Dependence

Applications to Other Addictions and Substance Misuse: New Behavioral Disorders?

Societal Impact of Substances

Definition of Terms

Key Facts

Summary Points

Chapter 2. Pathophysiology-Based Neuromodulation for Addictions: An Overview

Introduction

Finding Targets for Neuromodulation Intervention

Pathophysiology of Addiction

Neuromodulation Techniques and Brain Network Alterations

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 3. Gateway Hypothesis of Addiction and Substance Misuse: The Role of Neurophysiology and Psychological Mechanisms

Introduction

Neurophysiological Mechanisms

Transition to Addiction and Psychological Mechanisms

Personality of the Drug User

Conclusion

Summary and Key Points

Chapter 4. Children of Parents with Substance Use Disorder

Introduction

Models of Substance Use Disorder Vulnerability

From Models to Studies of Neurobiology of Children with Familial Substance Use Disorder

Neuroimaging Studies of Children with Familial Substance Use Disorder

Future Directions

Summary

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 5. Drugs of Abuse and the Internet

Introduction

Drugs Sold on the Internet

Conclusion

Definition of Terms

Key Facts on the Internet

Summary Points

Chapter 6. Trauma and Neurological Risks of Addiction

Introduction

Overview of Typology of Trauma

Neurobiology of Trauma

Basic Neurobiology of Drug Use and Addiction

Posttraumatic Stress and Cannabinoid Receptors

Applications to Other Addictions and Substance Misuse

Conclusion

Definition of Terms

Key Facts

Summary Points

Chapter 7. Emotional Self-Medication and Addiction

Introduction

ESM and Addiction in Humans

PSM and ESM in Nonhuman Animals

ESM Induced by Reward Loss

Future Directions: Bridging ESM and SUDs

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts about Self-Medication

Summary Points

Chapter 8. The Neurobiology of Comorbid Drug Abuse in Schizophrenia and Psychotic Disorders

Introduction

Epidemiological Data

Correlates of Comorbid Drug Abuse in Schizophrenia

Neurobiology of Comorbid Drug Abuse

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of the Neurobiology of Comorbid Drug Abuse in Schizophrenia

Summary Points

Part II. Tobacco

Section A. General Aspects

Chapter 9. Nicotine Chemistry, Pharmacology, and Pharmacokinetics

Introduction

Nicotine Chemistry

Nicotine Pharmacology

Nicotine Pharmacokinetics

Summary

Afterword

Definition of Terms

Key Facts: PET Neuroimaging and Nicotine

Summary Points

Chapter 10. Tobacco-Related Mortality among Individuals with Alcohol or Drug Use Disorders

Introduction

Prevalence of Tobacco Use in AODUD Populations

Tobacco-Related Diseases

A Review of Tobacco-Related Mortality among Individuals with AODUD

Best-Practice Guidelines Champion Smoking Cessation Integration into Addictions Treatment

Barriers to Implementation of Concurrent Smoking Cessation with AODUD Treatment

Staff Knowledge and Attitudes about Concurrent Smoking Cessation during AODUD Treatment

Attitudes toward Smoking Cessation among AODUD Treatment Clients

Effectiveness of Treatment for Nicotine Dependence Concurrent with AODUD Treatment

Efforts to Increase Access to Nicotine-Dependence Treatment for AODUD Populations

Other Policy Interventions to Reduce Tobacco-Related Mortality among Individuals with AODUD

Applications to Other Addictions and Substance Misuse

Conclusion

Definition of Terms

Key Facts of Contraband Tobacco Use in the AODUD Population

Summary Points

Chapter 11. Neurological Effects of Nicotine, Tobacco, and Particulate Matter

Introduction

Neurobiological Effects of Smoking Tobacco

The Rewarding Effects of Nicotine

Mechanism of Action: Nicotinic Acetylcholine Receptors

Addictive Properties of Tobacco Smoke

Tobacco Particulate Matter and Extracts

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Section B. Molecular and Cellular Aspects

Chapter 12. Rho GTPases and Their Regulators in Addiction: A Focus on the Association of a β2-Chimaerin Polymorphism with Smoking

Introduction

Rho GTPases and Nicotine Addiction

Chimaerins and Smoking

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Smoking Addiction

Summary Points

Chapter 13. Brain Orexin Receptors and Nicotine

Introduction

The Orexinergic System

The Hypothalamus and Orexin Receptors

Nicotine and Nicotinic Acetylcholine Receptors

Nicotine and the Orexinergic System

Human Studies of Nicotine on Orexin

Paradigms of Nicotine Exposure to Replicate Clinical Conditions

Nicotine Exposure on Orexin Expression

Nicotine, Orexin, Addiction, and Reward

Mechanisms Involved in Nicotine-Induced Orexin Expression Changes

Conclusion and Future Directions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts Regarding the Orexinergic System

Summary Points

Chapter 14. Nicotine and Stimulatory Effects on 5-HT DRN Neurons

Introduction

Neuronal Nicotinic Acetylcholine Receptors

The Dorsal Raphe Nucleus

Effects of Nicotine on 5-HT DRN Neuron Firing Rate and 5-HT Release

Behavioral Effects of Nicotine Mediated by Increases in Serotonin Release

Concluding Remarks

Application to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Microdialysis

Summary Points

Chapter 15. Critical Role of Cannabinoid CB1 Receptors in Nicotine Reward and Addiction

Introduction

Nicotine Reward and Dependence

Endocannabinoid System and Signaling

Cannabinoid Type 1 Receptors

The Role of CB1 Receptors in Brain Reward Processing in Nicotine Administration

Effects of CB1 Receptor Agonists and Antagonists on Nicotine Reward

CB1 Receptor Ligands and nAChRs

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 16. Targets of Addictive Nicotine in the Central Nervous System and Interactions with Alcohol

Introduction

Effects of Nicotine

Concurrent Effects of Nicotine with Alcohol

Dual Effects of Nicotine

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Nicotine and Its Targets

Summary Points

Chapter 17. Cytochrome P450 and Oxidative Stress as Possible Pathways for Alcohol- and Tobacco-Mediated HIV Pathogenesis and NeuroAIDS

Introduction

Alcohol and NeuroAIDS

Tobacco and NeuroAIDS

Concluding Remarks

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of NeuroAIDS

Summary Points

Chapter 18. Nicotine and Neurokinin Signaling

Introduction

Tachykinin Genes and Gene Products

Neuropeptide Distribution in the CNS

Receptor Distribution in the CNS

Neurokinin-Mediated Mechanisms in the CNS

Tachykinins and Addiction Mechanisms

Neurokinins and nicotine: cellular mechanisms

Neurokinins and Nicotine: Regulation of Mood and Affect

Neurokinins and the Symptoms of Nicotine Withdrawal

Applications to Other Addictions and Substance Misuse

Conclusions

Definition of Terms

Key Facts

Summary Points

Chapter 19. Neurotransmitter Systems and the Nicotine Dependence-Induced Withdrawal Syndrome: Dopamine, Glutamate, GABA, Endogenous Opioids, Endocannabinoids, Noradrenaline, Arginine Vasopressin, Neuropeptide Y, MAO, CREB, and Corticotropin-Releasing Factor

Introduction

Nicotine-Induced Neuroadaptations

Neural Basis of Nicotine Withdrawal

Neurotransmitters and Mediator Systems Involved in Nicotine Withdrawal

Application to Other Addictions and Substance Misuse

Definition of Terms

Summary Points

Chapter 20. Genetic Findings on the Relationship between Smoking and the Stress System

Introduction

The HPA Axis and the Molecular Effects of GCs

The Glucocorticoid Receptor-Coding Gene (NR3C1)

Functional Aspects of NR3C1 Polymorphisms

Effects of NR3C1 Polymorphisms on Smoking Behavior

The MR Coding Gene

Functional Aspects of NR3C2 Polymorphisms

Effects of NR3C2 Polymorphisms on Smoking Behavior

Potential for MR/GR Interactions beyond the Statistical Level

Perspectives

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 21. Genetic Variants of μ Opioid Receptor and Its Interacting Proteins in Smoking: A Focus on OPRM1 A118G, ARRB2, and HINT1

Introduction

OPRM1 Polymorphisms

OPRM1 and Smoking Behaviors

Pharmacogenetic Studies of OPRM1 in Smoking Cessation

ARRB2 and HINT1

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Smoking Related Phenotypes

Summary Points

Section C. Structural and Functional Aspects

Chapter 22. Characterization of Cue-Induced Reinstatement of Nicotine-Seeking Behavior in Smoking Relapse: Use of Animal Models

Introduction

Rat Model of Smoking Relapse: Response Reinstatement Paradigm

Cue-Induced Reinstatement of Nicotine-Seeking Responses

Interactions of Nicotine Cue with Stress and Nicotine Priming

Pharmacological Substrates Responsible for Cue-Induced Nicotine-Seeking Behavior

Applications to Other Addiction and Substance Misuse

Definition of Terms

Key Facts of Cue-Induced Reinstatement of Nicotine-Seeking Behavior

Summary Points

Chapter 23. Effects of Environmental Enrichment on Nicotine Addiction

Introduction

Behavioral Effects of Nicotine in Enriched Animals

Neural Effects of Enrichment on Nicotine Effects and Circuits

Conclusions and Future Directions

Application to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Environmental Enrichment

Summary Points

Chapter 24. Smokers with Severe Mental Illness

Introduction

Nicotine Addiction

Why Do More People with Mental Illness Smoke?

Facilitating Smoking Cessation

Conclusion

Applications to Other Addictions and Substance Misuse

Key Facts of Smoking among Those with Mental Illness

Summary Points

Chapter 25. Nicotine Dependence and Schizophrenia

Introduction

Epidemiology

Clinical Features

Etiological Relationship between Schizophrenia and Nicotine

Management

Application to Other Addictions and Substance Misuse

Definition Of Terms

Key Facts

Summary Points

Chapter 26. Unraveling the Role of the Amygdala in Nicotine Addiction

Introduction

The Role of Nicotine in Tobacco Addiction

The Amygdala

Nicotine Craving

Functional Neuroimaging Studies on Cue-Induced Nicotine Craving

Functional Neuroimaging Studies on Abstinence-Induced Craving

Functional Neuroimaging Studies on Altered Emotion Processing in Smokers

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Nicotine Addiction

Summary Points

Chapter 27. Nicotine and Cognition: Effects of Nicotine on Attention and Memory Systems in Humans

Introduction

Nicotine and Attention

Nicotine and Memory

Long-term Effects of Nicotine on Cognition

Indirect Effects of Nicotine

Applications to Other Addictions and Substance Misuse

Definition of Terms

Summary Points

Chapter 28. The Role of Appetitive and Aversive Smoking Cues in Tobacco Use Disorder with a Focus on fMRI

Introduction

Reactivity to Appetitive Smoking Cues—Clinical Relevance

Neural Correlates of Smokers to Appetitive Smoking Cues

Reactivity to Aversive Smoking Cues—Clinical Relevance

Neural Reactivity of Smokers to Aversive Smoking Cues

Conclusion

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Tobacco Use Disorder

Summary Points

Chapter 29. Different Effects of Cigarette Smoking on Neuropsychological Performance in Psychiatric Disorders

Introduction

Smoking and Cognitive Function in Healthy Subjects

Smoking and Cognitive Function in Schizophrenia

Smoking and Cognitive Function in Major Depressive Disorder

Smoking and Cognitive Function in Bipolar Disorder

Smoking and Cognitive Function in Obsessive-Compulsive Disorder

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 30. Tobacco Smoke Extract-Produced Behavioral Effects: Locomotor Sensitization and Self-Administration Studies

Introduction: Tobacco Smoke Extracts in Research

Behavioral Tests

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of History of Behavioral Nicotine/Tobacco Addiction Research

Summary Points

Chapter 31. The Psychological Threat of Mortality and Its Implications for Tobacco and Alcohol Misuse

Introduction

Psychological Defenses against Conscious Mortality Concerns: Implications for Substance Use

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts Concerning the Terror Management Health Model

Summary Points

Chapter 32. Nicotine Dependence and the Anterior Cingulate-Precuneus Pathway: Using Neuroimaging to Test Addiction Theories

Physical Dependence

Smoking and Brain Structure

Learning Theories of Addiction

Biological Theories of Addiction

Hypothesis Testing

What Impact Does This Have for Addiction Theorists?

Application to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Physical Nicotine Dependence

Summary Points

Chapter 33. Neural Effects of Nicotine: Peripheral Sensory Systems and Experience-Dependent Neural Sensitization

Introduction

Rapid Neural Activation Induced by Intravenous Nicotine

The Role of Peripheral Actions of Nicotine in Mediating Its Acute Neural Effects

Experience-Dependent Changes in the Neural, Physiological, and Behavioral Effects of Nicotine

The Role of Peripheral Actions of Nicotine in the Development of Nicotine-Induced Neural Sensitization

General Discussion

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Section D. Methods

Chapter 34. Cotinine Urinalysis for Tobacco Use

Introduction

Pharmacokinetics and Pharmacodynamics

Assays for Detection

Research and Clinical Applications of Urine Cotinine Detection

Sensitivity and Specificity Issues

Applications to Other Addictions and Substance Misuse

Comparison with Other Biomarkers of Tobacco Use

Conclusions

Definition of Terms

Key Facts

Summary Points

Part III. Alcohol

Section A. General Aspects

Chapter 35. Ethanol Metabolism and Implications for Disease

Introduction

The Physical Properties of Ethanol

International Variations in Alcohol Consumption

Alcohol and the Burden of Disease

Absorption and Distribution of Ethanol

Metabolism of Ethanol

Blood Ethanol Concentration

Applications to Other Addictions and Substance Misuse

Summary

Definition of Terms

Key Facts of Acetaldehyde

Summary Points

Chapter 36. Heavy Episodic Drinking or Binge Drinking: A Booming Consumption Pattern

Introduction

Definition of Binge Drinking

Consequences on Health and Possible Early Markers

Risk and Protection Factors Associated with BD

Personality Traits, Circadian Typology, and BD

Neuropsychological Impact of BD

Future Research on Prevention and/or Treatment on BD

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Neuropsychology in Binge Drinkers

Summary Points

Section B. Molecular and Cellular Aspects

Chapter 37. Alcohol and Endogenous Opioids

Neuropeptides as Target System

The Endogenous Opioid System

The Opioid–Alcohol Link

Endogenous Opioids in AUD

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Opioids

Summary Points

Chapter 38. Effects of Alcohol on Nicotinic Acetylcholine Receptors and Impact on Addiction

Introduction

Applications to Other Addictions and Substance Misuse

Conclusion

Definition of Terms

Summary Points

Chapter 39. Alcohol and Its Impact on Myelin

Introduction

The Myelination Process and Brain Development

Composition of Myelin

Pathophysiology of the Demyelination and Remyelination Processes in the CNS

Alcohol Abuse and White Matter Disturbances

Mechanisms of Alcohol-Induced Myelin Alterations

Applications to Other Addictions and Substance Misuse

Therapeutic Approaches

Definition of Terms

Key Facts

Summary Points

Chapter 40. The Effects of Acute and Chronic Ethanol Exposure on GABAergic Neuroactive Steroid Immunohistochemistry: Relationship to Ethanol Drinking

Introduction

Immunohistochemistry Methodology and Strengths in Neuroactive Steroid Research

GABAergic Neuroactive Steroids and Ethanol Interactions in Rats

Neuroactive Steroids and Ethanol Drinking in Rats

GABAergic Neuroactive Steroids and Ethanol Interactions in Mice

Neuroactive Steroids and Ethanol Drinking in Nonhuman Primates

Neuroactive Steroids and Ethanol Drinking in Humans

GABRA2 Genetic Polymorphisms

Genetic Polymorphisms and Neuroactive Steroids

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 41. Ethanol and Its Impact on the Brain’s Electrical Activity

Alcohol Abuse and Its Neurological Consequences

Influence of Alcohol on the Electrical Activity of the Brain

CSD as a Tool to Study the Effects of Alcohol on the Brain

Ethanol Influences CSD Propagation: The Role of Antioxidant Molecules

Applications to Other Addictions and Substance Misuse

Definitions and Explanations of Key Terms or Words Used in the Chapter

Key Facts of Electrophysiology

Summary Points

Chapter 42. Alcohol and Neuroimmune Interactions

Introduction

Microglia

Fetal Alcohol Spectrum Disorders

Adolescent and College-Age Alcohol Consumption

Adult Alcohol Consumption

Neuroimmune Signaling

Anti-inflammatory Therapeutics for Treatment of Alcohol Use Disorders

Summary

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 43. Role of Glutamate Transport in Alcohol Withdrawal

Introduction

Glutamate Signaling Under Normal Physiological Conditions

Glutamate Signaling During Alcohol Withdrawal

Contribution of Genetic Variation in Glutamate Signaling to Alcohol Withdrawal Risk and Severity

Preclinical Evidence for the Use of Ceftriaxone to Treat Acute AWS

Applications to Other Addictions and Substance Misuse

Summary and Conclusions

Definition of Terms

Key Facts on the Tricarboxylic Acid Cycle

Summary Points

Chapter 44. Ethanol, Vitamins, and Brain Dysfunction

Brain Atrophy Affects Both White Matter and Gray Matter

Functional Consequences

Pathogenesis of Neurotoxicity in Alcoholics

Liposoluble Vitamins

Hydrosoluble Vitamins

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 45. Phospholipase D: A Central Switch in the Development of Fetal Alcohol Spectrum Disorder

Fetal Alcohol Spectrum

Phospholipases D

Regulation of PLDs

Enzymatic Reactions of PLDs

Brain Cells and PLD

PLD Function

Effects of Ethanol In Vitro

Effects of Ethanol and PLD Deletion In Vivo

Applications to Other Addictions and Substance Misuse

Conclusion

Definition of Terms

Key Facts of Phospholipases D

Summary Points

Chapter 46. N-Methyl-d-Aspartate Receptor Subunits and Alcohol

Introduction

Ethanol’s Actions at the NMDAR: Role in the Subjective and Behavioral Effects of Alcohol

NMDAR Subunits and Ethanol

Applications to Other Addictions and Substance Misuse

Concluding Remarks

Definition of Terms

Key Facts of Glutamate

Summary Points

Chapter 47. Alcohol Dehydrogenase Alleles and Impact on Neuropathology

Introduction

Alcohol Metabolism

ADH Alleles and Alcohol Use Disorders

ADH Alleles and Effects on Neuropathology

Fetal Alcohol Spectrum Disorders

ADH Alleles and Neuropathology in FASD

Role of the ADH Alleles in the Fetus

Applications to Other Addictions and Substance Misuse

Definition of Terms

Summary Points

Chapter 48. ADH Cluster Genes, Genome-Wide Association Studies, and Alcohol Dependence

Introduction

Alcohol Metabolism and Major Genetic Factors

Genome-Wide Association Study and ADH Gene Cluster

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts about Alcohol Dependence

Summary

Chapter 49. Neuropathology of Gene Expression during Alcohol Withdrawal

Introduction

Conclusion

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts on the History of Alcohol Consumption

Summary Points

Chapter 50. The Quest of Candidate Gene in Alcohol Dependence: The Dopamine D2 Receptor (DRD2) Gene

Introduction

Molecular Genetics of Alcoholism

Subtypes of Alcoholism Identified in Han Chinese

Association Studies of the DRD2 Gene with Alcoholism Subtypes

The DRD2 Gene and Temperament Interaction in Subtyped Alcoholism

Summary

DEFINITION of Terms

Key Facts of Subtyped Alcoholism

Summary Points

Chapter 51. Acetaldehyde: A Reactive Metabolite

Introduction

Endogenous Aldehydes

Exogenous Acetaldehydes

Acetaldehyde Reactivity

Protein Adduct Formation

Damage to DNA

Protein Carbonylation/Oxidation and Cytotoxicity

Molecular Cytotoxic Mechanisms of Aldehydes

Acetaldehyde or Ethanol?

Human Health Risks

Concluding Remarks

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Brain Metabolism

Summary Points

Section C. Structural and Functional Aspects

Chapter 52. Cortical Morphology in Fetal Alcohol Spectrum Disorders: Insights from Computational Neuroimaging

Introduction

What Is Cortical Morphology?

Cortical Morphology in Fetal Alcohol Spectrum Disorders

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Fetal Alcohol Syndrome Disorders

Summary Points

Chapter 53. Abnormalities of Cerebellar Structure and Function in Alcoholism and Other Substance Use Disorders

Introduction

Prevalence of Substance Use Disorders

The Cerebellum and Addiction Connection

Structure and Function of the Cerebellum

Development of the Cerebellum

Alcohol Use Disorders and the Cerebellum

Cerebellar Abnormalities in SUD: Cause or Consequence?

Cerebellar Structure and Function in Other Substance Use Disorders

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of the Cerebellum

Summary Points

Chapter 54. Brain Volumes in Adolescents with Alcohol Use Disorder

Introduction

Voxel-Based Morphometry and Related Methods of Structural Brain Imaging

Hippocampal Volume Is Reduced in Adolescents with AUD

Prefrontal Cortex Volume Is Differential in Adolescents with Alcohol Use Disorder

Other Brain Regions Showing Differential Volumes in Adolescent AUD Compared to Controls

Moderating and Mediating Factors—Gender, Psychiatric Comorbidities, Family History of Alcohol Abuse, Childhood Trauma

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts about Brain Volume Differences in Alcohol Use Disorder

Summary Points

Chapter 55. Central Pontine Myelinolysis in Alcoholism: An Osmotic Demyelination Syndrome

Introduction

Pathophysiology

Pathology

Neuroimaging

Clinical Presentation

Treatment and Prognosis

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Key Facts of the Blood–Brain Barrier

Summary Points

Chapter 56. The Role of Brain Glucocorticoid Systems in Alcohol Dependence

Introduction

Alcohol Activates the Hypothalamic–Pituitary–Adrenal Axis

Chronic Alcohol Exposure Disrupts HPA Axis Function

Role of Brain Glucocorticoid Receptor Activity in the Transition to Alcohol Dependence

GR Structure, Chaperone Proteins, and Nuclear Cofactors

Induction of Transcriptional Activation by GR

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts Related to Alcohol Misuse

Summary Points

Chapter 57. Neuropathobiology of Alcohol-Induced Cognitive Deficits

Introduction

Neuropathological Mechanisms Associated with Alcohol-Induced Cognitive Deficits

Future Scope and Conclusions

Definition of terms

Key Facts on Alcohol-Induced Cognitive Deficit and Its Neuropathobiology

Summary Points

Chapter 58. Neuropathology in Neuropsychiatric Disorders Secondary to Alcohol Misuse

Wernicke Encephalopathy

Korsakoff Syndrome

Marchiafava–Bignami Disease

Alcohol Withdrawal Syndrome

Alcohol-Related Dementia

Alcoholic Cerebellar Degeneration

Other Neuropsychiatric Disorders

Application to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 59. Social Isolation and Ethanol Drinking: A Preclinical Model of Addiction Vulnerability in Males, but Not Females

Introduction

Sex Differences: From Acute Response to Alcohol to Neurobiological Consequences of Alcohol Dependence

Epidemiology by Sex: Association with Alcohol Use Disorders

Sex Differences: Neuroendocrine Responses in Vulnerable and Addicted Populations

Social Isolation as a Model of Addiction Vulnerability in Male Rodents

Hormones in Male and Female Rodents Exposed to Early Life Stress

Sex Differences in Alcohol Models: Females Drink More!

Models of an Addiction-Vulnerable Phenotype in Female Rats

Sex Differences in Addiction Vulnerability: Future Directions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Consequences Following Adolescent Social Isolation Model in Male versus Female Rats

Summary Points

Section D. Methods

Chapter 60. The Ultrarapid Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST-Lite) and Implications for Neuropathology

Introduction

Development of the ASSIST

ASSIST-Lite Protocol

Neuropathology as a Reason for Screening and Intervention

Conducting a Brief Intervention with an Illicit Drug User

Conclusion

Key Facts

Summary Points

Part IV. Cannabinoids

Section A. General Aspects

Chapter 61. Overview of Cannabis Use, Misuse, and Addiction

Introduction

Acute and Long-term Effects of Cannabis Use

Cannabis Misuse and the Risk of Addiction

Translational Research on Cannabis Use in Animal Models

Therapies for Cannabis Use and Withdrawal

Is There a Potential Therapeutic Value for Medical Cannabis?

Policy Changes in Cannabis Regulation

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of the Cannabinoid Tetrad Test

Summary Points

Chapter 62. An Overview of Major and Minor Phytocannabinoids

Introduction

Tetrahydrocannabinol Acid, Tetrahydrocannabivarinic Acid, and Cannabigerol Acid

Cannabigerol

Δ9-Tetrahydrocannabinol

Tetrahydrocannabivarin

Cannabidiol

Cannabichromene

Cannabinol

β-Caryophyllene

Applications to Other Addictions and Substance Misuse

Definition of Terms

Summary

Chapter 63. Treating the Phenomenon of New Psychoactive Substances: Synthetic Cannabinoids and Synthetic Cathinones

Introduction

Synthetic Cannabinoids

Synthetic Cathinones

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Synthetic Cannabinoids and Psychosis

Summary Points

Section B. Molecular and Cellular Aspects

Chapter 64. Role of Lipid Rafts and the Underlying Filamentous-Actin Cytoskeleton in Cannabinoid Receptor 1 Signaling

Cannabinoid Receptor 1 Signaling: A Forceful Regulator of Neuronal Development and Function

CB1 Signaling to the Major Effector Extracellular Signal-Regulated Kinase

CB1 Signaling to ERK Emanates from Lipid Rafts

Lipid Rafts, Filamentous-Actin Networks, and Microtubules Regulate CB1 Signaling and Localization

Formation of CB1 Signaling Complexes and Transactivation of Tyrosine Kinase Receptors in Lipid Rafts

Concluding Remarks

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of CB1

Summary Points

Chapter 65. Cannabinoid Agonists

Introduction

Endocannabinoids

Phytocannabinoids: Δ9-Tetrahydrocannabinol

Synthetic Cannabinoids

Cannabinoid Agonists in the Clinic

Application to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 66. Molecular Pharmacology of CB1 and CB2 Cannabinoid Receptors

Introduction

Introduction to Cannabinoid Receptor Research

Overview of Endocannabinoid System Molecular Biology

Overview of Cannabinoid Signaling in Cells

Summary and Applications to Other Addictions and Substance Misuse

Definition of Terms

Summary Points

Chapter 67. Does Agonist Efficacy Alter the In Vivo Effects of Cannabinoids: Girl, Could We Get Much Higher?

Introduction

Cannabinoid Agonist Classification

Herbal Incense: Not Your Parents’ Marijuana?

Preclinical Studies

Marijuana Dependence Studies in Humans

Dependence and Withdrawal Studies in Animals

Tolerance

Drug Discrimination

Reinforcement

If Not Efficacy, What, Then?

Conclusion

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 68. Cannabis, Cannabinoid Receptors, and Stress-Induced Excitotoxicity

Introduction

Endocannabinoid System and Stress: A Bidirectional Relationship

Stress and Cellular Damage/Death by Excitotoxicity

Cannabinoid Receptor Activation and Stress-Induced Excitotoxicity

Therapeutic Potential in Stress-Related Neuropsychopathologies

Definition of Terms

Key Facts of Excitotoxicity

Summary Points

Chapter 69. Cannabis, Endocannabinoid CB1 Receptors, and the Neuropathology of Vision

Introduction

Psychophysical Effects of Cannabinoids on Vision

Electrophysiological Effects of Cannabinoids on Vision

Conclusions and Future Directions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of the Cannabinoid System

Summary Points

Chapter 70. Cannabidiol and 5-HT1A Receptors

Introduction

Multiple Effects of Cannabidiol and Its Therapeutic Potential

Cannabidiol and 5HT1A Receptors

How Does Cannabidiol Interact with 5HT1A Receptors?

Are All Cannabidiol Effects Mediated by 5-HT1A Receptors?

Conclusion

Application to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 71. CB1 Receptor-Mediated Signaling Mechanisms in the Deleterious Effects of Spice Abuse

Introduction

Cannabinoid Receptors

Signal Transduction Mechanism of CB1R

CB2R Signaling

Spice Signaling

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Spice Products

Summary Points

Section C. Structural and Functional Aspects

Chapter 72. Cannabis Use Disorders and Brain Morphology

Introduction

Nosology of Cannabis Use Disorder

Neurocognitive Aspects of Cannabis Use Disorder

Structural Neuroimaging Studies Investigating Cannabis Use Disorder

Discussion

Applications to Other Addictions and Substance Misuse

Concluding Key Facts on the Association between Gray Matter and Cannabis Use Disorder

Definition of Terms

Key Facts of the Striatum

Summary Points

Chapter 73. Imaging Dopamine Alterations in Cannabis Dependence

Introduction

Imaging Methods Used to Study Dopamine in Humans

Effect of Acute Cannabinoid Administration on the Dopamine System

Effect of Chronic Cannabis Use on the Dopamine System

Conclusion

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts about Imaging the Dopamine System in Humans Using PET

Summary Points

Chapter 74. Cannabis and the Mesolimbic System

The Dopaminergic Mesolimbic System

Cannabinoids in the Reward Circuitry

Cannabis Dependence

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of the Addictive Spines in the Nucleus Accumbens

Summary Points

Chapter 75. Role of the Endocannabinoid System and Major Cannabis Constituents in the Reconsolidation and Extinction of Rewarding Drug-Associated Memories

Introduction

Essential Aspects about Learning and Memory Processing

Overview of the Endocannabinoid System

Using the Conditioned Place Preference Paradigm to Investigate the Role of the Endocannabinoid System in Memory Reconsolidation and Extinction

Role of the Endocannabinoid System in Learning and Memory Processing

The Endocannabinoid System and Reconsolidation of Rewarding Drug-Related Memories

The Endocannabinoid System and Reconsolidation of Aversive Memories

Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Reconsolidation of Drug, Appetitive, and Aversive Memories

Concluding Remarks

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Memory Reconsolidation

Summary Points

Chapter 76. Effects of Δ9-Tetrahydrocannabinol, Synthetic Cannabinoids, and Fatty Acid Amide Hydrolase Inhibitors on Mood and Serotonin Neurotransmission

Introduction

How to Assess If a Putative Drug Modulates Mood Using Animal Models

Δ9-Tetrahydrocannabinol and Serotonin Firing Activity

The Effect of WIN 55,212-2 on 5-HT Firing and Antidepressant-Like Activity

Fatty Acid Amide Hydrolase Inhibition, 5-HT Firing, and Antidepressant-Like Activity

Chronic Administration of CB1R Agonists in Adolescence and Adulthood: Implications for 5-HT Firing Activity

Conclusion

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 77. CB1 Cannabinoid Receptors and Aggression: Relationship to Cannabis Use

Introduction

The Endocannabinoid System

Cannabis and Aggression in Humans

Relation between Aggression and CB1 Receptor in Animal Studies

Conclusions

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts of Aggression

Summary Points

Chapter 78. Cannabis and Bipolar Manic Episodes

Substance Use and Bipolar Disorder

Childhood Trauma, Cannabis, and Bipolar Disorders

Impact of Cannabis Use on Mania Phenomenology

Impact of Cannabis Use on Bipolar Disorder Outcome

Cannabis Use and Onset Manic Episode

Cannabis Use and Psychosis

Mechanisms Underlying Cannabis Use and Manic Symptoms

Applications to Other Addictions and Substances Misuse

Definition of Terms

Key Facts of Mania and Bipolar Disorders

Summary Points

Chapter 79. White Matter, Schizophrenia, and Cannabis

Introduction

White Matter Changes in Schizophrenia

White Matter Changes with Cannabis Use

White Matter Changes with Cannabis Use in People with Schizophrenia

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts

Summary Points

Chapter 80. Electroencephalography and Cannabis: From Event-Related Potentials to Oscillations

Introduction

The Brain Cannabinoid System

Electroencephalography

Cannabinoids and ERPs

Cannabinoids and Neural Oscillations

Conclusion and Future Directions

Applications to Other Addictions and Substance Misuse

Defintion of Terms

Key Facts of Cannabis and Electroencephalography

Summary Points

Part V. Opioids

Section A. General Aspects

Chapter 81. Street Level Heroin, an Overview on Its Components and Adulterants

Introduction

An Overview of Opiates

Historical Review of Heroin

A Focus on the Heroin Production Process

Definition of Controlled Substances

Controlled Substances Act Schedules

Heroin Pharmacology

What Does Heroin Look Like?

Routes of Administration for Heroin

Body Packing of Heroin

Street Names and Slang Terms for Heroin

Component Analysis of Heroin

Medical Consequences of Street Heroin Abuse

Concluding Remarks

Application to Other Addictions and Substance Misuse

Key Facts

Chapter 82. Opioid Prescription Drug Abuse and Its Relation to Heroin Trends

Introduction

Trends

Heroin Availability on the World Market

Global Trends in Opioid and Opiate Abuse

Opiate and Opioid Overdose Deaths

United States

Trends in Treatment for Opiates and Opioids

Harm Reduction Response to Increasing Opioid and Heroin Abuse

Applications to Other Addictions and Substance Misuse

Conclusion

Definition of Terms

Key Facts

Summary Points

Section B. Molecular and Cellular Aspects

Chapter 83. Corticotropin-Releasing Factor Signaling at the Intersection of Pain and Opioid Addiction

Introduction

The Addicted Phenotype

Animal Models of Opioid Intake Escalation and Addiction

Chronic Opioid Exposure and Hyperalgesia

Opioid Addiction in Relation to Pain Management

Shared Neural Mechanisms and Neurocircuitry Underlying Pain and Opioid Addiction

Role of Corticotropin-Releasing Factor in Opioid-Induced Hyperalgesia and the Transition to Opioid Dependence

Role of Corticotropin-Releasing Factor Signaling in Chronic Pain States

Applications to Other Addictions and Substance Misuse

Definition of Terms

Key Facts Related to Opioid-Induced Hyperalgesia and Addiction