Addiction Medicine Science and Practice

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Cover Title Page Addiction Medicine: Science and Practice Copyright Dedication About the Editor Honors and Awards Coat of Arms Media More About Adial Pharmaceuticals Inc About the Global Institutes on Addictions (GIA) Contributors Preface From the Darkness Into the Light What’s Old Is New Again? Back to the Future Res ipsa loquitur: Confutatio Contents 1 - Emerging Health Perspectives Introduction Alcohol Use Illicit Drug Use Age Variations Nonmedical Use of Prescription Drugs Opioid Overdose Deaths Naloxone and Opioid Overdose Legislative, Regulatory, and Community Controls Over Opioid Prescribing Medication-Assisted Treatment Prescription Drug and Opioid Addiction Grant Program Comprehensive Addiction and Recovery Act 21st Century Cures Act State-Targeted Response to the Opioid Crisis Grants (Short Title: Opioid STR) Medication-Assisted Treatment Methadone Buprenorphine Physician Training Utilization of Substance Abuse Treatment Services Social Determinants of Health Perceived Risk of Harm With Substance Use Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health Screening, Brief Intervention, and Referral to Treatment Recovery as a Holistic System Health Insurance 2 - The Epidemiology of Alcohol and Drug Disorders What Is Epidemiology? Alcohol Consumption Drug Use Substance Use in the United States: A Public Health Problem When Does Use Become Pathological? Substance Abuse and Dependence Substance Disorders in the Diagnostic and Statistical Manual of Mental Disorders Substance Disorders: A Categorical or Dimensional Trait? Prevalence and Incidence of Substance Disorders The Course of Substance Disorders Analytic Epidemiology: The Etiology of Substance Disorders Availability—Temporal and Geographical Political Events Outlet Density Pricing, Laws, and Advertising Pricing Laws and Law Enforcement: Alcohol State Distribution Policies Grass-Roots Efforts Alcohol Marketing and Advertising Laws and Law Enforcement: Drugs Parental and Peer Influences Parental Modeling of Substance Use Parenting Practices Peers Stress Animal Models Early Stressors and Drug Use in Humans Religiosity Cognition, Personality Substance Expectancies and Motivations Personality Traits Subjective Reactions Psychiatric Comorbidity Genetics Family and Twin Studies of Alcohol and Drug Dependence Genetics in Epidemiology Studies Conclusion 3 - United States Federal Drug Policy Introduction History Federal Drug-Control Operations Policymaking and Budgeting Law Enforcement Prevention Treatment Research Issues in Policymaking Picking Battles Setting Minimum Standards for “Evidence” Appendix 4 - Historical Perspectives of Addiction Histories of Addiction Brain Disease Redux Alcohol and Other Drugs Alcohol: Predisposed or Culturally Determined Opiates and Other Illicit Drugs Licit Mind-Altering Drugs Smoking and Nicotine Rhetoric and Reality Taking History Seriously Acknowledgments 5 - Diagnosis and Classification of Substance Use Disorders Introduction The Nature of Substance Use Disorders Personality Disorder The Disease Concept Epidemiological and Sociological Formulations Learned Behavior Clinical Syndrome Neurobiological Disorder Biological and Social Risk Factors Achieving a Synthesis Substance Use Diagnoses in the DSM and ICD Systems Comparisons of DSM-IV, DSM-5, ICD-10, and ICD-11 Substance Use Disorder (DSM-5) Substance Dependence (ICD-10, ICD-11, and DSM-IV) Addiction as a Disease (ASAM, ISAM) Harmful Substance Use (ICD-10 and ICD-11) Hazardous Substance Use and Related Conditions Substance Intoxication (DSM-IV, DSM-5, ICD-10, and ICD-11) Substance Withdrawal (DSM-IV, DSM-5, ICD-10, and ICD-11) Substance-Induced Mental Disorders (DSM-IV, DSM-5, ICD-10, and ICD-11) Substance-Induced Delirium (DSM-IV, DSM-5, and ICD-11) Substance-Induced Psychotic Disorder (DSM-IV, DSM-5, ICD-10, and ICD-11) Substance-Induced Amnesic Syndrome (DSM-IV, DSM-5, ICD-10, and ICD-11) Substance-Induced Physical Disorders Substance-Related Social Problems Practical Approaches to Diagnosis The Distinction Between Research and Practice Approaches to the History Presenting Problems Substance Use History Intake Dependence Consequences and Harms Physical Consequences/Harms Psychiatric Consequences/Harms Social Consequences Antecedent Factors Key Aspects of the Physical Examination Mental State Examination Establishing a Provisional Diagnosis Laboratory Tests Imaging and Other Investigations Establishing the Final Diagnosis 6 - Drug Reinforcement in Animals Introduction Assessing Reinforcing Efficacy Progressive-Ratio Schedule Threshold Procedure Second-Order Schedules Choice Procedures Modeling Phases of Substance Use Disorder Animal Models of Drug Use Initiation Animal Models of Substance Use Disorder Animal Models of Relapse Conclusions 7 - Role of Human Laboratory Studies in the Development of Medications for Alcohol and Substance Use Disorders Introduction Role of the Human Laboratory in Evaluating the Abuse Liability of New Medications To Characterize Adverse or Harmful Effects To Characterize Its Comparative Pharmacological Profile To Evaluate Reinforcing Effects or Potential for Self-Administration Issues in Human Laboratory Studies of Abuse Liability Role of Subjective Effects Role of Subjective Euphoria Importance of Measuring Self-Administration Behavior Role of Environment and Cost in Controlling Self-Administration Role of Subject Population Variables Role of Craving Human Laboratory Studies of Pharmacological Agonist and Antagonist Treatments Utility of Evaluating Pharmacological Antagonist Treatments Utility of Evaluating Pharmacological Agonist Replacement Approaches Role of Human Laboratory Studies in Developing Medications for Alcohol Dependence Disulfiram Naltrexone Acamprosate Other Possible Medications for Alcohol Dependence Role of the Human Laboratory in Evaluating Medications for Cocaine Dependence Evaluation of Dopamine Agonists and Antagonists for Cocaine Treatment Evaluation of Stimulant-Replacement Strategies for Cocaine Evaluation of Cocaine Treatments Affecting Other Neurochemical Systems Evaluation of Dopaminergic Treatments for Methamphetamine Evaluation of Methamphetamine Treatments Affecting Other Neurochemical Systems General Conclusions Regarding Human Laboratory Studies 8 - Conditioning of Addiction Introduction Methods for Assessing the Conditioned Effects of Drugs of Abuse in Laboratory Animals Conditioned Place Preference Conditioned Tolerance Conditioned Cue Enhancement of Drug Self-Administration Second-Order Schedules of Reinforcement Cue- and Context-Induced Reinstatement of Drug-Seeking Behavior Incentive Salience Attribution Pavlovian-Instrumental Transfer Neural Substrates of Drug Conditioning: General Neurochemical Circuitry Amygdala Nucleus Accumbens Dorsal Striatum Ventral Tegmental Area Hippocampus Prefrontal Cortex Human Neuroimaging Studies Unconscious Processing of Drug-Related Cues Reinstatement Induced by Novel Cues Optogenetic Regulation of Cocaine Seeking Inhibition of Cue-Induced Cocaine Seeking by Synthetic Designer Receptors Structural Plasticity Induced by Drug-Associated Cues Conclusions 9 - Overlapping Striatal Circuits and Molecular Mechanisms in Rodent Models of Addiction and Depression Overview of Striatal Circuits Striatal MSN Subtype Activity in Addictive Drug Exposure and Behavior Striatal MSN Subtype Activity in Depression-Like Behavior MSN Subtype Signaling Mechanisms in Addictive Drug Exposure and Behavior Transcription Factors in MSN Subtypes in Addictive Drug Exposure and Behavior Molecular Mechanisms in Striatal Circuits in Stress and Depression-Like Behavior Conclusions 10 - The Role of Endocannabinoids in Amphetamine-Driven Actions in Dopamine Neurons: Implications for Understanding and Treating Dysfunction in the Mesolimbic Circuit Introduction Mesolimbic Dopamine Endocannabinoid Modulation of DA Amphetamine Amphetamine at Dopamine Terminals Amphetamine at the Cell Body Endocannabinoids and Amphetamine Conclusions 11 - Pain and Negative Affect Pain Is a Multidimensional Experience Chronic Pain and Negative Affect The Vicious Cycle of Pain and Negative Affect Comorbidity Pain as a Negative Reward Shared Brain Circuits The Amygdala Descending Pain Modulation Corticotrigeminal Pathways Thalamus and Cortex A Brighter Future? 12 - Genetic Vulnerability to Substance Use Disorders Introduction Heritability (h2) of SUDs Heritability Based on Family, Adoption, and Twin Genetic Studies SNP-Based Heritability (h2SNP) Genetic Architecture of Addiction Vulnerability Mapping Genetic Loci Influencing Vulnerability to SUDs Candidate Gene Analyses Genome-Wide Association Results for Addiction SNP Array-Based GWAS Sequencing-Based GWAS Interactions Between Genetic and Environmental Factors Missing Heritability Rare Variations of the DNA Sequence Assessing Polygenetic Risk Scores (PRS) Findings From SUD Genetic Studies Genetic Contributions Specific to Substances Genetic Contributions Common to Behavioral Phenotypes Underlying SUDs Phenotypes That Might Have Contributed to Balancing Selection of Addiction-Related Alleles Psychiatric and Neurologic Comorbidity Success in Smoking Cessation Failure of Control Experiments to Support Alternative Hypotheses for the Observed Genome-Wide Association Results An Evolutionary Perspective on Genetic Architecture of Addiction The Genetic Architecture for Substance Dependence in Individuals Epigenetics and Individual Differences in SUDs Ethical Issues in High-Density Genotyping of Individuals With Substance Use Disorders Summary and Conclusions Glossary 13 - The Assessment and Treatment of Addiction: Best Practices in a Direct-to-Consumer Age Introduction The Assessment The Stages of Addiction At-Risk Individuals Heavy Users Who Do Not Meet Criteria for Substance Use Disorders Patients in Recovery The Domains Genetics Physiological Interface End-Organ Damage Allostatic Changes Neurocognitive Functioning Family Interface Work and Vocational Interface Community Interface and Legal Problems Hedonic and Recreational Interface Spiritual Interface The Treatment At-Risk Individuals Heavy Users Who Do Not Meet Criteria for Use Disorders Use Disorder Patients Patients in Recovery New Frontiers 14 - Metabolomics in Drug Response and Addiction What Is Metabolomics? Substance Abuse and Its Effect on Health and Economy Substance Abuse Leads to Addiction Metabolomics: The Beginning Selection of Technology to Capture Metabolomic Changes Tissue and Organ of Interest Generating a Gene List Bioinformatics Tools and Analysis Transcription Regulatory Network in Drug Metabolomics Gene Selection and Literature Analysis Transcription Factor and Regulatory Elements Modeling Construction of Transcription Regulatory Network Application of Metabolomics in Solving Addiction Disorders Integration of Systems Biology to Medication Discovery 15 - Neuroimaging Findings in Substance Use Disorders Introduction Structural Alterations Brain Volume Gray Matter Volume White Matter Volume White Matter Microstructure Summary of Structural Brain Findings Dopamine and Other Neurotransmitter Systems Dopamine Other Neurotransmitters Systems Summary of Neurotransmitter Findings Functional Imaging Findings Alcohol and Other Drug-Cue Reactivity Nondrug Reward Reactivity Delay Discounting Response Inhibition Resting State Functional Connectivity Functional Imaging Summary Conclusion 16 - Neurobiological Basis of Drug Reward and Reinforcement Introduction Experimental Psychology Concepts of Reward and Reinforcement Neurotransmitters and Neural Circuitry: Involvement in Different Aspects of Reward, Reinforcement, and Addiction Models of Drug Use and Drug Addiction Actions of Addictive Drugs Within the Reinforcement and Reward Circuitry What Drives Drug Use, Abuse, and Addiction: The Direction of Future Research 17 - Neurobehavioral Toxicology of Substances of Abuse Ethanol (Alcohol) History Chemical Properties Pharmacokinetics Routes of Administration Absorption and Distribution Metabolism Elimination/Excretion Pharmacodynamics Neuropharmacological Effects Toxicology Cocaine History Pharmacodynamics Pharmacokinetics Distribution Metabolism/Elimination Toxicology Amphetamine and Amphetamine-Analogs History Mechanism of Action Pharmacokinetics Metabolism and Elimination Toxicology History Chemical Properties Pharmacokinetics Pharmacodynamics Toxicology Opiates History Mechanism of Action Pharmacokinetics Routes of Administration and Metabolism Toxicology Hallucinogens History Pharmacodynamics Mechanisms of Action Pharmacokinetics Routes of Administration Toxicology Therapeutic Use Cannabis History Chemical Properties Pharmacokinetics Routes of Administration Δ9-Tetrahydrocannabinol Distribution and Bioavailability Metabolism and Elimination Pharmacodynamics Pharmacology Cellular Effects Tissue Effects Immune Effects Systemic Effects Therapeutic Effects Toxicology Apoptosis Lung Cancer Head and Neck Cancer Mental Disorders-Psychosis Depression Drug Addiction Synthetic Cannabinoid Intoxication Treatment of Cannabis and Synthetic Cannabinoid Addiction Nicotine History Chemical Properties Pharmacokinetics Routes of Administration Distribution/Bioavailability Metabolism/Elimination Pharmacodynamics Pharmacological Effects Tissue Effects Systemic Effects Toxicology Acute Withdrawal Cardiopulmonary System Stroke Cancer Therapeutic Effects Treatment for Cessation of Smoking Inhalants History Mechanism of Action Smooth Muscle Relaxation NMDA GABA Dopamine Other Receptors and Ion Channels Pharmacokinetics Pharmacodynamics Toxicology Barbiturates History Chemical Properties Pharmacokinetics Routes of Administration Absorption and Distribution Metabolism and Excretion Pharmacodynamics Mechanism of Action Pharmacological Effects Toxicology Benzodiazepines History Chemical Properties Pharmacokinetics Routes of Administration Absorption and Distribution Metabolism and Excretion Pharmacodynamics Mechanism of Action Pharmacological Effects Toxicology 18 - Animal Models of Substance Use Disorders: Motivational Perspective Definitions Relevant to Animal Models Animal Models of Withdrawal Somatic Signs Motivational Signs Anxiety-Like Symptoms Dysphoria-Like Symptoms Reward Thresholds Escalation of Drug Self-Administration With Extended Access Withdrawal-Induced Drinking Protracted Abstinence Neurobiological Bases of Increased Drug Taking During Extended Access or Dependence Within-System Changes: Dopamine Between-System Changes: Role of Corticotropin-Releasing Factor Between-System Changes: Role of Other Neuropharmacological Systems Homeostatic Versus Allostatic View of Dependence Face Validity Construct Validity Relevance to Medications Development 19 - Novel Methodologies: Proteomic Approaches in Substance Abuse Research Introduction Protein Fractionation Cerebrospinal Fluid Cellular Domain Cytoplasm Nucleus Mitochondria Membrane Synaptosomes and Postsynaptic Density Separation Gel-Based Methods Two-Dimensional Gel Electrophoresis Two-Dimensional Difference in Gel Electrophoresis Chromatographic Separation of Proteins Isotope-Coded Affinity Tags (ICAT and iTRAQ) Top-Down Proteomics Mass Spectrometry Ion Source Mass Analyzers Protein Identification Protein Arrays Implementation for Drug Abuse Studies Proteomic Analysis of Cocaine Human Nonhuman Primate Rodent Proteomic Analysis of Alcohol Conclusion 20 - Neuroinflammatory Processes in Drug Addiction Innate Immune Signaling in the Brain Immune Cells of the Brain Pattern Recognition Receptors and Their Ligands Immune Signaling Molecules as Neuromodulators Addiction as a Neuroimmune Disease Neuroimmune Components of the Stages of Addiction Neuroimmune Signaling in Alcoholism The Role of Endogenous TLR Agonist DAMPs in the Pathology of Addiction Neuroimmune Activation and the Progression to Addiction Neuroimmune Basis of Addiction—A Work in Progress Future Immune Therapies for Addiction Toward Novel Addiction Treatment Strategies Based on Immune Pharmacology 21 - Alcohol: Clinical Aspects Introduction Alcohol-Related Disorders Age at Onset of Drinking Behavior Effects of Ethnicity, Gender, Place of Residence, and Religion on Alcohol Consumption Clinical Picture Signs and Symptoms Cardiovascular System Gastrointestinal System Hepatic System Endocrine System Rheumatic and Immune System Hematological/Hematopoietic System Central Nervous System Peripheral Neurological System Integumentary System (Skin) Nutritional Status Oncology Fetal Development Psychological and Psychiatric Complications of Alcohol Acute Effects Chronic Effects Conclusions 22 - Cocaine Introduction Historical Aspects Sex and Gender Differences Pregnancy and Effects of Prenatal Exposure Youth Criminality Cocaine Use Disorder Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Pharmacologic Treatments for Cocaine Dependence GABAergic Medications Dopaminergic Agents Medications Targeting Other Mechanisms: Dopamine-β-Hydroxylase Nonpharmacologic Treatments for Cocaine Dependence Intoxication Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Withdrawal Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Craving and Relapse Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Intoxication Delirium Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Cocaine-Induced Psychotic Disorder Definition/Diagnostic Criteria Subtypes Molecular/Biological Basis Treatment Approaches Cocaine-Induced Anxiety Disorder Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Cocaine-Induced Mood Disorder Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Cocaine-Induced Sexual Dysfunction Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches Cocaine-Induced Sleep Disorder Definition/Diagnostic Criteria Molecular/Biological Basis Treatment Approaches 23 - Nicotine Epidemiology The Reward Pathway Neuronal Adaptation Cognitive Impairment Effect on Comorbid Substance Use Nicotine and Negative Affect Genetics Heritability Genome-Wide Association Studies of Nicotine Dependence Candidate Gene Studies for Nicotine Dependence Genome-Wide Studies Predicting Nicotine Cessation Treatment Outcome Candidate Gene Studies Predicting Treatment Outcome Diagnosis Smoking and Psychiatric Comorbidities Prevention Science Treatment Nicotine Agonists Nicotine Antagonists Bupropion Mecamylamine Nicotine Partial Agonists Varenicline Cytisine Other Medications Nonpharmacological Treatments 24 - Cannabis: An Overview of the Empirical Literature Introduction Prevalence Pharmacokinetics Acute Intoxication Features Classification of Cannabis Use Disorder Motivational Bases of Cannabis Use Negative Correlates of Cannabis Use and Its Disorders Health-Related Problems Social Problems Psychological Problems Cannabis: Motivation to Quit, Reasons for Quitting, and Success in Quitting Motivation to Quit Reasons for Quitting Success in Quitting Cannabis: Overview of Clinical Issues Relevant to Practitioners Barriers to and Facilitators of Treatment Basic Competencies 25 - Opiates and Prescription Drugs Classification Etiology Epidemiology Patterns of Use Incidence of Substance Use Disorders Abuse of Opioid Analgesics Risks Associated With the Use of Opioid Analgesics Neurobiology Biological Effects of Use Psychological Effects of Use Diagnosis Psychiatric Comorbidity Co-occurring Psychiatric Disorders and the New Opioid-Dependent Population Iatrogenic Addiction Clinical Management Opiate Overdose Opiate Withdrawal Syndromes Opiate Withdrawal Treatment Opiate Pharmacotherapy Naltrexone Methadone Levo-Alpha Acetyl Methadol Buprenorphine Novel Anticraving Medications Psychosocial Treatment Outpatient Drug-Free Programs (Postmedication Withdrawal Treatment) Drug Courts Outpatient Treatment in the Setting of Methadone and Buprenorphine Maintenance Therapeutic Communities Conclusions Regarding Psychosocial Treatment Co-occurring Psychiatric Disorders The Incidence of Co-occurring Psychiatric Disorders Substance-Induced Disorders Versus Independent Disorders Managing Co-occurring Psychiatric Disorders Primary Prevention Conclusion 26 - Clinical Aspects of Methamphetamine Introduction Neurobiological Impact of Methamphetamine Use Acute and Chronic Physical Effects of Methamphetamine Use Sexual Behavior and Communicable Diseases Specific Populations Youth Women Pregnant Women and Their Children Criminal Offenders People With Co-occurring Disorders Reducing Harms Associated With Methamphetamine Use Managing Methamphetamine Intoxication Managing Acute Methamphetamine Psychosis Managing Chronic Methamphetamine Psychosis Managing Methamphetamine Withdrawal Treatment for People Who Use Methamphetamine Cognitive Behavioral Therapy Contingency Management Medications for Treatment of Methamphetamine Use and Methamphetamine Use Disorder Future Directions in Research and Practice 27 - Sedative-Hypnotics and Anxiolytics Introduction Intoxication and Overdose Tolerance and Withdrawal Substance Use Disorder Mood and Anxiety Disorders Cognitive Disorders Psychotic Manifestations Sleep Disorders Sexual Dysfunction Acknowledgments 28 - Clinical Aspects of Inhalant Addiction Types of Inhalants Being Abused Epidemiology Mechanisms of Action Morbidity and Mortality Psychiatric Disorders in Inhalant Users Inhalant Use Disorder Inhalant-Induced Disorders Inhalant Intoxication and Inhalant Intoxication Delirium Inhalant-Induced Persisting Dementia Inhalant-Induced Psychotic Disorder Inhalant-Induced Anxiety Disorder Inhalant-Induced Mood Disorder Prevention and Management Considerations 29 - Anabolic-Androgenic Steroids Introduction Epidemiology Pharmacology Chemical Structure Pharmacokinetics Urine Testing Patterns of Illicit Use Adverse Medical Effects Effects on the Endocrine System Effects on the Hepatic System Effects on the Circulatory System Psychiatric Aspects and Effects Neurobiology Addiction Screening and Assessment History Physical Mental Status Labs Treatment Anabolic-Androgenic Steroid Use Disorder Anabolic-Androgenic Steroid Withdrawal Severe Anabolic-Androgenic Steroid Use Disorder Anabolic-Androgenic Steroid-Induced Mood Disorder Anabolic-Androgenic Steroid-Induced Psychotic Disorder Conclusions 30 - Caffeine Introduction Main Sources of Caffeine and Patterns of Consumption Pharmacology of Caffeine Main Mechanism of Action Physical Dependence Tolerance Psychopharmacology of Caffeine: The Critical Processes of Caffeine Withdrawal and Withdrawal Reversal Performance and Mood Sleep and Wakefulness Mental Health and Well-Being The Epidemiology of Caffeine Disorders Dietary Caffeine and Physical Health: Cardiovascular Disease Acute Effects of Caffeine on Blood Pressure Epidemiology of Caffeine and Cardiovascular Disease Misclassification Confounding in Epidemiological Research Threshold Effects Epidemiology of Caffeine and Blood Pressure Chronic Effects of Dietary Caffeine on Blood Pressure Dietary Caffeine and Population Blood Pressure Levels Cancer All Cancers Lower Urinary Tract Pancreas Breast Colon Other Cancer Sites Maternal Consumption of Caffeine Pregnancy Outcomes Children and Adolescents Adverse Interactions Between Caffeine and Other Drugs Is Caffeine Addictive and Is There a Safe Level of Consumption? Does Caffeine Have Health Benefits? Type 2 Diabetes Mellitus Parkinson Disease and Age-Related Neurodegeneration Other Active Compounds in Caffeine Beverages Threats to the Integrity of Caffeine Science Industry Influences on Research Conflict of Interest and the Self-Serving Bias Public Policy and Regulation of Caffeine Exposure Reducing and Quitting Caffeine Conclusions 31 - Serotonergic Hallucinogens Introduction History Epidemiology Classification Mechanism of Action Serotonin Receptor Indolealkylamine Hallucinogens Lysergic Acid Diethylamide (LSD) Street Information Physiological and Psychological Effects Hallucinogen Use Disorder Adverse Effects The Bad Trip Hallucinogen Persisting Perceptual Disorder (HPPD) Psychosis Psilocybin Ibogaine Phenethylamine Hallucinogens Mescaline 3,4-Methylenedioxymethamphetamine (MDMA) Pharmacology Street Information Physiological and Psychological Effects Adverse Effects Management of Acute Toxicity Conclusions 32 - Ketamine and Phencyclidine Introduction Pharmacology Mechanism of Action Routes of Administration Epidemiology Ketamine Phencyclidine Use Disorders Diagnostic and Statistical Manual of Mental Disorders Criteria Tolerance and Withdrawal Intoxication Ketamine Psychological Effects Physiological Effects Management Phencyclidine Psychological Effects Physiological Effects Management Phencyclidine Intoxication Delirium Clinical Presentation Management Phencyclidine Organic Mental Disorder Chronic Use Addiction Treatment 33 - The Biology and Treatment of Gambling Disorder Introduction The Psychiatric Nosology of Gambling Disorder Cognitive Distortions Prevalence Estimates and Characteristics The Biochemistry of Gambling Disorder Serotonin Dopamine Norepinephrine The Genetics of Gambling Disorder The Neuropsychology of Gambling Disorder Neuroimaging Studies Treatment Behavioral Treatments Pharmacological Treatments Natural Recovery Prevention Efforts Research Challenges and Future Directions 34 - Implications of Food Addiction for Understanding and Treating Binge Eating Disorder Introduction History and Background Drugs as Food Food as Drugs Clinical and Psychological Parallels Loss of Control Tolerance and Withdrawal Cravings and Relapse Neurobiological Parallels Risk Factor Similarities Impulsivity Reward Sensitivity Impulsive Behavior and Decision-Making Deficits Negative Urgency and Emotion Regulation Treatment of Binge Eating Disorder: Integrating an Addiction Perspective Psychoeducation Managing Food Cravings and Difficulties With Inhibitory Control Dealing With Loss-of-Control Addressing Emotionally-Driven Eating Enhancing Commitment to Change and Relapse Prevention Summary and Conclusions 35 - Compulsive Buying Introduction Diagnosis and Classification Prevalence Rates and Subject Characteristics Economics and Consumerism Etiology and Course Comorbidity Cultural Considerations Assessment Treatment Future Research 36 - Sexual Behavior as an Addictive or Compulsive Phenomenon Introduction History of Sexual Addiction and Sexually Compulsive Behavior Sex Outside the Norm Clinical Criteria Etiology Carnes’ Addiction Model Coleman’s Compulsive Sexual Behavior Model Kalichman’s Impulse Control Model Bancroft’s Dual Control Model Measurement Compulsive Sexual Behavior Inventory Sexual Compulsivity Scale Cognitive and Behavioral Outcomes of Sexual Behavior Scale Implications for Clinical Practice Implications for Future Research 37 - New Era of Internet Addiction Research in China Introduction Internet and Smartphone Penetration in China Theoretical Origin and Definition Recent Internet Addiction Research in China National Internet Addiction Research in China Regional Internet Addiction Research in China Cross-Cultural Internet Addiction Research Mediating Effects Studies in Internet Addiction Research Internet Addiction Research in Special Groups Methodological Approaches in Internet Addiction Research Conclusion 38 - Hoarding as a Behavioral Addiction Overview Classification and Comorbidity Hoarding and Impulse Control Disorders Hoarding and Compulsive Acquisition Etiology/Biobehavioral Underpinnings of Hoarding Neuroimaging Electrophysiology Genetics Cognitive-Behavioral Theory and Evidence Information-Processing Deficits Emotional Attachment to Possessions Assessment of Compulsive Hoarding Treatment of Compulsive Hoarding Biological Treatments Psychological Treatments Conclusions 39 - Motivational Interviewing: Emerging Theory, Research, and Practice What Is Motivational Interviewing? Engaging Focusing Evoking Planning A Brief History of MI Theoretical Concepts and Emerging Models of MI Defining MI MI as an Activator of Autonomous Motivations and Growth MI as a Method to Move People Through Stages of Change MI as an Activator of Emotions and Openness MI as an Interpersonal Intervention MI as a Method to Resolve Ambivalence in the Direction of Change MI and an Approach to Align Behavior and Values Summary: Emerging Relational and Technical Components in a Model or Theory of MI Evidence About MI Evidence About Efficacy Using MI in Medical Settings to Improve Health Behaviors Using MI to Reduce or Prevent Addictive Behaviors Emergency Room MI for Heavy Drinking Youth Brief Interventions for Drinking Adolescents and Young Adults Prevention of Risky Drinking in College-Age Adults Drug Use Alternate Modalities for Addictive Behaviors Problem Gambling MI for Comorbid Alcohol and Depressive Disorders Evidence About MI Processes and Their Relationships With Outcomes Other Developments in MI MI Groups Preparing Clinicians to Use MI 40 - Cognitive Behavioral Therapy for Addiction Introduction Overview of Cognitive Behavioral Therapy Cognitive Model of Addiction Behavioral Model of Addiction Case Conceptualization Case Example Application of Cognitive Behavioral Therapy for Addiction General Components of Manualized Cognitive Behavioral Therapy for Addiction Contraindications Format/Length/Setting Expectations of Therapist for Client Functional Analysis Skills Training Manualized Sessions—Sequence of Therapy Topics Example of Skill Acquisition Research Support for Cognitive Behavioral Therapy in Addiction Literature Cocaine Methamphetamines Caffeine Nicotine Review of Treatment for Depressant Drugs Alcohol Benzodiazepines Barbiturates Hypnotics Cannabis Opioids Future Directions 41 - Community Reinforcement Approach and Contingency Management Therapies Introduction Community Reinforcement Approach Therapy Contingency Management Interventions Issues Hindering the Implementation of the Community Reinforcement Approach in Practice Issues Associated With Implementation of Contingency Management in Practice Prize-Based Contingency Management Cost-Effectiveness Challenges to Dissemination Conclusion 42 - Relapse Prevention and Recycling in Addiction Introduction Understanding the Concept of Relapse and Its Role in Recovery Relapse Prevention Models for Relapse Prevention Medical and Mutual Help Model Reward Deficit Model Cognitive-Behavioral Models Review of Relapse Prevention and Substance Abuse Studies Effectiveness Studies Across Addictive Behaviors Critical Mechanisms for Relapse Prevention Motivation Coping Self-Efficacy Strategies for Relapse Prevention Assessment Insight and Awareness Behavioral Coping Skills Cognitive Strategies Lifestyle Interventions New Approaches for Relapse Prevention Medications for Relapse Prevention When Relapse Prevention Fails A Life Course Perspective on Recovery Successive Approximations, Recycling, and Learning From the Past Treatment Recommendations 43 - Brief and e-Health Interventions for the Treatment of Alcohol or Other Drug Addiction Drug Use and Problems Drug Treatment in Primary Care and Nonspecialist Settings What Is Screening and Brief Intervention? Alcohol Tobacco Illicit Drugs Conclusions—Screening and Brief Interventions Improving Compliance/Adherence to Therapies Brief Behavioral Compliance Enhancement Treatment e-Health Interventions to Enhance Compliance to Therapies Conclusions—Compliance Enhancement Future Research Resources 44 - Self-Help Approaches for Addictions Defining Self-Help Why Use Self-Help? Is Self-Help Good for Everyone? Self-Help as Empowering Can Individuals Help Themselves? Natural Recovery Maturation Effects Nicotine Alcohol Marijuana Processes of Change Self-Help Drug Replacement Replacement and Caffeine Replacement and Nicotine Nicotine Replacement Options Replacement and Alcohol Bibliotherapy Perspectives in Bibliotherapy Bibliotherapy for Nicotine Bibliotherapy for Alcohol Bibliotherapy for Marijuana Expressive Writing Expressive Writing and Nicotine Expressive Writing and Alcohol Helplines Helplines for Nicotine Nicotine Helpline Services Characteristics of Nicotine Helpline Callers and Specific Protocols Nicotine Helplines and the Transtheoretical Model of Change Helplines for Alcohol and Illicit Drugs Helplines for Anabolic-Androgenic Steroids Helplines for Cocaine, Methamphetamines, and Opiates Helplines as Self-Help Religion, Spirituality, and Meditation Religion, Spirituality, and Nicotine Religion, Spirituality, and Alcohol Religion, Spirituality, and Other Substances Meditation and Mindfulness-Based Approaches Internet Resources Internet Resources for Nicotine Internet Resources for Alcohol Internet Resources for Other Substances Next Steps Conclusions 45 - Community Clinics Introduction Literature Review Methods History of Community Substance Abuse Treatment A New Era Begins Impact of the Community Mental Health Movement Effectiveness of Community Clinic Approaches 1935–1980 Community Responses to the 1980s Cocaine Epidemic Categories of Community Clinics Types of Community Clinics Therapeutic Communities Prize-Based Contingency Management Day Treatment With Abstinence Contingencies and Vouchers Cognitive Behavioral Treatment Relapse Prevention Integrated Group Therapy 12-Step Facilitation Faith-Based and Religiously Affiliated Programs Interventions for Specific Populations Use of Evidence-Based Services in Community Clinic Substance Abuse Treatment The National Institute on Drug Abuse’s National Drug Abuse Treatment Clinical Trials Network Drug Abuse Reporting Program Studies Additional Treatment Models The Matrix Model Challenges to Community-Based Clinics Funding Staffing Client-Centered Barriers Opportunities to Expand Evidence-Based Substance Use Disorder Interventions 46 - Unhealthy Alcohol and Other Drug Use in Primary Care Introduction Screening Screening for Alcohol Use Unhealthy Alcohol Use: Definitions Screening for Tobacco Use Screening for Other Drug Use Assessment Brief Intervention Management of Risky Alcohol and Drug Use Management of Alcohol Use Disorder Pharmacotherapy Counseling in Primary Care Management of Tobacco Use Management of Opioid Use Disorder: Pharmacotherapy Referral to Specialty Care Patients in Remission Treatment of Psychiatric Comorbidity Management of Withdrawal From Alcohol and Other Drugs Alcohol Withdrawal Opioid Withdrawal Medical Management (Including Preventive Care) of People With Unhealthy Alcohol and Other Drug Use Preventive Care Managing Medical Consequences in the Face of Ongoing Substance Use Pain Management Other Challenging Medical Situations Confidentiality Summary and Conclusions 47 - Criminal Justice System and Addiction Treatment Introduction Prevalence of Substance Abuse and Dependence Substance Abuse Comorbidities Smoking Psychiatric Disorders HIV/AIDS and Sexually Transmitted Infections Other Infectious Diseases Pharmacotherapies for Substance Use Community Corrections Probation and Parole Drug Court Treatment Accountability for Safer Communities Institutional Corrections Prisons and Jails Conclusion 48 - Adolescent Neurocognitive Development and School-Based Drug Abuse Prevention and Treatment Introduction Brief Overview: Neuroscience and Adolescents Negative Consequences of Drug Use on Teen Cognitive Function Brain Development and School-Based Drug Use Prevention and Treatment Need for Tailoring Prevention and Treatment Programs Current School-Based Prevention Practices and Executive Functions Schools as a Modality for Implementation of Cessation Programming Treatment Strategies and Executive Function Skills Motivation Enhancement and Motivational Interviewing Conclusions and Future Directions 49 - The Therapeutic Community for Drug Abuse Treatment: A Journey Yet Unfolding in the Recovery Movement Introduction Origins Early Expansion The Formative Years Admissions The Role of Family The Hierarchy of Roles The Interactive Healing Life Intellectual Exchange Small Group Interventions The General Meeting: A Response to Crisis and Bad Behaviors Treatment Duration The Therapeutic Community’s Coming of Age Therapeutic Community Research Early Therapeutic Community Studies The Treatment of Adolescents and Findings To the 21st Century Changing Therapeutic Community Practices The Future of Therapeutic Communities for the Treatment of Substance Use Disorders Effective Elements of Therapeutic Community Treatment Current Practices That Enhance the Therapeutic ­Community Approach Conclusion 50 - Substance Use–Focused Mutual-Help Groups: Processes and Outcomes Introduction Major Types of Substance Use-Focused Mutual-Help Groups Alcoholics Anonymous Narcotics Anonymous and Cocaine Anonymous Al-Anon and Nar-Anon Secular Organizations for Sobriety SMART Recovery Moderation Management LifeRing Participation in Mutual-Help Groups and Substance Use Outcomes Attendance and Substance Use Outcomes Involvement and Substance Use Outcomes Participation and Outcomes Other Than Substance Use Al-Anon Participation and Outcomes Connections Between Mutual-Help Groups and Treatment Participation in Treatment and Mutual-Help Groups Treatment, Mutual-Help Groups, and Substance Use Outcomes Interventions to Enhance 12-Step Group Participation Personal Factors, Participation, and Mutual-Help Group Outcomes Severity and Impairment Disease Model Beliefs and Religious and Spiritual Orientation Individuals With Substance Use and Psychiatric Disorders Women Adolescents and Emerging Adults Older Adults Race and Ethnicity Active Ingredients of Mutual-Help Groups Abstinence-Specific and General Support Goal Direction and Structure Involvement in Rewarding Activities Self-Efficacy and Coping Conclusions Acknowledgments 51 - Pharmacotherapy for Alcoholism and Some Related Psychiatric and Addictive Disorders: Scientific Basis and Clinical Findings Introduction Basic Science and Human Laboratory Studies Clinical Studies With Oral Naltrexone Clinical Studies With Depot Naltrexone Vivitrex or Vivitrol Naltrel Depotrex Nalmefene Glutamate Metabotropic Glutamate Receptor-5 Modulator and N-Methyl-d-Aspartate Antagonist—Acamprosate Other N-Methyl-d-Aspartate Receptor Antagonists GABA Synthesis and Glutamate Synthesis Modulator—Gabapentin Serotonin Selective Serotonin Reuptake Inhibitors Serotonin-1 Partial Receptor Agonist Serotonin-2 Receptor Antagonist Serotonin-3 Receptor Antagonists Acetylcholine: Cholinergic Receptor Antagonist—Varenicline Dopamine Dopamine Receptor Antagonists Dopamine Receptor Agonists Gamma-Aminobutyric Acid-B Receptor Agonist—Baclofen Alcohol Metabolism Disruptor: Disulfiram Potential Treatments on the Horizon Cannabinoid-1 Receptor Antagonists Other Neurochemicals and Small Molecules Combination Treatments Conclusions 52 - Alcohol Withdrawal: Treatment and Application Introduction Anticonvulsants in the Treatment of Alcohol Withdrawal Sodium Valproate Carbamazepine and Oxcarbazepine Gabapentin Topiramate Other Anticonvulsant Agents Alpha-2 Adrenergic Agonists Summary and Conclusions 53 - Pharmacotherapy of Cocaine Addiction Bottom–Up Approach: Modulation of Appetitive Drives Preclinical Data Bottom–Up Approach: Pharmacotherapy of Reversal Learning/Cognitive Targets Top–Down Approach Clinical Trials in Cocaine Addiction Cocaine Withdrawal Comorbid Populations Participant Heterogeneity Polysubstance Abuse Pharmacotherapy and Behavioral Therapy Combinations 54 - Opioid Overdose History Definitions Injury, Poisoning, and Certain Other Consequences of External Causes Mental, Behavioral and Neurodevelopmental Disorders: Mental and Behavioral Disorders Due to Psychoactive Substance Use Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Defining Fatal Overdose Epidemiology Worldwide Fatal Overdose Nonfatal Overdose United States Fatal Overdose Nonfatal Overdose Pathophysiology Risk Factors Risk Related to Substance Use Factors Risk Related to Medical History Factors Risk Related to Demographic Factors Risk Factors for Iatrogenic Overdose Prevention Primary Prevention Provider Education Prescription Guidelines Prescription Drug Monitoring Programs Insurance Company Monitoring, Pill Limits, and Care Coordination FDA Changes in Scheduling and Postmarketing Surveillance of Opioids Prescription Drug Identification Laws Electronic Prescriptions for Controlled Substances (EPCS) Laws Against Pill Mills and Doctor Shopping Screening Pain Patients for Substance Misuse Risk Public Awareness/Education Prescription Medication Disposal and “Take-Back” Abuse-Deterrent Formulations Nonreinforcing Opioids Increased Law Enforcement Interdiction Secondary Prevention Prescriber Education Public/Opioid User Awareness/Education Local Overdose Fatality Review Teams Increased Drug Treatment Safe Injection Facilities Heroin Maintenance Drug Testing Tertiary Prevention Public Education/Awareness Naloxone Distribution to Illicit Opioid Users Naloxone Distribution to Third Parties Naloxone Co-Prescribing to Patients Taking Opioids Naloxone With Law Enforcement and Other First Responders Good Samaritan Laws Outreach Programs Use of Technology Vaccines Management Supports Following an Overdose Conclusion 55 - Methamphetamine Mechanism of Action Clinical Use of Methamphetamine Diagnosis of Methamphetamine Use Disorder Escalation of Methamphetamine Use Pharmacokinetics of Methamphetamine Mechanisms of Methamphetamine Reward Human Studies in the Treatment of Methamphetamine Use Disorder Conclusions 56 - Potential Pharmacotherapies for Cannabis Dependence Introduction Detoxification and Relapse Prevention or Maintenance Phase Cannabinoid Neuropharmacology Studies on Laboratory Animals Studies on Human Research Participants Randomized Controlled Trials Relapse Prevention Medications Future Directions in Medication Development for Cannabis Dependence 57 - Hallucinogens Historical Perspectives Epidemiology Basic Pharmacology Psychological and Biological Effects Hallucinogen Use Disorders Hallucinogen-Induced Disorders Assessment and Treatment Hallucinogen Intoxication Assessment Differential Diagnosis Treatment Hallucinogen Abuse and Dependence Assessment Differential Diagnosis Treatment Hallucinogen Persisting Perception Disorder Assessment Differential Diagnosis Treatment Hallucinogen-Induced Psychotic Disorder Assessment Differential Diagnosis Treatment Hallucinogens as Treatment Tools for Addiction? 58 - Molecular Genetics and the Treatment of Addiction Overview Genetics and the Treatment of Addictions Pharmacogenetics and Pharmacogenomics Nicotine Alcohol Cocaine Opiates An Intermediate Phenotype-Driven Pharmacogenetics Approach Optimizing Psychosocial Treatments Through Genetics Translating Pharmacogenetic Approaches Into Practice Future Directions of Molecular Genetics and Addiction Treatment Summary and Conclusions 59 - Physical Considerations for Treatment Complications of Alcohol and Drug Use and Misuse Introduction Liver Alcohol Nicotine Opioids Cocaine Amphetamine Benzodiazepines Gut and Pancreas Alcohol Nicotine Opioids Cocaine Amphetamines Benzodiazepines Nervous System Alcohol Nicotine Opioids Cocaine Amphetamines Benzodiazepines Cardiovascular System Alcohol Nicotine Opioids Cocaine Amphetamines Benzodiazepines Oncology Alcohol Nicotine Opioids Cocaine Amphetamines Benzodiazepines Endocrinology Alcohol Nicotine Opioids Cocaine Amphetamines Benzodiazepines Nutrition and Body Composition Alcohol Nicotine Opioids and Cocaine Amphetamines Benzodiazepines 60 - Quadruple Diagnosis: Substance Use Disorder, Comorbid Psychopathology, Human Immunodeficiency Virus Infection, and Hepatitis C Virus Infection Introduction Scope of the Problem Substance Use Disorders (SUDs) Psychiatric Disorders Other Than SUDs Depressive Spectrum Disorders HIV-Associated Mania and Bipolar Affective Disorder in HIV Infection Psychosis and Thought Disorders Psychosocial Issues in Persons Living With HIV Hepatitis C Virus (HCV) Infection Stigma, HIV Infection, Hepatitis C Virus Infection, Substance Misuse and SUDs, and Other Psychiatric Disorders Role of SUDs and Other Psychiatric Disorders in the Treatment With and Adherence to Effective ART for HIV Infection and DAAs for... Risk-Taking Behaviors Assessment of the Quadruply Diagnosed SUD Treatment of the Quadruply Diagnosed Summary and Conclusions 61 - Substance Use Stigma As a Barrier to Treatment and Recovery Introduction What Is Stigma? Stigma Depends on Basic Verbal/Cognitive Processes Stigmatizing Thoughts Are Resistant to Change Stigma Is Sustained Through Cultural Practices Types and Levels of Stigma Toward Substance Abuse The Need to Study Stigma in Context Self-Stigma Coping and Self-Stigma Multiple Stigmatized Identities Stigmatizing Attitudes and Behavior of Friends and Family Stigma in Treatment Settings Stigma as a Barrier to Initial Treatment Engagement Stigma and Treatment Retention and Outcome Stigmatizing Attitudes and Behavior of Professional Staff Interventions to Reduce Stigma Reducing Public Stigma Reducing Stigma in the Health Care System Empowering Those in Recovery Stigma and the Emotion of Shame Conclusions 62 - Religiousness, Spirituality, and Addiction: An Evidence-Based Review Introduction Section I Definitions of Religiosity and Spirituality The Relationship Between Religiosity/Spirituality and Addiction Religiosity/Spirituality and Addiction Research: An Overview Section II Empirical Religiosity/Spirituality Questions in Addiction Research Spirituality as an Intervention and Outcome Spiritually Based 12-Step Therapy Religiosity/Spirituality as a Moderator in 12-Step Therapy Section III Religiosity/Spirituality and Community-Based 12-Step Programs Community-Based 12-Step Programs and Abstinence What Spiritual Practices Predict Benefit? Summary and Future Directions 63 - In Silico Models of Alcohol Kinetics: A Deterministic Approach Introduction Mechanisms of Alcohol Intoxication Alcohol Metabolism Individual Differences in the Rate of Alcohol Metabolism Mathematical Modeling of the Pharmacokinetics of Ethanol The Minimal Model of Ethanol Kinetics Population Averages Subject-Specific Identification In Silico Population In Silico Studies of Blood Ethanol Time-Concentration Experimental Setting of the Computer Simulation Conclusion 64 - In Silico Models of Alcohol Dependence Treatment: A Stochastic Approach Introduction Models to Measure Models to Simulate Models to Control Formal Description of Human Behavior and Social Conditioning Combining Biology and Behavior In Silico Methods Recurrent Bio-Behavioral Process of Alcohol Dependence and Treatment In Silico Models of Ethanol Metabolism Stochastic Model of Behavioral and Social Conditioning Population of In Silico “Subjects” Subjects Procedure Computational Algorithms Results Empirical Findings In Silico Versus In Vivo Responses to Placebo and Ondansetron Treatment Modeling Idiosyncratic Treatment Response Conclusions 65 - Dynamic and Systems-Based Models for Evaluating Hypotheses Related to Predicting Treatment Response Introduction Personalized Alcoholism Treatment Pharmacogenetics The Johnson Model A Dynamic Systems-Based Model Modeling and the Personalized Treatment of Alcoholism Conclusions 66 - Enhancing Positive Outcomes for Children of Substance-Abusing Parents Introduction Prevalence of Children of Substance Abusers Children’s Feelings and Beliefs About Parents’ Substance Misuse Differences Between Children of Alcoholics and Children of Other Drug Abusers Higher Risk for Addictions Genetic Risks Which Genes Are Involved? Characteristics or Phenotypes of Children of Alcoholics That Increase Their Risk Fetal Alcohol and Drug Exposure Adolescent Drinking and Brain Development Diversity of Outcomes in Children of Substance Abusers The Family Family Environmental Risk and Protective Factors Substance Abuse Impact on Parenting Child Abuse Potential Genetic Vulnerability to Harsh Parenting in Children of Alcoholics Linked to Anger, Stress, Depression, and Negative Health Outc... Resilience and Protective Factors in Children of Substance Abusers Prevention Programs Specifically for Children of Alcoholics School-Based Primary Prevention Programs Family-Focused Prevention Programs for Children of Alcoholics and Substance Abusers Community-Based Prevention Programs for Children of Alcoholics Family-Based Prevention and Treatment Family-Focused Interventions for Children of Parents With Substance Use Disorders Core Content of Effective Family Programs Effective Prevention Programs Programs That Increase Behavioral Control and Social Competency Programs to Increase Emotional Resilience, Happiness, Self-Esteem, and Humor Programs for Emotional Management and the Awareness of Feelings Programs to Increase Cognitive Resilience Characteristics Programs for Educational Interventions, Screening, and Referral Summary of Recommendations for Future Research and Policy Improvements 67 - Alcohol and Substance Abuse in African Americans Introduction Epidemiology Preventive and Risk Factors Impact on the Individual Comorbidity Treatment Conclusions 68 - Substance Use Disorders in Health Care Professionals Introduction Epidemiology of Alcohol and Other Drug Use by Health Care Professionals Etiology of Substance Use Disorders in Health Care Professionals Drug Access Family History of Alcohol and Drug Use Professional Invincibility Pharmacological Optimism Negative Proscriptions Social and Professional Influences Age and Substance Use Dentists Nurses Pharmacists Physicians Identifying Drug Problems in Health Care Professionals The Intervention of Health Care Professionals Prevention and Education 69 - Identification and Treatment of Alcohol or Drug Dependence in the Elderly Introduction Prevalence and Impact of Substance Use Among Older Adults Medication Misuse Vulnerabilities for Substance Use Problems Comorbidities Identifying Alcohol and Drug Use Problems in Older Adults Classification of Alcohol Use Patterns and Problems in Older Adults Drinking Guidelines for Screening Screening for Alcohol/Medication Problems in Older Adults Broad-Based Assessment of Substance Use Problems Use of Brief Alcohol Interventions With Older Adults With Substance Dependence Detoxification and Withdrawal New Models for Screening and Treatment Studies of Treatment Compliance in Older Adults Limitations of Treatment Outcome Research Future Trends: Impact of the Baby Boom Cohort 70 - Alcohol and Drugs of Abuse in Pregnant Women: Effects on the Fetus and Newborn, Mode of Action, and Maternal Treatment Introduction History of Alcohol Effects in Pregnancy Effects on the Developing Embryo and Fetus Fetal Alcohol Spectrum Disorder Anomalies of Organs Other Than the Brain Orofacial Clefts Cardiac Anomalies Reduced Fetal Growth Behavioral and Developmental Changes Mechanisms of Alcohol Teratogenicity Oxidative Stress Disturbed Metabolic Pathways: Prostaglandin Synthesis Effects on Neurons Epigenetic Changes Prevention and Treatment Prevention Treatment During Pregnancy Treatment of the Child With Fetal Alcohol Spectrum Disorder Lactation Prevention and Treatment of Alcohol-Exposed Pregnant Animals Animal Models for Alcohol-Induced Embryopathy Conclusions Heroin-Dependent Mothers in Pregnancy Relation Between Substance Abuse and Attention-Deficit/Hyperactivity Disorder Effects of Heroin and Opiates on the Fetus and Newborn Effects on Postnatal Development Intellectual Developmental Outcome Treatment of the Pregnant Mother Lactation Animal Models for Heroin- and Opiate-Induced Fetal Damage Conclusions Cannabis Neonatal Effects Postnatal Developmental and Behavioral Effects Lactation Animal Studies Conclusions Mothers Using Cocaine in Pregnancy Historical Background Effects of Cocaine on the Embryo and Fetus Developmental Outcome Effects of Gender Mechanisms of Action Prevention and Treatment Home Intervention Programs for Children Prenatally Exposed to Cocaine Intervention Programs for the Mothers Lactation Studies in Animals Conclusions 71 - Forensic Issues Introduction The Forensic Evaluation Process Medical and Legal Terminology and Reports of Evaluation Working With Attorneys: Testimony Compulsion and Responsibility Civil Matters Involuntary Commitment Civil Competencies Disability Professional Liability Confidentiality Duty to Protect or Warn Child Custody Criminal Matters Competence to Stand Trial Sanity and Diminished Capacity Sentencing Pregnancy, Harm to the Fetus, and Child Abuse Addiction in Criminal Populations Drug Courts Regulatory Matters Impairment and Fitness to Practice Tissue Testing Sports Conclusions 72 - Disability and Addiction Introduction Rehabilitation Act of 1973, Title V, Section 504 Americans With Disabilities Act Key Case Law for the Americans With Disabilities Act, 1990 Raytheon v. Hernandez The Sutton Trilogy Americans With Disabilities Act Amendments Act of 2008 History of Entitlements for People With Disabilities and the Place for People With Substance Use Disorders Policy, Treatment, and Medical Coverage Substance Use Disorders and Comorbid Disability Alcohol Injury Liver Disease Neurological and Social Functioning Immune System Cardiovascular System Skeletal System Drugs of Abuse Cocaine Heroin Methamphetamine 3,4-Methylenedioxymethamphetamine (“Ecstasy” or “Molly”) Inhalants Anabolic Steroids Prescription Medications Prenatal Substance Use: Associated Disability and Consequences Conclusions 73 - The Homeless Introduction Homelessness Historical Context Operationalizing Homelessness Population Size Estimates Chronic Versus Short Term A Critique Substance Use Disorders Association Between Substance Use Disorders and Other Risk Factors and Homelessness Prevalence Rates Alcohol and Drug Use Disorder Comorbidity Alcohol Use Disorder Prevalence Rates Other Drug Use Disorders Overall Prevalence Rates Drugs of Choice Injection Drug Use Looking Forward Nonsubstance Psychiatric Disorders Mood Disorders Anxiety Disorders Psychotic Disorders Personality Disorders Overall Prevalence Rates The Roles of Sex and Race in Psychiatric Disorders Among the Homeless Medical Illness HIV/AIDS Infectious Diseases Services for the Homeless Conclusions 74 - Opening New Vistas in Basic and Preclinical Addiction Research New Vistas in Neurobiological Alcohol and Drug Abuse Research New Vistas on the Genetic Level Genetics of Addictive Behavior Genome-Wide Association Studies in Addiction Research Forward Genetics in Preclinical Addiction Research Animal Models as the Basis for Forward Genetic Approaches Alterations in Gene Expression in Drug-Exposed Animals Convergent Translational Genomics Approach for ­Addictive Behavior Reverse Genetic Approaches for the Functional Validation of Candidate Genes New Vistas on the Molecular Level Primary Targets of Alcohol in the Central Nervous System Agonist-Directed Trafficking of Receptor Stimulus—A Key for Understanding Drug Action New Vistas in Alcohol- and Drug-Induced Synaptic Plasticity New Vistas on Neuronal Network Activity Multielectrode Recording to Reveal Neuronal Network Activity Underlying Alcohol- and Drug-Related Behavior Animal Brain Imaging to Identify the Neuroanatomical and Neurochemical Substrates of Addictive Behavior Reconsolidation of Alcohol- and Drug-Related Memories 75 - Therapeutic Use of Noninvasive Neuromodulation for Addictions Introduction Neurobiology of Addiction Role of Circuit-Based Interventions Noninvasive Brain Stimulation Techniques: An Overview Transcranial Magnetic Stimulation Transcranial Electrical Stimulation tES and TMS in Addictive Disorders tES/TMS in Substance Use Disorders tES/TMS in Nonsubstance Use Disorders Safety and Tolerability Summary and Future Directions 1 - National Institute on Drug Abuse (NIDA): Medications to Treat Opioid Use Disorder* Overview How Do Medications to Treat Opioid Use Disorder Work? Opioid Agonists and Partial Agonists (Maintenance Medications) Opioid Antagonists How Effective Are Medications to Treat Opioid Use Disorder? Methadone Buprenorphine Methadone and Buprenorphine Compared Naltrexone Buprenorphine and Naltrexone Compared What Are Misconceptions About Maintenance Treatment? What Is the Treatment Need Versus the Diversion Risk for Opioid Use Disorder Treatment? Diversion Risk of Buprenorphine Diversion Risk of Methadone What Is the Impact of Medication for Opioid Use Disorder Treatment on HIV/HCV Outcomes? Mitigating Factors Possibility of Dual Therapeutic Potential How Is Opioid Use Disorder Treated in the Criminal Justice System? Is Medication to Treat Opioid Use Disorder Available in the Military? What Treatment Is Available for Pregnant Mothers and Their Babies? Methadone and Buprenorphine as the Standard of Care for Opioid Use Disorder in Pregnancy How Much Does Opioid Treatment Cost? Is Naloxone Accessible? Effects of Naloxone Distribution Appendix 2 - TIP 63: Medications for Opioid Use Disorder Executive Summary Introduction Overall Key Messages Content Overview Part 1: Introduction to Medications for Opioid Use Disorder Treatment Part 2: Addressing Opioid Use Disorder in General Medical Settings Part 3: Pharmacotherapy for Opioid Use Disorder Part 5: Resources Related to Medications for Opioid Use Disorder References TIP Development Participants Expert Panelists TIP Chair TIP Expert Panelists SAMHSA’s TIP Champion Scientific Reviewers Buprenorphine Naltrexone Methadone Field Reviewers Publication Information Acknowledgments Disclaimer Public Domain Notice Electronic Access and Copies of Publication Recommended Citation Originating Office Nondiscrimination Notice Appendix 3 - The ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use* Executive Summary Purpose Background Scope of Guideline Intended Audience Qualifying Statement Overview of Methodology Summary of Recommendations Diagnosis Recommendations Part 2: Treatment Options Part 3: Treating Opioid Withdrawal Part 4: Methadone Part 5: Buprenorphine Part 6: Naltrexone Part 7: Psychosocial Treatment in Conjunction With Medications for the Treatment of Opioid Use Disorder Part 9: Special Populations: Individuals With Pain Part 10: Special Populations: Adolescents Part 11: Special Populations: Individuals With Co-occurring Psychiatric Disorders Part 12: Special Populations: Individuals in the Criminal Justice System Part 13: Naloxone for the Treatment of Opioid Overdose Abbreviations and Acronyms National Practice Guideline Glossary Introduction Purpose Background on Opioid Use Disorder Epidemiology Mortality and Morbidity Scope of Guideline Included and Excluded Medications Intended Audience Qualifying Statement Methodology Overview of Approach Task 1: Review of Existing Guidelines Review of Existing Clinical Guidelines Analysis of Clinical Guidelines Preparation of Literature Review on Psychosocial Interventions Task 2: Identification of Hypothetical Statements and Appropriateness Rating RAND/UCLA Appropriateness Method Guideline Committee Meeting Literature Review Creation and Revision of Guideline Outline Task 3: Comparative Analysis, Review, and Necessity Rating Committee Review and Rating Final Draft Outline Task 4: Drafting the National Practice Guideline Draft and Review Task 5: External Review External Review Comprehensive Assessment Medical History Physical Examination Assessment and History Considerations Specific to Females Laboratory Tests Assessment for Mental Health Status and Psychiatric Disorder Assessment for Alcohol and Substance Use and Treatment History Assessment for Co-Occurring Alcohol and Substance Use Assessment for Tobacco Use Assessment of Social and Environmental Factors Diagnosing Opioid Use Disorder DSM-5 Criteria for Diagnosis Withdrawal Scales Urine Drug Testing Summary of Recommendations Assessment Recommendations Diagnosis Recommendations Areas for Further Research Part 2: Treatment Options Introduction Pharmacotherapy Options Efficacy Considerations Treatment Setting Pharmacology Contraindications and Precautions Methadone Buprenorphine Naltrexone Summary of Recommendations Areas for Further Research Part 3: Treating Opioid Withdrawal Background Assessment of Patient for Opioid Withdrawal Medications in Opioid Withdrawal Withdrawal Management With Opioid Agonists Withdrawal Management With Alpha-2 Adrenergic Agonists Anesthesia-Assisted Withdrawal Management Summary of Recommendations Areas for Further Research Part 4: Methadone Background Patient Selection and Treatment Goals Precautions Arrhythmias Course of Treatment Induction Dosing Adverse Effects Psychosocial Treatment Monitoring Treatment Length of Treatment Switching Treatment Medications Switching to Buprenorphine Switching to Naltrexone Summary of Recommendations Areas for Further Research Part 5: Buprenorphine Background Formulations of Buprenorphine Patient Selection and Treatment Goals Precautions Alcohol or Sedative, Hypnotic, or Anxiolytic Use Course of Treatment Exhibit 4: Physician Qualifications for OBOT Induction Dosing At Induction After Induction Adverse Effects Psychosocial Treatment Monitoring Treatment Length of Treatment Switching Treatment Medications Switching to Naltrexone Switching to Methadone Summary of Recommendations Areas for Further Research Part 6: Naltrexone Background Formulations of Naltrexone: Oral Versus Extended-Release Injectable Patient Selection and Treatment Goals Oral Naltrexone Extended-Release Injectable Naltrexone Precautions Risk of Relapse and Subsequent Opioid Overdose Course of Treatment Induction Dosing Adverse Effects Psychosocial Treatment Monitoring Treatment Length of Treatment Switching Treatment Medications Summary of Recommendations Areas for Further Research Background Goals of Psychosocial Treatment for Opioid Use Disorder Components of Psychosocial Treatment for Opioid Use Disorder Efficacy of Psychosocial Treatments in Opioid Use Disorder Mutual Help Programs Adherence to Psychosocial Treatment Within Overall Treatment Psychosocial Treatment and Treatment With Methadone Psychosocial Treatment and Treatment With Buprenorphine Psychosocial Treatment and Treatment With Naltrexone Summary of Recommendations Areas for Further Research Part 8: Special Populations: Pregnant Women Background Assessment of Opioid Use Disorder in Pregnant Women Medical Examination Physical Examination Laboratory Tests Imaging Psychosocial Assessment Opioid Agonist Treatment in Pregnancy Treatment Management Team Opioid Agonists Versus Withdrawal Management Methadone Versus Buprenorphine Combination Buprenorphine/Naloxone Naltrexone in Pregnancy Naloxone in Pregnancy Methadone Induction Conception While in Treatment With Methadone Timing of Treatment in Pregnancy Buprenorphine Induction Dosing of Opioid Agonists During Pregnancy Methadone Dosing Buprenorphine Dosing Breastfeeding Summary of Recommendations Areas for Further Research Background General Considerations for All Patients With Pain Pain Management in Patients Using Opioids Methadone and Pain Management Acute and Chronic Pain Control Buprenorphine and Pain Management Acute Pain Control Chronic Pain Control Considerations for Buprenorphine in Surgery Naltrexone and Pain Management Considerations for Naltrexone in Surgery Summary of Recommendations Areas for Further Research Part 10: Special Populations: Adolescents Background Confidentiality in Treatment Pharmacotherapy Options for Adolescents Opioid Agonists: Methadone and Buprenorphine Efficacy Research on Agonists and Partial Agonists in Adolescents Opioid Antagonist: Naltrexone Psychosocial Treatment for Adolescents Summary of Recommendations Areas for Further Research Background Assessment of Psychiatric Co-occurrence Co-occurring Psychiatric Disorders and Suicide Risk Considerations With Specific Psychiatric Disorders Depression or Bipolar Disorder Schizophrenia Co-occurring Psychiatric Disorders and Agonist Treatment Methadone Buprenorphine Co-occurring Psychiatric Disorders and Antagonist Treatment Summary of Recommendations Background Effectiveness of Pharmacotherapy Methadone Buprenorphine Naltrexone Treatment Options Methadone and Buprenorphine Naltrexone Summary of Recommendations Areas for Further Research Introduction Patients and Significant Others/Family Members Individuals Trained and Authorized to Use Naloxone Safety and Efficacy of Bystander Administered Naloxone Routes of Administration Summary of Recommendations Part 14: Areas for Further Research Assessment and Diagnosis of Opioid Use Disorder (Part 1) Treatment Options (Part 2) Opioid Withdrawal Management (Part 3) Methadone (Part 4) Buprenorphine (Part 5) Naltrexone (Part 6) Special Populations: Pregnant Women (Part 8) Special Populations: Individuals With Pain (Part 9) Special Populations: Adolescents (Part 10) Special Populations: Individuals in the Criminal Justice System (Part 12) Appendices Appendix I: Clinical References Reviewed Appendix II: Bioequivalence Information and Charts Bioequivalence of Suboxone (Buprenorphine and Naloxone) Sublingual Tablets and Suboxone Sublingual Film Switching Between Suboxone (Buprenorphine and Naloxone) Sublingual Film and Suboxone Sublingual Tablets Switching Between Suboxone Sublingual Tablets or Films and Bunavail Buccal Film Dosage and Administration of Zubsolv Switching Between Zubsolv Sublingual Tablets and Other Buprenorphine/Naloxone Combination Products Appendix III: Guideline Committee Member Relationships With Industry and Other Entities Appendix V: External Reviewer Relationships With Industry and Other Entities