Addiction Medicine: Science and Practice

Cover
Title Page
Front Matter
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Appendix 1; National Institute on Drug Abuse (NIDA) Medications to Treat Opioid Use Disorder
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
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
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