Substance Use and Addictive Disorders Flashcards

Substance Use and Addictive Disorders

• Chapter 4 addresses substance use disorders linked to alcohol, caffeine, cannabis, hallucinogens (including PCP), inhalants, opioids, sedatives, hypnotics, anxiolytics, stimulants (including cocaine), tobacco, anabolic-androgenic steroids (AAS), and other substances like nitrous oxide and γ-hydroxybutyrate.

• Also covers gambling disorder, which DSM-5 classifies as a non-substance-related addictive disorder.

• Substance use disorders have shared characteristics but vary in pharmacology, intoxication, and associated behaviors.

Clinical Presentation

• Behavioral, physical, and psychological dependence are hallmarks of these disorders.

• The impact of substance use causes impairment regardless of the specific substance.

• Symptoms fall into four categories:

  • Pharmacologic symptoms

  • Symptoms of impaired use

  • Impairment in social domains

  • Use in risky or hazardous situations.

Terminology

• Dependence: Used in two ways:

  • Behavioral dependence: Focuses on substance-seeking activities and pathologic use patterns.

  • Physical dependence: Refers to the physical effects of repeated substance use.

• Psychological dependence (habituation): Characterized by craving to avoid a dysphoric state.

• Addiction/Addict: 'Addict' has a pejorative connotation.

• Addictions share neurochemical and neuroanatomical substrates, affecting brain reward areas similarly, whether substances, gambling, sex, stealing, or eating.

Diagnosis (DSM-5)

• Three major diagnostic categories:

  • Substance Use Disorder

  • Substance Intoxication

  • Substance Withdrawal

• Substance-Induced Mental Disorder is included for psychiatric presentations caused by substance use (rule-out criteria for DSM-5 and ICD-10).

• DSM-5 disorders are substance-specific. Clinicians should specify the substance when diagnosing.

Substance Use Disorder

• Diagnostic term for prolonged use and abuse of a substance (e.g., "alcohol use disorder" or "opioid use disorder").

Substance Intoxication

• A syndrome with specific signs and symptoms from recent ingestion or exposure (e.g., "alcohol intoxication" or "opioid intoxication").

Substance Withdrawal

• A substance-specific syndrome from the abrupt cessation of heavy, prolonged use (e.g., "alcohol withdrawal" or "opioid withdrawal").

DSM-5 and ICD-10 substance Use Disorder comparison.

• Diagnostic name

  • Alcohol use disorder

  • Cannabis use disorder

  • Hallucinogen use disorder

  • Inhalant use disorder

  • Opioid use disorder

  • Sedative/hypnotic/anxiolytic use disorder

  • Stimulant use disorder

  • Tobacco use disorder

• ICD-10: Mental and behavioral disorders due to

  • Use of alcohol

  • Use of opioids

  • Use of cannabinoids

  • Use of sedatives or hypnotics

  • Use of cocaine

  • Use of other stimulants, including caffeine

  • Use of hallucinogens

  • Use of tobacco

  • Use of volatile solvents

  • Indicate if includes a dependence syndrome

• Duration:

  • Symptoms occur within 12 months

• Symptoms:

  • Physiologic Symptoms:

    1. Tolerance

    2. Withdrawal (does not apply to inhalants and hallucinogens)

  • Symptoms typical of addiction or obsessive use

    3. Craving to use

  • Tolerance and withdrawal states

  • Adverse health effects of use: physiologic, cognitive or behavioral

  • Craving or difficulty controlling substance use

    4. Using more than intended

    5. Difficulty stopping or reducing use

    6. Spending significant time devoted to the substance (using, obtaining, recovering)

    7. Use despite acknowledging health problems (physical, mental) because of use

  • Psychosocial sequelae of use

    8. Using despite social, occupational or other adverse consequences

    9. Neglecting other responsibilities because of use

    10. Neglecting other activities because of use

    11. Risky or dangerous behaviors or situations because of use

  • Use despite acknowledging adverse consequences of use

  • Prioritizing the substance over other psychosocial obligations

• Required number of symptoms:

  • Two or more of the above

• Psychosocial consequences of symptoms:

  • Marked impairment and/or distress

• Exclusions:

  • Psychotic state

  • Nonalcoholic Korsakoff psychosis or syndrome

• Symptom specifiers

  • In a controlled environment: (i.e., access to the substance is restricted)

  • On maintenance therapy: (tobacco or opioids)

  • For hallucinogens or inhalants, specify the specific substance

• Associated specifiers:

  • Psychotic disorder (following substance use)

  • Amnesic syndrome (chronic memory loss because of use)

• Course specifiers

  • In early remission: no symptoms for 3–12 mo (craving may still be present)

  • In sustained remission: no symptoms for >12 mo (craving may still be present)

• Severity specifiers

  • Severity is measured by the number of symptoms present. See DSM-5 for ranges.

• Comments:

  • Note: ICD additionally defines “harmful use” as pattern of use causing harm to health, both physical and/or mental. This classification is independent of presence of a dependence syndrome.

  • Applies to the following substances:

    • Alcohol

    • Cannabis

    • Opioids

    • Sedatives, hypnotics, anxiolytics

    • Stimulants

    • Hallucinogens

    • Inhalants

    • Tobacco

DSM-5 and ICD-10 substance Intoxication comparison.

• Disorder

  • Diagnostic name

    • Alcohol intoxication

    • Caffeine intoxication

    • Cannabis intoxication

    • Hallucinogen intoxication

    • Inhalant intoxication

    • Opioid intoxication

    • Sedative/hypnotic/anxiolytic intoxication

    • Stimulant intoxication

  • ICD-10: Mental and behavioral disorders due to

    • Use of alcohol

    • Use of opioids

    • Use of cannabinoids

    • Use of sedatives or hypnotics

    • Use of cocaine

    • Use of other stimulants, including caffeine

    • Use of hallucinogens

    • Use of tobacco

    • Use of volatile solvents

      • Indicate if acute intoxication

• Duration:

  • Not specified

• Symptoms

  • Recent use of substance

  • Mood or behavioral problems resulting from that use

  • One or more substance-specific symptoms of intoxication (see individual substances for descriptions of the intoxication state)

  • Some mental change resulting from substance use: cognitive, psychological or behavioral

  • Symptoms due to the substance resolve when stopped

• Required number of symptoms

  • Specific to substance:

    • Stimulants: ≥2

    • Caffeine: ≥5 or more symptoms

    • Sedative/hypnotic/anxiolytics: ≥1

    • Opioids: ≥1

    • Inhalants: ≥2

    • Hallucinogens: ≥2 plus change in perception or alertness

    • Cannabis: ≥2

    • Alcohol: ≥1

• Exclusions

  • Medical condition

  • Other mental disorder

  • Intoxication with another substance

  • Intoxication due to poisoning

• Symptom specifiers

  • For cannabis, opioids, or stimulants: with perceptual disturbance: hallucinations but no loss or reality testing and not delirious

• Comments

  • Applies to the following substances:

    • Alcohol

    • Cannabis

    • Opioids

    • Sedatives, hypnotics, anxiolytics

    • Stimulants

    • Hallucinogens

    • Inhalants

    • Caffeine

DSM-5 and ICD-10 substance Withdrawal comparison.

• Disorder

  • Diagnostic name

    • Alcohol withdrawal

    • Caffeine withdrawal

    • Cannabis withdrawal

    • Opioid withdrawal

    • Sedative/hypnotic/anxiolytic withdrawal

    • Stimulant withdrawal

    • Tobacco withdrawal

  • ICD-10: Mental and behavioral disorders due to

    • Use of alcohol

    • Use of opioids

    • Use of cannabinoids

    • Use of sedatives or hypnotics

    • Use of cocaine

    • Use of other stimulants, including caffeine

    • Use of hallucinogens

    • Use of tobacco

    • Use of volatile solvents

      • Indicate withdrawal state

• Duration

  • Onset is specific to substance: sedatives/hypnotics/anxiolytics, stimulants: hours to days alcohol and cannabis: none listed opioids: minutes to days caffeine, tobacco: within 24 hr

• Symptoms

  • No or reduced use after prolonged or heavy use

  • Substance-specific symptoms (see individual substances for typical symptoms of withdrawal)

  • Group of symptoms occurring with cessation or reduction of a substance following period of prolonged and/or regular use

  • Symptoms are time limited and substance-specific

• Required number of symptoms

  • Specific to substance:

    • sedatives/hypnotics/anxiolytics: ≥2

    • alcohol: ≥2

    • stimulants: ≥2 plus dysphoric mood

    • opioids: ≥3

    • caffeine: ≥3

    • cannabis: ≥3

    • tobacco: ≥4

• Psychosocial consequences of symptoms

  • Distress and/or impairment in functioning

• Exclusions

  • Medical condition

  • Other mental disorder

  • Intoxication with or withdrawal from another substance

• Symptom specifiers

  • For alcohol and sedative/hypnotic/anxiolytic withdrawal: with perceptual disturbance: hallucinations but no loss or reality testing and not delirious

  • Withdrawal state with delirium

• Comments

  • Applies to the following substances:

    • Alcohol

    • Cannabis

    • Opioids

    • Sedatives, hypnotics, anxiolytics

    • Stimulants

    • Tobacco

    • Caffeine

Comorbidity

• Comorbidity is the occurrence of two or more psychiatric disorders in a single patient.

• 50% of addicts seeking treatment for alcohol, cocaine, or opioid dependence have a comorbid psychiatric disorder.

• Opioid, cocaine, and alcohol abusers with current psychiatric problems more likely to seek treatment.

• 35-60% of patients with substance abuse meet criteria for antisocial personality disorder.

• Patients who have antisocial personality disorder are likely to:

  • Use more illegal substances.

  • Have more psychopathology.

  • Be less satisfied with lives.

  • Be more impulsive, isolated and depressed.

Depression and Suicide

• Depressive symptoms are common among persons diagnosed with substance abuse or substance dependence.

• 1/3-1/2 people with opioid abuse/dependence + 40% of those with alcohol abuse/dependence meet criteria for MDD.

• Substance use is a major precipitating factor for suicide.

• Persons who abuse substances are ~$20$ times more likely to die by suicide than the general population.

• 15% of persons with alcohol abuse or alcohol dependence commit suicide (second only to major depressive disorder).

Treatment Approach

• Some recover without formal treatment, especially as they age.

• Brief interventions for less severe disorders (e.g., nicotine addiction).

• Change in motivation (cognitive change) has the best impact.

• Variety of interventions effective for those who do not respond or whose dependence is more severe.

• Treatment programs combine specific procedures, disciplines, and meet individual patient needs after assessment.

• Programs broadly grouped based on:

  • Detoxification vs. rehabilitation

  • Pharmacologic interventions

  • Individual therapy, Alcoholics Anonymous (AA), or therapeutic community principles.

• Addictive behaviors change through multiple stages:

  • Precontemplation

  • Contemplation

  • Preparation

  • Action

  • Maintenance

• Therapeutic alliance improves when treatment aligns with readiness to change.

• Pharmacologic agents exist for specific drug use disorders:

  • disulfiram, naltrexone, or acamprosate for alcoholism

  • methadone, levomethadyl acetate, or buprenorphine for heroin addiction

  • nicotine replacement, varenicline, or bupropion for tobacco.

• Extended treatment periods (at least 3 months) are likely to reduce drug use, antisocial behaviors, and psychological distress for dependent cocaine or heroin patients.

• Treatment outcomes vary due to the wide range of patients and circumstances.

• Professionally trained staff with comprehensive services improve retention and positive change for severe psychiatric difficulties.

• Brief counseling can be effective in reducing substance use for alcohol, tobacco, or cannabis problems.

• Illicit drug programs consider outcomes such as social functioning, employment, and criminal activity.

• Integrated treatment (same staff treating both psychiatric disorder & addiction) is more effective than parallel or sequential treatments.

• Managed care reduced hospital-based detoxification and residential rehabilitation programs for alcoholics.

• Outpatient counseling effective for private-sector alcoholics isn't always sufficient for illicit drug users with minimal social supports

• Treatment is often a worthwhile social expenditure.

• Lack of public support suggests substance dependence viewed as moral failing rather than medical disorder.

Epidemiology of Substance Use Disorders

• NIDA and NSDUH conduct periodic surveys of illicit drug use in the United States.

• In 2017, >19 million people (7% of the US population) had a substance-related disorder in the past year.

• More men than women abuse substances.

• Earlier substance use correlates with a higher likelihood of disorder.

• American Indian/Alaska Natives have the highest lifetime rate.

• Whites are more affected than blacks/African Americans.

• Those with some college education use more substances than those with less education.

• Unemployed have higher rates than employed.

Etiology

• Substance use disorders: complex psychiatric conditions with both biological and environmental factors.

• Multiple interacting factors influence drug-using behavior and impaired judgment.

• Drug availability, social acceptability, and peer pressures affect experimentation.

• Personality and individual biology determine response to drugs.

• Brain disease: changes in structure and neurochemistry of the brain transform voluntary drug use into compulsive drug use

• Drug-dependent individuals can modify their drug-using behavior in response to reinforcers or contingencies, the interaction of multiple factors is required to determine the etiology.

• Factors influence drug-using behavior itself:

  • Social and psychological situations

  • The person’s history

  • Reward

  • Aversion

  • Tolerance

  • Physical dependence

  • Sensitization

• Aversive qualities of withdrawal trigger drug use.

• Sensitization raises salience of drug stimuli.

Neurobiology of Substance Use Disorders

Genetic Factors

• Alcohol abuse has a genetic component.

• Other types of substance abuse have genetic pattern in development.

• RFLP: Associations with genes that affect dopamine production.

NeuroChemical Factors

• Receptors and Receptor systems

  • Researchers have identified connections with neurotransmitters or neurotransmitter receptors involved with most substances of abuse (except alcohol).

  • Opioids act on opioid receptors.

  • Long-term use of drugs modulates receptors -> exogenous substance needed to maintain homeostasis.

• Pathways and Neurotransmitters

  • Opioid,

  • Catecholamine (dopamine)

  • γ-aminobutyric acid (GABA) systems

  • Dopaminergic in ventral tegmental area (VTA): project to cortical and limbic -> reward

  • Locus ceruleus (adrenergic): mediates the effects of the opiates and the opioids

  • Brain-reward circuitry.

Psychology of Substance Use disorders

Psychodynamic Factors

• Substance abuse: masturbatory equivalent, a defense against anxious impulses, or a manifestation of oral regression.

• Self-medication: alcohol may control panic, opioids might diminish anger, and amphetamines may alleviate depression.

• Alexithymia: inability to find words to describe their feelings.

Learning and Conditioning

• Drugs reinforce antecedent behaviors by terminating aversive state e.g. pain, anxiety, or depression.

• Each drug use evokes rapid positive reinforcement.

• Paraphernalia and behaviors can become secondary reinforcers.

• Drug users respond to the drug-related stimuli with increased activity in limbic regions (amygdala/ anterior cingulate).
  In addition to operant reinforcement of drug-using and drug-seeking behaviors, withdrawal phenomena can be conditioned; craving may be independent of feelings of withdrawal.

• Conditions associated with the availability or use of a substance bring about the most intense craving.

Alcohol-Related Disorders

• Alcohol is a potent drug causing acute and chronic changes in neurochemical systems.

• Alcohol abuse can induce temporary psychological symptoms: depression, anxiety, and psychoses.

• Regular alcohol consumption leads to tolerance.

• Chronic alcohol use causes significant bodily adaptation; stopping abruptly can precipitate withdrawal syndromes (insomnia, autonomic hyperactivity, anxiety).

• Clinicians must consider alcohol's effects when evaluating life problems and psychiatric symptoms.

Diagnosis and Clinical Features (DSM-5 & ICD-10)

• Diagnoses follow a standard substance use disorder template.

• Indicators of an alcohol use disorder:

  • Daily need for large amounts of alcohol to function.

  • Regular heavy drinking limited to weekends.

  • Long periods of sobriety followed by heavy drinking binges lasting weeks or months.

• Associated behaviors:

  • Inability to cut down or stop drinking.

  • Repeated attempts to control drinking (e.g., "going on the wagon").

  • Binges (intoxication throughout the day for at least 2 days).

  • Consuming large alcohol amounts in one sitting.

  • Amnestic periods (blackouts).

  • Continued drinking despite knowledge of exacerbating a physical disorder.

  • Drinking non-beverage alcohol.

• Impaired social or occupational functioning:

  • Violence while intoxicated.

  • Absence from work/job loss.

  • Legal issues (arrests, traffic accidents).

  • Family/friend conflicts about alcohol consumption.

Case Example: Mark

• 45-year-old divorced man in the emergency room

• Consumed large quantities of beer and wine daily for over 5 years.

• Drinking pattern: approximately five beers and a fourth of wine a day since his divorce 5 years prior.

• Experienced blackouts and missed work frequently, leading to job losses.

• Poorly nourished and relying on beer as his prime source of nourishment.

• Alternates between apprehension and chatty, superficial warmth

• Rambling and unfocused speech.

• Confused about time and recognizes the physician at times, and other times confuses him with his brother.

• Gross hand tremor at rest.

• Attention shifts rapidly, hindering memory and calculation tests.

Levels of Impairment at Different Blood Alcohol Concentrations

• Table 4-4 outlines impairment levels at different blood alcohol concentrations (BAC).

• 20-30 \text{ mg/dL}, Slowed motor performance and decreased thinking ability

• 30-80 \text{ mg/dL}, Increases in motor and cognitive problems

• 80-200 \text{ mg/dL}, Increases in incoordination and judgment errors. Mood lability. Deterioration in cognition

• 200-300 \text{ mg/dL}, Nystagmus, marked slurring of speech, and alcoholic blackouts

• >300 \text{ mg/dL}, Impaired vital signs and possible death

• Legal intoxication in most US states: 80-100 mg ethanol per deciliter of blood (0.08-0.10 g/dL).

• Significant pharmacodynamic tolerance is likely if no significant motor/mental impairment occurs at approximately 150 mg/dL.

Alcohol Intoxication

• DSM-5 criteria include recent ethanol ingestion, maladaptive behavior, and physiological correlates.

Alcohol Withdrawal

• Can be severe, even without delirium, including seizures and autonomic hyperactivity.

• Predisposing/aggravating factors: fatigue, malnutrition, physical illness, depression.

• DSM-5 criteria: cessation/reduction of heavy, prolonged use + specific physical/neuropsychiatric symptoms.

  • Specification: “with perceptual disturbances.”

• Classic sign: tremulousness.

• Spectrum: psychotic/perceptual symptoms (delusions, hallucinations), seizures, delirium tremens (DTs; alcohol delirium in DSM-5).

• Table 4-5 outlines alcohol withdrawal progression.

• Progression may not be linear; DTs can occur without preceding stages.

• Tremor can resemble physiologic (high amplitude, >8 Hz) or familial tremor (bursts, <8 Hz).

• Other symptoms: irritability, GI issues (nausea, vomiting).

• Autonomic hyperactivity: anxiety, arousal, sweating, facial flushing, mydriasis, tachycardia, mild hypertension.

• Patients are generally alert but may startle easily.

Case Example: Mr. F

• 29-year-old heavy drinker for 8 years.

• One week of continuous drinking with friends and at local bars.

• Experienced shaky hands, nausea, and dry heaves, and anxiety.

• Marked resting and intention tremor, tremulous tongue and eyelids.

• Oriented with no memory impairment.

• Admitted to drinking several drinks each day for the past 8 years, but claimed it has not interfered with his work or relationships, and only having mild hangovers.

• Denied previous binges or daily need to drink to function.

• Admitted to never trying to reduce or stop drinking.

Withdrawal Seizures

• Stereotyped, generalized, tonic-clonic.

• Multiple seizures often occur 3-6 hours after the first.

• Status epilepticus is rare (<3%).

• Other causes should be considered (head injuries, CNS infections/neoplasms, cerebrovascular diseases).

• Long-term abuse can result in hypoglycemia, hyponatremia, and hypomagnesemia, which are associated with seizures.

Delirium Tremens (DTs)

• Monitor patients with alcohol withdrawal to prevent progression to alcohol withdrawal delirium.

• DTs: medical emergency with significant morbidity/mortality.

• Patients are a danger to self and others due to unpredictable behavior; may be assaultive or suicidal.

• Untreated DTs have a 20% mortality rate, usually due to intercurrent medical illness.

• Withdrawal seizures commonly precede DTs, but delirium can appear unheralded.

• Essential feature: delirium within 1 week of stopping/reducing alcohol intake.

• Symptoms: autonomic symptoms, perceptual, and psychomotor (Table 4-6).

Table 4-6 Delirium Tremens Symptoms

• Delirium

  • Confusion

  • Disorientation

• Hallucinations (tactile common)

• Delusions

• Autonomic hyperactivity

  • Tachycardia

  • Diaphoresis

  • Fever

  • Hypertension

• Anxiety

• Insomnia

• Fluctuating levels of psychomotor activity (ranging from lethargy to agitation)

• About 5% of hospitalized patients with alcohol-related disorders have DTs.

• May develop unexpectedly on the third hospital day, indicating a previously undiagnosed alcohol problem.

• Typically begins in 30s/40s after 5-15 years of heavy (binge-type) drinking.

• Physical illness (hepatitis, pancreatitis) predisposes to DTs.

Case Example: Mr. R

• 40-year-old man admitted to orthopedic department after falling and breaking his leg.

• Developed increasing nervousness and tremors on the third day of his hospital stay.

• Denied alcohol problems initially but wife admitted to large wine quantities for over 4 years.

• Wife planning divorce

• Rambling and incoherent speech; believed he was at work.

• Picking at bugs on his bedsheets (hallucinations).

• Disoriented in time and started easily by sounds.

• Sweating profusely and could not hold a glass without spilling some of the contents.

Alcohol-Induced Disorders

• Alcohol-Induced Persisting Dementia:

  • Poorly studied, heterogeneous, long-term cognitive problem.

  • Decreased intellectual functioning, cognitive abilities, and memory.

  • Recent memory difficulties, global cognitive impairment.

  • Brain function can improve with abstinence, but long-term disabilities are possible.

  • 50-70% have increased brain ventricles and shrinkage of cerebral sulci (reversible after a year of abstinence).

• Alcohol-Induced Persisting Amnestic Disorder:

  • Disturbance in short-term memory caused by prolonged heavy alcohol use.

  • Rare in persons younger than age 35.

• Wernicke-Korsakoff Syndrome:

  • Wernicke encephalopathy (acute symptoms) and Korsakoff syndrome (chronic condition).

  • Reversibility: Wernicke encephalopathy is entirely reversible with treatment, while only about 20% of patients with Korsakoff syndrome recover.

  • Pathophysiology: thiamine deficiency caused by poor nutrition or malabsorption.

  • Thiamine is a cofactor for critical enzymes and is involved in nerve impulse conduction and synaptic transmission.

  • Neuropathologic lesions are symmetrical and paraventricular, involving multiple brain regions.

Wernicke Encephalopathy

• Also known as alcoholic encephalopathy.

• Acute neurologic disorder characterized by:

  • Ataxia (primarily affecting gait).

  • Vestibular dysfunction.

  • Confusion.

  • Ocular motility abnormalities (horizontal nystagmus, lateral orbital palsy, and gaze palsy).

    • Usually bilateral but not necessarily symmetrical.

    • Other eye signs: sluggish reaction to light, anisocoria (unequal pupil size).

• May clear spontaneously or progress to Korsakoff Syndrome.

Korsakoff Syndrome

• Chronic amnestic syndrome following Wernicke encephalopathy.

• Cardinal features: impaired mental syndrome (especially recent memory) and anterograde amnesia in an alert and responsive patient.

• The patient may or may not have the symptom of confabulation.

Blackouts

• Discrete episodes of anterograde amnesia during alcohol intoxication.

• Intact remote memory but a specific short-term memory deficit (inability to recall events from the previous 5 or 10 minutes).

• Other intellectual faculties are well preserved, and they can perform complicated tasks and appear normal to casual observers.

• Caused by alcohol blocking the consolidation of new memories, likely involving the hippocampus and temporal lobe structures.

Alcohol-Induced Psychotic Disorder

• Approximately 3% of alcoholic persons experience auditory hallucinations or paranoid delusions during heavy drinking or withdrawal.

• The most common auditory hallucinations are voices, often maligning, reproachful, or threatening.

• Impaired reality testing is frequent, and mostly realize the hallucinatory nature of the symptoms after the episode.

• Hallucinations after alcohol withdrawal are considered rare, where the patient has a clear sensorium, a syndrome distinct from alcohol withdrawal delirium.

• Onset can occur at any age, and mostly occurs in those abusing alcohol for a long time.

• Hallucinations resolve within a week, but clinicians must consider other psychotic disorders if they linger.

Case Example: Mr. G

• 40-year-old unemployed man with Daily alcohol use for 15 years.

• Complained of hearing voices of men threatening to kill him.

• Alert and oriented.

Alcohol-Induced Mood Disorder

• Heavy intake of alcohol results in major depressive disorder, but improves within several days to 1 month of abstinence.

• 80% of alcoholic persons report intense depression histories.

• Only 10-15% have a history of Major depressive disorder but have stopped drinking heavily.

• Severe substance-induced depressions are likely to improve fairly rapidly with abstinence, without specific treatment for the depression.

• Watch and wait 2 to 4 weeks before starting antidepressant medications.

Case Example

• The primary care doctor requested a consult for a 42-year-old woman with alcohol use disorder who complained of persisting severe depressive symptoms despite 5 days of abstinence.

• Prominent sadness that had persisted for several weeks, difficulties concentrating, initial and terminal insomnia, and a feeling of hopelessness and guilt

• The psychiatrist made a provisional diagnosis of an alcohol-induced mood disorder.

• The patient had education, reassurance, and cognitive therapy to help her to deal with the depressive symptos

• After 3 weeks of abstinence, the patient was no longer significantly depressed, although she had some minor mood swings for several additional weeks.

Alcohol-Induced Anxiety Disorder

• Anxiety symptoms are also common in the context of acute and protracted alcohol withdrawal.

• Almost 80% of alcoholic persons report panic attacks during at least one acute withdrawal episode.

• During the first 4 weeks of abstinence, those with severe alcohol problems are likely to avoid some social situations for fear of being overwhelmed by anxiety.

• Symptoms are likely to diminish and disappear over time, if the patient only shows symptoms of anxiety in the context of heavy drinking, or shortly after abstinence

Case Example

• The primary care physician referred a 48-year-old woman for evaluation for her panic attacks.

• The workup included and atypical age of onset with blood results, which encouraged the clinician to probe further regarding the pattern of alcohol-related life problems with both the patient and, separately, her spouse.

• After the patient withdrew with benzodiazepines the panic symptoms diminished in intensity and disappeared.

• Working diagnosis: severe alcohol use disorder with alcohol-induced anxiety disorder.

Alcohol-Induced Sexual Dysfunction

• Formal diagnosis of sexual dysfunction related to alcohol intoxication.

Alcohol-Induced Sleep Disorder

• Diagnosed by a sleep disorder.

Unspecified Alcohol-Related Disorder

• Used when criteria for other diagnoses are not met.

Table 4-7 Neurologic and Medical Complications of Alcohol Use

• Alcohol intoxication

  • Acute intoxication

  • Pathologic intoxication (atypical, complicated, unusual)

  • Blackouts

• Alcohol withdrawal syndromes

  • Tremulousness (the shakes or the jitters)

  • Alcoholic hallucinosis (horrors)

  • Withdrawal seizures (rum fits)

  • Delirium tremens (shakes)

• Nutritional diseases of the nervous system secondary to alcohol abuse

  • Wernicke–Korsakoff syndrome

  • Cerebellar degeneration

  • Peripheral neuropathy

  • Optic neuropathy (tobacco–alcohol amblyopia)

  • Pellagra

• Alcoholic diseases of uncertain pathogenesis

  • Central pontine myelinolysis

  • Marchiafava–Bignami disease

  • Fetal alcohol syndrome

  • Myopathy

  • Alcoholic dementia

  • Alcoholic cerebral atrophy

• Systemic diseases due to alcohol with secondary neurologic complications

  • Liver disease

    • Hepatic encephalopathy

    • Acquired (non-Wilsonian) chronic hepatocerebral degeneration

  • Gastrointestinal diseases

    • Malabsorption syndromes

    • Postgastrectomy syndromes

    • Possible pancreatic encephalopathy

  • Cardiovascular diseases

    • Cardiomyopathy with potential cardiogenic emboli and cerebrovascular disease

    • Arrhythmias and abnormal blood pressure leading to cerebrovascular disease

  • Hematologic disorders

    • Anemia, leukopenia, thrombocytopenia (could possibly lead to hemorrhagic cerebrovascular disease)

  • Infectious disease, especially meningitis (especially pneumococcal and meningococcal)

  • Hypothermia and hyperthermia

  • Hypotension and hypertension

  • Respiratory depression and associated hypoxia

• Toxic encephalopathies, including alcohol and other substances

• Electrolyte imbalances leading to acute confusional states and, rarely, local neurologic signs and symptoms

  • Hypoglycemia

  • Hyperglycemia

  • Hyponatremia

  • Hypercalcemia

  • Hypomagnesemia

  • Hypophosphatemia

• Increased incidence of trauma

  • Epidural, subdural, and intracerebral hematoma

  • Spinal cord injury

  • Posttraumatic seizure disorders

  • Compressive neuropathies and brachial plexus injuries (Saturday night palsies)

  • Posttraumatic symptomatic hydrocephalus (normal pressure hydrocephalus)

  • Muscle crush injuries and compartmental syndromes

Other Alcohol-Related Neurologic Disorders

• We are restricting our discussion to the significant neuropsychiatric syndromes associated with alcohol use.

Alcoholic Pellagra Encephalopathy

• A diagnosis of potential interest to psychiatrists presented with a patient who appears to have Wernicke– Korsakoff syndrome but who does not respond to thiamine treatment.

Fetal Alcohol Syndrome

• Data indicate that women who are pregnant or are breast-feeding should not drink alcohol.

• The leading cause of intellectual disability in the United States, occurs when mothers who drink alcohol expose fetuses to alcohol in utero.

• The alcohol inhibits intrauterine growth and postnatal development.

• Microcephaly, craniofacial malformations, and limb and heart defects are common in affected infants.

• Short adult stature and development of a range of adult maladaptive behavior are also associated with fetal alcohol syndrome.

Women with alcohol-related disorders

• Have a 35% risk of having a child with defects.

• Mechanism: exposure in utero to ethanol or its metabolites and hormone imbalances increases the risk of abnormalities.

Laboratory Tests

• Adverse effects of alcohol appear in standard laboratory tests, which can be useful diagnostic aids in identifying persons with alcohol-related disorders.

• Table 4-9 lists some of the more useful tests, all of which are related to the damaging effects of alcohol.

Table 4-9 Laboratory Test Associated with Heavy Drinking State Markers of Heavy Drinking Useful in Screening for AUDs

• γ-glutamyltransferase (GGT) >35.0 U/L

• Carbohydrate-deficient transferrin (CDT) >3.0%

• Mean corpuscular volume (MCV) >91.0 μm3

• Serum glutamic oxaloacetic transaminase (aspartate aminotransferase) >45.0 IU/L

• Serum glutamic pyruvic transaminase (alanine aminotransferase) >45.0 IU/L

Comorbidity

• Psychiatric diagnoses most associated with alcohol-related disorders are:

  • Other substance-related disorders

  • Antisocial personality disorder

  • Mood disorders

  • Anxiety disorders.

• Most suggest that persons with alcohol-related disorders have a suicide rate than the general population.

Antisocial Personality Disorder

• Some studies suggest that antisocial personality disorder is particularly in men with an alcohol-related disorder and can precede the development of an alcohol-related disorder.

• Other studies, however, suggest that antisocial personality disorder and alcohol-related disorders are entirely distinct entities that are not causally related.

Mood Disorders

• About 30 to 40 percent of persons with an alcohol-related disorder meet the diagnostic criteria for major depressive disorder sometime during their lifetimes.

• Depression is more common in women than in men with these disorders.

• Several studies reported that depression is likely to occur in patients with alcohol-related disorders who have a high daily consumption of alcohol and a family history of alcohol abuse.

• Persons with alcohol-related disorders and major depressive disorder are at significant risk for suicide.

• Some clinicians recommend antidepressant drug therapy for depressive symptoms that remain after 2 to 3 weeks of sobriety.

• Patients with bipolar disorder are at risk of developing an alcohol-related disorder; they may use alcohol to self-medicate their manic episodes.

Anxiety Disorders

• Many persons use alcohol for its efficacy in alleviating anxiety.

• Roughly 25-50% of all persons with alcohol-related disorders also meet the diagnostic criteria for an anxiety disorder.

• Phobias and panic disorder are particularly frequent comorbid diagnoses in these patients.

• Persons with anxiety may use alcohol to self-medicate symptoms of agoraphobia or social phobia.

• Alcohol-related disorders are likely to precede the development of panic disorder or generalized anxiety disorder.

Suicide

• Most estimates of the prevalence of suicide among persons with alcohol- related disorders range from 10 to 15 percent, although alcohol use itself may be involved in a much higher percentage of suicides.

• Some investigators have questioned whether the suicide rate among persons with alcohol-related disorders is as high as the numbers suggest.

Table 4-10 Factors Associated with Suicide in Persons with Alcohol Use Disorder

• Presence of a major depressive episode

• Weak psychosocial support systems

• A serious coexisting medical condition

• Unemployment

• Living alone

Course and Prognosis

• Between 10 and 40 percent of alcoholic persons enter some formal treatment program.

• Several prognostic signs are favorable, listed in Table 4-11 some of the most predictive factors, and the combination of these predicts at least a 60 percent chance for one or more years of abstinence.

• Few studies have documented the long-term course, but researchers agree that 1 year of abstinence is associated with a good chance for continued abstinence over an extended period.

• Persons with severe drug problems (especially intravenous drug use or cocaine or amphetamine use disorders) and those who are homeless may have only a 10 to 15 percent chance of achieving 1 year of abstinence, however.

• Accurately predicting whether any specific person will achieve or maintain abstinence is impossible

Table 4-11 Alcohol Use Disorders: Positive Prognostic Signs

• No premorbid antisocial personality disorder

• Good psychosocial functioning

• Stable job

• Stable family

• No legal problems

• Adherence to treatment

• Factor reflecting life stability probably only explain 20% of less of the course of alcohol use disorders.

• These somewhat intangible factors are likely to include motivational levels and the quality of the patient’s social support system.

• Alcoholic persons with preexisting independent major psychiatric disorders are likely to run the course of their independent psychiatric illness.

• The goal is to minimize the symptoms of the independent psychiatric disorder in the hope that better life stability will be associated with a better prognosis for the patient’s alcohol problems.

Treatment of Alcohol Use Disorders

• 3 General steps are involved in treating the alcoholic person: intervention, detoxification, and rehabilitation.

• An alcoholic person with symptoms of depression sufficiently severe to be suicidal requires inpatient hospitalization for at least several days until the suicidal ideation disappears.

• The patient with alcohol use disorder must then be brought face-to-face with the reality of the disorder (intervention), be detoxified if needed, and begin rehabilitation.

Intervention

• The goal of intervention is to use the principles of motivational interviewing and brief interventions to help patients recognize the adverse consequences likely to occur if they do not stop drinking.

• A discussion of the presenting complaint (e.g., insomnia or depression) is a useful way to both show empathy and enhance motivation for change.

• We would emphasize how alcohol either created or contributed to these problems and reassure the patient that abstinence is possible.

• Repeat the same nonjudgmental, but persistent approach each time an alcohol-related problem arises.

• Most alcoholic persons need a series of reminders of how alcohol contributed to each developing crisis before they seriously consider abstinence as a long- term option.

Case Example: JP

• JP 47-year-old physician was confronted by his wife and daughter regarding his alcohol-related behavior.

• The family had emphasizing specific times and events when his impairment with alcohol occurred.

• They made an appointment with the clinician at an alcohol and drug treatment program.

Detoxification

• Most persons with alcohol use disorder have relatively mild symptoms when they stop drinking.

• The depressant withdrawal syndrome usually resembles a mild case of the flu.

• First step: is a Thorough physical examination.

• Second step: offer rest, adequate nutrition, and multiple vitamins, especially those containing thiamine.

Seizures

• Can occur suddenly and without other signs of withdrawal.

• About 1% of patients may have 1 single grand mal convulsion.

• Such patients require neurologic evaluation to rule out an independent seizure disorder.

• Assuming no other cause for the seizures is found, benzodiazepines are the treatment of choice for managing alcohol-related seizures.

• Anticonvulsants, although often used, do not appear to offer additional benefit.

Mild or Moderate Withdrawal.

• Occurs because the brain has physically adapted to the presence of a brain depressant and cannot function adequately in the absence of the drug.

• CNS Depressant: Sufficient brain depressant on the first day to diminish symptoms and then weaning the patient off the drug over the next 5 day.

• Benzodiazepines control most of the symptoms: Adequate treatment can be given with either short-acting drugs (e.g., lorazepam), or long-acting substances (e.g., chlordiazepoxide and diazepam).

• Diazepam or chlordiazepoxide should not be given IM as their IM absorption is erratic

• Titrate the dosage of the benzodiazepine, starting with a high dosage and lowering the dosage as the patient recovers

• Carbamazepine in daily doses of 800 mg may be as effective as benzodiazepines with the benefit of abuse liability, and is becoming common.

• When giving a long-acting agent, such as chlordiazepoxide, the clinician must avoid producing excessive sleepiness through overmedication

• When taking a short-acting drug, such as lorazepam, the patient must not miss any dose because rapid changes in benzodiazepine concentrations in the blood can precipitate severe withdrawal.

• Social model program of detoxification saves money by avoiding medications while using social supports.

• Some clinicians also use β-adrenergic receptor antagonists (e.g., propranolol) or α-adrenergic receptor agonists (e.g., clonidine) to block the symptoms of sympathetic hyperactivity, not effective for seizures or delirium.

Table 4-12 An Example Treatment for Alcohol Withdrawal

• Day 1: chlordiazepoxide 25 mg by mouth 3–4 times daily, hold if sedated

  • 1–2 additional doses if

    • The patient is jittery

    • Has increased tremor

    • Has autonomic dysfunction

• Day 2: give the total dose used on day 1 minus 20% divided across 3–4 doses

• Following days: continue a 20% decrease until no further medication is needed (4–5 days)

Severe Withdrawal:

• Extreme autonomic dysfunction, agitation, and confusion—that is, those with alcohol withdrawal delirium, or DTs.

• Best treatment is prevention.

• Immediate treatment is needed for a severe concomitant medical problem.

• Higher doses. Example regimens are 50 to 100 mg of chlordiazepoxide given every 4 hours orally, or lorazepam, given intravenously (IV) if oral medication is not possible.

• A high-calorie, highcarbohydrate diet supplemented by multivitamins is also essential.

• Seclusion Room: Physically restraining patients with the DTs is risky and may fight against the restraints to a dangerous level of exhaustion.

• Adjunctive antipsychotic medications, such as haloperidol, are sometimes used to control severe agitation and hallucinations, but may reduce the seizure threshold in patients.

• Diaphoresis and fever: Dehydration can be corrected with fluids given by mouth or IV.

• Psychotherapy: Warm, supportive psychotherapy in the treatment of DTs is essential.

Protracted Withdrawal:

• Symptoms of anxiety, insomnia, and mild autonomic overactivity are likely to continue for 2 to 6 months after the acute withdrawal has disappeared.

• These protracted withdrawal symptoms may enhance the probability of relapse.

• Medications are not helpful.

• Warn the patient, and discuss possible cognitive and behavioral approach.

Rehabilitation

• Rehabilitation includes 3 major components, which are listed in Table 4-13.

• Repetition will be necessary to ensure abstinence and develop day-to-day support.

Table 4-13 Three Components of Alcohol Rehabilitation

• Continued efforts to increase and maintain high levels of motivation for abstinence

• Work to help the patient readjust to a lifestyle free of alcohol

• Relapse prevention

Table 4-14 Stages of Alcohol Rehabilitation Treatment

• Early intensive period (2–4 wk)

  • Intervention (withdrawal treatment, preventing craving)

  • Optimizing physical and psychological functioning

  • Enhancing motivation

  • Reaching out to the family

• Long term (3–6 mo)

  • Individual and group counseling

  • Judicious avoidance of psychotropic medications unless needed for independent disorders

  • Involvement in self-help groups such as AA

• Alcoholism: after years of alcohol use, it develops a life of its own.

• Treatment approach remains the same regardless of setting, including both inpatient and outpatient treatments.

• The selection of the more intensive (and expensive) inpatient mode often depends on whether there are additional severe medical or psychiatric syndromes.

Counseling

• Should focus on day-to-day life issues to help patients maintain a high level of motivation for abstinence and to enhance their functioning in the first several months.

• Individual and group counseling is an option.

• Treatment session Should explore the consequences of drinking, the likely future course of alcohol-related life problems, and the marked improvement that results from abstinence.

• Minimum of three times a week for the first 2 to 4 weeks, followed by less intense efforts, perhaps once a week, for the subsequent 3 to 6 months.

• Much time should be spent discussing how to build a lifestyle free of alcohol: the need for a sober peer group, a plan for social and recreational events without drinking.

• Relapse Prevention: identifies situations in which the risk for relapse is high and learn how to cope when the craving for alcohol increases

• An essential part of relapse prevention is remind the patient about the appropriate attitude toward slips.

• Remind family members and close friends that rehabilitation is an ongoing process that lasts for 6 to 12 or more months.

Medication Treatment

• Little reason to prescribe antidepressant or anxiety medications if the patient does not have an independent psychiatric disorder.

• Medications are likely to lose their effectivness much faster then symptoms, and therefore lead to increased dosage.

• Controlled clinical trials, however, indicate no benefit in prescribing antidepressant medications or lithium.

• Mood disorder will clear before the medications can take effect, and patients who resume drinking while on the medications face significant potential dangers.

• Data from double-blind trials support modest effects for two medications only when offered in the context of cognitive-behavioral therapy (CBT):

  • Naltrexone and Acamprosate

  • A third that can be mentioned: alcohol-sensitizing agent disulfiram.

Naltrexone

• Opioid antagonist that appears to decrease craving for alcohol or blunt the rewarding effects of drinking.

• The COMBINE study demonstrated improvements., and a Cochrane review of naltrexone concluded that naltrexone was effective in reducing heavy drinking days.

• 50 mg/day.

• Side effects: Mild GI upset and lethargy.

Acamprosate

• Antagonizes neuronal overactivity related to the excitatory neurotransmitter glutamate, at least in part, by acting as an antagonist to N-methyl-D-aspartate (NMDA) receptors.

• May diminish mild anxiety, mood swings, and other sleep difficulties associated with protracted withdrawal syndrome.

• Typical dose: about 2,000 mg divided into three doses per day.

• Side effects: Mild GI problems such as diarrhea.

Disulfiram

• Alcohol-sensitizing agent given in daily doses of 250 mg before discharging the patient from the intensive first phase of outpatient rehabilitation or inpatient care.

• Goal: place the patient in a condition in which drinking alcohol precipitates an uncomfortable physical reaction.

• Does not have sufficient support for its effectiveness.

• Side effects: mood swings, rare instances of psychosis, the possibility of increased peripheral neuropathies, the relatively rare occurrence of other significant neuropathies, and potentially fatal hepatitis.

• Not given to patients with preexisting heart disease, cerebral thrombosis, diabetes, and some other conditions, because an alcohol reaction to the disulfiram could be fatal.

Topiramate

• Several studies using the anticonvulsant have reported improvement in drinking patterns.

Ondansetron

• Some data suggest that a 5-HT3 may be beneficial in alcohol use disorder treatment.

Alcoholics Anonymous

• Clinicians must recognize the potential importance of self-help groups such as AA.

• Helps patients understand the differences between specific groups.

• Patients with coexisting psychiatric disorders may need some additional education about AA.

• most studies indicate that participation in AA is associated with improved outcomes, as well as being cost-efficient.

Treatment of Alcohol-Related Disorders

Treatment of Alcohol-Induced Amnestic Disorders

• Wernicke encephalopathy responds rapidly to large doses of parenteral thiamine.

• The dosage of thiamine is usually initiated at 100 mg by mouth two to three times daily and continued for 1 to 2 weeks.

Thiamin

• Patients should include 100 mg of thiamine in each liter of the glucose solution when receiving IV administration of glucose solution.

• Treatment of Korsakoff syndrome is also thiamine given 100 mg by mouth two to three times daily.

Niacin

• A patient who appears to have Wernicke–Korsakoff syndrome but who does not respond to thiamine treatment, one should consider the diagnosis of alcoholic pellagra encephalopathy (see Other Alcohol-Related Neurologic Disorders).

  Alcohol-Related Problems and Epidemiology

  • Physical restraint and antipsychotics (e.g., haloperidol) may be needed for assaultive patients experiencing abrupt behavioral changes related to alcohol. This condition should be distinguished from complex partial epilepsy.

  • Temporal lobe spiking on EEG has been reported in some individuals with the disorder after consuming small amounts of alcohol.

  Epidemiology of Alcohol Use

  • Alcohol use disorder is a common psychiatric disorder in the Western world.

  • Alcohol-related problems contribute to 88,000 deaths annually in the United States.

  • Nearly 10,000 deaths result from alcohol-impaired driving.

  • Alcohol is the fifth leading risk factor for premature death and disability worldwide (WHO data).

  Prevalence of Drinking

  • Approximately 90% of the U.S. population has consumed alcohol at some point in their lives.

  • Most people begin drinking in their early to mid-teens.

  • By the end of high school, 80% of students have consumed alcohol, and over 60% have been intoxicated.

  • Two out of three men are drinkers at any given time.

  • There is an approximate ratio of 1.3 men to 1.0 women regarding persistent alcohol intake.

  • The highest prevalence of drinking is from the mid-to-late teens to the mid-20s.

  • Individuals with higher education and income are more likely to drink.

  • Jewish individuals have the highest proportion who consume alcohol but among the lowest rates of alcohol use disorders.

  • Some ethnicities, like the Irish, have higher rates of severe alcohol problems but also higher rates of abstention.

  • Over 60% of men and women in some Native American and Inuit tribes have had an alcohol use disorder.

  • The average adult in the U.S. consumes 2.4 gallons of absolute alcohol per year, a decrease from 5 gallons in the 1700s.

  • About 90% of all U.S. residents have consumed alcohol at least once.

  • Approximately 56% of U.S. adults used alcohol in the past month.

  • Alcohol is the third leading preventable cause of death in the U.S., after tobacco use and poor diet/physical inactivity.

  • Excessive alcohol use is associated with 2.5 million years of potential life lost annually in the U.S.

  • Alcohol causes 10% of all deaths among working adults.

  • Drunk drivers are involved in approximately 31% of all automotive fatalities.

  • Alcohol use and alcohol-related disorders are associated with about 25% of all suicides.

  Pathology and Effects of Alcohol

  • Alcohol refers to organic molecules with a hydroxyl group (–OH) attached to a saturated carbon atom.

  • Ethyl alcohol (ethanol) is the standard form of drinkable alcohol, with the chemical formula CH3–CH2–OH.

  • The tastes and flavors of alcoholic beverages result from their production methods, which create congeners (e.g., methanol, butanol, aldehydes, phenols, tannins, and trace metals).

  • Though congeners may have differential psychoactive effects, these are minimal compared to ethanol's effects.

  • A single drink typically contains about 12 g of ethanol.

    • 12 oz of beer (7.2 proof, 3.6% ethanol)

    • 4-oz glass of nonfortified wine

    • 1 to 1.5 oz of 80-proof (40% ethanol) liquor (e.g., whiskey or gin).

  • Beers vary in alcohol content and glass sizes and mixed drinks also range in alcohol content.

  • A single drink increases the blood alcohol level of a 150-lb man by 15 to 20 mg/dL.

  • The average person can metabolize this concentration in 1 hour.

  Absorption of Alcohol

  • The stomach absorbs about 10% of consumed alcohol, and the small intestine absorbs the rest.

  • Peak blood concentration is reached in 30 to 90 minutes.

  • Absorption is enhanced on an empty stomach and delayed with food.

  • Rapid drinking reduces the time to peak concentration; slower drinking increases it.

  • Absorption is most rapid with beverages containing 15 to 30% alcohol (30 to 60 proof).

  • Protective devices against high alcohol concentration include mucus secretion and closure of the pyloric valve, slowing absorption.

  • High alcohol concentration in the stomach can lead to pylorospasm, resulting in nausea and vomiting.

  • Once absorbed, alcohol distributes to all body tissues uniformly.

  • Tissues with a high proportion of water receive a high concentration of alcohol.

  • The intoxicating effects are more significant when the blood alcohol concentration is rising (Mellanby effect).

  Metabolism of Alcohol

  • Hepatic oxidation accounts for about 90% of alcohol metabolism.

  • The kidneys and lungs excrete the remaining 10% unchanged.

  • The rate of oxidation by the liver is constant and independent of energy requirements.

  • The body metabolizes about 15 mg/dL per hour, with a range of 10 to 34 mg/dL per hour.

  • Therefore, an average person oxidizes three-fourths of an ounce of 40% (80 proof) alcohol in an hour.

  • Excessive alcohol consumption history leads to the upregulation of necessary enzymes, resulting in rapid alcohol metabolism.

  • Two enzymes metabolize alcohol: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase.

    • ADH catalyzes the conversion of alcohol into acetaldehyde (a toxic compound).

    • Aldehyde dehydrogenase catalyzes the conversion of acetaldehyde into acetic acid.

    • Disulfiram inhibits aldehyde dehydrogenase.

  • Women have lower ADH blood content than men, which may account for their tendency to become more intoxicated after drinking the same amount of alcohol.

  • Decreased function of alcohol-metabolizing enzymes in some Asian persons can lead to more rapid intoxication and toxic symptoms.

  Alcohol's Effects on the Brain Biochemistry

  • Alcohol has prominent effects on almost all neurochemical systems, with different actions during intoxication versus withdrawal.

  • It significantly affects GABA complexes, especially the GABA-A receptor (GABAA), contributing to sedation, sleep induction, anticonvulsant effects, and muscle relaxation.

  • Ethanol impacts NMDA receptors, with dampened stimulatory effects during intoxication and heightened activity during withdrawal.

  • Alcohol acutely increases dopamine and its metabolites.

  • Chronic drinking changes dopamine receptor numbers and sensitivity, affecting intoxication and craving.

  • It impacts the pleasure centers in the VTA of the brain.

  • Alcohol increases serotonin in the synapses and upregulates serotonin receptors.

  • It acutely enhances the functioning of opioid-related brain systems and impacts adenosine, acetylcholine, and cannabinoid 1 (CB1) receptors.

  Behavioral Effects

  • Alcohol is a depressant, similar to barbiturates and benzodiazepines, with some cross-tolerance and cross-dependence.

  • At a blood alcohol level of 0.05%, thought, judgment, and restraint are loosened.

  • At a concentration of 0.1%, voluntary motor actions become clumsy.

  • Most states define legal intoxication as a 0.08% blood alcohol level.

  • At 0.2%, the function of the entire motor area of the brain is measurably depressed, and emotional behavior is affected.

  • At 0.3%, a person is commonly confused or stuporous.

  • At 0.4 to 0.5%, the person falls into a coma.

  • Higher levels affect primitive brain centers controlling breathing and heart rate, leading to death from respiratory depression or aspiration of vomitus.

  • Persons with long-term alcohol use disorders can tolerate higher concentrations of alcohol, appearing less intoxicated.

  Sleep Effects

  • Alcohol initially increases the ease of falling asleep (decreased sleep latency), but it adversely affects sleep architecture.

  • Alcohol use decreases rapid eye movement sleep (REM or dream sleep) and deep sleep (stage 4).

  • It results in more sleep fragmentation, with more and longer episodes of awakening.

  • drinking alcohol does not improve a person’s sleep.

  Other Physiologic Effects

  • Liver: Alcohol use can result in an accumulation of fats and proteins, producing a fatty liver.

  • Alcohol use is associated with alcoholic hepatitis and hepatic cirrhosis.

  • Gastrointestinal System: Long-term heavy drinking is associated with esophagitis, gastritis, achlorhydria, and gastric ulcers.

  • Esophageal varices can develop; rupture of the varices is a medical emergency.

  • Disorders of the small intestine, pancreatitis, pancreatic insufficiency, and pancreatic cancer are associated with heavy alcohol use.

  • Heavy alcohol intake affects food digestion and absorption and inhibits the intestine’s capacity to absorb nutrients (e.g., vitamins and amino acids), leading to vitamin deficiencies (particularly B vitamins).

  • Other Bodily Systems: Significant alcohol intake is associated with increased blood pressure, dysregulation of lipoprotein and triglyceride metabolism, and increased risk for myocardial infarction and cerebrovascular disease.

  • Alcohol consumption can increase resting cardiac output, heart rate, and myocardial oxygen consumption.

  • Alcohol intake can adversely affect the hematopoietic system and increase the incidence of head, neck, esophageal, stomach, hepatic, colonic, and lung cancer.

  • Acute intoxication may be associated with hypoglycemia.

  • Muscle weakness is another side effect of alcohol use disorders.

  • Alcohol intake raises the blood concentration of estradiol in women.

  Drug Interactions

  • The interaction between alcohol and other substances can be dangerous or fatal.

  • Alcohol is metabolized by the liver, and its prolonged use can lead to the acceleration of its metabolism.

  • Persons with alcohol-related disorders are tolerant to many drugs when sober but, when intoxicated, these drugs compete with alcohol, potentially leading to toxic concentrations.

  • The effects of alcohol and other CNS depressants are synergistic.

  • Sedatives, hypnotics, and drugs that relieve pain, motion sickness, head colds, and allergy symptoms must be used with caution by persons with alcohol-related disorders.

  • Narcotics depress the sensory areas of the cerebral cortex and can produce pain relief, sedation, apathy, drowsiness, and sleep; high doses can result in respiratory failure and death.

  • Combining sedative–hypnotic drugs, such as chloral hydrate and benzodiazepines, especially with alcohol, can produce a range of effects from sedation to motor and intellectual impairment to stupor, coma, and death.

  • It is important to warn patients about the dangers of combining CNS depressants and alcohol, particularly when driving or operating machinery.

  Etiology of Alcohol Use Disorders

  • Many factors affect the decision to drink, the development of temporary alcohol-related difficulties, and the development of alcohol use disorders.

  • The initiation of drinking probably depends mainly on social, religious, and personality characteristics, although genetic characteristics might also contribute.

  • The reasons for beginning to drink may differ from the factors that later lead to an alcohol use disorder.

  • A similar interplay between genetic and environmental influences contributes to many medical and psychiatric conditions.

  • A series of genetic influences likely combine to explain approximately 60 percent of the proportion of risk for alcohol use disorders, with the environment responsible for the remaining proportion of the variance.

  • It is the combination of a series of psychological, sociocultural, biologic, and other factors that are responsible for the development of severe, repetitive alcohol-related life problems.

  Psychological Theories

  • Various theories suggest that people use alcohol to reduce tension, increase feelings of power, and decrease the effects of psychological pain.

  • People with alcohol-related problems often report that alcohol decreases their feelings of nervousness and helps them cope with the day-to-day stresses of life.

  • The intake of low doses of alcohol in a tense social setting or after a stressful day enhances feelings of well-being and improved ease of interactions.

  • In high doses, especially at falling blood alcohol levels, however, most measures of muscle tension and psychological feelings of nervousness and tension are increased.

  • The tension-reducing effects of this drug might have an impact most on light to moderate drinkers or add to the relief of withdrawal symptoms but play a minor role in causing alcohol use disorders.

  Psychodynamic Theories

  • Some people may use alcohol to help them deal with harsh superegos and unconscious stress.

  Behavioral Theories

  • Expectations about the rewarding effects of drinking, cognitive attitudes toward responsibility for one’s behavior, and subsequent reinforcement after alcohol intake all contribute to the decision to drink again after the first experience with alcohol and to continue to imbibe despite problems.

  Sociocultural Theories

  • Theorists hypothesize that ethnic groups, such as Jews, who introduce children to modest levels of drinking during religious rituals and eschew drunkenness, have low rates of alcohol use disorders.

  • Cultural attitudes toward drinking, drunkenness, and personal responsibility for consequences are essential contributors to the rates of alcohol-related problems in a society.

  Childhood History

  • Several factors in the childhood histories of persons with later alcohol-related disorders and in children at high risk for having an alcohol-related disorder because one or both of their parents are affected.

  • Children at high risk for alcohol-related disorders possess deficits on neurocognitive testing, including a low amplitude of the P300 wave on evoked potential testing and abnormalities on electroencephalography (EEG) recordings.

  • Studies of high-risk offspring have also shown a generally blunted effect of alcohol compared with that seen in persons whose parents lacked an alcohol-related disorder.

  • A childhood history of attention-deficit/hyperactivity disorder (ADHD), conduct disorder, or both increases a child’s risk for an alcohol-related disorder as an adult.

  • Personality disorders, especially antisocial personality disorder, predispose a person to an alcohol-related disorder.

  Genetic Factors

  • Twin studies suggest that genes explain 60 percent of the variance, with the remainder relating to nonshared, probably adult environmental influences.

  Cannabis-Related Disorders

  • Cannabis is the most widely used illegal drug in the world.

  • Cannabis use has become a standard part of youth culture in most developed societies, with first use now occurring in the mid-to-late teens.

  Clinical Features

  • Most young people use cannabis to experience a “high,” characterized by feelings of mild euphoria, relaxation, and perceptual alterations.

  • Cognitive changes include impaired short-term memory and attention that makes it easy for the user to become lost in pleasant reverie and have difficulty sustaining goal-directed mental activity.

  • Motor skills, reaction time, motor coordination, and many forms of skilled psychomotor activity are impaired while the user is intoxicated.

  Diagnosis

  • The DSM-5 and ICD-10 include several diagnoses related to cannabis.

  • The DSM-5 includes the diagnoses of cannabis intoxication, cannabis intoxication delirium, cannabis withdrawal, cannabis use disorder, cannabis-induced psychotic disorder, cannabis- induced anxiety disorder, cannabis-induced sleep disorder, and unspecified cannabis-related disorder.

  • The ICD-10 includes cannabis-related disorders under the general heading of “Mental and behavioral disorders due to psychoactive substance use.”

  Cannabis Intoxication

  • Cannabis intoxication commonly heightens users’ sensitivities to external stimuli and subjectively slows the appreciation of time.

  • In high doses, users may experience depersonalization and derealization.

  • Cannabis use impairs motor skills, and this effect remains after the euphoriant effects have resolved.

  • For 8 to 12 hours after using cannabis, users’ impaired motor skills interfere with the operation of motor vehicles and other heavy machinery.

  • These effects are additive to those of alcohol.

  Cannabis Intoxication Delirium

  • Cannabis intoxication can markedly impair cognition and performance.

  • Even modest doses of cannabis impair memory, reaction time, perception, motor coordination, and attention.

  • High doses that also impair users’ levels of consciousness have marked effects on cognitive measures.

  Cannabis Withdrawal

  • Cessation of use in daily cannabis users results in withdrawal symptoms within 1 to 2 weeks of cessation.

  Cannabis Use Disorder

  • People who use cannabis daily for weeks to months are most likely to develop a cannabis use disorder.

  • The risk of developing cannabis use disorder is around one in ten for anyone who uses cannabis.

  • The earlier the age of first use, the more often cannabis has been used, and the longer it is used, the higher the risk of developing the disorder.

  Cannabis-Induced Psychotic Disorder

  • Cannabis-induced psychotic disorder, in which there is a genuine psychotic process, is rare; transient paranoid ideation, however, is common.

  • Florid psychosis is somewhat commonplace in countries in which some persons have long-term access to high potency cannabis.

  • The psychotic episodes are sometimes called “hemp insanity.”

  • When cannabis-induced psychotic disorder does occur, the affected person is likely to have a preexisting personality disorder.

  Cannabis-Induced Anxiety Disorder

  • Cannabis-induced anxiety disorder is common during acute intoxication, which in many persons, induces short-lived anxiety states often provoked by paranoid thoughts.

  • In such circumstances, ill-defined and disorganized fears may induce a panic attack.

  • Anxiety symptoms are the most common adverse effect of moderate cannabis use and correlate with the dose taken.

  • Inexperienced users are much more likely to experience anxiety symptoms than are experienced users.

  Unspecified Cannabis-Related Disorders

  • DSM-5 includes the category unspecified cannabis-related disorders for cannabis disorders that do not fit into the other diagnoses.

  • When either sleep disorder or sexual dysfunction symptoms are related to cannabis use, they almost always resolve within days or a week after cessation.

  Flashbacks

  • There are case reports of persons who have experienced sensations related to cannabis intoxication after the short-term effects of the substance have disappeared.

  Cognitive Impairment

  • Long-term use of cannabis may produce subtle forms of cognitive impairment in the higher cognitive functions of memory, attention, and organization and the integration of complex information.

  • The longer the period of heavy cannabis use, the more pronounced the cognitive impairment.

  Amotivational Syndrome

  • A person’s unwillingness to persist in a task characterizes the syndrome, which is associated with long-term heavy use.

  • People with the syndrome become apathetic and anergic, may gain weight, or appear slothful.

  Comorbidity

  • Cannabis users are at high risk for other substance use disorders.

  • Cannabis use may be comorbid with depression, anxiety, conduct disorder, and suicidality.

  Treatment and Rehabilitation

  • Treatment of cannabis use rests on the same principles as the treatment of other substances of abuse—abstinence and support.

  • Education should be a cornerstone of both abstinence and support programs.

  Medical Use of Marijuana

  • Cannabis was listed in the US Pharmacopeia until the end of the 19th century as a remedy for anxiety, depression, and GI disorders, among others.

  • Patients and doctors have used the drug to treat a variety of disorders, including nausea secondary to chemotherapy, HIV- associated weight loss, multiple sclerosis (MS) chronic pain, epilepsy, and glaucoma.

  • Dronabinol, a synthetic form of THC, has been approved by the US Food and Drug Administration (FDA) for the treatment of anorexia-associated weight loss in HIV and nausea and vomiting associated with chemotherapy; dronabinol is also under investigation for the treatment of obstructive sleep apnea.

  • Nabilone, which is a synthetic cannabinoid, has been approved for the treatment of nausea and vomiting associated with chemotherapy.

  • In 2013, cannabidiol was granted orphan drug status for the treatment of certain rare, intractable types of epilepsy in children.

  • Nabiximols, an oral spray consisting of natural cannabis extracts, is currently being investigated for the treatment of cancer pain.

  Epidemiology

  • Cannabis is the most widely used illegal drug in the United States, with an estimated 24 million users aged 12 and older in 2016 (approximately 9 percent of the population).

  Correlates

  • Rates of cannabis use in the user’s lifetime, the past year, and the past week are consistently higher among males than females, as are daily use and long- term daily use.

  Pathology of Cannabis

  • The plant Cannabis sativa is the source for cannabis preparations.

  • Delta-9-tetrahydrocannabinol (\Delta9-THC) is primarily responsible for the psychoactive effects of cannabis.

  • The most potent forms of cannabis come from the flowering tops of the plants or from the dried, black-brown, resinous exudate from the leaves, called hashish or hash.

  • The potency of marijuana preparations has increased in recent years because of improved agricultural techniques used in cultivation so that plants may contain up to 15 or 20 percent THC.

  Physical Effects of Cannabis Use

  • There is no documented case of death caused by cannabis intoxication alone.

  • The most serious potential adverse effects of cannabis use are those caused by inhaling the same carcinogenic hydrocarbons present in conventional tobacco.

  Neuropharmacology

  • The principal component of cannabis is Δ9-THC; however, the cannabis plant contains more than 400 chemicals, of which about 60 are chemically related to Δ9-THC.

  • In humans, Δ9-THC rapidly converts to 11- hydroxy-Δ9-THC, the metabolite that is active in the CNS.

  • A specific receptor for the cannabinols has been identified, cloned, and characterized.

  • The cannabinoid receptor, a member of the G-protein–linked family of receptors, is linked to the inhibitory G protein (Gi), which inhibits adenylyl cyclase.

  • The highest concentrations of the cannabinoid receptor are in the basal ganglia, hippocampus, and cerebellum, with lower concentrations in the cerebral cortex.

  • The brainstem lacks this receptor, explaining the drug’s minimal effects on respiratory and cardiac functions.

  • Tolerance to cannabis does develop, however, as does psychological dependence. The evidence for physiologic dependence is not as strong.

  • When smoking cannabis, the euphoric effects appear within minutes, peak in about 30 minutes, and last 2 to 4 hours.

  • Some motor and cognitive effects last 5 to 12 hours.

  • It requires about two to three times as much oral cannabis to be as potent as smoked cannabis.

  • Many variables affect the psychoactive properties of cannabis, including the potency of the cannabis used, the route of administration, the smoking technique, the effects of pyrolysis on the cannabinoid content, the dose, the setting, and the user’s experience, expectations, and unique biologic vulnerability to the effects of cannabinoids.