Substance & Alcohol Use Disorders – Comprehensive Study Notes

General Features of Substance-Related & Addictive Disorders

• DSM-5 includes both substance-related and one non-substance disorder (gambling).

• Substances covered: alcohol, caffeine, cannabis, hallucinogens (incl. PCP), inhalants, opioids, sedative-hypnotic-anxiolytics, stimulants (incl. cocaine), tobacco, anabolic-androgenic steroids, nitrous oxide, \gamma-hydroxybutyrate, others.

Core Symptom Clusters (shared across substances)

1. Pharmacologic symptoms

   • \text{Tolerance}

   • \text{Withdrawal} (not for inhalants/hallucinogens)

2. Impaired control / use

3. Social impairment

4. Risky/hazardous use

Terminology

• Behavioral dependence ⇢ pattern of pathological substance-seeking.

• Physical (physiologic) dependence ⇢ neuroadaptation → tolerance/withdrawal.

• Psychological dependence (habituation) ⇢ craving & use to avoid dysphoria.

• “Addiction” & “addict” carry pejorative connotations yet highlight shared neurobiology of reward circuitry across behaviors (sex, gambling, eating, stealing).

DSM-5 Major Diagnostic Categories

1. Substance Use Disorder (SUD)

2. Substance Intoxication

3. Substance Withdrawal

4. Substance-Induced Mental Disorder (rule-out in other DSM/ICD diagnoses)

Substance Use Disorder

• Substance-specific label (e.g., Alcohol Use Disorder).

• Duration: symptoms recur within 12\text{ mo}.

• ≥2 of 11 criteria (tolerance, withdrawal, craving, larger/longer use, unsuccessful cut-down, time spent, continued despite medical/psychological harm, social/occupational neglect, diminished activities, hazardous use, continued despite consequences).

• Severity specifiers: mild, moderate, severe (number of symptoms).

• Course specifiers: early remission 3{-}12\text{ mo}, sustained remission >12\text{ mo}, on maintenance, in controlled environment.

Substance Intoxication

• Recent use + maladaptive behavior/psychological change + ≥1 substance-specific physiologic sign.

• Required symptom counts vary (e.g., \ge5 for caffeine, \ge2 for cannabis).

Substance Withdrawal

• Cessation/reduction after heavy prolonged use + substance-specific symptom clusters.

• Onset & required counts vary by drug (e.g., opioid withdrawal: onset minutes–days, \ge3 symptoms).

• Specifiers: with perceptual disturbance, with delirium.

Comorbidity Patterns

• Up to 50\% of treatment-seeking alcohol/cocaine/opioid users have another psychiatric disorder.

• Antisocial Personality Disorder in 35{-}60\% of SUD pts.

• Major depressive disorder lifetime in 40\% alcohol, 33{-}50\% opioid users.

• Substance use → 20\times higher suicide risk; 15\% of alcohol-dependents die by suicide.

Treatment Overview

• Many remit spontaneously; brief interventions work for milder disorders (e.g., nicotine).

• Programs may focus on detoxification vs. rehabilitation; modalities include individual, group, family therapy, 12-step, therapeutic community, pharmacotherapy.

• Outcome improves with: ≥3\text{ mo} continuous treatment, comprehensive services, skilled staff.

• Stages of change: pre-contemplation, contemplation, preparation, action, maintenance – tailor motivational interviewing accordingly.

• Pharmacologic aids (examples): disulfiram, naltrexone, acamprosate (alcohol); methadone, buprenorphine (opioids); varenicline, bupropion, NRT (tobacco).

• Integrated care superior for dual-diagnosis (psychosis + SUD) vs. sequential or parallel.

Etiology Synopsis

• Multifactorial: genetic, neurobiologic, psychological, sociocultural, environmental.

• “Brain disease” model – structural/chemical changes (reward, motivation, memory circuits) are necessary but not sufficient.

Neurobiology & Genetics

• Key pathways: VTA → nucleus accumbens (dopamine), locus coeruleus (noradrenaline), amygdala, prefrontal cortex.

• Neurotransmitters: dopamine, endogenous opioids, GABA, glutamate, serotonin.

• Receptor adaptations (tolerance, sensitization); second-messenger & gene-regulation changes.

• Twin/adoption studies: heritability ≈ 40{-}60\% for alcohol, similar though weaker for other drugs; polymorphisms in dopamine & opioid genes implicated.

Psychological & Learning Factors

• Psychodynamic: oral regression, defense against anxiety, self-medication (e.g., opioids for anger).

• Learning/conditioning: positive reinforcement (euphoria, relief of distress); conditioned cues → craving; conditioned withdrawal.

Alcohol-Related Disorders

Clinical Patterns Suggesting AUD

• Daily large intake, weekend binges, long sober intervals then binges, blackouts, using despite medical issues, drinking non-beverage alcohol.

• Social/legal/occupational dysfunction (violence, DUIs, absenteeism).

Alcohol Intoxication

• Legal intoxication: 80{-}100\,\text{mg/dL} = 0.08{-}0.10\,g/dL.

• Impairment by blood level:

  • 20{-}30\,\text{mg/dL} ⇒ slowed cognition

  • 80{-}200\,\text{mg/dL} ⇒ ataxia, mood lability

  • >300\,\text{mg/dL} ⇒ vital sign compromise / death.

• Idiosyncratic/pathologic intoxication: abrupt aggressive states after small amounts.

Alcohol Withdrawal (timeline ⇒ Table 4-5)

• 6–8 h: tremulousness (“shakes”)

• 8–12 h: perceptual disturbances

• 12–24 h: generalized tonic-clonic seizures (“rum fits”)

• ≤72 h: Delirium Tremens (DTs) – confusion, hallucinations (often tactile), autonomic hyperactivity (tachycardia, HTN, fever), mortality \approx20\% untreated.

Other Alcohol-Induced Disorders

• Persisting dementias & amnestic disorder (Wernicke–Korsakoff): thiamine deficiency → ataxia, ophthalmoplegia, confusion, anterograde amnesia, confabulation.

• Blackouts (anterograde amnesia during intoxication).

• Alcohol-induced psychotic, mood, anxiety, sexual, sleep disorders.

Neurologic & Medical Complications (Table 4-7 highlights)

• Withdrawal syndromes (tremors, hallucinosis, seizures, DTs)

• Nutritional: Wernicke–Korsakoff, cerebellar degeneration, peripheral neuropathy, pellagra encephalopathy.

• Systemic: alcoholic hepatitis/cirrhosis, pancreatitis, cardiomyopathy, hematologic disorders, infections, trauma, fetal alcohol syndrome.

Laboratory Markers of Heavy Drinking (Table 4-9)

• \gamma-glutamyltransferase > 35\,\text{U/L}

• Carbohydrate-deficient transferrin > 3\%

• MCV > 91\,\mu m^3

• AST or ALT > 45\,\text{IU/L} (AST:ALT > 2:1 suggests alcohol).

Suicide Risk Factors in AUD (Table 4-10)

• Major depressive episode, poor supports, severe medical illness, unemployment, living alone.

Positive Prognostic Signs (Table 4-11)

• No antisocial personality, stable job/family, no legal problems, good psychosocial function, treatment adherence.

Treatment of AUD

1 – Intervention (Motivational Interviewing)

• Repeated, empathetic confrontation linking alcohol to presenting problems.

2 – Detoxification

• Rule out medical emergencies; give thiamine before glucose.

• Benzodiazepines (diazepam, chlordiazepoxide, lorazepam) titrated to light sedation; carbamazepine \approx effective.

• Example taper (Table 4-12): chlordiazepoxide 25 mg PO q6h day 1 ± extras → decrease 20 % daily ×4–5 days.

• DTs: high-dose benzos IV, fluids, nutrition, haloperidol for severe agitation, manage comorbid illness; mortality prevention.

3 – Rehabilitation (Table 4-13/4-14)

• Goals: sustain motivation, rebuild alcohol-free lifestyle, relapse prevention.

• Early phase 2–4 wk (counseling q3–4/wk, family involvement).

• Long term (3–6 mo+): CBT groups/individual, 12-step facilitation, social support.

Pharmacotherapies (Table 4-15)

Mutual-Help: Alcoholics Anonymous

• 24-h support, sober peer group, structured 12-step; clinician should address medication misconceptions and help select compatible meetings.

Treatment of Specific Complications

• Wernicke: thiamine 100 mg PO/IV TID ×1–2 wk (extend months for Korsakoff).

• Alcoholic pellagra encephalopathy: niacin 50 mg PO QID or 25 mg IM/IV BID–TID.

• Alcoholic hallucinosis: benzodiazepine withdrawal tx ± short-term antipsychotic.

Epidemiology (USA – Table 4-16)

• Ever drank: \approx90\% adults; current drinkers 60{-}70\%.

• Lifetime AUD: men >15\%, women >10\%.

• AUD among psychiatric pts: \approx30\%.

• Alcohol implicated in 88{,}000 deaths/yr; 31\% of road fatalities; 25\% of suicides.

• Higher prevalence: early onset, males, American Indian/Alaska Native, higher education for use but not AUD, unemployed.

Alcohol Pharmacology & Pathophysiology

• One drink ≈ 12 g ethanol → ↑BAL ≈ 15{-}20\,\text{mg/dL} in 70 kg man.

• Absorption: stomach 10\%, small intestine 90\%; peak 30–90 min; most rapid at 15{-}30\% alcohol concentration.

• Metabolism: hepatic ADH → acetaldehyde → ALDH → acetate; zero-order kinetics \approx15\,\text{mg/dL/h} (range 10–34).

• Women lower ADH, some Asians low ALDH → flushing.

• Neurochemistry: potentiates GABA_A, inhibits NMDA, ↑dopamine/serotonin/opioid tone.

• Sleep: ↓REM, ↓stage 4, ↑fragmentation despite ↓latency.

• Organ effects: fatty liver → hepatitis → cirrhosis; gastritis, ulcers, varices, pancreatitis; HTN, cardiomyopathy, CVA risk; cancers (head/neck, liver, colon, lung); anemia, infections; hypoglycemia; myopathy; ↑estradiol.

• Drug interactions: synergistic with other CNS depressants; competition for CYP metabolism  toxicity.

Etiologic Factors (Alcohol)

• Psychological: tension-reduction, self-medication, disinhibition.

• Behavioral: expectancy, reinforcement, role modeling.

• Sociocultural: norms toward drinking/drunkenness; early introduction not clearly protective.

• Childhood/Developmental risks: ADHD, conduct disorder, low P300, EEG variants, blunted intoxication response.

• Genetics (Table 4-17): first-degree relatives ×3–4 risk; twin & adoption studies → heritability \approx60\%; multiple gene variants (dopamine, opioid, GABA).