Substance-related Disorders

Must know

• Table: Alcohol Withdrawal StagesAlcohol withdrawal onset occurs within 6 to 12 hours after the last drink, peaks at 24 to 48 hours, and subsides over 5 to 7 days.

  • Alcohol withdrawal onset occurs within 6 to 12 hours after the last drink, peaks at 24 to 48 hours, and subsides over 5 to 7 days.
  • Stage 1 mild withdrawal develops at 6 to 12 hours, presenting with tremors, tachycardia, hypertension, diaphoresis, insomnia, and mild anxiety.
  • Stage 2 moderate withdrawal develops at 12 to 24 hours, adding motor agitation, pronounced autonomic instability, and transient visual, tactile, or auditory hallucinations with an intact sensorium.
  • Stage 3 withdrawal seizures peak at 24 to 48 hours as generalized tonic-clonic events; up to 30% of untreated seizure cases progress to delirium tremens.
  • Stage 4 severe withdrawal or delirium tremens emerges at 48 to 96 hours, causing severe confusion, fluctuating orientation, autonomic storm (fever, profuse sweating, extreme tachycardia), and carries up to a 15% mortality rate if untreated.
  • A CIWA-Ar score over 15 indicates severe withdrawal requiring active pharmacotherapy, while a score under 8 to 10 requires supportive care without medications.
• Spoken Teaching: Stages and TimelinesLong-acting benzodiazepines like chlordiazepoxide and diazepam are first-line agents for alcohol withdrawal detoxification because their active hepatic metabolites provide a smooth auto-taper. However, in patients with severe hepatic impairment, advanced cirrhosis, or elderly individuals, lorazepam, oxazepam, or temazepam (the LOT drugs) are first-line because they bypass hepatic oxidation and undergo direct renal-safe glucuronidation.

  • Always administer thiamine (Vitamin B1) prior to IV glucose administration in patients with suspected or actual alcohol use disorder. Glucose loading without thiamine rapidly consumes remaining thiamine coenzymes during pyruvate oxidation, triggering or worsening acute Wernicke's encephalopathy (the clinical triad of acute delirium, gait ataxia, and ophthalmoplegia).
  • Do not assume that a low CIWA score or a history of major depression determines treatment setting. A past history of delirium tremens or alcohol withdrawal seizures is the single most prominent risk factor favoring immediate medical hospitalization rather than outpatient detoxification.
  • Long-acting benzodiazepines like chlordiazepoxide and diazepam are first-line agents for alcohol withdrawal detoxification because their active hepatic metabolites provide a smooth auto-taper. However, in patients with severe hepatic impairment, advanced cirrhosis, or elderly individuals, lorazepam, oxazepam, or temazepam (the LOT drugs) are first-line because they bypass hepatic oxidation and undergo direct renal-safe glucuronidation.

  Board trap. Do not assume that a low CIWA score or a history of major depression determines treatment setting. A past history of delirium tremens or alcohol withdrawal seizures is the single most prominent risk factor favoring immediate medical hospitalization rather than outpatient detoxification.

  Safety. Always administer thiamine (Vitamin B1) prior to IV glucose administration in patients with suspected or actual alcohol use disorder. Glucose loading without thiamine rapidly consumes remaining thiamine coenzymes during pyruvate oxidation, triggering or worsening acute Wernicke's encephalopathy (the clinical triad of acute delirium, gait ataxia, and ophthalmoplegia).

• Signs of Delirium Tremens (DTs)Alcohol withdrawal timeline: Autonomic hyperactivity and hand tremors begin within 6 to 24 hours of the last drink, withdrawal seizures peak between 12 and 48 hours, and delirium tremens typically emerges between 48 and 96 hours.

  • Alcohol withdrawal timeline: Autonomic hyperactivity and hand tremors begin within 6 to 24 hours of the last drink, withdrawal seizures peak between 12 and 48 hours, and delirium tremens typically emerges between 48 and 96 hours.
  • Signs of delirium tremens: Delirium tremens is a life-threatening medical emergency characterized by profound delirium, disorientation, severe autonomic instability, marked tachycardia, fever, hypertension, diaphoresis, agitation, and visual or tactile hallucinations.
  • Primary risk factor for hospitalization: A prior history of delirium tremens is the single most significant predictor of recurrent severe withdrawal and dictates immediate inpatient hospital admission.
  • Clinical Institute Withdrawal Assessment: The CIWA-Ar scale evaluates 10 withdrawal domains on a 0 to 67 scale, where a score of 15 or greater indicates severe withdrawal requiring aggressive medication management.
  • First-line pharmacotherapy: Benzodiazepines such as lorazepam, chlordiazepoxide, or diazepam are the gold standard to suppress central nervous system irritability and prevent seizures or DTs.
  • Wernicke-Korsakoff prevention: Thiamine (vitamin B1) at 100 mg to 250 mg daily must always be administered prior to intravenous glucose to prevent acute Wernicke encephalopathy and chronic Korsakoff psychosis.
• Progression of Alcohol WithdrawalMild withdrawal occurs within 6 to 24 hours and presents with anxiety, insomnia, mild tremors, diaphoresis, palpitations, and gastrointestinal upset.

  • Mild withdrawal occurs within 6 to 24 hours and presents with anxiety, insomnia, mild tremors, diaphoresis, palpitations, and gastrointestinal upset.
  • Withdrawal seizures occur within 12 to 48 hours and present as brief, generalized tonic-clonic events.
  • Alcoholic hallucinosis occurs within 12 to 24 hours and presents with visual, auditory, or tactile hallucinations while orientation remains intact.
  • Delirium tremens occurs within 48 to 96 hours and presents with clouding of consciousness, global disorientation, severe psychomotor agitation, and autonomic hyperactivity.
• Assessment and Scoring with CIWA-ArEvaluated domains include nausea and vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation.

  • Evaluated domains include nausea and vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation.
  • Scores under 8 reflect mild withdrawal manageable with supportive care.
  • Scores between 8 and 14 reflect moderate withdrawal where symptom-triggered medication is initiated.
  • Scores of 15 or higher indicate severe withdrawal with a high risk for delirium tremens, requiring inpatient admission and protocol-driven benzodiazepine administration.
• Clinical Management and Medical SafeguardsBenzodiazepines are the first-line drug class for managing acute alcohol withdrawal and preventing delirium tremens. Long-acting agents like chlordiazepoxide and diazepam provide a smooth tapering effect in patients with healthy hepatic function. Short-acting agents lacking active hepatic metabolites, specifically lorazepam, oxazepam, and temazepam, are preferred in patients with advanced liver disease, elevated transaminases, or elderly age.

  • Delirium tremens carries a mortality rate up to 5 percent due to cardiovascular collapse, hyperthermia, electrolyte derangements, or respiratory failure. Continuous vital sign monitoring, parenteral fluids, and continuous cardiac monitoring in an inpatient unit are required.
  • Test writers often construct stems where a malnourished or intoxicated patient receives intravenous glucose before thiamine. Administering glucose without thiamine depletes remaining thiamine cofactors during glycolysis, directly precipitating Wernicke encephalopathy. Always give thiamine before or alongside glucose.
  • Another frequent trap presents a patient with a low current CIWA-Ar score who has a documented past history of delirium tremens. A prior history of DTs overrides a low initial score and mandates inpatient detoxification rather than outpatient management.
  • Benzodiazepines are the first-line drug class for managing acute alcohol withdrawal and preventing delirium tremens. Long-acting agents like chlordiazepoxide and diazepam provide a smooth tapering effect in patients with healthy hepatic function. Short-acting agents lacking active hepatic metabolites, specifically lorazepam, oxazepam, and temazepam, are preferred in patients with advanced liver disease, elevated transaminases, or elderly age.

  Board trap. Test writers often construct stems where a malnourished or intoxicated patient receives intravenous glucose before thiamine. Administering glucose without thiamine depletes remaining thiamine cofactors during glycolysis, directly precipitating Wernicke encephalopathy. Always give thiamine before or alongside glucose.

  Safety. Delirium tremens carries a mortality rate up to 5 percent due to cardiovascular collapse, hyperthermia, electrolyte derangements, or respiratory failure. Continuous vital sign monitoring, parenteral fluids, and continuous cardiac monitoring in an inpatient unit are required.

• Alcohol Withdrawal Seizures vs Delirium TremensThink: Seizures occur early with clear sensorium, whereas DTs occur late with severe delirium.

  • Think: Seizures occur early with clear sensorium, whereas DTs occur late with severe delirium.
  • Onset timeline: Seizures peak at 12 to 48 hours post-cessation. DTs peak at 48 to 96 hours post-cessation.
  • Clinical presentation: Seizures are brief, self-limiting generalized tonic-clonic episodes without persistent confusion once postictal. DTs present with sustained clouding of consciousness, disorientation, terrifying hallucinations, and fluctuating vital signs.
  • Setting priority: Seizures require immediate acute medical evaluation, while DTs require continuous inpatient or intensive care monitoring.
• Wernicke Encephalopathy vs Korsakoff PsychosisThink: Wernicke is acute and reversible, whereas Korsakoff is chronic and irreversible.

  • Think: Wernicke is acute and reversible, whereas Korsakoff is chronic and irreversible.
  • Wernicke presentation: Acute triad of delirium, gait ataxia, and oculomotor dysfunction such as nystagmus or ophthalmoplegia.
  • Korsakoff presentation: Chronic neurocognitive disorder marked by severe anterograde and retrograde amnesia with confabulation.
  • Diagnostic logic: High-dose thiamine reverses Wernicke signs but cannot reverse established Korsakoff structural damage in the mammillary bodies and thalamus.
• Table: Overview — Stimulants and OpioidsStimulant intoxication presents with sympathetic hyperarousal including tachycardia (resting heart rate up to 140 beats per minute or higher), severe hypertension (such as 180/115 mmHg), dilated pupils (mydriasis), muscle weakness, diaphoresis, and acute paranoia or psychosis.

  • Stimulant intoxication presents with sympathetic hyperarousal including tachycardia (resting heart rate up to 140 beats per minute or higher), severe hypertension (such as 180/115 mmHg), dilated pupils (mydriasis), muscle weakness, diaphoresis, and acute paranoia or psychosis.
  • Stimulant withdrawal features a severe mood crash characterized by depressed mood, profound fatigue, vivid unpleasant dreams, psychomotor agitation or retardation, and increased appetite.
  • Opioid intoxication presents with classic central nervous system depression characterized by pupillary miosis (pinpoint pupils), respiratory depression, bradycardia, hypotension, hypothermia, and lethargy, whereas acute overdose is emergently reversed using naloxone.
  • Opioid withdrawal involves multi-system distress measured by the Clinical Opioid Withdrawal Scale (COWS), where a score of 5 to 12 indicates mild withdrawal, 13 to 24 indicates moderate withdrawal, 25 to 36 indicates moderately severe withdrawal, and greater than 36 indicates severe withdrawal.
  • First-line non-opioid symptom management for opioid withdrawal targets specific organ systems using clonidine for autonomic hyperactivity, ondansetron for nausea, loperamide for diarrhea, NSAIDs for body aches, and trazodone for insomnia.
  • Naltrexone (oral or monthly intramuscular Vivitrol) reduces alcohol and opioid cravings by blocking endogenous opioid receptors, but it is strictly contraindicated in patients actively taking opioids or scheduled for procedures requiring opioid analgesia (such as major dental surgery) due to the risk of precipitating acute severe withdrawal.
• Pupil Findings and Autonomic ToneStimulants (such as dextroamphetamine, amphetamine, methamphetamine, methylphenidate, and cocaine) stimulate sympathetic pathways, causing dilated pupils (mydriasis), tachycardia, elevated blood pressure, and diaphoresis during intoxication.

  • Stimulants (such as dextroamphetamine, amphetamine, methamphetamine, methylphenidate, and cocaine) stimulate sympathetic pathways, causing dilated pupils (mydriasis), tachycardia, elevated blood pressure, and diaphoresis during intoxication.
  • Opioids (such as heroin, morphine, oxycodone, hydrocodone, fentanyl, and methadone) suppress central autonomic tone, causing pinpoint pupils (miosis), bradycardia, hypotension, and respiratory depression during intoxication.
  • Pupillary reversal in withdrawal: Pupils constrict or remain normal during stimulant withdrawal, whereas pupils dilate (mydriasis) accompanied by rhinorrhea, lacrimation, piloerection (gooseflesh), and yawning during opioid withdrawal.
• Intoxication vs Withdrawal ContrastStimulant Intoxication vs Withdrawal: Intoxication produces intense energy, euphoria, hypervigilance, anorexia, cardiac arrhythmias, and potential psychosis. Withdrawal produces the exact opposite physical and psychological state, marked by a severe energy crash, depressed mood, fatigue, vivid dreams, psychomotor agitation, and intense craving.

  • Stimulant Intoxication vs Withdrawal: Intoxication produces intense energy, euphoria, hypervigilance, anorexia, cardiac arrhythmias, and potential psychosis. Withdrawal produces the exact opposite physical and psychological state, marked by a severe energy crash, depressed mood, fatigue, vivid dreams, psychomotor agitation, and intense craving.
  • Opioid Intoxication vs Withdrawal: Intoxication produces analgesia, sedation, euphoria, and respiratory depression. Withdrawal produces multi-system autonomic, gastrointestinal, and musculoskeletal hyperactivity, including muscle cramps, severe joint pain (arthralgia), abdominal cramping, and profuse diarrhea.
• Behavioral and Pharmacotherapy StrategiesStimulant Use Disorder: No FDA-approved maintenance medication currently exists for amphetamine or cocaine dependence. Behavioral therapy, social skills training, and contingency contracting (rewarding negative drug screens with vouchers or gift cards) serve as primary interventions.

  • Stimulant Use Disorder: No FDA-approved maintenance medication currently exists for amphetamine or cocaine dependence. Behavioral therapy, social skills training, and contingency contracting (rewarding negative drug screens with vouchers or gift cards) serve as primary interventions.
  • Opioid Use Disorder: Managed with medication-assisted treatment (MAT). Methadone acts as a full mu-opioid agonist, buprenorphine acts as a partial mu-opioid agonist, and naltrexone acts as an opioid antagonist to block euphoria and reduce cravings.
• Board Exam SignpostsFor non-opioid management of autonomic opioid withdrawal symptoms, clonidine is the first-line choice to suppress sympathetic overactivity.

  • For non-opioid management of autonomic opioid withdrawal symptoms, clonidine is the first-line choice to suppress sympathetic overactivity.
  • For opioid overdose with respiratory depression, naloxone is the immediate first-line emergency reversal agent.
  • Naltrexone must never be administered to a patient who is actively using opioids or who has scheduled elective surgery or dental procedures requiring opioid analgesics within the upcoming month, as it will precipitate severe, immediate opioid withdrawal.
  • Naltrexone is also contraindicated in patients with acute hepatitis or acute liver failure.
  • Stimulant intoxication can trigger life-threatening hypertensive crises, myocardial infarction, lethal cardiac arrhythmias, and hyperthermia.
  • Test writers often confuse naltrexone (a long-acting oral or IM opioid antagonist used for cravings in alcohol and opioid maintenance) with naloxone (a short-acting emergency antagonist used for acute opioid overdose reversal).
• Table: Overview — Cannabis and HallucinogensCannabis metabolites are lipophilic and remain detectable in urine for up to 1 month in regular users smoking 2 to 3 days per week.

  • Cannabis metabolites are lipophilic and remain detectable in urine for up to 1 month in regular users smoking 2 to 3 days per week.
  • Cannabis use in adolescents and young adults with underlying psychiatric vulnerability can precipitate or exacerbate schizophrenia and psychotic symptoms.
  • Therapeutic applications for THC include nausea, chronic pain, HIV or AIDS cachexia, cancer, glaucoma, multiple sclerosis, and epilepsy.
  • Cannabis tolerance develops with regular use, but physical dependence is low. Withdrawal manifests as irritability, restlessness, insomnia, anorexia, and mild nausea.
  • Hallucinogens include naturally occurring psilocybin and mescaline, alongside synthetic agents such as LSD, PCP, MDMA, and ketamine.
  • Hallucinogens alter serotonin and glutamate neurotransmission, producing profound perceptual distortions, synesthesias, and depersonalization without causing a physical withdrawal syndrome.
• SignpostsIntoxication management for cannabis or hallucinogens focuses on supportive care, a calm low-stimulation environment, physical safety, and symptom control.

  • Cannabis use in vulnerable adolescents and young adults significantly increases the risk of unmasking or worsening schizophrenia and psychotic spectrum disorders.
  • Confusing urine screening elimination windows. Single use clears rapidly, but regular use 2 to 3 days per week stores THC in adipose tissue, causing positive urine screens for up to 1 month.
  • Intoxication management for cannabis or hallucinogens focuses on supportive care, a calm low-stimulation environment, physical safety, and symptom control.

  Board trap. Confusing urine screening elimination windows. Single use clears rapidly, but regular use 2 to 3 days per week stores THC in adipose tissue, causing positive urine screens for up to 1 month.

  Safety. Cannabis use in vulnerable adolescents and young adults significantly increases the risk of unmasking or worsening schizophrenia and psychotic spectrum disorders.

• Cannabinoids (Cannabis)Neuropharmacology and Desired Effects: THC acts on central cannabinoid receptors. Desired effects include euphoria, relaxation, heightened sensory perception, and appetite stimulation.

  • Neuropharmacology and Desired Effects: THC acts on central cannabinoid receptors. Desired effects include euphoria, relaxation, heightened sensory perception, and appetite stimulation.
  • Approved and Medical Indications: Medical cannabis serves patients with nausea, chronic pain, HIV or AIDS cachexia, cancer, glaucoma, multiple sclerosis spasticity, and epilepsy.
  • Adverse Effects and Risks: Heavy chronic use is linked to chronic respiratory conditions, lung disease, cerebral structural alterations, executive function deficits, and heightened seizure susceptibility.
  • Dependency and Withdrawal Profile: Tolerance develops over time. True physical dependence is minimal. Withdrawal features mild irritability, restlessness, insomnia, anorexia, and mild nausea.
  • Urinary Elimination Timeline: Regular consumption of 2 to 3 days per week extends urine metabolite excretion up to 1 month.