Psychiatry/Behavioral · PANCE / PANRE

Stimulant Use Disorder

Problematic cocaine or amphetamine-type stimulant use meeting >=2 of 11 DSM-5-TR criteria in 12 months.

Also known as: cocaine use disorder, methamphetamine use disorder, stimulant addiction

Overview

A pattern of amphetamine-type or cocaine use leading to clinically significant impairment or distress, with >=2 of 11 DSM-5-TR criteria in 12 months. Methamphetamine and cocaine deaths are rising sharply, often driven by fentanyl co-exposure.

Epidemiology

Past-year cocaine use ~2%; methamphetamine ~0.6% of US adults; substantial increase in stimulant-involved overdose deaths in last decade.

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Question 1PsychiatryMedium
A 28-year-old man presents to the ED with agitation, mydriasis, hypertension (170/100), tachycardia, diaphoresis, and visual hallucinations after a party. He insists "spiders are crawling on the walls." Toxicology is pending. Which of the following is the most likely cause?
  • APhencyclidine (PCP) intoxication
  • BAnticholinergic toxidrome from jimson weed
  • CCocaine or amphetamine intoxication
  • DAlcohol withdrawal delirium
Reveal answer & full explanation
Correct answer: C — Cocaine or amphetamine intoxication
  • APhencyclidine (PCP) intoxication
  • BAnticholinergic toxidrome from jimson weed
  • CCocaine or amphetamine intoxication
  • DAlcohol withdrawal delirium

Why Cocaine or amphetamine intoxication is correct

  • The picture is a classic sympathomimetic toxidrome: mydriasis, hypertension, tachycardia, hyperthermia, diaphoresis, and agitation
  • Tactile/visual hallucinations (formication, "bugs on the walls") are characteristic of stimulant intoxication
  • Onset after a recreational party setting fits cocaine or amphetamine use
  • Benzodiazepines (lorazepam) are first-line for the agitation, hypertension, tachycardia, and seizure risk
  • Avoid beta-blockers alone — unopposed alpha stimulation can worsen hypertension and coronary vasospasm

Why the others are wrong

  • Phencyclidine (PCP) intoxication — right-concept-wrong-agent; PCP causes vertical/rotary nystagmus, dissociation, and extreme violence rather than this pure adrenergic surge
  • Anticholinergic toxidrome from jimson weed — shares mydriasis, tachycardia, hypertension, and hallucinations, but anticholinergic poisoning produces hot dry flushed skin and urinary retention rather than the diaphoresis described here
  • Alcohol withdrawal delirium — overlaps agitation, autonomic hyperactivity, and visual hallucinations, but follows cessation in a physiologically dependent drinker roughly 48-96 hours after the last drink, not acute onset during a party

Additional high-yield points

  • Sympathomimetic vs anticholinergic toxidrome: both cause mydriasis, tachycardia, and hyperthermia, but sympathomimetics produce diaphoresis (wet skin) whereas anticholinergics produce dry skin and urinary retention
  • Formication (the sensation of insects crawling on skin) strongly suggests chronic stimulant use ("cocaine bugs")
  • Cocaine-associated chest pain warrants benzodiazepines and nitrates; give aspirin and treat as ACS if ischemia is present
Question 2PsychiatryMedium
A 29-year-old man is brought to the emergency department by police after he was found pacing outside a store shouting that people were following him. He is hypervigilant, diaphoretic, and intermittently agitated. Temperature is 38.6 C, heart rate 128/min, and blood pressure 168/102 mm Hg; pupils are dilated, skin is moist, and there are excoriated lesions on the arms with marked dental decay. He reports not sleeping or eating for two days. A partner who arrives reports that over the past year his use of a smoked stimulant has escalated to near-daily, that he has repeatedly tried and failed to cut down, and that he was fired after continuing to use despite warnings. A urine drug screen is positive for amphetamines. Which of the following is the most likely diagnosis?
  • AAmphetamine use disorder
  • BSerotonin toxicity syndrome
  • CPrimary psychotic disorder
  • DBipolar I disorder, manic
Reveal answer & full explanation
Correct answer: A — Amphetamine use disorder
  • AAmphetamine use disorder
  • BSerotonin toxicity syndrome
  • CPrimary psychotic disorder
  • DBipolar I disorder, manic

Why Amphetamine use disorder is correct

  • The collateral history establishes a problematic 12-month pattern: escalating near-daily use, repeated failed attempts to cut down, and continued use despite job loss — meeting DSM-5-TR criteria for a stimulant use disorder (>=2 of 11 criteria over 12 months), with the substance specified as amphetamine-type by the positive screen.
  • The acute picture is a classic sympathomimetic toxidrome confirming the agent: hyperthermia, tachycardia, hypertension, mydriasis, diaphoresis (moist skin), agitation, and paranoia from the mesolimbic dopamine surge of amphetamine.
  • Methamphetamine-specific clues reinforce chronic use: dental decay ("meth mouth"), excoriated skin from picking, and the days of anorexia and insomnia.

Why the others are wrong

  • Bipolar I disorder, manic — can mimic stimulant intoxication with decreased sleep and agitation, but it is diagnosed only when symptoms persist independent of substance use; the positive amphetamine screen, the autonomic toxidrome, and the documented problematic use pattern point to a substance-related disorder.
  • Primary psychotic disorder — implies persistent psychosis with a chronic course independent of intoxication; here psychosis arises acutely alongside a sympathomimetic toxidrome and a positive amphetamine screen, so it is stimulant-related rather than primary.
  • Serotonin toxicity syndrome — shares the hyperthermia, tachycardia, hypertension, and agitation, but it requires a serotonergic agent and is defined by inducible clonus, hyperreflexia, and lower-extremity-predominant rigidity, none of which are present, and it would not explain the 12-month pattern of escalating stimulant use.
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Risk factors

  • Family history of SUD
  • Comorbid mood, anxiety, ADHD, PTSD
  • Sexual minority status (methamphetamine and chemsex)
  • Adolescent onset
  • Concurrent opioid or alcohol use
  • Access and environmental exposure

Pathophysiology

Cocaine blocks dopamine, norepinephrine, and serotonin reuptake; amphetamines also promote release from vesicles. Both produce intense mesolimbic dopaminergic surge driving reinforcement. Chronic use produces dopaminergic depletion and prefrontal dysfunction.

Clinical presentation

Symptoms

  • Intoxication: euphoria, hypervigilance, increased energy, anorexia, tachycardia, hypertension, mydriasis, sweating, hyperthermia, tremor, paranoia, psychosis, seizures
  • Severe: arrhythmia, MI, stroke, hyperthermia, rhabdomyolysis, excited delirium
  • Withdrawal ('crash'): dysphoria, fatigue, hypersomnia, increased appetite, vivid unpleasant dreams, anhedonia — peaks days 1-3, gradual improvement

Signs / physical exam

  • Sympathomimetic toxidrome: tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis, agitation
  • Methamphetamine: dental decay ('meth mouth'), excoriated skin from picking, weight loss
  • Cocaine: nasal septal perforation (insufflation), pulmonary hemorrhage (crack lung)
  • Cardiac: chest pain, arrhythmia

Differential diagnosis

  • Primary psychotic disorder — Persistent psychosis beyond intoxication; chronic course
  • Bipolar mania — Distinguish by independent history and persistence of symptoms with abstinence
  • Hyperthyroidism, pheochromocytoma — Sustained tachycardia, HTN, suppressed TSH or elevated metanephrines
  • Anticholinergic toxicity — Dry skin, urinary retention, ileus — distinct from sympathomimetic toxidrome
  • Serotonin syndrome / NMS — Recent medication exposure, hyperreflexia/clonus vs rigidity

Diagnostic workup

Diagnostic criteria

DSM-5-TR: Problematic pattern of stimulant use causing impairment/distress with >=2 of 11 criteria over 12 months. Specify substance (amphetamine-type vs cocaine). Severity by criterion count.

Labs

  • Urine drug screen (cocaine metabolite benzoylecgonine; amphetamines/methamphetamine)
  • ECG, troponin in chest pain
  • CBC, CMP, CK (rhabdomyolysis), UA
  • Pregnancy test

Imaging

  • Head CT for altered mental status, seizure, focal deficit (stroke risk elevated)
  • Echocardiogram if prolonged use (cardiomyopathy) or suspected endocarditis (IV use)

Diagnostic algorithm

FeatureCocaineMethamphetamine
Duration of effect30-60 min8-24 hours
Half-life~1 h~10-12 h
RouteIN, smoked (crack), IVSmoked, IV, IN, PO
Characteristic complicationsMI, septal perforation, crack lungMeth mouth, skin picking, psychosis
Treatment of agitationBenzodiazepinesBenzodiazepines
Cocaine vs methamphetamine — clinical features and complications.

Treatment

First-line

  • No FDA-approved pharmacotherapy for stimulant use disorder
  • Behavioral therapies are mainstay: contingency management (strongest evidence), cognitive behavioral therapy, community reinforcement approach, matrix model
  • Acute intoxication/agitation: benzodiazepines (lorazepam, diazepam) for agitation, HTN, tachycardia, seizures
  • AVOID beta-blockers in cocaine intoxication (unopposed alpha vasoconstriction) — use benzodiazepines, nitrates, CCBs
  • Cooling for hyperthermia; supportive care for rhabdomyolysis

Second-line / adjunct

  • Off-label pharmacotherapy with modest evidence: bupropion + naltrexone combination (methamphetamine), topiramate, mirtazapine (methamphetamine + MSM), modafinil
  • Treat comorbid psychiatric illness
  • Harm reduction: education, fentanyl test strips, naloxone given co-use
  • Residential treatment for severe disease

Complications

  • Cardiovascular: MI, arrhythmia, aortic dissection, sudden death, cardiomyopathy, accelerated atherosclerosis
  • CNS: hemorrhagic and ischemic stroke, seizures, intracranial hemorrhage from HTN surges
  • Psychiatric: stimulant-induced psychosis, mood/anxiety symptoms, suicidality
  • Pulmonary: crack lung, pulmonary hypertension
  • Infectious: HIV/HCV from IV use; STIs from chemsex
  • Pregnancy: placental abruption, preterm birth, IUGR
  • Overdose with fentanyl contamination

PANCE pearls

  • Cocaine-associated chest pain: avoid beta-blockers (unopposed alpha vasoconstriction worsens coronary spasm); use benzodiazepines + nitrates + aspirin; CCB or phentolamine for refractory HTN.
  • Stimulant-induced psychosis can persist for weeks after cessation, especially methamphetamine; consider short-course atypical antipsychotic.
  • Contingency management has the strongest evidence base — financial incentives for stimulant-negative urines reliably reduce use.
  • Co-use of opioids (intentional or via fentanyl contamination) is driving stimulant overdose deaths — distribute naloxone and fentanyl test strips.

References

  • ASAM 2024 — ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder (2024)
  • SAMHSA TIP 33 — SAMHSA TIP 33: Treatment for Stimulant Use Disorders
  • NIDA — NIDA Research Reports: Cocaine and Methamphetamine
  • DSM-5-TR — American Psychiatric Association. DSM-5-TR (2022)

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