Cocaine and Other Stimulant Use Disorder: Diagnosis and Management

1. Epidemiology and Background

2. Neurobiology and Mechanism

3. DSM-5 Diagnosis

Stimulant Use Disorder (DSM-5)

1. Use in greater quantities or durations than intended
2. Persistent desire or unsuccessful efforts to cut down/control use
3. Great deal of time spent on drug-related activities
4. Craving for the stimulant
5. Recurrent use causing failure to fulfill major role obligations
6. Persistent use despite social or interpersonal problems caused by it
7. Important activities given up due to use
8. Recurrent use in physically hazardous situations
9. Use despite knowing it causes physical or psychological harm
10. Tolerance (need for markedly increased amount for same effect, or diminished effect with same amount)
11. Withdrawal (characteristic syndrome or use to relieve/avoid withdrawal)

• Mild: 2-3 criteria
• Moderate: 4-5 criteria
• Severe: 6+ criteria

4. Clinical Features

Intoxication

Withdrawal

• Dysphoric mood
• Fatigue, vivid/unpleasant dreams
• Hypersomnia
• Increased appetite
• Bradycardia
• Drug cravings, anhedonia, depressive symptoms

5. Associated Conditions and Complications

Stimulant-Induced Disorders

• Psychotic disorder: paranoia occurs in 50-70% of cocaine users and ~30% of methamphetamine users during heavy use. Non-bizarre paranoid delusions are typical (fear of police/dealers). Tactile hallucinations ("cocaine bugs" - formication) are characteristic. Cocaine psychosis usually resolves within hours; methamphetamine psychosis may persist days to weeks. A diagnosis of stimulant-induced psychotic disorder is made when symptoms exceed those typical of intoxication alone.
• Depressive disorder: from withdrawal; can meet MDD criteria if severe
• Anxiety disorder
• ADHD (co-occurrence is common)

Medical Complications

• Cardiovascular: sinus tachycardia (most common dysrhythmia), AF, SVT, ventricular tachycardia/fibrillation, torsades de pointes (from hypokalemia), wide-complex tachycardia (Na-channel blockade), Brugada pattern, myocardial ischemia/infarction, cardiomyopathy
• Neurological: intracranial hemorrhage, ischemic stroke, grand mal seizures
• Route-specific: intranasal - sinusitis, nasal septal perforation, nasopalatine necrosis; inhalation - oropharyngeal burns, pneumothorax/pneumopericardium; IV/skin-popping - cellulitis, abscesses, endocarditis, HIV, hepatitis B/C; Clostridium botulinum infection
• Adulterants: atropine, phenacetin, hydroxyzine, ketamine, lidocaine, levamisole (associated with agranulocytosis)

6. Differential Diagnosis

7. Assessment and Investigations

• Cocaine metabolites (benzoylecgonine): detectable 2-4 days in routine users; up to 2 weeks in heavy users
• Methamphetamine: 3-5 days
• Synthetic cathinones: often NOT detected by routine screening; gas chromatography required if strongly suspected

• Seizures/neurological deficit: CT head or MRI (hemorrhagic or ischemic stroke)
• Chest pain/arrhythmia: ECG, cardiac enzymes
• Respiratory symptoms: chest X-ray (pneumonitis, pneumomediastinum)
• Injection use: blood cultures, hepatitis B/C serology, HIV testing
• Signs of systemic infection: CBC, cultures

8. Management

8a. Treatment Setting

• Medical/psychiatric conditions require intensive stabilization (severe depression with SI, persistent psychosis)
• Failed lower level of care
• Need to remove from drug-triggering environment
• Polysubstance dependence requiring medically supervised detoxification (alcohol, sedatives, opioids)
• Acute medical emergencies (CVA, MI, arrhythmia, sepsis)

8b. Intoxication and Withdrawal (Acute Management)

8c. Psychosocial Treatments (Cornerstone of Chronic Management)

1. Contingency Management (CM) - Most robust behavioral treatment. Rewards drug-free urine samples and treatment attendance with prizes/incentives (variable-ratio reinforcement schedule). Average cost ~$200/patient for 12 weeks. Improves abstinence rates and treatment retention. Effective in both cocaine and methamphetamine use disorder, including in patients on methadone maintenance.
2. Cognitive Behavioral Therapy (CBT) - Focuses on identifying triggers, developing coping skills, relapse prevention. Strong evidence, especially when combined with other treatments or pharmacotherapy.
3. Twelve-Step Facilitation (TSF) - Disease model approach; most studied in cocaine use disorder specifically. Promotes engagement with groups such as Cocaine Anonymous/Narcotics Anonymous.

8d. Pharmacotherapy

• Psilocybin: A landmark 2026 RCT in JAMA Network Open (Hendricks et al.) showed single-dose psilocybin (25 mg/70 kg) + manualized CBT psychotherapy produced significantly higher cocaine abstinent days (β = 28.95, 95% CI 18.22-39.67; p<0.001), greater likelihood of complete abstinence (OR 18.37; p=0.007), and longer time to first lapse (HR 0.28; p=0.001) vs. active placebo at 180 days. No serious adverse events. Sample size was small (n=40), but results are notable.
• Cocaine and methamphetamine vaccines - under development; challenge is the small molecular size
• Transcranial magnetic stimulation (TMS) / transcranial direct current stimulation (tDCS) - under investigation; some evidence for craving reduction and improved executive function
• Epigenetic modifiers - early phase research

9. Co-occurring Conditions

• ADHD: Common co-occurrence. Stimulant medications may be carefully used with close monitoring when ADHD is independently diagnosed, with proper documentation and structured prescribing.
• Mood disorders: 1-month rule for differentiating stimulant-induced vs. independent. Bipolar disorder requires careful history to separate from stimulant-induced mood cycling.
• HIV/Hepatitis: Screen all patients with injection use history.
• Polysubstance use: Alcohol, opioids, and cocaine are frequently co-used. Methadone maintenance patients have shown benefit from CM. Opioid use disorder management does not preclude cocaine use disorder treatment.

10. Prognosis

• High baseline use severity
• Positive urine toxicology at treatment entry
• Withdrawal symptoms at baseline
• Injection route of administration
• Persistent psychosocial stressors

Key Recent Evidence (2023-2026)

Important note: The psilocybin trial (PMID 42096204) is a small single-center RCT and not yet practice-changing, but it represents potentially significant emerging evidence for a disorder with no FDA-approved pharmacotherapy.

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry (11.3 - Stimulant-Related Disorders), pp. 3974-4011
• Goldman-Cecil Medicine, pp. 4192-4211
• Rosen's Emergency Medicine, pp. 2631-2660
• Minozzi et al., Cochrane Database Syst Rev 2024 - Psychosocial interventions for stimulant use disorder
• Hendricks et al., JAMA Netw Open 2026 - Psilocybin RCT for cocaine use disorder