Cocaine and Other Stimulant Use Disorder: Clinical Assessment, Diagnosis, and Management

1. Overview and Epidemiology

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry

2. Pharmacology and Mechanism

• Goldman-Cecil Medicine; Katzung's Basic and Clinical Pharmacology

3. Clinical Assessment

3a. Screening

• CAGE-AID (adapted for drugs)
• DAST-10 (Drug Abuse Screening Test)
• AUDIT-C (includes polysubstance context)
• Urine drug screen (cocaine metabolites - benzoylecgonine - detectable 2-4 days after single use, up to 10-12 days in heavy users)

3b. Signs of Intoxication

• Mydriasis (dilated pupils)
• Tachycardia, hypertension
• Diaphoresis or chills
• Psychomotor agitation
• Elevated temperature
• Nausea/vomiting
• Euphoria, grandiosity, increased energy, decreased appetite
• At higher doses: anxiety, irritability, paranoia, psychosis

• Seizures (grand mal - occur with intoxication, not withdrawal)
• Myocardial infarction (vasospasm + accelerated atherosclerosis)
• Intracranial hemorrhage
• Ventricular tachyarrhythmias, Brugada-type pattern
• Hyperthermia, rhabdomyolysis
• Agitated delirium ("excited delirium")

• Kaplan and Sadock's Synopsis of Psychiatry (Table 4-30); Rosen's Emergency Medicine; Goldman-Cecil Medicine

3c. Cocaine Washout Syndrome

• Rosen's Emergency Medicine

3d. Withdrawal Features

• Profound fatigue, hypersomnia
• Increased appetite ("carbohydrate craving")
• Dysphoria, anhedonia, depression (can be serious)
• Powerful craving for the drug
• "Suicide Sundays" in MDMA users (post-serotonin depletion low mood)

• Goldman-Cecil Medicine; Kaplan & Sadock's Comprehensive Textbook

4. Diagnosis

DSM-5-TR: Stimulant Use Disorder

1. Using more than intended or for longer than intended
2. Persistent desire to cut down or inability to control use
3. Significant time spent obtaining, using, or recovering from stimulant effects
4. Craving or strong desire/urge to use
5. Recurrent use failing to fulfill major role obligations (work, school, home)
6. Continued use despite persistent social/interpersonal problems caused by use
7. Important activities given up or reduced
8. Recurrent use in physically hazardous situations
9. Continued use despite knowing it is causing physical or psychological harm
10. Tolerance (need for increased amounts; 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 or more criteria

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry

DSM-5 Stimulant Intoxication

• Tachycardia/bradycardia, hypo/hypertension
• Mydriasis
• Sweating or chills
• Nausea/vomiting
• Psychomotor agitation/retardation
• Weight loss
• Muscular weakness, respiratory depression
• Chest pain, arrhythmias
• Confusion, seizures, dyskinesias, dystonias, or coma

DSM-5 Stimulant Withdrawal

Stimulant-Induced Psychiatric Disorders (rule out independent disorder)

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry

5. Differential Diagnosis

• Mania or hypomania - binge cycles can closely mimic bipolar disorder
• Schizophrenia/brief psychotic disorder - vs stimulant-induced psychosis
• PCP intoxication - shares sympathomimetic + psychotic features with cocaine
• Hyperthyroidism, pheochromocytoma - tachycardia, diaphoresis, anxiety
• Other stimulant intoxication (MDMA, bath salts, ephedrine)
• Sedative-hypnotic withdrawal (agitation, diaphoresis, seizures - but has its own signs)

6. Complications by Route and Organ System

• Rosen's Emergency Medicine; Goldman-Cecil Medicine

7. Management

7a. Acute Intoxication (Emergency Management)

• Supportive care is the mainstay - no specific antidote
• Agitation/paranoia: Benzodiazepines (first-line); antipsychotics (second-line - note QT prolongation risk; avoid haloperidol if Brugada pattern suspected)
• Hypertension/chest pain: Benzodiazepines, nitrates, calcium channel blockers. Avoid beta-blockers (risk of unopposed alpha-adrenergic vasoconstriction worsening ischemia)
• Hyperthermia: Active cooling, benzodiazepines
• Seizures: Benzodiazepines; exclude hypoglycemia and structural causes
• Arrhythmias: Sodium bicarbonate for wide-complex tachycardia from Na+ channel blockade; treat hypokalemia
• Most patients recover spontaneously within hours

7b. Withdrawal

• Generally outpatient management - does not require hospitalization
• Supportive care: sleep, nutrition, hydration
• Short-term benzodiazepines for severe agitation or anxiety
• Monitor for serious depression and suicidal ideation (especially methamphetamine)

7c. Treatment Setting

• Persistent psychosis or suicidality
• Medical complications (MI, stroke, infection)
• Co-occurring disorders requiring intensive treatment
• Multiple drug dependencies (alcohol, opioid co-dependence requiring monitored detox)
• Failure at lower levels of care / need to remove from drug-using environment

7d. Psychosocial Treatments (Cornerstone of Care)

• Uses operant conditioning: positive reinforcement (vouchers, cash prizes) for drug-free urine screens and treatment attendance
• Systematic reviews consistently show CM is more effective than CBT, 12-step, and other behavioral strategies for stimulant use disorders
• A "fishbowl" intermittent reinforcement schedule (variable ratio) maximizes engagement
• Practical challenge: implementing real-world incentive structures

• Identifies and modifies thoughts, beliefs, and behaviors that trigger or maintain use
• Teaches coping skills for cravings, high-risk situations, relapse prevention
• Well-studied for cocaine use disorder

• Connects patients to mutual-help groups and peer support
• Community Reinforcement Approach (CRA) integrates 12-step principles with CBT
• Self-help involvement and sponsorship are among the most consistently identified positive prognostic factors

• Structured intensive outpatient program combining CBT, family therapy, 12-step participation, and drug testing - widely used for methamphetamine
• NYSDOH/ASAM 2023 Guideline; Kaplan & Sadock's Comprehensive Textbook of Psychiatry

7e. Pharmacotherapy

• Goldman-Cecil Medicine; Kaplan & Sadock's Comprehensive Textbook; NYSDOH 2025 Guideline

7f. Harm Reduction

• Naloxone provision (fentanyl is now commonly adulterating cocaine supplies)
• Fentanyl test strip education
• Safer use supplies (clean needles, pipes)
• HIV and hepatitis C screening and treatment
• STI screening
• Safe sex counseling

8. Co-occurring Disorders (Dual Diagnosis)

• Depression (very common post-cessation; anhedonia is the strongest predictor of poor prognosis)
• ADHD (shared dopaminergic vulnerability; can predate and drive stimulant use)
• PTSD (associated with more persistent impairment even if not predicting more cocaine use in treatment)
• Bipolar disorder (binge-withdrawal cycles mimic BD; careful timeline essential)
• Antisocial personality disorder

9. Prognosis

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry

Recent Evidence Updates (2024-2026)

• Contingency management remains confirmed as the strongest behavioral intervention across a 2025 systematic review [PMID: 39545650]
• Aripiprazole is not effective for stimulant use disorder without psychiatric comorbidities (2025 systematic review) [PMID: 40623320]
• Crack cocaine treatment review (2026) comparing multiple interventions reinforces behavioral approaches as superior to pharmacotherapy alone [PMID: 41871216]
• The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder (2023/2024) is the current North American gold standard - published in Journal of Addictive Medicine (2024; 18[1S]:1-56)

1. No FDA-approved medication for cocaine/amphetamine use disorder - behavioral therapy (especially contingency management) is the proven cornerstone
2. Stimulant withdrawal is not medically dangerous - no need for hospital detox in most cases; risk is psychological (depression, suicidality)
3. Avoid beta-blockers in cocaine-associated chest pain or hypertension - use benzodiazepines and CCBs
4. Symptoms persisting >1 month of abstinence = independent psychiatric disorder, not stimulant-induced
5. Always screen cocaine users for fentanyl co-exposure given current supply contamination
6. Bupropion XR + naltrexone is the only pharmacotherapy combination with robust RCT evidence (for methamphetamine, not cocaine)

Management of Cocaine Use Disorder

1. Guiding Principles

1. No FDA-approved pharmacotherapy exists - behavioral treatments are the primary, evidence-based intervention
2. Treatment intensity should match severity - most patients start in outpatient settings (cocaine withdrawal is not medically dangerous)
3. Address the whole person - co-occurring psychiatric disorders, medical complications, social determinants, and harm reduction are all part of care

2. Treatment Setting

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry

3. Behavioral / Psychosocial Treatments

3a. Contingency Management (CM) - STRONGEST EVIDENCE

• Mechanism: Operant conditioning - targeted behaviors (drug-free urine screens, attendance) are reinforced with immediate tangible rewards (vouchers, prize draws)
• Evidence: A 2024 Cochrane systematic review (64 RCTs, 8,241 participants) found that among psychosocial interventions, CM most consistently improves continuous abstinence and reduces dropout; 73% of included studies were in cocaine/crack users [PMID: 38357958]
• Schedule: Intermittent (variable ratio) reinforcement - "fishbowl" prize draws on a chance-based escalating schedule maximizes engagement
• ASAM/AAAP 2024 Recommendation: CM is the primary component of the behavioral treatment plan (Strong Recommendation)
• Practical challenge: Implementing real-world incentive programs (funding, regulatory constraints); telehealth-based CM platforms are emerging

3b. Cognitive Behavioral Therapy (CBT)

• Identifies high-risk situations, cognitive distortions, and maladaptive behaviors that trigger or sustain cocaine use
• Teaches coping skills: drug refusal, stress management, relapse prevention, managing craving
• ASAM/AAAP 2024: Strong Recommendation to use CBT alongside CM
• Widely studied specifically in cocaine use disorder; 7 RCTs in the Cochrane review
• Can be delivered individually or in group format; telemedicine delivery is a Strong Recommendation for patients with access barriers

3c. Community Reinforcement Approach (CRA)

• Comprehensive operant-based therapy that restructures daily reinforcers - work, family, recreation, social relationships - so a drug-free life is more rewarding than using cocaine
• Moderate evidence for achieving and sustaining abstinence in CUD
• ASAM/AAAP 2024: Conditional Recommendation alongside CM

3d. 12-Step Facilitation (TSF) / Narcotics Anonymous (NA)

• Facilitates engagement with mutual-help groups
• Self-help involvement and having a sponsor are among the strongest positive prognostic factors identified in outcome studies
• Most 12-step outcome research has focused specifically on cocaine use disorder
• ASAM/AAAP 2024: Conditional Recommendation

3e. The Matrix Model

• Structured 16-week intensive outpatient program combining: individual CBT, family education, 12-step participation, regular urine drug testing, and social support
• Originally developed for stimulant use disorders; well-validated for cocaine and methamphetamine
• ASAM/AAAP 2024: Conditional Recommendation

3f. Motivational Interviewing (MI)

• Builds intrinsic motivation for change, particularly useful at earlier stages of readiness
• 3 RCTs in the 2024 Cochrane review; evidence suggests MI reduces dropout and increases engagement with further treatment
• Best used at initial contact or with ambivalent patients to facilitate entry into more intensive behavioral programs

3g. Digital / Technology-Based Interventions

• Evidence-based apps and web platforms (e.g., CBT4CBT) can be used as add-on components to in-person care
• ASAM/AAAP 2024: Should not be used as standalone treatment (Low certainty, Strong Recommendation)
• Kaplan & Sadock's Comprehensive Textbook of Psychiatry; ASAM/AAAP 2024; Cochrane Review 2024 [PMID: 38357958]

4. Pharmacotherapy

4a. Medications with ASAM/AAAP 2024 Conditional Recommendations for CUD

• ASAM/AAAP 2024 Guideline [PMC11105801]; Kaplan & Sadock's Comprehensive Textbook of Psychiatry

4b. Medications with Insufficient or Negative Evidence for CUD

4c. Emerging / Investigational

5. Management of Acute Intoxication

6. Management of Withdrawal

• Supportive: sleep hygiene, nutrition, hydration
• Monitor closely for severe depression and suicidality (especially first 1-2 weeks)
• Short-term benzodiazepines for severe anxiety/agitation if needed
• Start behavioral treatment as early as possible - motivation is often high in early withdrawal
• There is no approved medication for withdrawal management; "cocaine crashout" is self-limiting

7. Management of Co-occurring Disorders

8. Harm Reduction

• Naloxone provision to all cocaine users (fentanyl co-exposure is leading cause of cocaine-related overdose deaths)
• Fentanyl test strip education and provision
• Safer use supplies (clean needles, pipes, cookers)
• HIV, hepatitis B/C screening and linkage to treatment
• STI screening
• Safer sex counseling
• Wound care and abscess screening for injection users

9. Special Populations

• CM is highly effective for reducing substance use in pregnancy (abstinence rates 36-46% vs 10-18% standard care)
• Medication safety data for CUD agents in pregnancy is limited - avoid pharmacotherapy when possible
• Coordinate with obstetrics; monitor fetal growth

• Group behavioral treatment should use peer-age groups - mixing with older adults reduces effectiveness and exposes younger patients to negative peer influence (ASAM/AAAP 2024)
• Higher emphasis on family-based interventions

• Cocaine use dramatically increases HIV transmission risk and impairs ART adherence
• CM is effective in this population; integrate HIV care and addiction treatment

10. Prognosis and Monitoring

• Regular urine drug screens (cocaine metabolite benzoylecgonine - detectable 2-4 days after single use, up to 12 days in heavy users)
• Monitor mood, cognition, psychiatric symptoms
• Track employment, social functioning, housing stability

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry

Summary: Management Algorithm

DIAGNOSIS CONFIRMED (≥2 DSM-5-TR criteria)
            │
            ▼
    Assess severity + comorbidities + readiness
            │
            ├─► HARM REDUCTION (all patients) - Naloxone, fentanyl test strips, safer use
            │
            ├─► BEHAVIORAL TREATMENT (cornerstone - all patients)
            │       │
            │       ├─ Contingency Management (PRIMARY - strongest evidence)
            │       ├─ CBT (Strong Recommendation, alongside CM)
            │       ├─ CRA / Matrix Model (Conditional)
            │       └─ 12-Step / NA facilitation (Conditional)
            │
            ├─► PHARMACOTHERAPY (adjunctive, off-label, low-certainty)
            │       │
            │       ├─ Topiramate + MAS-ER (best pharmacotherapy evidence, moderate certainty)
            │       ├─ Topiramate alone (if AUD co-occurs)
            │       ├─ Bupropion (if depression or tobacco use co-occurs)
            │       ├─ Modafinil (if no AUD)
            │       └─ Disulfiram (if AUD co-occurs)
            │
            ├─► TREAT CO-OCCURRING DISORDERS
            │
            └─► STEP UP to residential/inpatient if outpatient fails or comorbidities require it

1. CM is the single most evidence-supported treatment for CUD - prioritize access to it
2. No drug "works" for cocaine the way methadone works for opioids - behavioral treatment is not optional
3. Always provide naloxone - fentanyl in the cocaine supply makes every use potentially fatal
4. Avoid beta-blockers in acute cocaine toxicity
5. Symptoms of depression or psychosis persisting beyond 4 weeks of abstinence require independent psychiatric evaluation
6. The topiramate + MAS-ER combination has the best pharmacotherapy evidence base per ASAM/AAAP 2024 (moderate certainty, conditional recommendation)
7. GLP-1 agonists and ketamine are the most watched emerging agents as of 2025-2026