What is the role of propranolol (beta blocker) in treating cocaine use disorder?

Propranolol in Cocaine Use Disorder: Limited Evidence for Treatment, Contraindicated in Acute Intoxication

Propranolol should NOT be used in acute cocaine intoxication due to risk of unopposed alpha-stimulation causing paradoxical hypertension and worsened coronary vasospasm, but may have a narrow role in treating cocaine use disorder in carefully selected patients with severe withdrawal symptoms who are not acutely intoxicated. 1, 2, 3

Critical Distinction: Acute Intoxication vs. Chronic Treatment

Acute Cocaine Intoxication (CONTRAINDICATED)

Beta-blockers including propranolol are contraindicated during acute cocaine intoxication because they block beta-2 receptors while leaving alpha-adrenergic stimulation unopposed, potentially worsening coronary vasospasm and causing paradoxical hypertension. 1, 2, 3

• A case report documented propranolol-induced hypertensive crisis in a cocaine-intoxicated patient, requiring nitroprusside for blood pressure control despite heart rate reduction. 3
• The American Heart Association explicitly recommends against beta-blockers in patients showing signs of acute intoxication (euphoria, tachycardia, hypertension). 2
• First-line treatment for acute cocaine-related cardiovascular complications should be benzodiazepines, nitroglycerin, and calcium channel blockers (verapamil or diltiazem). 1, 2

Chronic Treatment for Cocaine Use Disorder (LIMITED EVIDENCE)

The evidence for propranolol as a treatment for cocaine use disorder itself is mixed and limited to small trials:

Potential Benefits in Severe Withdrawal

• Propranolol may reduce cocaine use ONLY in patients with severe cocaine withdrawal symptoms. 4, 5
• In a placebo-controlled trial of 108 patients, propranolol showed no overall benefit, but exploratory analysis found better treatment retention and lower urinary benzoylecgonine levels in the subgroup with severe withdrawal symptoms. 4
• Among highly medication-adherent patients with severe withdrawal, propranolol was associated with better retention and higher abstinence rates compared to placebo. 5
• Propranolol consistently reduced cocaine withdrawal symptom severity across trials. 4, 5

Preclinical Evidence

• Animal studies demonstrate that chronic propranolol (15 mg/kg daily) prevented escalation of cocaine self-administration and partially reversed established escalation patterns. 6
• Propranolol dose-dependently decreased motivation for cocaine under progressive ratio schedules without affecting saccharin self-administration, suggesting specificity for cocaine. 6

Clinical Algorithm for Propranolol Use

Step 1: Rule Out Acute Intoxication

• Do NOT use propranolol if patient shows: euphoria, acute tachycardia (>100 bpm), hypertension (SBP >150 mmHg), or recent cocaine use within 4-6 hours. 2, 7
• Cocaine metabolites can be detected in urine for 24-48 hours in most cases, up to 22 days in chronic heavy users. 8

Step 2: Assess Withdrawal Severity

• Consider propranolol ONLY for patients with severe cocaine withdrawal symptoms (autonomic arousal, anxiety, craving). 4, 5
• Patients without severe withdrawal symptoms showed no benefit from propranolol in clinical trials. 4, 5

Step 3: Ensure Medication Adherence

• Propranolol efficacy was demonstrated only in highly medication-adherent patients. 5
• Patients with active substance use disorders often have poor medication compliance. 1

Step 4: Monitor for Complications

• If patient relapses to cocaine use while on propranolol, risk of unopposed alpha-stimulation exists. 2, 3
• Patient counseling about negative interactions between cocaine use and beta-blockade is essential. 2

Common Pitfalls to Avoid

• Never administer propranolol or any beta-blocker during acute cocaine intoxication - this can cause paradoxical hypertension and worsened coronary vasospasm. 1, 2, 3
• Do not use propranolol as first-line treatment for cocaine use disorder in unselected patients - evidence supports use only in those with severe withdrawal symptoms. 4, 5
• Avoid assuming labetalol (combined alpha-beta blocker) is safe in acute intoxication - it should only be used if a vasodilator was given within the previous hour. 1, 7
• Do not prescribe propranolol without ensuring patient understands the danger of concurrent cocaine use. 2

Preferred Alternatives for Cocaine Use Disorder

Behavioral interventions remain the primary evidence-based treatment for cocaine use disorder: 8

• Contingency management combined with community reinforcement approach has demonstrated efficacy. 8
• No pharmacological agent has strong evidence for treating cocaine use disorder in general populations. 4, 5
• Transcranial magnetic stimulation is under investigation for reducing cocaine craving. 8