Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 42096204 · doi:10.1001/jamanetworkopen.2026.11029
What was done
In a quadruple-blind, active placebo-controlled trial at a single US medical center, 40 participants with cocaine use disorder motivated to quit and without significant comorbidities were randomized 1:1 to receive a single oral dose of psilocybin (25 mg per 70 kg) or active placebo (100 mg diphenhydramine). All participants received manualized cognitive-behavioral psychotherapy approximately 1 month before and 1 month after the drug session. Outcomes included percentage of cocaine-abstinent days, complete abstinence rates, and time to first lapse through 180 days post-treatment, assessed via timeline followback and confirmed by urinalysis.
What was found
Of 40 enrolled participants (median age 50.0 years; 82.5% men; 82.5% Black; 65% with annual income ≤$20,000), 36 completed the 180-day follow-up. Compared with active placebo, psilocybin recipients had a significantly higher percentage of cocaine-abstinent days (β = 28.95; 95% CI, 18.22-39.67; P < .001), greater odds of complete abstinence (odds ratio = 18.37; 95% CI, 1.92-2468.17; P = .007), and reduced risk of lapse over time (hazard ratio = 0.28; 95% CI, 0.13-0.60; P = .001). No serious adverse events occurred.
Why it matters
There are currently no approved pharmacotherapies for cocaine use disorder; these findings provide initial randomized controlled evidence that psilocybin combined with psychotherapy can promote sustained cocaine abstinence in a historically underrepresented population.
Limits
The sample size was small (n = 40), yielding very wide confidence intervals for complete abstinence. The study was conducted at a single site, excluded patients with significant comorbidities, had 4 participants lost to follow-up, and used an active placebo that may not maintain complete blinding against psychedelic effects.
Cited by
- supports Clinical trials investigating psilocybin for substance use disorders include studies on alcohol use disorder at NYU and cocaine dependence at the University of Alabama.