Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial

Does psilocybin combined with psychotherapy elicit abstinence from cocaine in people with cocaine use disorder relative to active placebo plus psychotherapy?

This randomized clinical trial tested whether psilocybin-assisted psychotherapy could help people with cocaine use disorder achieve and maintain abstinence.

“Importance  Cocaine use disorder is a serious public health problem and no medications have been proven effective for its treatment.

Objective  To evaluate psilocybin in the treatment of cocaine use disorder. It was hypothesized that psilocybin, compared with placebo, would yield a higher percentage of cocaine abstinent days, a greater likelihood of complete abstinence from cocaine, and a greater latency to first cocaine lapse through 180 days after end of treatment.

Design, Setting, and Participants  Randomized, quadruple-blind, placebo-controlled clinical trial at a major medical research center in the Deep South of the US. Participants were individuals with cocaine use disorder who were motivated to quit and without significant comorbidities, recruited between May 2015 and August 2023 with data collection completed in May 2024.

Interventions  Participants were randomized (1:1) to receive a single oral dose of psilocybin (25 mg per 70 kg of body weight) or active placebo (100 mg diphenhydramine). All participants received manualized psychotherapy that incorporated cognitive-behavioral treatment approximately 1 month before and 1 month after an all-day investigational drug treatment session.

Main Outcomes and Measures  Percentage of cocaine abstinent days, rates of complete cocaine abstinence, and time to first cocaine lapse through 180 days after end of treatment, assessed by timeline followback interview and confirmed with urinalysis. Hypotheses were formulated before data collection and analyses followed intention-to-treat principles.

Results  Of the 40 participants, 33 (82.5%) were men, the median (IQR) age was 50.0 (43.8-56.0) years, 33 (82.5%) were Black, and 7 (17.5%) were White. Most participants had lower socioeconomic status, with 26 participants (65%) having an annual income of $20 000 or less. Four participants were lost to follow-up, resulting in 36 participants who completed assessments through 180 days after end of treatment. Psilocybin recipients had a higher percentage of cocaine abstinent days (β = 28.95; 95% CI, 18.22-39.67; P < .001), greater likelihood of complete cocaine abstinence (odds ratio, 18.37; 95% CI, 1.92-2468.17; P = .007), and a reduced risk of cocaine lapse over time (hazard ratio, 0.28; 95% CI, 0.13-0.60; P = .001) than active placebo recipients. No serious adverse events occurred.

Conclusions and Relevance  In this randomized clinical trial, psilocybin appeared to be safe and efficacious for treating cocaine use disorder among individuals from underrepresented and vulnerable populations. Further research is warranted to replicate and expand these findings.”

This is one of the first randomized controlled trials suggesting a psychedelic-assisted intervention may help treat cocaine use disorder, a condition for which there are currently no FDA-approved medications. A single supervised psilocybin session combined with structured psychotherapy produced significantly better cocaine abstinence outcomes than placebo plus psychotherapy over six months.

The results are promising, but the study is still an early-stage trial with a relatively small sample, so larger replication studies are needed before the approach could become standard treatment

Hendricks PS, Lappan SN, Shelton RC, et al. Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(5):e2611029. Read Paper

For more psychedelic news and research, visit the psychedelic health professional network homepage.