JAMA network openMay 7, 2026

Psilocybin as a Treatment for Cocaine Addiction: A Randomized Clinical Trial

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 28, 2026

Abstract

Essence

Psilocybin with psychotherapy improved cocaine abstinence outcomes versus active placebo with psychotherapy in motivated adults with cocaine use disorder.

Evidence

Randomized quadruple-blind placebo-controlled trial in 40 participants found psilocybin increased cocaine-abstinent days (beta 28.95), raised complete abstinence odds (odds ratio 18.37), and lowered lapse risk (hazard ratio 0.28) through 180 days, with no serious adverse events.

Caveat

The trial was small, used a single-center sample of motivated participants without major comorbidities, and the very wide confidence interval for complete abstinence shows substantial uncertainty.

Simplified

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.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02037126.