Psilocybin Achieved 30% Complete Cocaine Abstinence. The Placebo Got Zero.

For cocaine use disorder, the medicine cabinet has always been empty. No FDA-approved medications. No buprenorphine analog. No pharmacological safety net of the kind that transformed opioid overdose rates over the past two decades. Clinicians working with people who use cocaine have had contingency management and cognitive behavioral therapy — both effective, neither widely available, neither sufficient for the roughly 5 million Americans who meet criteria for cocaine use disorder.

A randomized controlled trial published May 7, 2026, in JAMA Network Open suggests that a single dose of psilocybin, combined with structured psychotherapy, may be the most significant pharmacological candidate this field has ever had.

The trial, led by Peter S. Hendricks at the University of Alabama at Birmingham with collaborators at Johns Hopkins, enrolled 40 adults with cocaine use disorder who were motivated to stop using. Participants received either 25 mg of psilocybin per 70 kg body weight or 100 mg of diphenhydramine (active placebo), alongside manualized cognitive behavioral psychotherapy including preparation sessions, one all-day drug session, and five integration sessions. At the 180-day follow-up, the results were stark: six of 20 psilocybin participants — 30% — achieved complete abstinence. Zero placebo participants achieved complete abstinence. The psilocybin group reported cocaine use averaging 1.5 times per month; the placebo group averaged 12 times per month. The hazard ratio for relapse was 0.28 in the psilocybin arm.

The study population is worth noting: more than 80% of participants were Black, 65% earned under $20,000 annually, and the median age was 50, with a median of 26 years since first cocaine use. This is not a sample of young professionals at a psychedelic retreat. This is a population historically excluded from clinical trials, historically underserved by treatment programs, and historically carrying the heaviest burden of stimulant use disorder. The signal that psilocybin works for them — in that context, in those circumstances — is the most important finding in the study.

The numbers demand honest qualification, and Hendricks’ team provides it. The sample size of 40 produces wide confidence intervals. Blinding integrity was compromised — 90% of psilocybin recipients correctly identified their assignment, which is expected for a psychoactive compound but creates measurement confounds. The lead researcher also served as primary therapist, introducing the possibility of allegiance bias. The authors explicitly describe these results as “hypothesis-generating rather than confirmatory.” A larger trial is needed and should be funded.

Still: 30% complete abstinence versus 0% in a six-month follow-up is not a noise pattern. For a condition with no approved pharmacological treatment and a relapse rate that has historically discouraged investment in new trials, this result is news. It is the kind of signal that, if replicated in a larger study, changes how cocaine use disorder is treated.

The psychedelics-empathogens FDA priority voucher pathway, which the FDA opened in April 2026 for Compass Pathways, Usona, and Transcend, does not currently include cocaine use disorder as an indication. It should be on the short list for the next expansion.