Single psilocybin dose with therapy increased cocaine abstinence in a 40-person trial

The question

Can a single dose of psilocybin, given alongside structured psychotherapy, help people with cocaine use disorder stop using cocaine?

What they did

Forty adults with cocaine use disorder who wanted to quit were recruited at one US medical research centre between May 2015 and August 2023. They were randomly assigned to a single oral dose of psilocybin (25 mg per 70 kg of body weight) or an active placebo (100 mg diphenhydramine, an antihistamine that causes noticeable effects). Everyone also received manual-based psychotherapy including cognitive-behavioural methods, about one month before and one month after the all-day dosing session. Cocaine use was tracked by structured interview and confirmed with urine testing for 180 days after treatment ended.

What they found

Of the 40 participants, 33 (82.5%) were men, 33 (82.5%) were Black, and the median age was 50.0 years; 26 (65%) had an annual income of $20,000 or less. Four people were lost to follow-up, leaving 36 who completed assessments through 180 days. The psilocybin group had a higher percentage of cocaine-free days (β = 28.95; 95% CI, 18.22-39.67), were more likely to be completely abstinent (odds ratio, 18.37; 95% CI, 1.92-2468.17), and had a lower risk of returning to cocaine use over time (hazard ratio, 0.28; 95% CI, 0.13-0.60). No serious adverse events occurred.

The fine print

With only 40 participants at a single centre, the results are preliminary and the confidence range around the abstinence odds was extremely wide (1.92 to 2468.17), meaning the true size of that effect is very uncertain. Participants were motivated to quit and had no significant other medical or psychiatric conditions, so they may not represent everyone with cocaine use disorder. Psilocybin’s noticeable effects can make blinding difficult even with an active placebo, follow-up ended at 180 days, and this summary is based on the abstract only.

What it means

In a small but carefully designed trial, one psilocybin session combined with psychotherapy was linked to more cocaine-free days over six months than an active placebo, with no serious adverse events reported. Larger trials are needed before any conclusions about routine treatment can be drawn.

Evidence grade: Moderate. A randomized, quadruple-blind, placebo-controlled trial with a well-defined outcome, but the sample was small (40 people) and from a single site.

This summary is based on the study’s published abstract.