Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial.
Level 2 - randomized trial
Double-blind randomized clinical trial.
PubMed 36001306 · doi:10.1001/jamapsychiatry.2022.2096
What was done
In a double-blind trial at two US academic centers, 95 adults (aged 25 to 65 years) with DSM-IV alcohol dependence and at least 4 heavy drinking days in the prior 30 days were randomized to receive 12 weeks of psychotherapy plus two day-long medication sessions at weeks 4 and 8. Participants received either psilocybin (25 mg/70 kg in session 1; 25–40 mg/70 kg in session 2) or an active placebo, diphenhydramine (50 mg in session 1; 50–100 mg in session 2). The primary outcome was the percentage of heavy drinking days assessed over the 32-week double-blind period following the first medication session.
What was found
Of 95 randomized participants, 93 received study medication and were analyzed. Over the 32-week post-first-dose period, the mean percentage of heavy drinking days was 9.7% in the psilocybin group compared to 23.6% in the diphenhydramine group, a mean difference of 13.9% (95% CI, 3.0% to 24.7%; P = .01). Mean daily alcohol consumption (drinks per day) was also lower in the psilocybin group. No serious adverse events occurred among participants who received psilocybin.
Why it matters
This study provides randomized controlled evidence that high-dose psilocybin combined with psychotherapy produces sustained reductions in heavy drinking days among individuals with alcohol use disorder relative to an active placebo.
Limits
The study sample was modest (n = 95) and largely non-Hispanic White (78.9%), limiting generalizability across diverse populations. The abstract does not address whether functional unblinding occurred due to the distinct psychoactive effects of psilocybin, and individuals with major co-occurring psychiatric or drug use disorders were excluded.