REVIEW OF: Bogenschutz MP et al, JAMA Psychiatry 2022;79(10):953–962

STUDY TYPE: Randomized controlled trial

Over the past decade, there has been great interest in the therapeutic potential of psychedelics. Psilocybin, otherwise known as “magic mushrooms,” has garnered special attention for its potential efficacy in depression, anxiety, end-of-life care, and now alcohol use disorder (AUD).

In this 32-week, double-blind, randomized controlled trial, 95 participants with AUD were randomized to two groups: a psilocybin group (n=49) with a dose of 25–50 mg/70 kg, and an active placebo group (n=46) that received diphenhydramine 25–100 mg. The drugs were administered in two eight-hour sessions at weeks four and eight. Participants also received a total of 12 psychotherapy sessions before, between, and after the two drug administrations. The primary endpoint was percentage of heavy drinking days, which was determined using a self-report technique called the “timeline follow-back method,” and hair and fingernail samples were tested for the alcohol metabolite ethylglucoronide to confirm self-reported abstinence.

The researchers found that over the course of the study, the psilocybin group had a significant reduction in heavy drinking days compared to the diphenhydramine group (9.7% vs 23.6%; p=0.01). The difference was apparent as early as the fifth week, only one week after the first drug administration. Additionally, at 32 weeks, mean daily alcohol consumption was lower in the psilocybin group compared to the diphenhydramine group (1.17 vs 2.26 standard drinks per day; p=0.01). Apart from some minor and transient side effects, psilocybin was well tolerated.

To contextualize this study’s results, meta-analysis found that the number needed to treat (NNT) to prevent heavy drinking with naltrexone was 12 (Jonas DE et al, JAMA 2014;311(18):1889–1900). This means that 12 patients would have to receive naltrexone to prevent one patient from engaging in heavy drinking. The NNT to prevent heavy drinking for psilocybin in this trial was 4.5. 

At first glance, these results seem impressive, but there are some significant limitations to keep in mind. First, outcome measures largely depended on self-reporting, and about half of the participants did not follow up for laboratory confirmation of abstinence. Also, >90% of the participants correctly guessed which intervention they were receiving; adequate blinding remains a challenge for many psychedelic trials. The median household income of the participants was $100,000, which raises questions about generalizability and recruitment bias. And finally, the FDA’s Schedule I restriction means that utilizing psilocybin treatment outside of a research setting is all but impossible, except for a few places (Oregon, and perhaps soon Colorado).

CARLAT TAKE

This study shows some impressive results for psilocybin as a potential new treatment for AUD, albeit with significant study limitations and concerns about generalizability. Though promising, psilocybin remains an investigational treatment that is not ready for prime time just yet. But keep an eye out for future developments; given the enthusiasm for psychedelics, more are sure to come.