Reference: JAMA Psychiatry. 2022 Aug 24 early online
Clinical Take-Home Point: Don’t start recommending magic mushrooms to treat alcohol dependence, yet. Maybe try therapy, which has already been shown to work.
EBM Pearl: Self-selection bias, recall bias, and an inappropriate control intervention that leads to inadequate blinding can all result in overestimation of benefit in favor of the intervention.
A recent trial published in JAMA Psychiatry has received a lot of attention for what looks like impressive effects of psilocybin, the psychoactive ingredient in certain *magic* mushrooms for decreasing alcohol use in adults with alcohol dependence. But is this psychedelic really the magical antidote to alcoholism we’re hoping for?
Study recruitment began with local media advertisements offering 12 weeks of CBT and motivational interviewing for alcohol dependence and the chance to receive psilocybin for medical treatment. As a bonus, everyone was offered free psilocybin at the end of the trial regardless of group assignment. Ninety-five adults with alcohol dependence were randomized to receive a single dose of either psilocybin or diphenhydramine at week 4 and again at week 8 during each of two full-day extended motivational guidance sessions. That’s it — two doses. Data collection continued for 32 weeks after the first dose of medication and showed that the percentage of self-reported heavy drinking days was lower in the psilocybin group (9.7% vs 23.6%). Daily alcohol consumption was also lower in the psilocybin group. Interestingly, there were no adverse events related to psilocybin, but a few patients in the diphenhydramine group had inpatient psych admissions and one had a Mallory Weiss tear.
Magic mushrooms: there’s nothing they can’t do, right? Well, the methods chosen for this trial may have made the mushrooms seem more magical for several reasons. First, we have self-selection bias. Something is inherently different about a population that responds to an advertisement compared to those who don’t. The participants in this study were probably thinking that the intervention would work, which leads us to the second problem: inadequate blinding. Over 90% of both participants and study therapists correctly guessed treatment assignment during medication sessions. So this plus the self-selection bias means that the people in the control group figured out that they didn’t get psilocybin and were then more likely to think their intervention didn’t work. Third, the investigators asked about drinking every 4 weeks; trying to remember how much you drank a month ago can be a little hard, and this can result in recall bias. There is certainly reason to hope psilocybin is a potential therapeutic option for alcohol dependence, but ultimately it will require more rigorous study.
For more information, see the topic Alcohol Use Disorder in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Nicole Jensen, MD, Family Physician at WholeHealth Medical. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Dan Randall, MD, Deputy Editor at DynaMed; Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed; and Sarah Hill, MSc, Associate Editor at DynaMed.