Psilocybin in alcohol use disorder and comorbid depressive symptoms

Depression after alcohol detox is a big risk factor for relapse to drinking, so this study looked at psychedelic assisted psychotherapy with psilocybin (the active ingredient in magic mushrooms) to see if they could improve outcomes. Two groups were randomized; one group received a 25mg dose and the other got a placebo of 1mg which is an inactive microdose. A few different outcome measures were different between the groups: number of drinking days, craving scores, and relapse rates were all better in the 25mg group, suggesting psilocybin has a genuine effect in facilitating staying quit from drinking. Still, this is a small study, enrolling only 30 individuals, so as they say, more research needs to be done. Check out the link below for the full article. While psilocybin is still not available for medical use in the United States, it will likely be in the coming years at which point it’s worth considering. For now, ketamine assisted psychotherapy remains the only medically available psychedelic, which also has robust anti-addiction properties; confusingly, it also sometimes precipitates a ketamine use disorder, so it’s worth closely considering the risks and benefits, and working with an experienced clinician.

Luquiens A, Belahda D, Graux C, Igounenc N, Serrand C, Rochefort P, et al. Psilocybin in alcohol use disorder and comorbid depressive symptoms: Results from a feasibility randomized clinical trial. Addiction. 2025. https://doi.org/10.1111/add.70152

full text: https://onlinelibrary.wiley.com/doi/10.1111/add.70152

psychedelics for addiction

“The first major impact of a psychedelic experience in the 20th century in relation to addiction was that of Bill Wilson, the founder of Alcoholics Anonymous. He had an atropine-induced revelatory experience that he described as follows: “Suddenly the room lit up with a great white light. I was caught up in an ecstasy which there are no words to describe. It seemed to me in my mind’s eye, that I was on a mountain and that a wind not of air but of spirit was blowing. And then it burst upon me that I was a free man.” Bill’s psychedelic spiritual experience changed his life—through it he felt he was able to escape from the shackles of alcohol dependence, becoming permanently abstinent (for more details on the history of psychedelics, see Nutt, 2023).”

— Nutt et al.

Psychedelics, including more broadly, MDMA and ketamine, along with the classical psychedelics like LSD and psilocybin/psilocin, are being studied more and more as treatments for substance use disorders (ie, addictions). More studies means more data in support of their use, and already we are seeing such clinical trials demonstrating hopeful effects of ketamine on treatmnet of alcohol use disorder, opioid use disorder, cocaine use disorder, and cannabis use disorder. Use in these indications are still being studied, and it’s unclear how ketamine would be marketed given it’s a generic drug and being used off label. The limited data we have on the FDA approved ketamine product (esketamine nasal spray, AKA Spravato), suggests it is less effective than generic racemic ketamine, at least for treatment of depression. It is certainly much more expensive ($600-900 instead of $2-3). It is possible that a company will try to gain FDA approval for one of these indications, but then they would risk clinicians simply using generic ketamine off label, bypassing their formulation, and decreasing their profit potential. It makes me wonder if any company will actually invest in the work to carry out FDA trials for this.

Nutt DJ, Morgan C, Klaire S. A Perspective on Psychedelics as Treatments for Addictions. Journal of Studies on Alcohol and Drugs. 2024. 202485:5,583-588

full text: https://www.jsad.com/doi/full/10.15288/jsad.23-00032

Rolling stone article, "The Psychedelic Miracle"

Earlier this month Rolling Stone published an article about the clinical use of psychedelics in underground clinics.*  It's an interesting read and delves in the motivations and experiences of a number of medical and allied professionals who opt to provide such agents as MDMA, ayahuasca, or magic mushroms (containing psilocybin) in unregulated settings.  That professionals will take on potential legal risk from practicing with these substances is a testament to their belief that they work, and something that is being gradually backed up by high quality scientific studies.  Several organizations are working on this process to formally medicalize these agents and bring them to legal clinical use, such as Hefter, MAPS, and others (see my resources page for links and more reading).  The available clinical data suggests that the classical hallucinogens such as psilocybin, LSD, and ayahuasca (which contains DMT) may have greater efficacy and duration of effect for depression and processing trauma, but it is hard to say concretely without further clinical trials, several of which are in the process due to the efforts of the above mentioned organizations.  Until that time, it seems that ketamine is the only clinically available (and legal) psychedlic available.  

*As as aside, Rolling Stone labels psychedelics as "miracle", which I am always hesitant to endorse as such.  The clinical trial data thus far shows large effect sizes and a relatively benign side effect profile, though with the caveat that these outcomes are carefully structured and take place in controlled medical settings.  As the article mentions, based on the authors personal account of several illicit psychedelic treatments, there can be significant personal turmoil during the healing and integration process; such treatments are not without their risks, and it is very likely that such treatments will not work for everyone.  There does, however, seem to be a correlation between subjects who achieve a mystical experience and better treatment outcomes, at least with the classical hallucinogens.  So perhaps it is more appropriate to term it "a miraculous experience"?

Link: http://www.rollingstone.com/culture/features/how-doctors-treat-mental-illness-with-psychedelic-drugs-w470673