Psilocybin-Assisted Therapy Can Treat Alcohol Use Disorder, Trial Finds

Despite the adverse medical, psychosocial, and economic harms associated with alcohol use disorder (AUD), less than 4% of patients receive medication to treat their disorder. In fact, no new compounds for treating AUD have been approved by the US Food and Drug Administration (FDA) since the year 2004, and those which have been approved often only have a small effect size.

As a result, novel medications for treating AUD are sorely needed. Recently, there has been a renewed interest in investigating the potential of psychedelic-assisted psychotherapy in tackling addiction and substance abuse disorders, including AUD.

Published today in JAMA Psychiatry, the first controlled trial of psilocybin for AUD reports that psilocybin-assisted psychotherapy significantly reduces the occurrence of heavy drinking days in people with AUD, compared to what can be achieved with psychotherapy and placebo medication.

Although the issue of effective treatment blinding remains an issue when studying psychedelics, the trial authors say that their findings provide support for further study into psilocybin-assisted treatments for AUD.

Average heavy drinking days decrease with psilocybin treatment

A total of 95 participants with an alcohol dependence diagnosis took part in this double-blind randomized clinical trial, of which 49 were assigned to receive psilocybin and 46 to receive the antihistamine drug diphenhydramine as a non-hallucinogenic placebo.

All participants were assessed on their alcohol use and general health during initial enrollment screening, at baseline (week 0), and in weeks 4, 5, 8, 9, 12, 24 and 36 of the study. Psilocybin or the active placebo diphenhydramine was administered in two, 8-hour sessions in weeks 4 and 8 of the trial. In these sessions, the participants were accompanied by two qualified therapists and encouraged to make use of eye masks and music playlists provided. Additional medications to treat severe anxiety or hypertension, if it arose, were also available.

Participants were also offered a total of 12 psychotherapy sessions: four leading up to the first medication session, four to bridge the gap between the two sessions, and a final four in the month following the second (and final) medication session.

The researchers found that psilocybin treatment was associated with a significant reduction in heavy drinking days. The percentage of heavy drinking days within the psilocybin group fell significantly, from around 56% of days during screening to just 9.7% by the end of the follow-up period. In contrast, the percentage of heavy drinking days was around 23.6% at the follow-up for the active placebo group. 

Participants who were treated with psilocybin were also significantly more likely to report no heavy drinking days than those in the diphenhydramine group, and to have higher rates of complete abstinence by the follow-up period.

First clinical trial reinforces early findings from the 1960s

While this is, to the authors’ knowledge, the first controlled trial of psilocybin for AUD, the results found here do fall in line with the findings of earlier work carried out in the late-1960s with classic psychedelics, including LSD.

Across the six randomized clinical trials published between 1966 and 1971 investigating LSD’s effect on AUD, it was found that treatment with the psychedelic resulted in remission nearly twice as often as in those given comparator drugs.

More recently, a 2015 open-label study found that moderately high doses of psilocybin were well tolerated in individuals with alcohol dependence, and tended to result in large reductions in drinking over a 32-week period.

“The findings reported by Bogenschutz et al underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia,” wrote Henry R. Kranzler and Emily E. Hartwell in an accompanying editorial also published in JAMA Psychiatry. Kranzler is professor of psychiatry and the director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine, where Hartwell is also a postdoctoral fellow.

“Insights gained into the mechanism of [psilocybin’s] effects could also enhance medications development for AUD by identifying novel targets that, if exploited, could ultimately increase the use of FDA-approved medications to treat the disorder.”

The difficulty with studying psychedelics

Psilocybin treatment was also very well tolerated in this new controlled trial, with the drug group reporting no serious adverse events and fewer adverse events overall than the active placebo group. The most common side effect to treatment was headache, which was reported by just over 40% of the psilocybin group. Two members of the group were given oral diazepam to treat feelings of anxiety that arose during their second drug session, but this was resolved quickly. There were no reports of any disturbances that could indicate psychosis.

“Adverse events associated with psilocybin administration were mostly mild and self-limiting, consistent with other recent trials evaluating the effects of psilocybin in various conditions,” the researchers wrote. “However, it must be emphasized that these safety findings cannot be generalized to other contexts.”

“The study implemented measures to ensure safety, including careful medical and psychiatric screening, therapy and monitoring provided by 2 well-trained therapists including a licensed psychiatrist, and the availability of medications to treat acute psychiatric reactions.”

In addition to the stringent safety precautions, the researchers also list the large sample size and high participant retention rates as particular strengths of this trial.

However, the trial also had several limitations. While the study size was large, it did not have adequate power to evaluate effects in specific subgroups, such as women, ethnic and racial minority groups, or those with a psychiatric comorbidity.

Another major limitation was the ineffectiveness of the diphenhydramine in maintaining the study blind, with 93.6% of participants correctly guessing their treatment assignment after the first drug session. This is a well-known obstacle in psychedelics study and one which the field continues to reckon with.

“The lack of a suitable comparator limits the ability to mask treatment conditions, so that double-blind designs may be impossible,” Kranzler and Hartwell wrote. “This is important because expectancies can strongly influence both the therapeutic and adverse effects of the medications, and an adequate control is needed to differentiate the expected effects from the pharmacologic ones.”

Despite these limitations, both the study authors and the accompanying editorial writers believe that these new results support further study into the effectiveness of psilocybin-assisted psychotherapy as a treatment for adults with AUD.