Psychedelic-Assisted Psychotherapy Gets a Win for Alcohol Addiction

Psilocybin-assisted psychotherapy cut heavy drinking days in people with alcohol use disorder (AUD), according to a small randomized trial.

In combination with motivational enhancement therapy and cognitive behavioral therapy, psilocybin led to a greater reduction in the percentage of heavy drinking days for AUD patients versus an active placebo, reported Michael Bogenschutz, MD, of the NYU Langone Center for Psychedelic Medicine at NYU Langone Health in New York City, and colleagues.

At 32 weeks, 9.71% of days involved heavy drinking for those in the psilocybin group versus 23.57% for those on diphenhydramine, for a mean between group difference of 13.86% (95% CI 3.00-24.72, P=0.01), according to the findings in JAMA Psychiatry.

The group assigned to the two capsules of high-dose psilocybin -- a compound found in psychedelic mushrooms -- also experienced a greater reduction in the average number of drinks per day compared to the control group by this time point, at 1.17 versus 2.26 drinks per day, respectively (mean difference 1.09, 95% CI 0.27-1.92).

"The treatment effects observed in our study were considerably larger than those reported in meta-analyses of approved treatments for alcohol use disorder," Bogenschutz said during an NYU press conference on Wednesday.

He also highlighted the lasting effects of the treatment combo.

"It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication," Bogenschutz said. "This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms."

This is an important finding, according to Bogenschutz, because it shows potential for a treatment option in an underserved population of patients. He noted that an estimated 14% of U.S. adults suffer from AUD, and it leads to more than 100,000 deaths per year.

The results suggest that psilocybin could be an effective treatment when combined with psychotherapy in a clinically controlled setting, which could eventually address this lack of options for individuals with AUD, according to Henry Kranzler, MD, and Emily Hartwell, PhD, both of the University of Pennsylvania in Philadelphia, writing in an accompanying editorial.

"Pharmacological treatments, a cornerstone of intervention for most psychiatric disorders, are particularly underused in treating AUD, with less than 4% of patients with AUD receiving a medication approved by the [FDA] to treat the disorder," they wrote.

They cautioned however that the current study was not able to effectively blind participants, as psilocybin led to a "high average intensity of experience" versus the "low average intensity" reported by the diphenhydramine group.

"This difference undermined the masking of treatment such that greater than 90% of participants and therapists correctly guessed the treatment assignment with high confidence during both medication sessions," Kranzler and Hartwell stated. "The lack of a suitable comparator limits the ability to mask treatment conditions, so that double-blind designs may be impossible. 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."

Bogenschutz said there is unfortunately not a better placebo option for studying psilocybin or any drug that has "overt psychological effects that are easily distinguished."

Other study limitations included the fact that it did not have adequate power to assess effects in subgroups, such as women and ethnic/racial minority groups.

"These results should not be generalized to less controlled settings, where the risks of psilocybin would be considerably larger and benefits have not been demonstrated," said Bogenschutz. "But if these effects hold up in future trials, psilocybin will be a real breakthrough in the treatment of alcohol use disorder."

From 2014 to 2020, a total of 95 participants (mean age 46 years, 79% white, 56% men) were offered 12 weeks of psychotherapy and randomly assigned to either psilocybin or diphenhydramine at two academic centers. The medication was administered during two day-long sessions at 4 and 8 weeks. The researchers assessed outcomes over a 32-week double-blind period after the first dose of study medication.

During the screening period, participants reported a baseline percentage of heavy drinking days -- five or more daily drinks for men, four or more for women -- as 56.48% for the psilocybin group and 48.57% for the placebo group. These percentages declined to 24.11% and 21.31%, respectively, at 4 weeks.

In this period, participants received four psychotherapy sessions and attempted to stop drinking prior to the medication intervention.

Participants also reported an average 5.20 daily drinks in the psilocybin group and 4.33 drinks per day for the placebo group at baseline, which at 4 weeks dipped to 2.77 and 2.19 daily drinks, respectively.

The medication regimen included psilocybin (25 mg/70 kg) or diphenhydramine (50 mg) during the first session, and psilocybin (25-40 mg/70 kg) or diphenhydramine (50-100 mg) during the second session.

Participants were ages 25 to 65 and had a DSM-IV diagnosis of alcohol dependence, along with at least 4 days of heavy drinking days in the 30 days prior to screening. Exclusion criteria were major psychiatric and drug use disorders, hallucinogen use, contraindicated medical conditions, use of any exclusionary medications, or current treatment for AUD.

Comment