Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder

Summary & key facts

In a carefully controlled study, about 95 adults with alcohol use disorder all got 12 weeks of psychotherapy and were randomly given either two high-dose psilocybin sessions or an active placebo during two day-long medication visits. Over about 32 weeks after the first dose, the group that got psilocybin had far fewer heavy drinking days than the placebo group. The psilocybin group also drank less on average per day, and there were no serious safety problems reported in people who received psilocybin. The authors say these results support doing more research on psilocybin-assisted therapy for alcohol problems.

Key facts:

• Who was studied: about 95 adults aged 25 to 65 who met criteria for alcohol dependence and had at least four heavy drinking days in the month before screening.
• What they did: everyone received 12 weeks of guided psychotherapy and two day-long medication sessions at weeks 4 and 8; people were randomly assigned to get either high-dose psilocybin or an active placebo medicine.
• Main finding: over the 32-week follow-up, the psilocybin group had about 10% heavy drinking days, while the placebo group had about 24% heavy drinking days, a difference of roughly 14 percentage points.
• Drinking amount: average daily alcohol use was also lower in the psilocybin group compared with the placebo group.
• Safety: no serious adverse events were reported among the people who received psilocybin in this study.
• Limits on who this applies to: the study excluded people with other major psychiatric or drug-use disorders, people already in treatment for alcohol problems, and people with prior hallucinogen use, so the findings may not apply to all people with alcohol problems.
• What it means: the study shows psilocybin given with psychotherapy produced bigger reductions in heavy drinking than an active placebo plus psychotherapy, but the authors say more research is needed before this becomes a standard treatment.

Abstract

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, Setting, and Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions: Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main Outcomes and Measures: The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results: A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and Relevance: Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial Registration: ClinicalTrials.gov Identifier: NCT02061293.

Topics

Forensic Toxicology and Drug Analysis Pain Management and Placebo Effect Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Alcohol Alcohol use disorder Alternative medicine Biochemistry Chemistry Diphenhydramine Hallucinogen Histamine Internal medicine Medicine Pathology Placebo Psilocybin Psychiatry Psychology Randomized controlled trial Relapse prevention

Substances

Psilocybin

Conditions & symptoms

Addiction Substance abuse disorder Addiction or harmful habbits