Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study

Abstract

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration ( p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 ( r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms. TRIAL REGISTRATION: NCT02061293

In the evidence

This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Psilocybin for addiction ↑Supports

  Abstinence did not increase before psilocybin but rose significantly after administration, with gains largely maintained to 36 weeks and no significant treatment-related adverse events.

  Synthesized October 22, 2026

• State of the evidence: Addiction ↑Supports

  Abstinence did not increase significantly before psilocybin but increased significantly after psilocybin administration, with gains largely maintained to 36 weeks and no significant treatment-related adverse events.

  Synthesized September 20, 2026

• State of the evidence: Psilocybin ↑Supports

  Abstinence from alcohol increased significantly following psilocybin administration, and gains were largely maintained at follow-up to 36 weeks.

  Synthesized September 20, 2026