Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder

This Phase II, randomized, quadruple‑masked, parallel trial (n=36) will evaluate the safety and preliminary efficacy of psilocybin‑assisted psychotherapy in adults aged 18–65 with severe alcohol use disorder, with primary outcomes including percent heavy drinking days and adverse effects and secondary measures of cue‑induced craving and neural response by fMRI. Participants will be randomised 1:1 to a low‑dose or full‑dose psilocybin arm and will complete two supervised dosing sessions paired with a standardised psychotherapy protocol. Participants in the low‑dose arm receive oral psilocybin capsules of 10 mg at the first session with an optional escalation to 15 mg at the second session; the full‑dose arm receives 30 mg at the first session with an optional escalation to 40 mg at the second session. Dosing sessions occur in a controlled clinical setting four weeks apart with preparatory and integration sessions delivered by a dyad of trained therapists, continuous monitoring during dosing, and support from a peer recovery coach plus optional outpatient addiction treatment. Eligible participants are recruited up to 90 days after completing inpatient withdrawal management; outcomes are assessed through 48 weeks after the second dose, including percent heavy drinking days (weeks 0–24 after the first dose), adverse events at multiple post‑treatment timepoints, cue‑induced craving (baseline, 4 and 24 weeks after the second treatment), and fMRI measures one week before and one week after the second psilocybin session.