This Phase II, non-randomised, single-arm sequential dose-finding trial (n=72) will evaluate group retreat psilocybin therapy for healthcare clinicians with symptoms of depression and loss of meaning in their work. It will assess the feasibility, safety, and preliminary clinical effects of different preparation “doses” before a single psilocybin retreat session. Participants will be healthcare clinicians aged 25-70 years who are currently in clinical practice and have moderate or greater depressive symptoms. The study uses three sequential cohorts, each with 8 participants per retreat and 3 retreats per cohort, comparing 7 preparation sessions (6 virtual and 1 in-person), 4 preparation sessions (3 virtual and 1 in-person), and 2 preparation sessions (1 virtual and 1 in-person). The psilocybin dose depends on antidepressant use: 25 mg plus an optional 10 mg booster for those not taking an antidepressant, or 35 mg plus an optional 10 mg booster for those taking an antidepressant. The intervention includes preparation sessions, a single psilocybin session, and integration sessions, with outcomes collected at 1 week, 1 month, and 3 months after the retreat.
In this single-arm Phase 2 study, the researchers are assessing the feasibility of the group retreat format for clinicians and explores different 'doses' of preparation. A sequential dose-escalation design is used. The study will recruit healthcare clinicians (physicians, nurses, nurse practitioners, physician assistants) aged 25-70 years currently in clinical practice with moderate or greater symptoms of depression and loss of meaning during the past 5 years. Each participant will be in a group cohort of 8, and 3 cohorts will be tested at each dose level. The objectives are safety, feasibility, mechanism testing, and outcomes.
In this non-randomized trial, the dose of psilocybin will be as follows: for participants not taking an antidepressant, the dose will be psilocybin 25 mg + optional booster 10 mg; for participants who are taking an antidepressant the dose will be psilocybin 35 mg + optional booster 10 mg,