Phase I/II study (n=62 estimated) testing two fixed psilocybin doses (10 mg then 25 mg, one month apart) combined with either 12-session PA-CBT or 6-session minimal supportive therapy in adults with major depressive disorder to assess feasibility, acceptability and preliminary efficacy.
This study includes a Phase I open trial (n≈12) of psilocybin-assisted CBT (PA-CBT) followed by a Phase II randomized, parallel-group trial (n≈50) comparing PA-CBT (12 sessions) with a minimal supportive therapy condition (6 sessions).
All participants receive two oral psilocybin sessions (10 mg then 25 mg, one month apart). Outcomes include feasibility, acceptability, adherence, and clinical measures of depressive symptoms (HAM-D) and safety assessments.
Two oral psilocybin doses (10 mg then 25 mg, one month apart) combined with 12-session manualised cognitive behavioural therapy (PA-CBT).
10 mg then 25 mg, one month apart
Twelve sessions of manualised cognitive behavioural therapy (preparation, integration and CBT skills).
Two oral psilocybin doses (10 mg then 25 mg, one month apart) combined with 6 sessions of minimal supportive, non-directive therapy (3 sessions preparation, 3 sessions supportive integration).
10 mg then 25 mg, one month apart
Six sessions: 3 preparation sessions (including ~3 hours preparation) and 3 hours supportive integration after dosing; non-directive supportive therapy.