This Phase I/II, randomised trial (n=50) will evaluate the acceptability and feasibility of psilocybin-assisted cognitive behavioural therapy (PA-CBT) for patients with major depressive disorder (MDD). Participants will receive either 12 sessions of CBT combined with two doses of psilocybin (10 mg and 25 mg, taken orally) or 6 sessions of minimal supportive therapy alongside the same psilocybin doses. The primary objectives include assessing the integration of psilocybin with psychotherapy and examining its clinical benefits as an adjunct to CBT. In this two-arm trial, participants in the experimental group will undergo a structured CBT programme, which includes psychoeducation and skills training, while those in the active comparator group will receive supportive therapy focused on preparation and integration of the psilocybin experience. Both groups will have a one-month interval between the two psilocybin sessions. Key outcome measures will include client satisfaction, retention rates, and changes in depression severity as assessed by the Hamilton Depression Rating Scale over a follow-up period of seven months. The study is set to begin in January 2026 and aims for completion by November 2027.
The primary objectives of this clinical investigation are to (1) determine the acceptability and feasibility of joining psilocybin-assisted therapy with cognitive-behavioral therapy (PA-CBT) for patients with depression, (2) optimize CBT to most effectively integrate the psilocybin experience with psychotherapy and (3) examine the clinical benefit of psilocybin as an adjunct to cognitive-behavioral therapy (CBT) for major depressive disorder.
This study is a randomized, two-arm, fixed dose trial that will test the feasibility, acceptability, and participant and therapist adherence to PA-CBT. Both treatment arms will receive two doses of psilocybin (10mg and then 25mg, separated by one month). In Phase II, participants will be randomized (1:1) to either a 12-session PA-CBT or a 6-session standard psilocybin-assisted therapy (PAT) condition (3 hours of preparation plus 3 hours of supportive therapy integration following the psilocybin experiences).
Participants will receive 12 sessions of cognitive-behavioral therapy (CBT) along with two psilocybin-drug sessions -- the first following the third CBT session (10mg of psilocybin, taken orally) and the second following the sixth CBT session (25mg of psilocybin, taken orally).
Unmatched intervention: cognitive behavioral therapy
Participants will receive 6 sessions of supportive, non-directive therapy along with two psilocybin-drug sessions -- the first following the third therapy session (10mg of psilocybin, taken orally) and the second following the fourth therapy session (25mg of psilocybin, taken orally).
Unmatched intervention: Minimal supportive therapy