Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: Comparing One Versus Two Doses of Psilocybin (PSI-1V2)
Randomized, parallel Phase II trial (n=92) comparing one versus two psilocybin doses (25 mg) with psilocybin-assisted psychotherapy in adults with treatment-resistant depression; first dose randomised 1 mg vs 25 mg, second dose open-label 25 mg.
Details
This randomized, parallel-group study compares the efficacy and safety of one versus two psilocybin dosing sessions (25 mg) delivered with supervised psilocybin-assisted psychotherapy in adults with treatment-resistant major depressive disorder.
The primary outcome is change in MADRS from baseline to Week 8; safety assessments include adverse event monitoring, vitals during dosing, dissociative and psychotomimetic effects, treatment-emergent mania, and suicidality. Secondary outcomes include quality of life, functioning, cognition, and durability of benefit over six months.
Each dosing session involves two therapists supporting the participant for approximately 6–8 hours; the first session is randomized and blinded (1 mg vs 25 mg) while the second session is open-label 25 mg for all participants.