This randomised, triple-blind, active placebo-controlled Phase II study (n=144) compares oral psilocybin 25 mg and 5 mg versus a nicotinamide placebo in patients with treatment-resistant depression, with two dosing sessions and psychotherapeutic support.
Multi-centre, randomized, parallel-group trial evaluating safety and efficacy of oral psilocybin (25 mg and 5 mg) versus nicotinamide 100 mg active placebo in adults with treatment-resistant major depression; two dosing sessions spaced six weeks apart.
Dosing is delivered under structured psychotherapeutic conditions with three preparatory and four integration sessions; participants remain hospitalised overnight after each dosing for monitoring. Outcomes include depressive symptoms (HAM-D), safety labs, ECG, and adverse events.
Placebo comparator arm receiving nicotinamide 100 mg at session 1 and 25 mg psilocybin at session 2 per protocol sequencing.
Nicotinamide 100 mg at session 1 (placebo); session 2 receives 25 mg psilocybin per protocol.
Low-dose first session then full dose at second session (5 mg → 25 mg).
Session 1: 5 mg; Session 2: 25 mg
High-dose sequences including 25→5 mg or 25→25 mg across two sessions.
Sequences: 25 mg at session1 then 5 mg at session2, or 25 mg at both sessions
In this triple‑blind, active placebo‑controlled randomised trial (n=144) of adults with treatment‑resistant depression, two 25 mg doses of psilocybin plus adjunct psychotherapy produced clinically meaningful reductions in depressive symptoms on exploratory secondary measures but did not significantly improve the pre‑second‑dose HAMD17 response rate versus nicotinamide.