Double-blind, randomised, parallel-group Phase II study (n=104 actual) comparing a single 25 mg oral dose of psilocybin to a single 100 mg oral dose of niacin (active placebo) in participants with MDD, assessed to Day 43 post-dose.
Randomised, triple-masked, parallel-group trial enrolling adults 21–65 with DSM-5 major depressive disorder to compare a single 25 mg oral dose of synthetic psilocybin versus 100 mg oral niacin (active placebo). Participants receive identical Set and Setting (SaS) procedures.
The SaS protocol includes preparatory meetings with facilitators, an extended supervised dosing session (typically several hours), and post-dose integration sessions. Primary outcome is change in depressive symptoms from baseline to Day 43; safety and tolerability are also assessed.
Single 25 mg oral psilocybin with Set and Setting (SaS) protocol.
Encapsulated synthetic psilocybin; administered with SaS protocol.
Single 100 mg oral niacin (active placebo) with Set and Setting (SaS) protocol.
Active placebo (niacin) 100 mg; encapsulated.
This systematic review (s=8) analyses completed controlled trials of psychedelics for depression, including psilocybin, LSD, ayahuasca, and DMT, all in Phase II or I/II. It evaluates methodological patterns against the draft European Medicines Agency guideline revision, highlighting challenges such as unblinding, expectancy, and adverse event characterisation, while calling for larger studies to assess long-term efficacy and safety.