Psilocybin Mechanism of Action (MOA)
Randomised, quadruple-blind, placebo-controlled parallel trial (n=60) testing whether 5-HT2A blockade with pimavanserin (34 mg) alters the subjective and antidepressant effects of a single 25 mg oral dose of psilocybin in people with MDD.
Details
This is a randomised, quadruple-blind, parallel-group treatment study in adults (21–80 y) with Major Depressive Disorder. Participants receive a single 25 mg oral dose of psilocybin plus either pimavanserin 34 mg or matching placebo.
Assessments occur before dosing and at multiple post-dose timepoints up to five weeks, including clinical depression scales and neuroimaging to probe the role of 5-HT2A signalling in subjective psychedelic effects versus antidepressant response.
Safety precautions include withdrawal of serotonergic drugs prior to dosing, ECG and lab monitoring, and MRI compatibility screening.