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.
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.
Single oral dose psilocybin (25 mg) with single oral pimavanserin (34 mg).
Pimavanserin 34 mg (Nuplazid)
Single oral dose psilocybin (25 mg) with matching placebo.
Matching placebo