A Randomized Neuroimaging Trial of Psilocybin in Depression

The goal of this neuroimaging clinical trial is to test whether psilocybin produces significant immediate changes in functional brain activity in networks associated with mood regulation and depression compared to placebo in patients with depression. The trial aims to determine if psilocybin: 1. Changes connectivity within brain networks associated with mood and depression 2. Changes blood flow in brain regions associated with mood and depression Participants will be attend two treatment sessions where they receive an oral medication and supportive psychotherapy. At each session, participants will undergo an MRI scan after drug administration but prior to psychotherapy. Participants will be randomly to assigned to one of two groups that will receive, 1) microcrystalline cellulose (25mg) at the first visit and psilocybin (25mg) at the second visit, or 2) psilocybin (25mg) at both visits, respectively. Differences between groups will be compared to understand what effects on brain activity are specific to psilocybin.

NCT Number	NCT06072898
Lead Sponsor	Sunnybrook Health Sciences Centre
Conditions	Depressive Disorder, Major Depressive Disorder
Enrollment	50 participants
Start Date	2025-05-28
Primary Completion	2028-05 (estimated)
Study Completion	2029-05 (estimated)
Updated on ClinicalTrials.gov	2026-03-30