NCT06072898

A Randomized Neuroimaging Trial of Psilocybin in Depression

Engaging Mood Brain Circuits With Psilocybin: a Randomized Neuroimaging Trial in Depression

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Sunnybrook Health Sciences Centre · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Depressive Disorder
• Major Depressive Disorder

Interventions

Type	Name	Description
DRUG	Psilocybin	Psilocybin (\[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate), 25mg PO.
OTHER	Microcrystalline cellulose	MCC (excipient), 25mg PO.
BEHAVIORAL	Supportive psychotherapy	Supportive psychotherapy in the form of reassurance, integration, and de-escalatory techniques (if needed). Facilitating rapport and a positive environment.

Timeline

• Start date: 2025-05-28
• Primary completion: 2028-05-01
• Completion: 2029-05-01
• First posted: 2023-10-10
• Last updated: 2026-03-30

Locations

1 site across 1 country: Canada

Regulatory

• FDA-regulated drug study