Actively Recruiting

Phase 2
Age: 18Years - 64Years
All Genders
NCT06072898

A Randomized Neuroimaging Trial of Psilocybin in Depression

Led by Sunnybrook Health Sciences Centre · Updated on 2026-03-30

50

Participants Needed

1

Research Sites

204 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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

Official Title

A Randomized Neuroimaging Trial of Psilocybin in Depression

Who Can Participate

Age: 18Years - 64Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Able and voluntarily willing to provide written informed consent at the screening visit
  • Age over 18 and under 65 years
  • Able to complete all protocol required assessment tools without assistance or alteration and comply with all study visits
  • Have a responsible individual or caregiver able to monitor participant at home for 24 hours after each treatment visit
  • Have a psychiatrist and/or general practitioner able to provide psychiatric follow-up care
  • MINI confirmed diagnosis of major depressive disorder (MDD), recurrent or single episode, without psychotic features, current episode lasting at least 3 months
  • Depression of at least moderate severity defined by a Hamilton Depression Rating Scale (HAMD-17) score greater than 17
Not Eligible

You will not qualify if you...

  • Current or past bipolar I/II disorder, schizophrenia, schizoaffective disorder, psychotic disorder, or delusional disorder
  • Clinical diagnosis of antisocial personality disorder and/or paranoid personality disorder
  • Active clinical diagnosis of borderline personality disorder
  • Depression secondary to other medical conditions or bipolar I and II disorder
  • Family history of first degree relative with schizophrenia, primary psychotic disorder, or bipolar disorder
  • Any symptoms of psychosis or hypomania/mania
  • History of one or more suicide attempts in past year requiring hospitalization
  • Personal circumstances or behavior incompatible with safe exposure to psilocybin
  • Women who are pregnant, nursing, or planning pregnancy
  • Lifetime history of hallucinogen substance use disorder or substance-induced psychosis
  • Positive urine drug screen for illicit drugs or drugs of abuse at screening, one week prior to treatment, or during trial
  • Abnormal clinically significant physical exam, vital signs, ECG, or lab tests
  • QTc prolongation on ECG
  • Uncontrolled or insulin-dependent diabetes
  • History of seizure disorder except ECT or childhood febrile seizures
  • Diagnosis of mild or major neurocognitive disorder
  • History of stroke, recent myocardial infarction within 1 year, uncontrolled hypertension, or significant arrhythmia within 1 year
  • Other major concurrent illnesses interfering with study results or participant safety
  • Exposure to psilocybin or other psychedelics in past 12 months or during current depressive episode
  • History of moderate or greater substance or alcohol use disorder in past 12 months
  • Current enrollment or participation within 30 days in another interventional depression study
  • Blood count abnormalities not resolved by serial testing

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N3M5

Actively Recruiting

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Research Team

E

EMBRACE Team

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

CROSSOVER

Primary Purpose

BASIC_SCIENCE

Number of Arms

2

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