Actively Recruiting

Phase 2
Age: 18Years - 64Years
All Genders
ID06072898

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

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

50

Participants Needed

1

Research Sites

52 weeks

Total Duration

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AI-Summary

What this Trial Is About

This clinical trial studies adults aged 18 to 64 with moderate depression to see if psilocybin causes immediate changes in brain activity related to mood and depression. Researchers compare brain connectivity and blood flow after taking psilocybin versus a placebo to understand its effects on mood regulation. The study is randomized and carefully monitors brain changes using MRI scans. Participants attend two treatment sessions where they receive oral medication and supportive psychotherapy. One group takes a placebo at the first visit and psilocybin at the second, while the other group receives psilocybin at both visits. MRI scans are done after medication but before psychotherapy to observe brain activity changes. Supportive psychotherapy helps create a positive and reassuring environment during treatments. During the study, participants complete various depression and mood assessments up to six weeks after treatment. Researchers measure brain blood flow and connectivity changes within three weeks. Additional tests evaluate depressive symptoms, anxiety, cognitive function, and mystical experiences. Participants must have support at home for 24 hours after treatment and ongoing psychiatric care. The study lasts up to eight weeks, including follow-up assessments to ensure safety and monitor effects.

CONDITIONS

Brief 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
  • Over 18 and under 65 years old
  • Able to complete all required assessment tools without assistance or alteration
  • Have a responsible individual/caregiver to monitor you at home for 24 hours after each treatment visit
  • Have a psychiatrist and/or general practitioner able to provide psychiatric follow-up care
  • Have a confirmed diagnosis of major depressive disorder (MDD), recurrent or single episode without psychotic features, with 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...

  • History or current diagnosis of bipolar I/II disorder, schizophrenia, schizoaffective disorder, psychotic or delusional disorder
  • Clinical diagnosis of antisocial, paranoid, or borderline personality disorder
  • Depression secondary to other medical conditions or bipolar disorders
  • Family history of schizophrenia, primary psychotic disorder, or bipolar disorder
  • Symptoms consistent with psychosis or mania/hypomania
  • Suicide attempt requiring hospitalization in the past year
  • 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 at screening or during trial
  • Abnormal clinical examination, vital signs, ECG, or lab tests including QTc prolongation
  • Uncontrolled or insulin-dependent diabetes
  • History of seizure disorder except specific types
  • Diagnosis of neurocognitive disorders
  • Recent stroke, heart attack, uncontrolled hypertension, or serious arrhythmia
  • Other major illnesses interfering with study or participant safety
  • Psilocybin or other psychedelic use within 12 months prior to screening or during current depressive episode
  • History of moderate or greater substance or alcohol use disorder in past year
  • Current or recent participation in other interventional depression studies
  • Abnormal blood counts not resolved by serial testing

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Up to 6 weeks

Participants receive psilocybin or placebo capsules orally along with supportive psychotherapy in a randomized crossover design, with two treatment visits.

2 treatment visits with supportive psychotherapy

Follow-up

Duration - Up to 8 weeks

Participants are monitored with various assessments to evaluate brain function and mood changes after treatment.

Multiple follow-up assessments up to 8 weeks

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

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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Published Research Related To This Trial

Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression.

Joshua M Poulin, Gregory E Bigford, Krista L Lanctôt...

https://pubmed.ncbi.nlm.nih.gov/38956594