A Randomized Neuroimaging Trial of Psilocybin in Depression

NCT ID: NCT06072898

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-25
• Study Completion Date: 2028-06-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Staged Active Treatment Arm (Psilocybin-Psilocybin)

This group will receive psilocybin (25mg) at the first and second treatment visit, along with supportive psychotherapy.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

Psilocybin (\[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate), 25mg PO.

Supportive psychotherapy

Intervention Type: BEHAVIORAL

Supportive psychotherapy in the form of reassurance, integration, and de-escalatory techniques (if needed). Facilitating rapport and a positive environment.

Placebo to Active Delayed-Start Treatment Arm (MCC-Psilocybin)

This group will receive microcrystalline cellulose (25mg) at the first treatment visit and psilocybin (25mg) at the second treatment visit, along with supportive psychotherapy.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

Psilocybin (\[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate), 25mg PO.

Microcrystalline cellulose

Intervention Type: OTHER

MCC (excipient), 25mg PO.

Supportive psychotherapy

Intervention Type: BEHAVIORAL

Supportive psychotherapy in the form of reassurance, integration, and de-escalatory techniques (if needed). Facilitating rapport and a positive environment.

Interventions

Psilocybin

Psilocybin (\[3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate), 25mg PO.

Intervention Type: DRUG

Microcrystalline cellulose

MCC (excipient), 25mg PO.

Intervention Type: OTHER

Supportive psychotherapy

Supportive psychotherapy in the form of reassurance, integration, and de-escalatory techniques (if needed). Facilitating rapport and a positive environment.

Intervention Type: BEHAVIORAL

Other Intervention Names

MCC

Eligibility Criteria

Inclusion Criteria

• Able and voluntarily willing to provide written informed consent at the screening visit.
• Over 18 and under 65 years old
• Able to attend all study visits and complete all required assessment tools without assistance or alteration
• Have a responsible individual/caregiver who is able to monitor the participant at home for 24 hours after each treatment visit
• Must have a psychiatrist and/or general practitioner who is able to provide psychiatric follow-up care
• Mini International Neuropsychiatric Interview (MINI)-confirmed diagnosis of depressive disorder, recurrent or single episode, without psychotic features where the duration of the current episode is at least 3 months
• Depression of at least moderate severity as defined by a Hamilton Depression Rating Scale (HAMD-17) score >17

Exclusion Criteria

• Uncontrolled or insulin-dependent diabetes
• Women who are pregnant (self-report or via urine test), nursing, or planning a pregnancy during the timespan of the study
• History of seizure disorder except for seizures from electroconvulsive therapy and/or febrile seizures in childhood
• History of stroke, recent myocardial infarction (< 1 year from signing of ICF), uncontrolled hypertension (blood pressure > 140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF
• Abnormal and clinically significant results on a physical examination performed within one month of study participation by a general practitioner, vital signs, ECG, or laboratory test at screening
• QTc prolongation on ECG defined by > 450 ms in males and > 460 ms in females in V5 on a 12-lead ECG
• Positive urine drug screen for illicit drugs or drugs of abuse at screening, a week prior to treatment, and during the trial (any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion)
• Serial blood counts to achieve a value to meet eligibility -- abnormalities in screening/baseline blood work (complete blood counts, electrolyte panel, etc.) will be reviewed by MD, then repeated serially until abnormalities resolve
• Any symptoms consistent with psychosis
• Any symptoms consistent with hypomania and/or mania as assessed by a psychiatrist
• Other personal circumstances or behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin
• Current or past history of bipolar I/II disorder, schizophrenia, schizoaffective disorder, psychotic disorder, or delusional disorder as assessed by a structured clinical interview (MINI)
• ≥ 1 suicide attempt in the past year requiring hospitalization, defined using the Columbia Suicide Severity Rating Scale (CSSRS) (Q6 (past year) = "y") and clinical interview with a psychiatrist
• History of substance use and/or alcohol use disorder, of moderate severity or greater, in the past 12 months
• Lifetime history of substance use disorder with a hallucinogen
• Lifetime history of substance-induced psychosis
• Depression secondary to other medical conditions or bipolar I and II disorder
• Family history of a first degree relative with a diagnosis of schizophrenia or a primary psychotic disorder and/or bipolar disorder
• Exposure to psilocybin or any other psychedelic in the past 12 months prior to screening and/or during the current MDE and use of psychedelics, such as ayahuasca/LSD, during the current depressive episode
• A clinical diagnosis of antisocial personality disorder and/or paranoid personality disorder (defined as meeting DSM-5.0 criteria) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at a clinical interview by a psychiatrist
• An active clinical diagnosis of borderline personality disorder as confirmed by the MINI 7.0
• Diagnosis of any mild or major neurocognitive disorder meeting DSM-5 criteria and based on clinical interview/cognitive screening by a psychiatrist
• Current enrolment in an interventional study for depression or participation in such within 30 days of screening
• Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Sean Michael Nestor

Psychiatrist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sean M Nestor, PhD MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Bradley J MacIntosh, PhD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Research Institute

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

EMBRACE Team

Role: CONTACT

embrace@sunnybrook.ca

416-480-4085

Facility Contacts

EMBRACE Team

Role: primary

embrace@sunnybrook.ca

416-480-4085

References

Poulin JM, Bigford GE, Lanctot KL, Giacobbe P, Schaffer A, Sinyor M, Rabin JS, Masellis M, Singnurkar A, Pople CB, Lipsman N, Husain MI, Rosenblat JD, Cao X, MacIntosh BJ, Nestor SM. Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression. Trials. 2024 Jul 3;25(1):441. doi: 10.1186/s13063-024-08268-6.

Reference Type: DERIVED

PMID: 38956594 (View on PubMed)

Other Identifiers

5423

Identifier Type: -

Identifier Source: org_study_id