A Randomized Neuroimaging Trial of Psilocybin in Depression

NCT06072898 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 5423
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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. 1.Changes connectivity within brain networks associated with mood and depression
2. 2.Changes blood flow in brain regions associated with mood and depression

Conditions

Depressive Disorder; Major Depressive Disorder

Keywords

Psilocybin; Neuroimaging; MRI; Depression; Psychotherapy; Psychedelic

Outcome Measures

Primary Outcomes (2)

• Regional Cerebral Blood Flow

  Changes in cerebral blood flow within three a priori-defined brain regions relevant to mood regulation and depression as assessed by arterial spin labeling acutely at expected peak drug concentration during treatment visits.

  Up to 3 weeks

• Montgomery-Asberg Depression Rating Scale (MADRS) Changes

  Changes in the MADRS relative to baseline at study follow-up visits. Higher scores with respect to the MADRS minimum (0) and maximum (60) values represent a worse treatment outcome .

  Up to 6 weeks

Secondary Outcomes (23)

• Functional Network Connectivity

  Up to 3 weeks

• 17-item Hamilton Depression Rating Scale (GRID-HAMD-17)

  24 hours

• Incidence of response

  up to 6 weeks

• Incidence of remission

  up to 6 weeks

• Patient Health Questionnaire 9-item (PHQ-9)

  up to 6 weeks

Other Outcomes (1)

• Blood biomarkers

  up to 5 weeks

Study Arms (2)

Staged Active Treatment Arm (Psilocybin-Psilocybin)

EXPERIMENTAL

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

Drug: Psilocybin; Behavioral: Supportive psychotherapy

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

EXPERIMENTAL

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

Drug: Psilocybin; Other: Microcrystalline cellulose; Behavioral: Supportive psychotherapy

Interventions

Psilocybin DRUG

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

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

Microcrystalline cellulose OTHER

MCC (excipient), 25mg PO.

Also known as: MCC

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

Supportive psychotherapy 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); Staged Active Treatment Arm (Psilocybin-Psilocybin)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Able and voluntarily willing to provide written informed consent at the screening visit
• Over 18 and under 65 years old
• Able to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits
• Must have a responsible individual/caregiver who is able to monitor the participant at home for 24 hours after each treatment visit in the study
• Must have a psychiatrist and/or general practitioner who is able to provide psychiatric follow-up care
• Have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, 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

You may not qualify if:

• 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)
• A clinical diagnosis of antisocial personality disorder and/or paranoid personality disorder (defined as meeting DSM-5 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.
• 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
• Any symptoms consistent with psychosis
• Any symptoms consistent with hypomania and/or mania as assessed by a psychiatrist
• Personal history of ≥ 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
• Other personal circumstances or behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin
• Women who are pregnant (self-report or via urine test), nursing, or planning a pregnancy
• Lifetime history of substance use disorder with a hallucinogen
• Lifetime history of substance-induced psychosis
• 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)
• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

RECRUITING

Related Publications (1)

• 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.

  PMID: 38956594 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Major; Depression

Interventions

Psilocybin; microcrystalline cellulose

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Sean M Nestor, PhD MD FRCPC

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Bradley J MacIntosh, PhD

  Sunnybrook Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

EMBRACE Team

CONTACT

416-480-4085; embrace@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Model Details: This study will use a 2-group one-way delayed-start (AB/BB) design, with one group receiving placebo at the first visit and the investigational drug at second, and another group receiving the investigational drug at both visits. An interim analysis will be performed after 20 participants have completed the study to assess preliminary efficacy and safety trends.

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 10, 2023
• Study Start: May 28, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The trial protocol will be published, or accepted for publication, in a peer-reviewed journal prior to study initiation and related documents (protocol, ICF, etc) will then be made available. Results will be published in a manuscript as soon as possible after study completion, thereafter this record will be updated to include results. After study completion, IPD will be made available to other researchers who provide a sound proposal and whose uses of the data will adhere to institutional data sharing policies.

Locations

CA (1)