The Effects of Psilocybin on Self-Focus and Self-Related Processing in Major Depressive Disorder

NCT06247839 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2024P000137
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label functional Magnetic Resonance Imaging (fMRI) study will assess the effects of a single dose of psilocybin on rumination and the neural correlates of rumination in individuals with major depressive disorder.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (4)

• Change in Massachusetts General Hospital Rumination Questionnaire (MGH-RQ)

  A transdiagnostic state measure of rumination over the previous two weeks consisting of 9 items on a 5 point Likert scale from 0 (Never/Rarely) to 4 (All The Time).

  Baseline, and 3 weeks, 6 weeks, 9 weeks, and 12 weeks after psilocybin administration.

• Change in Resting-State Functional Connectivity

  Changes in resting-state activity during functional magnetic resonance imaging(fMRI) scans.

  Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

• Change in Self-Attribution Task performance

  Participants are shown words one at a time and asked to answer if each of the words apply to 'Self' or 'Other'.

  Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

• Change in Task-Based Activity during Self-Attribution Task

  Changes in activity in the default mode network during functional magnetic resonance imaging(fMRI) scans while participants perform a self-attribution task.

  Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

Secondary Outcomes (12)

• Change in Montgomery-Asberg Depression Rating Scale(MADRS)

  Baseline, the day before psilocybin administration and at 1 day, 1 week, 2 weeks, 3 weeks, 6 weeks, 9 weeks and 12 weeks after psilocybin administration.

• Change in Quick Inventory of Depressive Symptomatology Self Report - 16 item (QIDS-SR-16)

  Baseline, the day before psilocybin administration and at 1 day, 1 week, 2 weeks, 3 weeks, 6 weeks, 9 weeks and 12 weeks after psilocybin administration.

• Change in Positive and Negative Affect Schedule (PANAS)

  Baseline, the day of psilocybin administration and at 3 weeks and 12 weeks after psilocybin administration.

• Change in Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS)

  Baseline and 3 weeks and 12 weeks after psilocybin administration.

• Change in Ruminative Response Scale (RRS)

  Baseline and 12 weeks after psilocybin administration.

Study Arms (1)

Psilocybin

EXPERIMENTAL

25mg Psilocybin

Drug: Psilocybin

Interventions

Psilocybin DRUG

COMP360 (Brand name of psilocybin to be used)

Psilocybin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Must be able to sign the informed consent form (ICF). Participants will demonstrate capacity to provide informed consent by demonstrated understanding of the protocol and what their involvement in the study requires from them.
• Be 18-55 years of age at screening.
• At least moderate Major Depressive Disorder (MDD; single or recurrent episode as informed by Diagnostic and Statistical Manual Version 5 (DSM-V); if single episode, duration of ≥ 3 months and ≤ 3 years) based on clinical assessment and a structured clinical interview, the Mini International Neuropsychiatric Interview Version 7.02 (MINI).43
• Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS)44 score ≥ 18 at Screening and at Baseline.
• Failure to respond to an adequate dose and duration of 1, 2, 3, or 4 pharmacological treatments for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment History Response Questionnaire (MGH-ATRQ)45 and using the supplementary advice on additional antidepressants not included in MGH-ATRQ. Augmentation with an add-on treatment counts as a second treatment, provided it is approved for the adjunctive treatment of MDD.
• McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) \< 7 at Screening.
• Participants will also have to successfully undergo a taper off of all psychotropic medications under the supervision of a study psychiatrist and in coordination with their treatment team, which will be completed at least 2 weeks prior to Baseline Scan. Please see below regarding details about discontinuation of antidepressants.
• A score \> 40 on the Wechsler Test of Adult Reading.46
• Be right-handed as determined by the Edinburgh Handedness Inventory.48
• Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.
• Have ongoing established mental health care.

You may not qualify if:

• Patients meeting any of the following criteria are to be excluded from the study:
• Current, past history, or family history, of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structured clinical interview (version 7.0.2 MINI).
• Positive Magnetic Resonance screen (e.g., metal implant, claustrophobia, etc).
• Prior electroconvulsive therapy and/or ketamine for current episode.
• Current cognitive behavioral therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of Baseline.
• Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening.
• Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)49 within the past year, at Screening or at Baseline, or; (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during clinical interview.
• Significant homicide risk as defined by clinical interview.
• Depression secondary to other severe medical conditions.
• Currently taking benzodiazepines daily.
• Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as well as exposure to psilocybin or other psychedelics within one year of screening.
• Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of childbearing potential must have a negative urine pregnancy test at Screening and Day Before Psilocybin.
• Cardiovascular conditions: recent stroke (\< 1 year from signing of consent), recent myocardial infarction (\< 1 year from signing of ICF), hypertension (blood pressure \> 140/90 mmHg) or corrected QT interval \> 450 msec) or clinically significant arrhythmia within 1 year of signing the ICF, current anticoagulant therapy, aneurysmal disease.
• Uncontrolled insulin dependent diabetes.
• Seizure disorder.

Sponsors & Collaborators

• Sharmin Ghaznavi: lead
• COMPASS Pathways: collaborator

Study Sites (1)

Athinoula A. Martinos Center for Biomedical Imaging

Charlestown, Massachusetts, 02129, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sharmin Ghaznavi, M.D., Ph.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah G Richter, M.A.

CONTACT

6177262290; cnpcogneuro@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: February 8, 2024
• Study Start: September 10, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

US (1)