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

NCT ID: NCT06247839

Last Updated: 2025-05-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-10
• Study Completion Date: 2026-06-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Psilocybin

25mg Psilocybin

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

COMP360 (Brand name of psilocybin to be used)

Interventions

Psilocybin

COMP360 (Brand name of psilocybin to be used)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Be 18-55 years of age at screening.

3. 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

4. Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS)44 score ≥ 18 at Screening and at Baseline.

5. 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.

6. McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) < 7 at Screening.

7. 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.

8. A score > 40 on the Wechsler Test of Adult Reading.46

9. Be right-handed as determined by the Edinburgh Handedness Inventory.48

10. Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.

11. Have ongoing established mental health care.

Exclusion Criteria

Patients meeting any of the following criteria are to be excluded from the study:

1. 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).

2. Positive Magnetic Resonance screen (e.g., metal implant, claustrophobia, etc).

3. Prior electroconvulsive therapy and/or ketamine for current episode.

4. 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.

5. Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening.

6. 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.

7. Significant homicide risk as defined by clinical interview.

8. Depression secondary to other severe medical conditions.

9. Currently taking benzodiazepines daily.

10. 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.

11. 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.

12. 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.

13. Uncontrolled insulin dependent diabetes.

14. Seizure disorder.

15. Positive urine drug screen for illicit drugs or drugs of abuse (to include but not limited to opiates, phenylcyclohexyl piperidine(PCP), cocaine, amphetamines, methamphetamines, benzodiazepines, barbiturates, and cannabis) at Screening and Day Before Psilocybin. 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.

16. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years.

17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.

18. Current enrollment in any investigational drug or device study or participation in such within 6 months of Screening.

19. Current enrollment in an interventional study for depression or participation in such within 6 months of Screening Visit.

20. Non-native speakers of English.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

COMPASS Pathways

INDUSTRY

Sponsor Role: collaborator

Sharmin Ghaznavi

OTHER

Sponsor Role: lead

Responsible Party

Sharmin Ghaznavi

Psychiatrist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sharmin Ghaznavi, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Athinoula A. Martinos Center for Biomedical Imaging

Charlestown, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sarah G Richter, M.A.

Role: CONTACT

cnpcogneuro@mgh.harvard.edu

6177262290

Facility Contacts

Sarah Richter

Role: primary

cnpcogneuro@mgh.harvard.edu

Other Identifiers

2024P000137

Identifier Type: -

Identifier Source: org_study_id