Clinical TrialMajor Depressive Disorder (MDD)PsilocybinRecruiting

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

This open-label interventional trial (n=20) will assess the effects of a single dose of psilocybin (25 mg COMP360) on rumination and its neural correlates in individuals with major depressive disorder (MDD).

Target Enrollment
20 participants
Study Type
Phase III interventional
Design
Non-randomized

Detailed Description

Open-label single-group fMRI study administering a single 25 mg dose of COMP360 psilocybin to adults (18–55) with moderate MDD to assess changes in rumination and associated neural activity.

Primary outcomes include behavioural measures of rumination and neuroimaging markers; participants must taper psychotropic medications prior to baseline and have ongoing mental health care.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

Psilocybin

experimental

Single-group open-label administration of 25 mg COMP360 psilocybin.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    COMP360 formulation (25 mg)

Participants

Ages
18 – 55
Sexes
Male & Female

Inclusion 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).
  • 4. Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) 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) 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.
  • 8. A score > 40 on the Wechsler Test of Adult Reading.
  • 9. Be right-handed as determined by the Edinburgh Handedness Inventory.
  • 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

  • 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) 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 at Screening and Day Before Psilocybin.
  • 16. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder, epilepsy, intellectual disability, or any other disease/procedure/accident/intervention which might be 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.

Study Details

Locations

Athinoula A. Martinos Center for Biomedical Imaging — Charlestown, Massachusetts, United States

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