Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression

NCT07226232 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: MHBC-002-25S
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this multi-site randomized controlled trial is to evaluate the efficacy and risks of psilocybin for the treatment of depression in U.S. military Veterans with and without (±) concurrent posttraumatic stress disorder.

Conditions

Major Depression

Keywords

depression; psilocybin; veterans; post-traumatic stress disorder

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Rating Scale (MADRS)

  10-item clinician-administered rating scale for depression. Scored 0 to 60; higher score indicates more severe symptomatology.

  2 weeks

Secondary Outcomes (1)

• Swiss Psychedelic Side Effects Inventory Overall Score

  one day

Other Outcomes (4)

• Clinician-Administered PTSD Scale for DSM-5 - Revised

  one month

• Hamilton Depression Rating Scale

  two weeks

• Patient Health Questionnaire 9

  two weeks

Study Arms (2)

Control

ACTIVE COMPARATOR

Psilocybin comparator dose

Drug: Psilocybin

Intervention

EXPERIMENTAL

Psilocybin intervention dose

Drug: Psilocybin

Interventions

Psilocybin DRUG

Psilocybin comparator dose

Also known as: COMP360

Control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veteran of the U.S. military who is English-speaking
• Signed informed consent and HIPAA
• Adults \</= 75 years of age
• Meets DSM-5 criteria for current major depressive episode (MDE)
• MADRS \>/= 20 at baseline
• Failure to respond satisfactorily to \>/= 2 antidepressant treatments for \>/= 8 weeks, including \>/= 2 weeks at an adequate dose (\>/= 50% of the FDA-approved uppermost dose) for major depression. Augmentation with a medication for depression (e.g., neuroleptics, lithium, levothyroxine) is considered a separate course of treatment.
• If applicable, concurrent \& permitted antidepressants must be at stable doses for \>/= 4 weeks prior to baseline (see allowed \& prohibited medication list)
• Participants of child-bearing potential must have negative pregnancy test \& agree to adhere to a medically acceptable method of birth control during the study
• Has a responsible adult who will provide transportation to the participant's home or place of lodging on the days of psilocybin administration

You may not qualify if:

• Lifetime bipolar, schizophrenia spectrum, or other psychotic disorders
• First-degree relative with history of bipolar I, schizophrenia spectrum or other psychotic disorder
• Presence of psychotic symptoms (e.g., MDE with psychotic symptoms)
• Sedative-hypnotic, stimulant, inhalant and/or opioid use disorder within past 6 months (lifetime substance use disorder is allowed at the discretion of the LSI)
• Severe alcohol and/or cannabis use disorder within the past 6 months (mild or moderate alcohol and/or cannabis use is allowed at the discretion of the LSI)
• Lifetime hallucinogen persisting perception or hallucinogen use disorders
• Use of psilocybin, ayahuasca, mescaline, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), peyote, or 3,4-methylenedioxymethamphetamine (MDMA) within past 6 months
• Participant agrees to not use psychedelics (listed above) during the study, except as prescribed by the study protocol
• Taking prohibited medication within 2 weeks of baseline (see allowed and prohibited concomitant medication list)
• History of severe traumatic brain injury (TBI)
• Diagnosis of dementia or related progressive neurocognitive disorder
• Suicidal ideation/behavior Type 4 or Type 5 intensity on C-SSRS within past 6 months of baseline
• Psychiatric inpatient treatment within past 3 months of baseline
• Treatment with electroconvulsive therapy, deep brain stimulation, vagus nerve stimulation, or transcranial magnetic stimulation within 3 months of baseline
• Implanted central nervous system device

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (5)

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, 35233-1927, United States

Location

Tuscaloosa VA Medical Center, Tuscaloosa, AL

Tuscaloosa, Alabama, 35404-5015, United States

Location

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

Location

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19104-4551, United States

Location

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Stress Disorders, Post-Traumatic

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Lori Lynne Davis, MD AB

  Birmingham VA Medical Center, Birmingham, AL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lori L Davis, MD AB

CONTACT

(205) 554-3819; lori.davis@va.gov

Anchal Ghera, MS

CONTACT

(205) 899-1273; anchal.ghera@va.gov

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only pharmacist will know the treatment assignment. All others are masked to treatment assignment. For the 1st of 2 dosing sessions, Veterans are randomized to receive one of two doses of psilocybin. One month later, participants return for a 2nd psilocybin dosing session in which all participants get the same dose of psilocybin.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Enrolled participants who meet eligibility criteria and attend 3 preparatory visits with a psychological support facilitator will be randomized to either the control group or the intervention group in parallel until the primary endpoint at week 4 post randomization.

Study Record Dates

• First Submitted: November 5, 2025
• First Posted: November 10, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 2, 2030
• Study Completion (Estimated): April 30, 2031
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: At the conclusion of the study after a data repository has been made operational.
• Access Criteria: De-identified data of those participants who signed informed consent, to include baseline demographics and clinical characteristics, primary outcome measure over time, treatment assignment, secondary safety outcomes, and exploratory outcomes. Data will be available for 6 years after the closure of the main study.

Locations

US (5)