Recruiting
Phase 3

Psilocybin

Sponsor:

VA Office of Research and Development

Code:

NCT07226232

Conditions

Major Depression

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Psilocybin

Psilocybin

Study Details

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

Study ID

NCT07226232

Start date

Aug 3, 2026

Status verified date

Aug, 2026

Completion date

Jun 30, 2031

Anticipated

Primary completion date

Dec 2, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 XX 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
  • Treatment with evidence-based psychotherapy (EBP) for MDD or PTSD within 2 weeks prior to baseline. If receiving EBP therapy, he/she must complete treatment at least 2 weeks prior to baseline. Other forms of non-EBP psychotherapy for MDD or PTSD are allowed to continue during the study period.
  • Pregnancy or lactation, or anticipated pregnancy or breastfeeding during the active treatment phase
  • History of myocardial infarction, congestive heart failure, diabetic ketoacidosis, brain cancer, stroke and/or severe cardiac disease
  • Clinically significant cardiac, pulmonary, renal, liver and/or other medical disease that, in the opinion of the investigator, may contraindicate the use of psilocybin, interfere with the interpretation of study results and/or constitute a health risk for the participant if they take part in the study
  • Seizure disorder, except for seizures due to fever or withdrawal from a substance
  • Clinically significant hypertension (>160/95 mmHg), hypotension (<90/60 mmHg) tachycardia (>100 bpm at rest), QTc prolongation (>450 msec men; >470 msec women) or clinically significant arrhythmia on ECG
  • Clinically significant abnormal laboratory results on chemistry panel, liver function tests, complete blood count, and/or thyroid stimulating hormone
  • Positive urine drug screen for illicit drugs of abuse (except for THC) at screening or baseline
  • Prior allergic, adverse reaction or adverse experience to a psilocybin formulation
  • Litigating for disability income for a mental disorder outside the VA compensation and pension process

Study Design

Enrollment

240 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Control

Psilocybin comparator dose

experimental: Intervention

Psilocybin intervention dose

Interventions

Psilocybin

Psilocybin comparator dose

Psilocybin

Psilocybin Intervention Dose

Primary outcome measure

  • Montgomery-Asberg Rating Scale (MADRS) [ Time Frame: 2 weeks ]

Central Contacts and Locations

Central contacts

Lori L Davis, MD AB

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

Anchal Ghera, MS

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

Locations

Birmingham VA Medical Center, Birmingham, AL

Recruiting

Birmingham, Alabama, United States, 35233-1927

Contacts

Lori L Davis, MD AB

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

Anchal Ghera, MS

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

Principal Investigator:

Lori Lynne Davis, MD AB

Tuscaloosa VA Medical Center, Tuscaloosa, AL

Recruiting

Tuscaloosa, Alabama, United States, 35404-5015

Contacts

Patricia Pilkinton, MD

205-554-2000patricia.pilkinton@va.gov

Kaleb Murry, MS

2055542000kaleb.murry@va.gov

VA Portland Health Care System, Portland, OR

Recruiting

Portland, Oregon, United States, 97207-2964

Contacts

Christopher Stauffer, MD

503-781-1205christopher.stauffer@va.gov

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

Recruiting

Philadelphia, Pennsylvania, United States, 19104-4551

Contacts

Michael Thase, MD

215-823-5800michael.thase@va.gov

Mora Grehl, MS

2158235800

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

Recruiting

Seattle, Washington, United States, 98108-1532

Contacts

Rebecca Hendrickson, MD

206-277-1337rebecca.hendrickson@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Aug 14, 2026

Last verified

Aug, 2026

Keywords

  • depression
  • psilocybin
  • veterans
  • post-traumatic stress disorder

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-08-14.