Tests psilocybin for hard-to-treat depression in veterans

Trial details

Who runs it

VA Office of Research and Development

Trial code

NCT07226232

Record updated

23 October 2026

Original description

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.Read full original descriptionShow less

A Multi-site Randomized Controlled Trial of Psilocybin for Treatment-Resistant Depression (TRD) in Veterans

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.

Inclusion: Veteran of the U.S. military who is English-speaking; Signed informed consent and Health Insurance Portability and Accountability Act (HIPAA); Adults </= 75 years of age; Meets DSM-5 criteria for current major depressive episode (MDE); Montgomery-Asberg Rating Scale (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: Taking prohibited medication within 2 weeks of baseline (see allowed and prohibited concomitant medication list); Treatment with electroconvulsive therapy, deep brain stimulation, vagus nerve stimulation, or transcranial magnetic stimulation within 3 months of baseline; 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; 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; Lifetime bipolar, schizophrenia spectrum, or other psychotic disorders; First-degree relative with history of bipolar I, schizophrenia spectrum or other psychotic disorder; 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; History of severe traumatic brain injury (TBI); Diagnosis of dementia or related progressive neurocognitive disorder; Psychiatric inpatient treatment within past 3 months of baseline; 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; Litigating for disability income for a mental disorder outside the VA compensation and pension process; 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; Presence of psychotic symptoms (e.g., MDE with psychotic symptoms); 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; Suicidal ideation/behavior Type 4 or Type 5 intensity on C-SSRS within past 6 months of baseline; Implanted central nervous system device; Pregnancy or lactation, or anticipated pregnancy or breastfeeding during the active treatment phase.

ClinicalTrials.gov NCT07226232