Psilocybin for Treatment-Resistant Depression in Veterans
This study is testing psilocybin to see if it can help U.S. military Veterans with depression that hasn't responded well to other treatments (treatment-resistant depression). It also looks at Veterans who might also have post-traumatic stress disorder (PTSD). You could be eligible if you are a U.S. military Veteran, speak English, are between 18 and 75 years old, and have been diagnosed with major depression that hasn't improved after trying at least two antidepressant treatments. The main goal is to see how much your depression symptoms improve after two weeks, measured by a scale called the Montgomery-Asberg Rating Scale (MADRS). The study is currently unclear on its recruitment status and plans to enroll 240 participants.
- Study design
- This is a multi-site, double-blind, randomized controlled trial. This means neither you nor your study team will know which dose of psilocybin you receive first.
- What's involved
- You will have two psilocybin dosing sessions, along with psychological support before, during, and after each session. Outcomes will be measured at 2 and 4 weeks after each dosing session.
- Compensation
- Not stated in the trial record.
- Follow-up
- Longer-term follow-up will be conducted over 6 months after treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07226232
Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression
Recruiting
PHASE3Ages 18–75InterventionalTreatmentVA Office of Research and DevelopmentGovernment-funded
~240 participants
Updated 2026-08-14 on ClinicalTrials.gov
What's tested:Psilocybin
At a glance
Recruiting sites
5 of 5 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Montgomery-Asberg Rating Scale (MADRS)
Measured over 2 weeks
Conditions
Where it's being run
5 sites across 4 statesAlabama2
Oregon1
Pennsylvania1
Washington1
Study leadership
- Lori Lynne Davis, MD AB · PRINCIPAL_INVESTIGATOR · Birmingham VA Medical Center, Birmingham, AL
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
What this trial measures
- Montgomery-Asberg Rating Scale (MADRS)2 weeks
10-item clinician-administered rating scale for depression. Scored 0 to 60; higher score indicates more severe symptomatology.