NCT07226232 Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression
| NCT ID | NCT07226232 |
| Status | Recruiting |
| Phase | Phase 3 |
| Sponsor | VA Office of Research and Development |
| Condition | Major Depression |
| Study Type | INTERVENTIONAL |
| Enrollment | 240 participants |
| Start Date | 2026-08-03 |
| Primary Completion | 2030-12-02 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 3 trials are large pivotal studies comparing the treatment to current standard of care or placebo. Your participation directly contributes to the evidence needed for regulatory approval.
This trial targets 240 participants in total. It began in 2026-08-03 with a primary completion date of 2030-12-02.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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.
Eligibility Criteria
Inclusion Criteria: * 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 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
Contact & Investigator
Lori Lynne Davis, MD AB
PRINCIPAL INVESTIGATOR
Birmingham VA Medical Center, Birmingham, AL
Frequently Asked Questions
Who can join the NCT07226232 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 75 Years, studying Major Depression. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT07226232 trial and what does that mean for participants?
Phase 3 trials are large-scale studies comparing the new treatment to existing standards of care or a placebo. They provide the evidence needed for regulatory approval. This trial targets 240 participants.
Is NCT07226232 currently recruiting?
Yes, NCT07226232 is actively recruiting participants. Contact the research team at lori.davis@va.gov for enrollment information.
Where is the NCT07226232 trial being conducted?
This trial is being conducted at Birmingham, United States, Tuscaloosa, United States, Portland, United States, Philadelphia, United States and 1 additional location.
Who is sponsoring the NCT07226232 clinical trial?
NCT07226232 is sponsored by VA Office of Research and Development. The principal investigator is Lori Lynne Davis, MD AB at Birmingham VA Medical Center, Birmingham, AL. The trial plans to enroll 240 participants.
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