The VA has launched PIVOT, a randomized, double-blind trial testing pharmaceutical-grade psilocybin for treatment-resistant major depressive disorder in at least 240 veterans across five VA centers through June 2031. Participants will receive two doses—one at baseline and a second one month later—each with psychotherapy, and be assessed two to four weeks after dosing and at six months. Earlier small studies, including a 12-person Ohio State trial, reported promising safety signals and PTSD symptom improvements, but the VA and federal agencies warn against self-medication and emphasize research in controlled clinical settings.
VA Launches PIVOT Trial to Test Pharmaceutical-Grade Psilocybin for Treatment-Resistant Depression and PTSD
A worker harvests and weighs psychedelic mushrooms at the Filament Health Corp. lab in Canada in 2024. (James MacDonald/Bloomberg via Getty Images)
The Department of Veterans Affairs (VA) has launched a large, multi-site clinical trial to evaluate whether pharmaceutical-grade psilocybin—the active compound in so-called "magic mushrooms"—can be used safely and effectively to treat veterans with treatment-resistant major depressive disorder (MDD), many of whom also have post-traumatic stress disorder (PTSD).
Study Overview: The Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression (PIVOT) study aims to enroll at least 240 veterans and will run at five VA medical centers through June 2031. The randomized, double-blind trial will compare a single dose of psilocybin with a placebo, each given alongside therapeutic support; a second dose will be administered one month later, also with psychotherapy. Participants will be assessed two to four weeks after each dosing session and again at a six-month follow-up.
Study Sites and Safety Measures
The PIVOT study will be conducted at five VA facilities: Birmingham VA Health Care System and Tuscaloosa VA Medical Center (Alabama); VA Portland Health Care System (Oregon); Cpl. Michael Crescenz VA Medical Center (Philadelphia); and VA Puget Sound Health Care System (Seattle). VA officials emphasize that the trial will use pharmaceutical-grade drugs and take place in safe, controlled clinical settings with trained clinical staff.
"Far too many veterans are living with mental health conditions that don't respond to available treatments," VA Secretary Doug Collins said. "This clinical trial reflects another step toward evaluating new options and offering meaningful relief for those who have worn the uniform."
Prior Research and Context
Last month, researchers at Ohio State University's Center for Psychedelic Drug Research and Education published results from a small, 12-person pilot study examining psilocybin-assisted therapy in veterans with severe PTSD. After two doses of synthetic psilocybin combined with psychotherapy and integrative care, 9 of 12 participants (75%) no longer met clinical criteria for PTSD. That study reported no serious adverse events such as suicidal behavior; non-serious side effects included headache, anxiety and dizziness.
The VA also noted that its staff are involved in about 20 clinical trials of psychedelic therapies, including work on MDMA and LSD. Prior MAPS-sponsored MDMA-assisted therapy studies reported large improvements in PTSD symptoms among veteran participants (87% showed significant symptom improvement at four months; 71% no longer met diagnostic criteria at study end). However, development of MDMA-based treatment has faced regulatory hurdles: in 2024 the Food and Drug Administration requested additional research after declining an approval application.
Federal Coordination And Warnings
The decision to expand VA psychedelic research follows an executive order directing the Food and Drug Administration (FDA) to accelerate reviews of certain psychedelic therapies and calling for collaboration among the FDA, the Department of Health and Human Services (HHS), and the VA. HHS and the VA have since signed agreements to coordinate clinical trial participation, train clinicians to deliver any approved psychedelic medications, and collect clinical data to inform regulators, clinicians and patients.
Important Safety Message: VA officials strongly discourage veterans from self-medicating with psychedelics or replacing evidence-based treatments with unprescribed substances. The PIVOT trial is testing controlled, clinical use of pharmaceutical-grade psilocybin only under professional supervision.
Researchers will monitor depression symptom levels, overall clinical response, and side effects throughout the trial to build rigorous evidence on psilocybin's potential role in treating difficult-to-treat depression and co-occurring PTSD among veterans.
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