In brief
- The VA (U.S. Department of Veterans Affairs) has opened recruitment for the PIVOT trial, which will treat 240 veterans with treatment-resistant depression across five hospitals nationwide.
- There is no placebo group: all participants receive psilocybin, with only the initial dose varying between groups.
- The drug used is COMP360, Compass Pathways’ synthetic psilocybin formulation, which is already in advanced phase 3 trials for treatment-resistant depression in the general population.
On August 3, the U.S. Department of Veterans Affairs (VA) began enrolling the first participants in PIVOT, a phase 3 clinical trial evaluating psilocybin for veterans with treatment-resistant major depression, with or without associated post-traumatic stress disorder. The study, sponsored by the VA’s own Office of Research and Development, joins a wave of institutional trials that have placed psilocybin on the radar of the American public health system in recent months.
A placebo-free design
PIVOT will recruit 240 veterans between the ages of 18 and 75 at five VA medical centers: Birmingham and Tuscaloosa (Alabama), Portland (Oregon), Philadelphia (Corporal Michael J. Crescenz VA Medical Center), and Seattle (VA Puget Sound). To qualify for the study, participants must have a major depressive episode with a score of at least 20 on the MADRS (Montgomery-Åsberg) scale and must have unsuccessfully tried two or more conventional antidepressants.
The unique aspect of the design is the absence of an inert placebo arm. Both groups receive COMP360, the pharmaceutical-grade synthetic psilocybin developed by Compass Pathways, in two dosing sessions spaced one month apart, always accompanied by psychological support. What varies between groups is the dose administered in the first session; in the second session, all participants receive the same amount. The primary endpoint is measured two weeks after the second session, comparing MADRS scores between the two groups, with symptom monitoring continuing for up to six months.
Institutional context
The launch of the trial comes months after President Trump signed an executive order in April 2026 regarding the “acceleration of medical treatments for serious mental illnesses,” which, among other things, seeks to streamline participation in clinical trials involving psychedelic substances. VA Secretary Doug Collins stated in the agency’s press release that “too many veterans live with mental health conditions that do not respond to available treatments,” as justification for opening this avenue of research within the public health system. According to the trial registry (NCT07226232), the primary completion is expected in December 2030, with the full study closing in June 2031—a timeline that reflects the scale and rigor of the project.
What this implies
PIVOT is currently in the recruitment phase, not a study with results; we will not know if psilocybin outperforms the low-dose control for several years. The design without an inert placebo addresses a real problem in psychedelic research—the difficulty of blinding patients to what they have received—though it does not entirely eliminate this limitation, as both groups experience subjective effects, albeit at different intensities. That said, the fact that the U.S. public health system is directly funding this research for veterans—a demographic with particularly high rates of treatment-resistant depression and suicide—is an indicator of how far clinical research with this substance has become normalized within institutions traditionally conservative on the subject.
Source
- U.S. Department of Veterans Affairs. VA launches psilocybin trial for Veterans with treatment-resistant depression. VA News, August 5, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
