Veterans with treatment-resistant depression will receive experimental doses of psilocybin at five VA hospitals, including Philadelphia, as researchers test a promising but still unapproved psychedelic treatment
The Trump administration is moving ahead with an experiment that will give psychedelic drugs to veterans suffering from severe depression, putting some of the nation’s former service members at the center of an accelerating federal effort to determine whether psilocybin can become a legitimate psychiatric medicine.
The Department of Veterans Affairs announced Aug. 5 that it is launching a randomized clinical trial of psilocybin — the psychoactive substance associated with so-called magic mushrooms — in veterans diagnosed with treatment-resistant major depressive disorder, including some who also have post-traumatic stress disorder.
One of the five research sites is the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, putting veterans from the region within reach of an experiment that sits near the frontier of psychiatric medicine. Other sites are in Birmingham and Tuscaloosa, Alabama; Portland, Oregon; and Seattle.
The word “experiment” is not rhetorical shorthand. Psilocybin remains an investigational treatment for depression rather than an FDA-approved therapy, and the purpose of the trial is precisely to determine whether it is sufficiently effective and safe.
The experiment also comes with an important distinction: Veterans who volunteer are not simply being handed psychedelic drugs.
VA says participants will receive pharmaceutical-grade psilocybin under controlled conditions, with psychological support and safety procedures developed with the Food and Drug Administration. Researchers will compare two dosage levels while measuring depression, side effects, and patients’ assessments of their symptoms.
The scientific question confronting the government is consequential because the evidence surrounding psilocybin is simultaneously encouraging and incomplete.
Some clinical trials have produced striking improvements in depression.
Others have uncovered warning signs — including panic, paranoia, elevated blood pressure, suicidal thoughts and, in rare cases, persistent perceptual disturbances.
In other words, psilocybin might become an important psychiatric medicine.
Researchers are still determining the price patients may pay for its benefits.
Trump orders VA to accelerate psychedelic research
The VA initiative follows President Donald Trump’s April 18 executive order, “Accelerating Medical Treatments for Serious Mental Illness,” which directed federal agencies to encourage clinical-trial participation and examine ways of accelerating development of new treatments for serious psychiatric disorders. The administration specifically included psychedelic drugs among the therapies it wants federal researchers to investigate.
The result is an extraordinary turn for substances that spent decades on the margins of American medicine.
The VA says it is now involved in 20 active clinical trials involving psychedelic therapies for mental health conditions.
“Far too many Veterans are living with mental health conditions that don’t respond to available treatments,” VA Secretary Doug Collins said in announcing the new trial.
Collins said the administration intends to pursue new approaches that could provide relief to veterans for whom conventional therapies have failed.
The government’s willingness to experiment with psychedelics reflects both the desperation surrounding treatment-resistant mental illness and a remarkable rehabilitation of drugs long associated primarily with counterculture and recreational use.
Psilocybin acts principally through the brain’s serotonin system and can produce profound alterations in perception, thought, mood and sense of self.
Those effects are part of the reason researchers believe the drug may have therapeutic value.
They are also part of the reason it cannot be treated like an ordinary antidepressant.
Promising evidence — with a large asterisk
Clinical research provides legitimate reasons for optimism.
A randomized clinical trial published in JAMA involving 104 adults with major depressive disorder found that a 25-milligram dose of psilocybin administered with psychological support produced a rapid and sustained reduction in depressive symptoms compared with an active placebo. No serious treatment-emergent adverse events were recorded after treatment.
That sounds reassuring.
The details are more complicated.
From the day of treatment through nine days afterward, 82% of patients receiving psilocybin experienced at least one drug-related treatment-emergent adverse event, compared with 44% receiving the control treatment.
Four of the 50 psilocybin patients — 8% — experienced severe drug-related adverse events. Researchers reported severe migraine, headache and illusion, while another patient experienced a panic attack and paranoia.
That does not mean psilocybin is unacceptably dangerous.
It means the drug is powerful enough that its risks cannot responsibly be separated from the controlled clinical environment in which researchers administer it.
A broader 2024 JAMA Network Open analysis examined six randomized, double-blind clinical trials involving 528 patients.
Researchers found that therapeutic psilocybin was significantly more likely than comparison treatments to produce headache, nausea, anxiety, dizziness and elevated blood pressure.
Nausea was especially notable, occurring at substantially higher rates among patients receiving psilocybin.
The reassuring part was that the acute adverse effects generally resolved within 48 hours, and the analysis found no statistically significant increased risk of paranoia or transient thought disorder overall.
The less reassuring conclusion was equally important: Researchers said rare and long-term adverse effects still require further study.
That uncertainty is one reason clinical trials exist.
Newer research raises additional safety questions
More recent evidence has complicated the picture further.
A randomized trial published in JAMA Psychiatry in 2026 studied a 25-milligram dose of psilocybin with psychotherapy in patients suffering from treatment-resistant depression — a population particularly relevant to the new VA study.
Researchers found evidence of clinically meaningful improvement on some measures but said the trial did not demonstrate a statistically significant benefit on its primary outcome.
More troubling were several safety signals.
Researchers reported higher levels of suicidal ideation on psilocybin dosing days — 4% compared with 1% to 2% in the comparison groups.
Two serious adverse reactions were reported after the 25-milligram dose, including one case of hallucinogen persisting perception disorder, a condition in which perceptual disturbances can continue after the immediate effects of a hallucinogenic drug have disappeared.
The researchers nevertheless reported that most participants tolerated the treatment and concluded that psilocybin might have clinically meaningful antidepressant effects.
Their ultimate conclusion was appropriately less spectacular than some of the psychedelic renaissance’s publicity:
The trial was inconclusive.
That is an especially important word when the prospective patients are veterans already suffering from serious psychiatric illnesses.
Why the clinical setting matters
The VA’s safeguards make the new study fundamentally different from veterans obtaining mushrooms or other psychedelics and attempting to treat themselves.
Participants will receive standardized pharmaceutical-grade material rather than mushrooms of uncertain potency. Dosage will be controlled. Patients will be screened and observed. Psychological support will accompany treatment, and medical personnel will be available if blood pressure rises or a participant experiences severe anxiety, panic or other complications.
The FDA itself has recognized that psychedelic research presents unusual challenges.
In July, the agency issued final guidance specifically addressing clinical investigations of psychedelic drugs, acknowledging growing interest in their therapeutic potential while establishing recommendations for researchers studying them.
Those precautions matter because psilocybin does not simply function as a conventional pill that quietly changes neurotransmitter concentrations while a patient goes about the day.
It can acutely alter perception and consciousness.
A patient’s psychological condition, physical surroundings, dosage, supervision and expectations can therefore matter enormously.
The experience that advocates describe as transformative can become frightening for another patient.
That is why findings from carefully screened participants receiving precisely measured pharmaceutical psilocybin in supervised research settings should not automatically be extrapolated to unsupervised recreational use.
‘Breakthrough’ does not mean ‘approved’
The psychedelic revival has also produced confusion about another regulatory term.
The FDA has granted “breakthrough therapy” designation to psychedelic drug-development programs.
That does not mean the FDA has concluded that psilocybin is proven safe and effective for routine treatment of depression.
Breakthrough therapy designation is intended to expedite the development and review of promising treatments for serious conditions. The treatment still must produce evidence sufficient for regulatory approval.
The VA says it will not consider routine clinical use of psychedelic therapies outside research unless and until the FDA approves them.
For now, veterans participating in PIVOT will therefore be research subjects receiving an experimental therapy under informed-consent and clinical-trial protocols.
That distinction should not be buried beneath the administration’s enthusiasm for innovation.
Nor should the term “experimental” automatically be interpreted as reckless.
Virtually every medicine available today was experimental before researchers established whether it worked and what risks accompanied it.
The ethical question is whether the experiment is scientifically justified, participation is genuinely voluntary, risks are clearly communicated and safeguards are adequate — particularly when the participants are people suffering from serious psychiatric illness.
A population with little room for political hype
The potential reward is considerable.
Treatment-resistant depression is precisely what its name suggests: Patients continue suffering despite treatments that help others.
For veterans who have cycled through medications and psychotherapy without adequate relief, an effective new treatment could be life-changing.
That makes them ideal candidates for carefully designed research.
It also makes them a population deserving unusual protection from political exaggeration.
Neither Trump’s enthusiasm nor decades of stigma surrounding psychedelic drugs can answer the scientific question.
Only evidence can.
Psilocybin is not snake oil simply because it is psychedelic.
It is not a miracle cure simply because early studies have generated excitement.
Existing clinical evidence suggests that carefully administered psilocybin can produce significant antidepressant effects in some patients. It also establishes that the drug can cause unpleasant and occasionally severe reactions, while important questions about uncommon complications, long-term safety, durability of benefits and which patients face the greatest risks remain unanswered.
That is precisely what the VA experiment is supposed to determine.
The agency itself is warning veterans not to get ahead of the science.
It “strongly discourages” veterans from self-medicating with psychedelics or substituting them for established mental health treatments and advises patients to consult their health care providers before changing treatment.
The PIVOT trial is registered as NCT07226232 and will examine veterans with treatment-resistant major depressive disorder, including participants who also have PTSD.
The Trump administration is betting that a drug once synonymous with America’s psychedelic counterculture may eventually help heal some of the psychological wounds carried home from military service.
Perhaps it will.
But the veterans entering these clinics will be doing something more consequential than participating in a psychedelic renaissance.
They will be helping the government discover whether the treatment is actually safe enough to become medicine.
And until those experiments provide the answer, that question remains open.
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