Summary: The first U.S. clinical trial evaluating psilocybin-assisted therapy in military veterans with treatment-resistant post-traumatic stress disorder (PTSD) has demonstrated significant safety and clinical efficacy.
The 11-week pilot trial combined 14 to 16 hours of preparation and integration psychotherapy with two synthetic psilocybin dosing sessions (15 mg and 25 mg). One month post-treatment, 75% of participants (9 of 12) achieved full PTSD remission, with an average clinician-rated symptom score reduction of 27.5 points.
The protocol produced no serious adverse events, no increase in suicidal ideation, and demonstrated that non-drug psychotherapy acts as an essential substrate that psilocybin catalyzes to achieve durable therapeutic breakthroughs.
Key Facts
- High Remission Efficacy: 75% of trial participants (9 out of 12 veterans with severe treatment-resistant PTSD) no longer met diagnostic criteria for PTSD one month after treatment completion.
- Symptom Reduction Magnitude: Clinician-administered assessment scales revealed a mean decrease of 27.5 points in overall PTSD symptom severity from baseline to one month post-treatment.
- Favorable Safety Profile: No serious adverse events or significant increases in suicidal ideation were observed; the most common transient side effect was mild post-dosing headache.
- Structured Dosing & Therapy Protocol: The 11-week trial framework integrated 8 hours of preparatory psychotherapy, two synthetic psilocybin administration sessions (15 mg followed by 25 mg), and 6 to 8 hours of post-dosing integration therapy.
- Synergistic Catalyst Mechanism: Quantitative tracking revealed measurable symptom reductions during prep therapy alone, with massive acceleration following psilocybin administration, supporting the model that psilocybin acts as a pharmacological catalyst for deep psychotherapeutic processing.
Source: Ohio State University
The first U.S. clinical trial of psilocybin-assisted therapy in veterans with PTSD who got no relief from conventional treatments has established that the protocol is safe, causing no serious adverse events or increases in suicidal thinking or behavior.
But the preliminary clinical results exceeded researchers’ expectations: In the pilot trial with 12 veterans, 75% of participants were in remission one month after the study’s end. Their symptoms no longer met the criteria for post-traumatic stress disorder.
“For a population with severe treatment-resistant PTSD, these results are striking,” said Stacey Armstrong, first author of the new study, published today (July 30, 2026) in Communications Medicine.
“While treatments do work for some veterans with PTSD, they’re falling short for many, leaving veterans to continue to search for solutions, which can lead to treatment dropout, long-term disability and elevated suicide risk,” said Armstrong, senior researcher and associate director of the Center for Psychedelic Drug Research and Education (CPDRE) in The Ohio State University College of Social Work.
“It’s this unmet need that inspires us.”
The 11-week trial period combined eight hours of psychotherapy followed by two doses, 15 milligrams and 25 milligrams, of synthetic psilocybin, the active ingredient in magic mushrooms. Six to eight more hours of integrative therapy followed the drug treatment.
From baseline to one month after treatment was finished, there was an overall average drop of 27.5 points in clinician-rated PTSD symptoms among the group. Nine participants had a clinical response to treatment and were in remission. No severe adverse events occurred, with the most common side effect being a mild headache after taking psilocybin. Suicidal ideation scores did not significantly change from baseline to one month post-treatment.
Future papers from this study will assess the treatment’s effectiveness up to six months after the trial, as well as biological changes and effects on other PTSD-related problems like sleep disorders and substance use, said Alan Davis, senior author of the study, director of the CPDRE and associate professor of social work at Ohio State.
Anecdotal observations, and previous research showing that depression remission endured for five years after an earlier psilocybin trial that Davis co-led, suggest the combined therapies could have staying power for many people whose symptoms are not eased by traditional therapies.
“It’s been an incredible honor to work with veterans in this study, many of whom have been suffering with PTSD for decades or longer,” said Davis, who also holds faculty appointments in psychology and internal medicine at Ohio State.
“Some experiences we’ve seen in actual treatment sessions are extremely profound and meaningful. The ability for them to go back and to revisit really difficult events that happened to them and to find a new way of understanding them and a new way of moving forward in their life has really been exciting.”
One participant’s experience
To be eligible for the trial, veterans had to have severe PTSD that was considered treatment-resistant. The need for help in this population became quite evident as participant recruitment began: Over 3,600 applicants reached out to partake in online prescreening and 668 were assessed for eligibility. Though the initial goal was 15 participants, the final number was 12 – nine men and three women.
Zachariah Collett, a U.S. Army veteran from Washington Court House, Ohio, considers himself one of the lucky ones who was selected to participate.
Collett joined the Army in 2002 as an enlisted soldier and later became a military police corps paratrooper, serving a 28-month combat tour in Iraq. By age 25 he was medically retired. Among the diagnoses and service-connected disabilities that led to retirement was post-traumatic stress disorder.
His symptoms included nightmares, a short temper, feeling constantly on guard and being angry virtually all the time – leading to behavior that had a negative effect on his family.
“I was just absolutely tortured by the internal struggle, the internal dialogue, the noise inside my head and the inability even to just be still,” Collett said. Years of trying counseling and medications didn’t help.
It was an intensive 41-day self-discovery experience combining a healthful diet with a series of integrative therapies that first put Collett on the path to healing. When he later learned about the psilocybin trial, he saw it as the perfect opportunity – and medicine – to take a “deeper dive.”
Now three years out from the treatment, he said the psilocybin-assisted therapy had a profound effect on him, his family and his marriage.
“For the first six months to a year, I felt like I had this fantastic set of training wheels while I’m relearning the way to act in situations,” he said. “That’s the great thing about this medicine. It’s gentle and it allowed me the space to rediscover, or discover, things I didn’t know I was capable of doing.
“It allowed me the opportunity to create peace, and stillness, and acceptance, and forgiveness and grace – all those things opposite of resentment and anger and hatred. It’s rather beautiful.”
Where the magic happens
A rigorous psychotherapy schedule is a key part of the process, with evidence from the trial suggesting that PTSD symptoms were lowered even before the drug was administered.
“There is this big question in the psychedelic therapy field right now about how much of this is a drug effect, how much of this is a therapy effect, and how much is a combination of the two,” Davis said.
This study, the first to try to answer the question, found a drop in PTSD symptoms from baseline to the end of preparation therapy, with a much larger reduction after the psilocybin doses.
“This treatment is more than just a drug,” Davis said. “The drug itself is a catalyst for the deep work that opens a window for people to perhaps access things they wouldn’t be able to access emotionally otherwise, and what that does is catalyze the therapeutic process after.
“That’s where the magic actually happens. It happens in the therapy, and in the changes that people start to make in their lives after the treatment’s concluded.”
The research team acknowledges that pilot studies with no control group tend to produce larger effect sizes than standard clinical trials. They hope to secure funding to follow up with a larger randomized, controlled clinical trial.
“Recognizing the tools that we have don’t work so well and recognizing the significant burden of PTSD in the United States carried by our servicemen and women and veterans, this seemed like the right direction to go,” Armstrong said. “Too many veterans right now are suffering despite the treatments that we have, and that’s why we feel that this research is important.”
Davis, who has been studying psychedelics as a component of mental health treatment for the past 16 years, said, “This is a very exciting time for psychedelic-assisted therapy research. These treatments are generally safe, well tolerated and showing a strong signal of efficacy.”
Funding: This research was supported by Ohio State’s College of Social Work, The Center for Psychedelic Drug Research and Education, the Clinical Research Center/Center for Clinical Research Management of The Ohio State University Wexner Medical Center and Ohio State’s College of Medicine.
Additional co-authors were Adam Levin, Nathan Sepeda, Hillary Shaub, Taweh Hunter, Angela Douglas and Rafaelle Lancelotta, all of Ohio State.
Key Questions Answered:
A: Enrolled veterans suffered from severe, service-connected PTSD that was explicitly categorized as treatment-resistant, meaning years of conventional counseling and psychiatric medications had failed to provide meaningful clinical relief.
A: Trial data showed that while preparatory psychotherapy produced measurable initial symptom reductions, psilocybin administration caused a dramatically larger reduction. The drug serves as a biological catalyst that temporarily opens an emotional window, enabling veterans to process traumatic memories during subsequent integration therapy.
A: The research team is conducting longitudinal follow-ups to evaluate symptom durability up to six months post-trial, alongside biomarker analyses assessing sleep and substance use. Funding is also being pursued for a larger randomized, double-blind, placebo-controlled clinical trial.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this PTSD and psychopharmacology research news
Author: Emily Caldwell
Source: Ohio State University
Contact: Emily Caldwell – Ohio State University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Safety, Feasibility, and Preliminary Clinical Outcomes of Psilocybin-Assisted Therapy for Veterans with Treatment-Resistant PTSD: A phase 2 non-randomized clinical trial” by Stacey Armstrong, Adam Levin, Nathan Sepeda, Hillary Shaub, Taweh Hunter, Angela Douglas, Rafaelle Lancelotta, Alan Davis. Communications Medicine
DOI:10.1038/s43856-026-01767-4
Abstract
Safety, Feasibility, and Preliminary Clinical Outcomes of Psilocybin-Assisted Therapy for Veterans with Treatment-Resistant PTSD: A phase 2 non-randomized clinical trial
Background
Psilocybin-assisted therapy (PAT) shows promise for treating PTSD in adults but hasn’t been studied in U.S. military Veterans, who face higher symptom severity and suicide risk.
Methods
This open-label pilot trial evaluated the safety and feasibility of PAT in Veterans with severe, treatment-resistant PTSD. The clinical trial was pre-registered at ClinicalTrials.gov (NCT05554094). The eligibility criteria were that participants be U.S. military Veterans aged 21–64 with a DSM 5 diagnosis of PTSD for at least six months, and a Clinician-Administered PTSD Scale for DSM 5 (CAPS-5) total severity score ≥35.
PTSD was also required to be treatment-resistant. Clinical outcomes were assessed at the Center for Psychedelic Drug Research and Education in Columbus, OH. Twelve participants received eight hours of therapy followed by two psilocybin dosing sessions at 15 mg and 25 mg, spaced 2–3 weeks apart, of synthetic psilocybin, along with approximately eight hours of post-psilocybin therapy.
Follow-up occurred at four weeks post-second dosing. The primary endpoints were safety (i.e., the type, severity, frequency of adverse events) and suicidal ideation/behavior (as measured by the Columbia Suicide Severity Rating Scale (CSSR-S)) from baseline to 1-month post-second psilocybin administration. The secondary endpoints were PTSD symptom severity rated by a clinician and the participant. Exploratory analyses included the impact of psychotherapy and expectancy on PTSD symptom severity.
Results
Of the 668 participants who completed the online pre-screener, 13 consented and enrolled, 1 withdrew before the first dosing session, and 12 fulfilled the study requirements. No serious adverse events occurred; non-serious adverse events included headaches, anxiety, and dizziness. There was no increase in suicidal ideation or behavior during the trial, and heart rate and blood pressure remained within safe limits during the psilocybin sessions.
There was a large (d = 2.30) and significant (p < 0.001) reduction (mean difference = 27.5, 95% CI: 19.9 to 35.1) in clinician-rated PTSD symptoms from baseline through 1-month follow-up, with 75% having a treatment response and in remission from PTSD. While expectancy did not predict changes in PTSD symptoms, pre-dosing symptom change during the preparation phase of treatment did. Clinician adherence ratings were 98% across all study visits.
Conclusions
Findings reveal that PAT is safe, well-tolerated, and shows preliminary clinical improvement for PTSD, suggesting that PAT may offer therapeutic relief for Veterans with severe treatment-resistant PTSD.
