Safety, feasibility, and preliminary clinical outcomes of psilocybin-assisted therapy for veterans with severe, treatment-resistant PTSD: an open-label pilot clinical trial.

backgroundPsilocybin-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.

methodsThis 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.

resultsOf 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.

conclusionsFindings 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.