Psilocybin-­assisted therapy may be safe and show early clinical efficacy in US military veterans with severe post­traumatic stress disorder.

Researchers conducted the single-­center pilot trial to evaluate the safety, feasibility, and preliminary clinical outcomes of psilocybin­-assisted therapy in veterans with severe, treatment-­resistant post­traumatic stress disorder (PTSD). Twelve patients aged 21 to 64 years completed the nearly 11-week intervention, which included 8 hours of preparatory psychotherapy, two psilocybin dosing sessions (15 mg followed by 25 mg administered 2 to 3 weeks apart), approximately 8 hours of integration psychotherapy, and a 1-month follow­up. The primary outcomes were safety, including adverse events and suicidal ideation or behavior. Secondary outcomes included clinician-­ and patient­-rated PTSD symptom severity.

Clinician­-rated PTSD symptoms improved substantially over the study period. Mean scores on the Clinician­Administered PTSD Scale for DSM­5 decreased by 27.5 points from baseline to 1 month following the second dosing session. Overall, 75% of the patients achieved both a treatment response, defined as at least a 50% reduction in clinician-rated severity, and remission, while 83% experienced a clinically meaningful improvement of at least 15 points.

Patient­-reported symptoms showed similar results. Scores on the PTSD Checklist for DSM­5 declined by 1 week following the second dosing session and remained improved at the 1-month assessment.

The researchers reported no serious adverse events and no increases in suicidal ideation or behavior during the study period. The most common treatment-­related adverse events were headache, anxiety, and dizziness, all of which were transient and mild to moderate in severity. Heart rate and blood pressure remained within the prespecified safety parameters during the dosing sessions.

Exploratory analyses suggested that symptom improvement began during the preparatory psychotherapy phase. The patients who experienced larger reductions in clinician­-rated symptoms prior to receiving psilocybin demonstrated greater improvements at 1 month. By contrast, participants’ treatment expectations were not associated with clinical outcomes. Adherence to study visits averaged 98%.

The study enrolled just 12 participants, used an open­-label, uncontrolled design, and followed patients for 1 month posttreatment. The predominantly White study population and restrictive eligibility criteria may limit generalizability. In addition, because all participants received structured psychotherapy alongside psilocybin, the independent contribution of psilocybin to the observed improvements could not be determined.

Psilocybin­-assisted therapy may be a feasible approach for veterans with severe, treatment-­resistant PTSD, although larger randomized controlled trials are needed to establish its efficacy and longer-­term safety.

“In summary, findings from this open-­label trial indicate that [psilocybin-assisted therapy] is safe and contributed to remission of PTSD in three­-quarters of our sample of military Veterans suffering from severe, treatment­-resistant PTSD. While further research is needed, this promising signal paves the way for future trials to establish the safety and efficacy of this intervention in the population,” wrote lead study author Stacey B. Armstrong, of the Center for Psychedelic Drug Research and Education at the College of Social Work at The Ohio State University, and colleagues.

Full disclosures of the study authors can be found in the study.

Source: Communications Medicine