Psilocybin-Assisted Tx Shows Early Promise in Severe PTSD

Psilocybin-assisted therapy (PAT) was well tolerated and associated with substantial reductions in posttraumatic stress disorder (PTSD) symptoms in US military veterans with severe, treatment-resistant disease in a small pilot study.One month after treatment, nine of the 12 participants (75%) met the study criteria for both treatment response and remission.“For a population with severe treatment-resistant PTSD, these results are striking,” lead author Stacey B. Armstrong, PhD, senior researcher and associate director of the Center for Psychedelic Drug Research and Education at The Ohio State University, Columbus, Ohio, said in a statement.“Our findings are broadly consistent with a recent open-label study of psilocybin-assisted therapy in adults with PTSD from the general population, which also reported substantial reductions in PTSD symptoms,” she told Medscape Medical News.The study was published online on July 30 in Communications Medicine.A Population in NeedVeterans are a particularly important population to study because their PTSD tends to be more severe, chronic and treatment resistant compared to PTSD in civilians, Armstrong noted.PTSD is estimated to affect between 10.1% and 30.9% of US military veterans, and about two thirds of veterans who receive standard-of-care psychotherapies do not respond to treatment, the investigators noted. More than one third drop out of treatment.“There is, therefore, an urgent need for novel treatments in this population,” the investigators wrote.Although PAT has shown promise for several psychiatric conditions and, more recently, PTSD, it had not previously been evaluated specifically in US military veterans with severe, treatment-resistant PTSD.To evaluate the safety and feasibility of PAT in this population, the investigators conducted an open-label pilot study that also explored preliminary clinical outcomes.The study included 12 veterans aged 21-64 years with severe, treatment-resistant PTSD that persisted despite standard antidepressant treatment and psychotherapy. Most index traumas were related to combat or war-zone exposure.The study population was medically stable and underwent extensive screening. Those with bipolar or psychotic disorders, recent moderate or severe substance use disorders, certain cardiovascular conditions, epilepsy with seizures, or a history of a medically significant suicide attempt were excluded.Participants were required to discontinue antidepressants and other serotonergic medications before enrollment, in consultation with their prescribing healthcare providers.The approximately 11-week intervention included 8 hours of preparatory psychotherapy, two 8-hour psilocybin dosing sessions 2-3 weeks apart, and 6-8 hours of integration therapy. Participants received 15 mg of synthetic psilocybin at the first session and 25 mg at the second.More Than a Drug EffectThe primary endpoints were safety and suicidal ideation and behavior. No serious adverse events occurred, and treatment-related adverse events were mild-to-moderate and transient, most commonly headache, anxiety, and dizziness.Suicidal ideation did not change significantly over the study. Two participants reported past-month suicidal ideation at baseline compared with three who reported passive ideation at 1 month; no increase in suicidal behavior was observed.The study’s primary endpoints were safety and suicidal thoughts and behavior. PTSD symptom outcomes were secondary endpoints.Mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores dropped from 39.7 at baseline to 33.3 after preparatory therapy but before psilocybin dosing, and to 12.2 at 1 month after the second dose.From baseline to 1 month, mean CAPS-5 scores declined by 27.5 points (P <.001; Cohen’s d = 2.30). Nine participants met criteria for both response and remission, and 10 had a clinically meaningful response.Armstrong said one of the most interesting findings was the reduction in clinician-rated PTSD symptoms during the intensive preparation phase, before participants received psilocybin, suggesting that the preparation itself may have contributed to the observed benefits. Greater improvement during preparation predicted better outcomes at 1 month.“As a psychologist, I find that particularly noteworthy because it mirrors what we have long known in traditional psychotherapy; meaningful change can begin when people feel safe, supported, and understood,” Armstrong said.Symptom improvement accelerated after psilocybin administration, suggesting that both the preparatory therapy and psilocybin may have contributed to the observed benefits, Armstrong said.Durability UnknownThe researchers acknowledged that the small sample, open-label design, absence of a control group, short follow-up, and predominantly White study population limit interpretation and generalizability.Armstrong emphasized that the study was intended as proof of concept research.“Ultimately, larger randomized controlled trials that include both veteran and civilian participants will be needed to determine the extent to which these findings generalize across different types of trauma exposure, demographic groups, and clinical presentations,” she said.The researchers followed participants for 6 months and are preparing those findings for publication.“PTSD is often a chronic condition that can persist for years or decades, so understanding whether symptom improvements are maintained over time is critical,” Armstrong said.Other key questions remain, including which patients are most likely to benefit, whether one or two doses are optimal, and the relative contributions of preparation, psilocybin dosing, and integration therapy to treatment outcomes.“We are still in the relatively early stages of understanding how best to deliver psychedelic-assisted therapies for PTSD,” Armstrong said.PAT remains investigational and is not approved in the US for PTSD or any other indication.The study 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. Disclosures for study author are available with the original study publication.