Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial
Agrawal, M., Das, S., Goodwin, G. M., McGowan, N. M., Modlin, N. L., Rucker, J. J., Simmons, H., Tofil-Kaluza, A., Yehuda, R.
This Phase II, nonrandomised open-label trial (n=22) tested a single 25 mg dose of psilocybin with psychological support in adults with PTSD. It found the treatment to be safe and well-tolerated, with common side effects such as headache, nausea, crying, and fatigue resolving quickly. Clinically meaningful reductions in PTSD symptoms were observed at weeks 4 and 12, alongside improvements in functioning and quality of life.
Abstract
Background: Post-traumatic stress disorder (PTSD) is a debilitating condition for which there are few efficacious treatments. Psilocybin is being studied for use in treatment-resistant depression but has not yet been investigated in PTSD.Aims: The trial’s primary outcome was to investigate the safety and tolerability of single-dose psilocybin in participants with PTSD.Methods: This was a Phase 2, nonrandomized, open-label, multicenter trial. Secondary outcomes were changes in PTSD symptoms (Clinician-Administered PTSD Scale for DSM-5 (CAPS-5); PTSD Checklist for DSM-5 (PCL-5)), functional impairment (Sheehan Disability Scale; SDS) and quality of life (EQ-5D-5L index score).Results: Amongst the 22 participants enrolled (63.6% female; mean (SD) age, 39.0 (7.91) years), there was a total of 117 treatment-emergent adverse events (TEAEs); 70 (59.8%) were reported on administration day, of which 64/70 (91.4%) resolved by the end of the next day. TEAEs commonly included headache (n = 11; 50.0%), nausea (n = 8; 36.4%), crying (n = 6; 27.3%) and fatigue (n = 6; 27.3%). There were no serious TEAEs or TEAEs leading to study withdrawal. Pre-post comparisons indicated a clinically meaningful change from Baseline in mean CAPS-5 total score at Week 4 (−29.9 (14.06)) and Week 12 (−29.5 (15.43)), which was associated with the intensity of psychedelic experience on Day 1. PCL-5 scores showed symptom reduction was rapid and sustained until Week 12. SDS total score and EQ-5D-5L index score showed similar improvements.Conclusions: Psilocybin at a dose of 25 mg, administered with psychological support, may be safe, well-tolerated and associated with symptomatic improvement in adults with PTSD. Further investigation is warranted.