Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial
Niall M. Mcgowan, James Rucker, Rachel Yehuda, Manish Agrawal, Nadav Liam Modlin, Hollie Simmons, Agata Tofil-Kaluza, Shriya Das, Guy M. Goodwin
Journal of Psychopharmacology August 29, 2025 DOI: 10.1177/02698811251362390 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phase 2, nonrandomized, open-label, multicenter trial Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Adults with PTSD |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | Single dose, with follow-up to 12 weeks |
| Topics | Psilocybin PTSD |
| Keywords | Tolerability Open label Clinical trial Hallucinogen Anesthesia |
| Citations | 10 |
| Registration | NCT05312151 |
| Key findings | A single 25 mg dose of psilocybin with psychological support was safe, well-tolerated, and associated with clinically meaningful reductions in PTSD symptoms at 4 and 12 weeks. |
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. Clinical
Trial Registration: ClinicalTrials.gov Identifier: NCT05312151 (https://clinicaltrials.gov/study/NCT05312151)
Comparable studies
Other non-randomized and open-label trials on psilocybin for PTSD, most cited first.