Niall M McGowan, James J Rucker, Rachel Yehuda, Manish Agrawal, Nadav Liam Modlin, Hollie Simmons, Agata Tofil-Kaluza, Shriya Das, Guy M Goodwin
{"title":"调查单剂量裸盖菇素治疗创伤后应激障碍的安全性和耐受性：一项非随机开放标签临床试验。","authors":"Niall M McGowan, James J Rucker, Rachel Yehuda, Manish Agrawal, Nadav Liam Modlin, Hollie Simmons, Agata Tofil-Kaluza, Shriya Das, Guy M Goodwin","doi":"10.1177/02698811251362390","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aims: </strong>The trial's primary outcome was to investigate the safety and tolerability of single-dose psilocybin in participants with PTSD.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 (<i>n</i> = 11; 50.0%), nausea (<i>n</i> = 8; 36.4%), crying (<i>n</i> = 6; 27.3%) and fatigue (<i>n</i> = 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov Identifier: NCT05312151(https://clinicaltrials.gov/study/NCT05312151).</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251362390"},"PeriodicalIF":5.5000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial.\",\"authors\":\"Niall M McGowan, James J Rucker, Rachel Yehuda, Manish Agrawal, Nadav Liam Modlin, Hollie Simmons, Agata Tofil-Kaluza, Shriya Das, Guy M Goodwin\",\"doi\":\"10.1177/02698811251362390\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Aims: </strong>The trial's primary outcome was to investigate the safety and tolerability of single-dose psilocybin in participants with PTSD.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 (<i>n</i> = 11; 50.0%), nausea (<i>n</i> = 8; 36.4%), crying (<i>n</i> = 6; 27.3%) and fatigue (<i>n</i> = 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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov Identifier: NCT05312151(https://clinicaltrials.gov/study/NCT05312151).</p>\",\"PeriodicalId\":16892,\"journal\":{\"name\":\"Journal of Psychopharmacology\",\"volume\":\" \",\"pages\":\"2698811251362390\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/02698811251362390\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/02698811251362390","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial.
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.
期刊介绍：
The Journal of Psychopharmacology is a fully peer-reviewed, international journal that publishes original research and review articles on preclinical and clinical aspects of psychopharmacology. The journal provides an essential forum for researchers and practicing clinicians on the effects of drugs on animal and human behavior, and the mechanisms underlying these effects. The Journal of Psychopharmacology is truly international in scope and readership.
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