First Study of Psilocybin in PTSD Shows Promise, Safety of Treatment Approach

James Rucker, PhD
Credit: King's College London

A psilocybin treatment for posttraumatic stress disorder (PTSD) shows promise, meeting its primary safety endpoint and available efficacy endpoints in an open-label phase 2 study.

Announced on May 08, 2024 by Compass Pathways, topline results of the trial, which Compass suggested could be the first study reporting on the feasibility of psilocybin as a potential treatment for PTSD, indicate use of COMP360 was well-tolerated, with no reports of serious adverse events, and was associated with a meaningful and sustained symptom improvement relative to baseline.

“PTSD is commonly underdiagnosed and even when recognized it is often left untreated. There have been no new medicines approved for the treatment of PTSD in over two decades, and effective treatment options are limited. It’s promising to see positive signals from this study of investigational COMP360 psilocybin treatment in people with PTSD,” said principal investigator James Rucker, MBBS, PhD, a consultant psychiatrist and lead for The Psychoactive Trials Group at King’s College London.¹

The May 2024 announcement follows a December 2023 announcement from Compass Pathways indicating initial safety findings at 24 hours post-dosing were consistent with the safety profile of COMP360 in other psychiatric conditions. An investigational psilocybin treatment, COMP360 is also subject of a phase 2b clinical trial in treatment resistant depression published in the New England Journal of Medicine in 2022.^1,2,3

The current phase 2 study in PTSD was an open-label, multi-center study assessing the safety and tolerability of a single 25 mg dose along with psychological support among a cohort of adult patients with PTSD resulting from trauma in adulthood. The trial’s primary endpoint was safety at week 12. Secondary endpoints of interest included secondary endpoints were change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from baseline and change in Sheehan Disability Scale (SDS) total score from baseline.¹

Conducted at 3 sites in the US and England, a total of 22 adult patients were recruited for the study. This cohort had a mean age at time of screening of 39 and a mean baseline a CAPS-5 total score of 47.5 (minimum of 25; maximum of 64). The release from Compass noted patients diagnosed with complex PTSD were not included in the study.¹

Results announced by Compass Pathways indicated administration was well-tolerated, with 0 serious adverse events observed in the trial. headache (n=11 or 50.0%), nausea (n=8 or 36.4%), crying (n=6 or 27.3%), and fatigue (n=6 or 27.3%) were reported as treatment-emergent adverse events among the cohort.¹

The release highlighted 2 adverse events of suicidal ideation occurred and resolved during the study. According to the release, the first was a moderate and transient event that resolved on administration day in a patient who went on to be a responder, and it was deemed to be related to study drug. The second event was mild and occurred at week 7 in a non-responder, resolved during the study, and was considered to be possibly related to study drug. Of note, both participants had previous history of suicidality as measured by the Columbia-Suicide Severity Rating Scale.¹

Upon assessment of secondary endpoints, results suggested the mean CAPS-5 total score experienced a 29.9-point reduction by week 4 and a 29.5-point reduction by week 12, with decreases in mean SDS total score of 1.7 point reduction by week 4 and a 14.4 point reduction by week 12 also observed among the study cohort. Additionally, the release from Compass Pathways spotlighted the apparent early onset of symptom improvement, with a 15-point improvement or greater in CAPS-5 score observed among 81.8% by week 4 and 77.3% by week 12.¹

According to the release, 0 patients withdrew from the study and no patients returned to antidepressant medication treatment during the trial, with 63.6% in remission at week 4 and 54.5% in remission at week 12.¹

“These results, with early and lasting improvement in symptoms following a single administration of COMP360, are highly encouraging,” said Guy Goodwin, FMedSci, chief medical officer of Compass Pathways.¹ “These observations, even with a small, open-label study, suggest that COMP360 could provide a clinically meaningful benefit and substantially improve patient daily function and quality of life. The well tolerated safety profile for COMP360 in patients with PTSD, with no serious adverse events observed, advance our understanding of potential applications of COMP360. We look forward to submitting the full results of this study for publication and potential presentation at an upcoming medical conference.”

References:

1. COMPASS Pathways. Compass Pathways announces durable improvement in symptoms through 12 weeks in open-label phase 2 study of Comp360 psilocybin in post-traumatic stress disorder. COMPASS Pathways. May 8, 2024. Accessed May 9, 2024. https://ir.compasspathways.com/news-releases/news-release-details/compass-pathways-announces-durable-improvement-symptoms-through.
2. COMPASS Pathways. Compass Pathways announces investigational Comp360 psilocybin treatment was well-tolerated in phase 2 study of post-traumatic stress disorder. Compass Pathways. December 19, 2023. Accessed May 9, 2024. https://ir.compasspathways.com/news-releases/news-release-details/compass-pathways-announces-investigational-comp360-psilocybin.
3. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022;387(18):1637-1648. doi:10.1056/NEJMoa2206443