COMP360 · program

Psilocybin (COMP360) for Post-traumatic stress disorder

Phase 2/3ActiveCOMPASS Pathways plc (CMPS)

Indications for COMP360: Treatment-resistant depression · Phase 3 Anorexia nervosa · Phase 2 Post-traumatic stress disorder · Phase 2/3 Major depressive disorder · Phase 2

COMP360 psilocybin is in development for PTSD as a secondary indication behind TRD. A single-dose open-label Phase 2 study (NCT05312151, n=22) showed a rapid and durable CAPS-5 reduction sustained to 12 weeks. On 2026-01-07 the FDA accepted the IND for a late-stage pivotal program; the Phase 2b/3 'REDEFINE Study' (NCT07570654) is registered as not-yet-recruiting with a planned Sep 2026 start, randomizing two administrations of 25mg vs 1mg with CAPS-5 change to Week 8 as the primary endpoint.

Data current as of

Development timeline

Phase 2/3Jan 2026 – Sept 2026
  1. UpcomingPivotal Phase 2b/3 PTSD trial (REDEFINE / NCT07570654) planned to start; FDA accepted the IND on 2026-01-07.
  2. FDA accepted the IND for COMP360 in PTSD, enabling the late-stage Phase 2b/3 'REDEFINE' program (two administrations 25mg vs 1mg; CAPS-5 to Week 8). Trial NCT07570654 registered as not-yet-recruiting (planned start Sep 2026).↗
Phase 2Nov 2024
  1. metOpen-label Phase 2 PTSD study showed durable CAPS-5 improvement through 12 weeks (-29.5 points from a 47.5 baseline) after a single 25mg dose; no serious adverse events.↗

Readouts

  • third quarter 2026AnticipatedRegulatoryNCT07570654

    Pivotal Phase 2b/3 PTSD trial (REDEFINE / NCT07570654) planned to start; FDA accepted the IND on 2026-01-07.

  • 2024-11-19ReportedTopline datametNCT05312151

    Open-label Phase 2 PTSD study showed durable CAPS-5 improvement through 12 weeks (-29.5 points from a 47.5 baseline) after a single 25mg dose; no serious adverse events. ↗

Clinical trials in Post-traumatic stress disorder

NCT07570654REDEFINE (COMP202)Phase 2/3Activen=300

Redefine Study: A Study Evaluating the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder

Started Sept 2026· Primary completion Nov 2028

NCT05312151COMP360 PTSD open-label Ph2Phase 2Completedn=22

The Safety and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder

Started Jun 2022· Primary completion Feb 2024· 📍 3 sites across 2 countries (United States, United Kingdom)

metprimaryTreatment-emergent adverse events (safety, primary)

Primary safety endpoint met: no serious adverse events; no participant withdrawals; no participant returned to antidepressant medication during the study. Most common TEAEs were headache, nausea and crying.

metsecondaryCAPS-5 total score change from baseline at Week 12 (single 25mg, open-label) — -29.5 points (47.5 -> 18.0)

Durable efficacy signal: mean CAPS-5 fell 29.9 points at Week 4 and 29.5 points at Week 12 from a baseline of 47.5; response (>=15-pt reduction) 81.8% at Week 4 and 77.3% at Week 12. Open-label, uncontrolled. Published in Journal of Psychopharmacology, Sept 2025.

Formulations

FormulationRouteRegimenPharmacokinetics
COMP360 oral capsule (25 mg)Immediate-release solid oral capsule (synthetic crystalline psilocybin), administered once with psychological support
25 mg single oral dose (also studied at 1 mg and 10 mg comparator doses)
OralSingle doset½ 3 h · Tmax 2 h · F 52.7%

Mechanism of action (compound-wide)

Psilocybin is a prodrug rapidly converted in vivo to psilocin (4-OH-DMT), the active serotonergic agent. Effects are driven primarily by 5-HT2A partial agonism, with additional agonism at 5-HT2C, 5-HT1A and 5-HT2B and weaker activity at TAAR1. Reported affinities vary widely across assays.

TargetActionAffinity
5-HT2AprimaryHTR2APartial agonistpEC50 7.6ⓘ
5-HT1AHTR1AAgonist—ⓘ
5-HT2BHTR2BAgonistpKi 8.33ⓘ
5-HT2CHTR2CAgonistpKi 6.85ⓘ
TAAR1TAAR1AgonistKi 1.4 nMⓘ

← Full COMP360 compound page (identity, identifiers, all indications)

Sources

  1. 5-HT2A/2C/1A and TAAR1 in the head-twitch response (psilocybin) — Int. J. Mol. Sci.
  2. Durable improvement through 12 weeks in open-label Phase 2 PTSD study — Compass Pathways IR
  3. FDA Acceptance of IND Application for PTSD (Phase 2b/3 enabled) — Business Wire
  4. psilocin — IUPHAR/BPS Guide to Pharmacology (Ligand 11291) — IUPHAR/BPS
  5. psilocin — Ligand Activity Charts — IUPHAR/BPS
  6. Psilocybin — Wikipedia
  7. Publication of Phase 2 PTSD study results (CAPS-5 -29.9 wk4 / -29.5 wk12) — Business Wire
  8. Redefine Study: A Study Evaluating the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder (NCT07570654) — ClinicalTrials.gov
  9. The Safety and Tolerability of COMP360 in Participants With PTSD (NCT05312151) — ClinicalTrials.gov