Psychedelic · COMP360

Psilocybin (COMP360)

Phase 3COMPASS Pathways plc (CMPS)
  • Breakthrough Therapy
  • FDA Rolling Review
  • Commissioner's National Priority Voucher
  • ILAP (UK)

Compass Pathways' proprietary synthetic formulation of psilocybin — a serotonergic psychedelic prodrug — in Phase 3 development as a single-dose treatment, given with psychological support, for treatment-resistant depression.

Also known as: COMP360, Psilocybin, 520-52-5

Data current as of

Modality
Psychedelic
Chemical class
tryptamine, Indole alkaloid, Organophosphate ester
DEA schedule
Schedule I
Chemistry
Achiral · Prodrug
Mechanism
5-HT2A Partial agonist
Highest phase
Phase 3
Lead indication
Treatment-resistant depression
Developer
COMPASS Pathways plc (CMPS)
Designations
Breakthrough Therapy, FDA Rolling Review, Commissioner's National Priority Voucher, ILAP (UK)
Trials
7 tracked · 194 sites
Next catalyst
after primary completion (Nov 2024) — Topline data (Anorexia nervosa)

Mechanism of action

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ⓘ

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%

Development timeline

Phase 3Jun 2025 – Dec 2026
  1. UpcomingFull NDA submission targeted (FDA rolling review underway).Treatment-resistant depression↗
  2. FDA granted rolling NDA review; Compass awarded Commissioner's National Priority Voucher.Treatment-resistant depression↗
  3. metCOMP006 met its primary endpoint: -3.8 MADRS (two 25mg doses vs 1mg) at Week 6 (p<0.001).Treatment-resistant depression↗
  4. metCOMP005 met its primary endpoint: -3.6 MADRS vs placebo at Week 6 (p<0.001).Treatment-resistant depression↗
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.Post-traumatic stress disorder
  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).Post-traumatic stress disorder↗
Phase 2Oct 2022 – Sept 2025
  1. UpcomingPhase 2 COMP360 recurrent-MDD topline anticipated (estimated primary completion Sep 2025); no results reported yet.Major depressive disorder
  2. 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.Post-traumatic stress disorder↗
  3. UpcomingPhase 2 anorexia nervosa proof-of-concept (NCT05481736) completed Nov 2024; topline EDE result not yet disclosed.Anorexia nervosa
  4. Phase 2 study of COMP360 in recurrent MDD (NCT05733546) started; first participant enrollment window opened.Major depressive disorder
  5. Phase 2 proof-of-concept trial NCT05481736 started (first participant period); randomised 25mg vs 1mg COMP360 with psychological support, primary endpoint EDE global score at Week 4. Launch announced 28 Jul 2022.Anorexia nervosa↗

Psilocybin (COMP360) for Treatment-resistant depression

Phase 3ActiveTreatment-resistant depression indication →

Both pivotal Phase 3 trials (COMP005, COMP006) met their primary MADRS endpoints (p<0.001). As of mid-2026 the program is in the regulatory-filing window: a rolling NDA is underway, full submission targeted Q4 2026, with FDA Breakthrough Therapy designation and an April 2026 Commissioner's National Priority Voucher that could compress review.

Readouts

  • fourth quarter 2026AnticipatedRegulatory

    Full NDA submission targeted (FDA rolling review underway). ↗

  • 2026-02-17ReportedTopline datametNCT05711940

    COMP006 met its primary endpoint: -3.8 MADRS (two 25mg doses vs 1mg) at Week 6 (p<0.001). ↗

  • 2025-06-23ReportedTopline datametNCT05624268

    COMP005 met its primary endpoint: -3.6 MADRS vs placebo at Week 6 (p<0.001). ↗

Psilocybin (COMP360) for Anorexia nervosa

Phase 2CompletedAnorexia nervosa indication →

A Phase 2 proof-of-concept program evaluating COMP360 psilocybin therapy (25 mg vs 1 mg, with psychological support) in anorexia nervosa, an indication with no approved pharmacological treatment. The single multi-centre, double-blind, randomised, controlled trial (NCT05481736), run across UK and US sites, completed in November 2024 with 32 participants enrolled. As of mid-2026 no topline results have been publicly disclosed; Compass's reported priorities are the TRD (lead) and PTSD programs.

Readouts

  • after primary completion (Nov 2024)DelayedTopline dataNCT05481736

    Phase 2 anorexia nervosa proof-of-concept (NCT05481736) completed Nov 2024; topline EDE result not yet disclosed.

Psilocybin (COMP360) for Major depressive disorder

Phase 2ActiveMajor depressive disorder indication →

A single Phase 2 study (NCT05733546) evaluating COMP360 psilocybin, given with psychological support, in adults with recurrent major depressive disorder (up to four prior antidepressant failures in the current episode — broader than the treatment-resistant definition used in the lead TRD program). Participants are randomized 1:1:1 to COMP360 25mg, 10mg, or 1mg. The trial is active, not recruiting, with an estimated September 2025 primary completion. The primary endpoint is safety/tolerability; MADRS change at Week 3 and Week 6 (25mg vs 1mg) is a secondary efficacy endpoint. No efficacy/topline results have been published for this MDD study to date.

Readouts

  • September 2025AnticipatedTopline dataNCT05733546

    Phase 2 COMP360 recurrent-MDD topline anticipated (estimated primary completion Sep 2025); no results reported yet.

Psilocybin (COMP360) for Post-traumatic stress disorder

Phase 2/3ActivePost-traumatic stress disorder indication →

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.

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

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

NCT05711940COMP006Phase 3Activen=572

Phase III, Randomised, Double-blind, Controlled Study of Two Administrations of COMP360 in Treatment-resistant Depression

Started Feb 2023· Primary completion Feb 2026· 📍 116 sites across 12 countries (United States, United Kingdom, Canada, Czechia)

metprimaryMADRS change at Week 6 (two 25mg doses vs 1mg) — -3.8 points (<0.001)

Second pivotal Phase 3; two doses 3 weeks apart. 95% CI [-5.8, -1.8]. Magnitude noted as modest by some analysts.

NCT05733546Phase 2Activen=102

A Phase II, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of COMP360 in Participants With Recurrent Major Depressive Disorder

Started Jan 2023· 📍 5 sites across 1 country (United States)

NCT05624268COMP005Phase 3Activen=255

Phase III, Randomised, Double-blind, Placebo-controlled Study of COMP360 in Treatment-resistant Depression

Started Jan 2023· Primary completion May 2025· 📍 40 sites across 1 country (United States)

metprimaryMADRS change at Week 6 (single 25mg vs placebo) — -3.6 points (<0.001)

First pivotal Phase 3; first Phase 3 efficacy readout for a classic psychedelic. 95% CI [-5.7, -1.5].

NCT05481736Phase 2Completedn=32

Efficacy and Safety of COMP360 Psilocybin Therapy in Anorexia Nervosa: a Proof-of-concept Study

Started Oct 2022· Primary completion Nov 2024· 📍 5 sites across 3 countries (United States, Ireland, United Kingdom)

pendingprimaryChange from baseline in EDE (Eating Disorder Examination) global score at Week 4 (25mg vs 1mg)

Primary endpoint of the Phase 2 proof-of-concept study. Trial reached completion (18 Nov 2024) but no results have been posted to ClinicalTrials.gov and no topline press release was found as of 25 Jun 2026.

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.

NCT03775200COMP001 (P-TRD)Phase 2Completedn=233

The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression

Started Mar 2019· Primary completion Jul 2021· 📍 25 sites across 10 countries (United States, United Kingdom, Netherlands, Canada)

metprimaryMADRS change at Week 3 (25mg vs 1mg) — -6.6 points (<0.001)

Phase 2b dose-ranging; single 25mg dose significantly reduced MADRS vs 1mg at Week 3. Published NEJM (Goodwin 2022).

Conference coverage

COMP360 appears in 36 CNS Pulse conference abstracts:

+ 28 more.

Related compounds

Other 5-HT2A compounds

Identifiers

Sources

  1. 5-HT2A/2C/1A and TAAR1 in the head-twitch response (psilocybin) — Int. J. Mol. Sci.
  2. A Phase II Study of COMP360 in Participants With Recurrent Major Depressive Disorder (NCT05733546) — ClinicalTrials.gov
  3. COMP001 / P-TRD (NCT03775200) — ClinicalTrials.gov
  4. COMP005 (NCT05624268) — ClinicalTrials.gov
  5. COMP006 (NCT05711940) — ClinicalTrials.gov
  6. COMP360 Phase 3 (COMP006) efficacy data — Psychiatric Times
  7. COMPASS Pathways launches phase II clinical trial of psilocybin therapy in anorexia nervosa — Compass Pathways IR
  8. Compass Pathways Successfully Achieves Primary Endpoint in First Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression — Compass Pathways IR
  9. Compass Pathways Successfully Achieves Primary Endpoint in Second Phase 3 Trial Evaluating COMP360 Psilocybin for Treatment-Resistant Depression — Compass Pathways IR
  10. Durable improvement through 12 weeks in open-label Phase 2 PTSD study — Compass Pathways IR
  11. Efficacy and Safety of COMP360 Psilocybin Therapy in Anorexia Nervosa: a Proof-of-concept Study (NCT05481736) — ClinicalTrials.gov
  12. FDA Acceptance of IND Application for PTSD (Phase 2b/3 enabled) — Business Wire
  13. FDA rolling NDA review + Commissioner's National Priority Voucher — Business Wire
  14. psilocin — IUPHAR/BPS Guide to Pharmacology (Ligand 11291) — IUPHAR/BPS
  15. psilocin — Ligand Activity Charts — IUPHAR/BPS
  16. Psilocybin — Wikipedia
  17. Publication of Phase 2 PTSD study results (CAPS-5 -29.9 wk4 / -29.5 wk12) — Business Wire
  18. Redefine Study: A Study Evaluating the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder (NCT07570654) — ClinicalTrials.gov
  19. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression (Goodwin 2022) — NEJM
  20. The Safety and Tolerability of COMP360 in Participants With PTSD (NCT05312151) — ClinicalTrials.gov