COMP360 · program

Psilocybin (COMP360) for Major depressive disorder

Phase 2ActiveCOMPASS 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

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.

Data current as of

Development timeline

Phase 2Jan 2023 – Sept 2025
  1. UpcomingPhase 2 COMP360 recurrent-MDD topline anticipated (estimated primary completion Sep 2025); no results reported yet.
  2. Phase 2 study of COMP360 in recurrent MDD (NCT05733546) started; first participant enrollment window opened.

Readouts

  • September 2025AnticipatedTopline dataNCT05733546

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

Clinical trials in Major depressive disorder

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)

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. A Phase II Study of COMP360 in Participants With Recurrent Major Depressive Disorder (NCT05733546) — ClinicalTrials.gov
  3. psilocin — IUPHAR/BPS Guide to Pharmacology (Ligand 11291) — IUPHAR/BPS
  4. psilocin — Ligand Activity Charts — IUPHAR/BPS
  5. Psilocybin — Wikipedia