GH001 · program

Mebufotenin (inhaled 5-MeO-DMT, GH001) for Postpartum depression

Phase 2ActiveGH Research PLC (GHRS)

Indications for GH001: Treatment-resistant depression · Phase 2 Postpartum depression · Phase 2 Bipolar depression · Discontinued

Inhaled GH001 (mebufotenin, 5-MeO-DMT) for postpartum depression. A Phase 2a, single-arm, open-label proof-of-concept trial (GH001-PPD, NCT05804708, n=10) met its primary endpoint with a mean -35.4-point MADRS reduction from baseline to Day 8 (p<0.0001; ~96% reduction) and 100% remission (MADRS <=10) by Day 8, with remission achieved within ~2 hours of the final dose. The trial was terminated early due to challenging recruitment after sufficient patients completed to establish proof of concept. Full results were published in the Journal of Clinical Psychiatry in June 2026. PPD is a non-lead indication behind treatment-resistant depression; no pivotal Phase 3 in PPD has been announced.

Development timeline

Phase 2Mar 2023 – Jun 2026
  1. metPhase 2a postpartum depression results published in Journal of Clinical Psychiatry (DOI 10.4088/JCP.25m16284)
  2. metGH001 Phase 2a POC in postpartum depression met primary endpoint: -35.4-point MADRS reduction at Day 8 (p<0.0001), 100% remission
  3. Phase 2a open-label proof-of-concept trial of inhaled GH001 in postpartum depression (NCT05804708) initiated (study start date).

Readouts

  • 2026-06-03ReportedFull resultsmetNCT05804708

    Phase 2a postpartum depression results published in Journal of Clinical Psychiatry (DOI 10.4088/JCP.25m16284)

  • 2025-01-10ReportedTopline datametNCT05804708

    GH001 Phase 2a POC in postpartum depression met primary endpoint: -35.4-point MADRS reduction at Day 8 (p<0.0001), 100% remission

Clinical trials in Postpartum depression

NCT05804708Phase 2Discontinuedn=10

A Phase 2 Clinical Trial of GH001 in Patients with Postpartum Depression

Started Mar 2023· Primary completion Aug 2024· 📍 4 sites across 2 countries (United Kingdom, Netherlands)

metprimaryMADRS total score change from baseline to Day 8 — -35.4 points (SD 5.5; 95% CI -39.32 to -31.48; ~96% reduction) (<0.0001)

Single-arm open-label POC (n=10 women with PPD). Mean -35.4-point MADRS reduction at Day 8 (p<0.0001); 100% (10/10) achieved remission (MADRS <=10) by Day 8, with remission within ~2 hours of final dose (-31.4 at 2h; -36.0 at Day 2, both p<0.0001). Secondary: +34.1-point (56%) Barkin Index of Maternal Functioning at Day 8. Well tolerated, no treatment-related SAEs, no treatment-emergent suicidal ideation/behavior. CT.gov hasResults=false; figures from company PR + JCP publication. (CT.gov primary-outcome timepoint is listed as Day 7; published headline result is the Day-8 value.)

Formulations

FormulationRouteRegimenPharmacokinetics
GH001 (inhaled/vaporized 5-MeO-DMT)Vaporized (Volcano Medic vaporization system); proprietary GMP-grade 5-MeO-DMT formulation delivered by pulmonary inhalation, with an individualized dose-escalation (IDE) regimen of up to three doses interspaced ~3 h on a single dosing day.
Single ascending doses of 2, 6, 12, and 18 mg in the Phase 1 healthy-volunteer dose-ranging study; also administered as an individualized dose-escalation regimen.
InhaledSingle dose

Mechanism of action (compound-wide)

5-MeO-DMT is a serotonergic psychedelic acting primarily as a 5-HT2A and 5-HT1A agonist; psychedelic effect attributed mainly to 5-HT2A. Notably high 5-HT1A affinity relative to other classic psychedelics.

TargetActionAffinity
5-HT2AprimaryHTR2AAgonist
5-HT1AHTR1AAgonist

← Full GH001 compound page (identity, identifiers, all indications)

Sources

  1. 5-MeO-DMT ligand activity — IUPHAR/BPS
  2. A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N,N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers — PMC / peer-reviewed journal
  3. GH Research Announces Primary Endpoint Met in Two Phase 2a POC Trials with GH001 (PPD + bipolar II) — GH Research PLC
  4. Inhaled Mebufotenin (GH001) for Adult Patients With Postpartum Depression: A Phase 2a Open-Label Clinical Trial — Journal of Clinical Psychiatry
  5. Phase 2 Clinical Trial of GH001 in Postpartum Depression (NCT05804708) — ClinicalTrials.gov