GH001 · program
Mebufotenin (inhaled 5-MeO-DMT, GH001) for Treatment-resistant depression
Indications for GH001: Treatment-resistant depression · Phase 2 Postpartum depression · Phase 2 Bipolar depression · Discontinued
Inhaled GH001 (mebufotenin) for treatment-resistant depression. Phase 2b (GH001-TRD-201, NCT05800860, n=81) met its primary endpoint: -15.5-point placebo-adjusted MADRS reduction on Day 8 (p<0.0001); 57.5% Day-8 remission vs 0% placebo. US clinical hold lifted 5 Jan 2026; global pivotal Phase 3 planned for 2026. Bipolar II and postpartum Phase 2 programs were terminated early after proof-of-concept.
Development timeline
Clinical trials in Treatment-resistant depression
NCT05800860GH001-TRD-201Phase 2Completedn=81
Phase 2b Trial of GH001 in Treatment-resistant Depression (with OLE)
metprimaryMADRS change at Day 8 (placebo-adjusted) — -15.5 points (<0.0001)
57.5% Day-8 remission vs 0% placebo; ~73-78% remission at 6 months (OLE). Results from company PR (CT.gov hasResults=false).
NCT05839509GH001-BD-202Phase 2Discontinuedn=6
A Phase 2 Clinical Trial of GH001 in Patients with Bipolar II Disorder and a Current Major Depressive Episode
metprimaryMADRS change from baseline at Day 8 — -16.8 points (51.9%) (0.0099)
Single-arm, open-label POC (n=6, all completed): -16.8-point (51.9%) reduction in MADRS total score from baseline (mean baseline 32.0) at Day 8 (p=0.0099); 33.3% (2/6) of patients in remission (MADRS <=10) at Day 8. GH001 well tolerated; no treatment-related serious adverse events; no TEAEs of mania or hypomania. Figures from company PR (2025-01-10) and the ACNP GH001-BD-202 poster; CT.gov hasResults=false.
NCT05804708Phase 2Discontinuedn=10
A Phase 2 Clinical Trial of GH001 in Patients with Postpartum Depression
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
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| 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. | Inhaled | Single dose | — |
Mechanism of action
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.
| Target | Action | Affinity |
|---|---|---|
| 5-HT2AprimaryHTR2A | Agonist | —ⓘ |
| 5-HT1AHTR1A | Agonist | —ⓘ |
← Full GH001 compound page (identity, identifiers, all indications)
Sources
- 5-MeO-DMT ligand activity — IUPHAR/BPS
- 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
- A Phase 2 Clinical Trial of GH001 in Patients with Bipolar II Disorder and a Current Major Depressive Episode (GH001-BD-202, NCT05839509) — status TERMINATED — ClinicalTrials.gov
- FDA lifts clinical hold on GH001 — GH Research PLC
- GH Research Announces Primary Endpoint Met in Two Phase 2a POC Trials with GH001 (bipolar II and postpartum depression) — GH Research PLC
- GH Research Announces Primary Endpoint Met in Two Phase 2a POC Trials with GH001 (PPD + bipolar II) — GH Research PLC
- GH001 Phase 2b TRD primary endpoint met — GH Research PLC
- GH001-TRD-201 (NCT05800860) — ClinicalTrials.gov
- Phase 2 Clinical Trial of GH001 in Postpartum Depression (NCT05804708) — ClinicalTrials.gov