GH001 · program
Mebufotenin (inhaled 5-MeO-DMT, GH001) for Bipolar depression
Indications for GH001: Treatment-resistant depression · Phase 2 Postpartum depression · Phase 2 Bipolar depression · Discontinued
Inhaled GH001 (mebufotenin, 5-MeO-DMT) for bipolar II disorder with a current major depressive episode. Single-arm, open-label Phase 2a proof-of-concept trial (GH001-BD-202, NCT05839509, n=6) MET its primary endpoint: -16.8-point (51.9%) reduction in MADRS total score from baseline at Day 8 (p=0.0099), with 33.3% (2/6) of patients in remission (MADRS <=10) at Day 8 and no treatment-related serious adverse events and no mania/hypomania TEAEs. The trial was terminated early after enrolling 6 patients: GH Research determined recruitment was more challenging than anticipated and that sufficient participants had completed to establish proof of concept. GH Research has prioritized the TRD program (Phase 3 planned 2026); the bipolar II indication is not being advanced as a lead program.
Development timeline
- metGH001 met primary endpoint in Phase 2a bipolar II depression POC: -16.8-point (51.9%) MADRS reduction at Day 8 (p=0.0099), 33% Day-8 remission (n=6)↗
- GH001-BD-202 (NCT05839509) terminated after enrolling 6 of a planned larger cohort; sponsor concluded recruitment was more challenging than anticipated and that sufficient participants had completed to establish proof of concept. Bipolar II not advanced as a lead program (TRD prioritized). (Trial completion date 2024-12-05; status change reflects program closure.)
Readouts
- 2025-01-10ReportedTopline datametNCT05839509
GH001 met primary endpoint in Phase 2a bipolar II depression POC: -16.8-point (51.9%) MADRS reduction at Day 8 (p=0.0099), 33% Day-8 remission (n=6) ↗
Clinical trials in Bipolar depression
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.
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
- GH Research Announces Primary Endpoint Met in Two Phase 2a POC Trials with GH001 (bipolar II and postpartum depression) — GH Research PLC