Psychedelic · GH001

Mebufotenin (inhaled 5-MeO-DMT, GH001)

Phase 2GH Research PLC (GHRS)

GH Research's proprietary inhaled (vaporized) mebufotenin (5-methoxy-N,N-dimethyltryptamine, 5-MeO-DMT), a short-acting serotonergic psychedelic, dosed as up to three escalating doses in a single day for treatment-resistant depression.

Also known as: GH001, Mebufotenin, 5-MeO-DMT

Data current as of

Modality
Psychedelic
Chemical class
tryptamine, 5-methoxytryptamine, indolealkylamine
DEA schedule
Schedule I
Chemistry
Achiral
Mechanism
5-HT2A agonist
Highest phase
Phase 2
Lead indication
Treatment-resistant depression
Developer
GH Research PLC (GHRS)
Trials
3 tracked · 22 sites

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.

TargetActionAffinity
5-HT2AprimaryHTR2AAgonist—ⓘ
5-HT1AHTR1AAgonist—ⓘ

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—

Development timeline

Phase 2Mar 2023 – Jun 2026
  1. metPhase 2a postpartum depression results published in Journal of Clinical Psychiatry (DOI 10.4088/JCP.25m16284)Postpartum depression↗
  2. FDA lifted clinical hold on GH001; global pivotal Phase 3 in TRD planned for 2026.Treatment-resistant depression↗
  3. Phase 2b in TRD met primary endpoint: -15.5-point placebo-adjusted Day-8 MADRS (p<0.0001), 57.5% remission vs 0%.Treatment-resistant depression↗
  4. 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)Bipolar depression↗
  5. metGH001 Phase 2a POC in postpartum depression met primary endpoint: -35.4-point MADRS reduction at Day 8 (p<0.0001), 100% remissionPostpartum depression↗
  6. Phase 2a open-label proof-of-concept trial of inhaled GH001 in postpartum depression (NCT05804708) initiated (study start date).Postpartum depression
DiscontinuedDec 2024
  1. 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.)Bipolar depression

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

Phase 2ActiveTreatment-resistant depression indication →

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.

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

DiscontinuedDiscontinuedBipolar depression indication →

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.

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) ↗

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

Phase 2ActivePostpartum depression indication →

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.

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

NCT05800860GH001-TRD-201Phase 2Completedn=81

Phase 2b Trial of GH001 in Treatment-resistant Depression (with OLE)

Started May 2023· Primary completion Oct 2024· 📍 11 sites across 6 countries (Germany, Spain, Ireland, Czechia)

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

Started Apr 2023· Primary completion Nov 2024· 📍 7 sites across 3 countries (Germany, Netherlands, United Kingdom)

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

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.)

Conference coverage

GH001 appears in 4 CNS Pulse conference abstracts:

Related compounds

Other 5-HT2A compounds

Identifiers

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. 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
  4. FDA lifts clinical hold on GH001 — GH Research PLC
  5. GH Research Announces Primary Endpoint Met in Two Phase 2a POC Trials with GH001 (bipolar II and postpartum depression) — GH Research PLC
  6. GH Research Announces Primary Endpoint Met in Two Phase 2a POC Trials with GH001 (PPD + bipolar II) — GH Research PLC
  7. GH001 Phase 2b TRD primary endpoint met — GH Research PLC
  8. GH001-TRD-201 (NCT05800860) — ClinicalTrials.gov
  9. Inhaled Mebufotenin (GH001) for Adult Patients With Postpartum Depression: A Phase 2a Open-Label Clinical Trial — Journal of Clinical Psychiatry
  10. Phase 2 Clinical Trial of GH001 in Postpartum Depression (NCT05804708) — ClinicalTrials.gov