2026 ECNP Congress

PS02-2129

Inhaled mebufotenin (GH001) improves quality of life across multiple domains in patients with treatment-resistant depression

Bernhard T. Baune — T. Benway, B. Brennan, W.J. Cubała, D. Gregory, R. MacIsaac, M.E. Thase · University of Münster, Department of Psychiatry, Münster, Germany

2026 ECNP Congress

Background

Patients with treatment-resistant depression (TRD) experience significant impairment in health-related quality of life (HRQoL) which is substantially greater than that observed in patients with treatment-responsive major depressive disorder [1]. Current therapies for TRD are limited, and there is substantial unmet need for treatments offering rapid therapeutic benefit with sustained meaningful improvement in daily functioning. GH001, a synthetic formulation of mebufotenin (5-MeO-DMT) for pulmonary inhalation, demonstrated rapid reductions in depressive symptoms versus placebo in a Phase 2b trial (NCT05800860) in patients with TRD at Day 8 (Montgomery–Åsberg Depression Rating Scale [MADRS] least-squares mean difference, −15.5; P<0.0001) [2]. The median duration of psychoactive effects was 11 minutes, and at 99.0% (285/288) of treatment visits, patients were discharge ready at 1-hour post-dose on the dosing day.

Aims

This analysis examines the effects on quality of life as measured by the Quality of Life, Enjoyment, and Satisfaction Questionnaire–Short Form (Q-LES-Q-SF).

Methods

In the double-blind part, 81 patients with TRD were randomised 1:1 to receive a single-day individualised dosing regimen (IDR) of GH001 (up to three escalating doses of 6, 12, and 18 mg) or placebo. All patients transitioned to a 6-month open-label extension (OLE), during which up to five GH001 IDR treatments could be administered based on MADRS score criteria, safety, and tolerability. This trial was conducted under the supervision of qualified healthcare professionals, providing psychological support per standard of care, but without any planned psychotherapeutic intervention before, during, or after dosing. The Q-LES-Q-SF, a 16-item patient-reported measure of enjoyment and satisfaction across areas of daily life, was assessed at baseline and Day 8 after each treatment, and all scheduled OLE visits (Day 15 and monthly up to Month 6/end of treatment). Total scores and scores across four ad hoc investigational domains (mood and psychological well-being; social and relationship life; physical health and ability; work, housing, leisure, and daily functioning) were evaluated; the Q-LES-Q-SF has no official subscale scoring system.

Results

Baseline Q-LES-Q-SF total scores were 27.9 (8.98) and 25.3 (8.14) for the GH001 and placebo groups, respectively. At Day 8, the least-squares mean (SE) change from baseline was 20.6 (1.8) for GH001 (n=37) versus −0.8 (1.7) for placebo (n=40) (P<0.0001). Mean percentage improvements were observed across all four investigated domains at Day 8: mood and psychological well-being (+32.8%), social and relationship life (+32.3%), physical health and ability (+25.1%), and work, housing, leisure, and daily functioning (+20.3%) for GH001, compared with minimal changes for placebo (+1.0%, +1.5%, 0.0%, and −1.0%, respectively). Among patients who completed the 6-month OLE, the total mean (SD) change from baseline in Q-LES-Q-SF was 24.8 (14.1). Mean percentage domain-level improvements were sustained at 6 months after infrequent treatment.

Conclusions

GH001 led to rapid and significant and meaningful improvement in patient-reported quality of life at Day 8, with benefits sustained at 6 months among OLE completers after infrequent treatment. Meaningful improvements were observed across all investigated domains suggesting the rapid and durable antidepressant effects of GH001 translate into meaningful gains in patients’ wellbeing and satisfaction.

References

  1. DiBernardo A, Lin X, Zhang Q, et al. Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study. BMC Psychiatry. 2018;18(1):352. DOI: 10.1186/s12888-018-1920-7. PMID: 30373547. PMCID: PMC6206859.
  2. Cubała WJ, Bajbouj M, Bauer M, et al. GH001 vs Placebo in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. Published online March 25, 2026. doi:10.1001/jamapsychiatry.2026.0096.