A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression
In a Phase 1/2 trial of 16 adults with treatment‑resistant depression, inhaled 5‑MeO‑DMT (GH001) was evaluated as single doses (12 mg, 18 mg) and as an individualized regimen of up to three ascending doses in one day. GH001 was well tolerated and produced ultra‑rapid antidepressant effects, with remission at day 7 in 7/8 (87.5%) patients in the individualized dosing group, markedly higher than the single‑dose arms.
Authors
- Johannes Ramaekers
- Nathalie Mason
- Eline Theunissen
Published
Abstract
Background
Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD.
Methods
The Phase 1 part (n = 8) of the trial investigated two single dose levels of GH001 (12 mg, 18 mg) with a primary endpoint of safety, and the Phase 2 part (n = 8) investigated an individualized dosing regimen (IDR) with up to three increasing doses of GH001 (6 mg, 12 mg, and 18 mg) within a single day, with a primary endpoint of efficacy, as assessed by the proportion of patients in remission (MADRS ≤ 10) on day 7.
Results
Administration of GH001 via inhalation was well tolerated. The proportion of patients in remission (MADRS ≤ 10) at day 7 was 2/4 (50%) and 1/4 (25%) in the 12 mg and 18 mg groups of Phase 1, respectively, and 7/8 (87.5%) in the IDR group of Phase 2, meeting its primary endpoint (p < 0.0001). All remissions were observed from day 1, with 6/10 remissions observed from 2 h. The mean MADRS change from baseline to day 7 was −21.0 (−65%) and − 12.5 (−40%) for the 12 and 18 mg groups, respectively, and − 24.4 (−76%) for the IDR.
Conclusion
Administration of GH001 to a cohort of 16 patients with TRD was well tolerated and provided potent and ultra-rapid antidepressant effects. Individualized dosing with up to three doses of GH001 on a single day was superior to single dose administration.Clinical
Research Summary of 'A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression'
Introduction
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonergic tryptamine that acts primarily at 5-HT1A and 5-HT2A receptors and, when inhaled, produces very rapid (seconds) but short-lived (minutes) psychoactive effects. Naturalistic use and observational surveys of 5-MeO-DMT (including toad-venom sources and synthetic preparations) have reported subjective improvements in well-being and reduced depressive symptoms in some users. Other serotonergic tryptamines (for example psilocybin and DMT) have shown antidepressant effects in clinical trials, but it remains unknown whether 5-MeO-DMT can produce therapeutic benefit in major depressive disorder, what dose(s) are required, and how best to manage the considerable inter-individual variability in acute effects. The authors set out to investigate safety and potential antidepressant efficacy of GH001, a vapourised pharmaceutical-grade formulation of 5-MeO-DMT, in patients with treatment-resistant depression (TRD). The trial comprised a Phase 1 component testing single doses (12 mg and 18 mg) with safety as the primary endpoint, and a Phase 2 component testing an individualized dosing regimen (IDR) of up to three escalating doses (6 mg, 12 mg, 18 mg within a single day) with the primary efficacy endpoint of remission (MADRS ≤ 10) at day 7. The IDR was motivated by short duration of 5-MeO-DMT effects and the aim to adapt dosing to individual response while limiting unnecessary high exposure.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- Authors
- APA Citation
Reckweg, J. T., van Leeuwen, C. J., Henquet, C., van Amelsvoort, T., Theunissen, E. L., Mason, N. L., Paci, R., Terwey, T. H., & Ramaekers, J. G. (2023). A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression. Frontiers in Psychiatry, 14. https://doi.org/10.3389/fpsyt.2023.1133414
References (16)
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Davis, A. K., Barsuglia, J. P., Lancelotta, R. et al. · Journal of Psychopharmacology (2018)
Uthaug, M. V., Lancelotta, R., van Oorsouw, K. et al. · Psychopharmacology (2019)
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Palhano-Fontes, F., Barreto, D., Onias, H. et al. · Psychological Medicine (2018)
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Show all 16 referencesShow fewer
Carhart-Harris, R. L., Giribaldi, B., Watts, R. et al. · New England Journal of Medicine (2021)
Nichols, C. D., Nichols, D. E., Johnson, M. W. · Clinical Pharmacology and Therapeutics (2016)
Gallimore, A. R., Strassman, R. J. · Frontiers in Pharmacology (2016)
Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (2019)
Romeo, B., Hermand, M., Pétillion, A. et al. · Journal of Psychiatric Research (2021)
Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)
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