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Cited by 96Psychedelics and Drug StudiesTreatment of Major DepressionTryptophan and brain disorders

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

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Reckweg, Johannes T., van Leeuwen, Cees J., Henquet, Cécile, van Amelsvoort, Therese, Theunissen, Eef L., Mason, Natasha L., Paci, Riccardo, Terwey, Theis H. +1 more·2023·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2023.1133414PMC PMC10319409
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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 Trial registration: Clinicaltrials.gov Identifier NCT04698603.

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  • In the 2 identified studies of 5-MeO-DMT, no SAEs or NSAEs of medical or psychiatric significance were reported.

    “In the 2 identified studies of 5-MeO-DMT, 1 in healthy participants (n = 22)18 and the other among participants with treatment-resistant depression (n = 16),19 no SAEs or NSAEs of medical or psychiatric significance were reported.”

    From Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis (2024) · cites this paper as [19]

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Authors
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.
Affiliations
Maastricht University (NL)
Corresponding author
  • Reckweg, Johannes T.
  • Ramaekers, Johannes G.
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2023-06-20
Volume
14
Pages
1133414-1133414
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2023.1133414
PMC
PMC10319409
OpenAlex
W4381433809
Cited by
96
References
9
Citations by year
2026: 30 · 2025: 38 · 2024: 23 · 2023: 5
FWCI
27.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
treatment-resistant depression, 5-MeO-DMT, psychedelics, inhalation administration, antidepressant efficacy, remission, safety, serotonergic psychedelics

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