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
Johannes T. Reckweg, Cees van Leeuwen, Cécile Henquet, Therese van Amelsvoort, Eef L. Theunissen, Natasha L. Mason, Riccardo Paci, Theis H Terwey, Johannes G. Ramaekers
Frontiers in Psychiatry June 20, 2023 DOI: 10.3389/fpsyt.2023.1133414 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phase 1/2 clinical trial Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Adult patients with treatment-resistant depression |
| Dose | 12 mg, 18 mg; individualized regimen up to 6 mg, 12 mg, and 18 mg |
| Duration | Single-day dosing, 7-day follow-up |
| Topics | 5-MeO-DMT Depression DMT |
| Keywords | Clinical trial Individualized dosing Psychedelics hallucinogens Entheogens Psychedelic medicine Mental health psychiatry Psychological treatment Behavioral health Medical studies Scientific research Depression treatment antidepress |
| Citations | 86 |
| Registration | NCT04698603 |
| Key findings | An individualized dosing regimen of inhaled 5-MeO-DMT (GH001) produced a 87.5% remission rate at day 7 in patients with treatment-resistant depression, outperforming single-dose administration. |
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.