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 – June 20, 2023
Source: OpenAlex
Summary
A potent new antidepressant approach for treatment-resistant depression shows promise: an individualized dosing regimen of the psychedelic 5-MeO-DMT. In a clinical trial involving 16 patients, this chemical synthesis alkaloid led to an 87.5% remission rate by day 7, a key clinical endpoint. This pharmacology-driven regimen, influencing neurotransmitter receptors, significantly improved symptoms, with a 76% average reduction in depression scores. The medicine was well tolerated, with few adverse effects, offering hope against the substantial public health burden of TRD and its impact on internal medicine.
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.