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

• Published in: Frontiers in psychiatry Vol. 14; p. 1133414
• Main Authors: Reckweg, Johannes T, van Leeuwen, Cees J, Henquet, Cécile, van Amelsvoort, Therese, Theunissen, Eef L, Mason, Natasha L, Paci, Riccardo, Terwey, Theis H, Ramaekers, Johannes G
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.06.2023
• Subjects: 5-MeO-DMT; clinical trial; individualized dosing; psychedelics; Psychiatry; treatment-resistant depression; clinical trial; psychedelics; treatment-resistant depression; 5-MeO-DMT; individualized dosing
• ISSN: 1664-0640; 1664-0640
• DOI: 10.3389/fpsyt.2023.1133414

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. The Phase 1 part (  = 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 (  = 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. 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 (  < 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. 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. : Clinicaltrials.gov Identifier NCT04698603.