Citation

Reckweg JT, van Leeuwen CJ, Henquet C, van Amelsvoort T, Theunissen EL, Mason NL, Paci R, Terwey TH, Ramaekers JG. Front. Psychiatry 2023; 14.

Copyright

(Copyright © 2023, Frontiers Media)

DOI

10.3389/fpsyt.2023.1133414

PMID

unavailable

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. Copyright © 2023 Reckweg, van Leeuwen, Henquet, van Amelsvoort, Theunissen, Mason, Paci, Terwey and Ramaekers.

Language: en

Keywords

adult; human; female; male; depression; clinical trial; Brief Psychiatric Rating Scale; disease severity; clinical article; headache; anxiety disorder; drug safety; drug efficacy; drug tolerability; nausea; cohort analysis; remission; paresthesia; drug dose regimen; dizziness; Montgomery Asberg Depression Rating Scale; Article; single drug dose; abdominal discomfort; open study; phase 2 clinical trial; muscle spasm; sensory dysfunction; antidepressant activity; treatment resistant depression; treatment-resistant depression; mental disease assessment; Columbia suicide severity rating scale; psychedelics; Clinician Administered Dissociative States Scale; phase 1 clinical trial; digit symbol substitution test; 5-MeO-DMT; individualized dosing; mebufotenin; psychomotor vigilance task