AUTHOR=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. 

TITLE=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

JOURNAL=Frontiers in Psychiatry

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1133414

DOI=10.3389/fpsyt.2023.1133414

ISSN=1664-0640

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>The Phase 1 part (<italic>n</italic> = 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 (<italic>n</italic> = 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.</p></sec><sec><title>Results</title><p>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 (<italic>p</italic> &lt; 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.</p></sec><sec><title>Conclusion</title><p>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.</p><p><bold>Clinical Trial registration</bold>: <ext-link xlink:href="http://Clinicaltrials.gov" ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink">Clinicaltrials.gov</ext-link> Identifier NCT04698603.</p></sec>