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. 2021 Nov 25:12:760671.
doi: 10.3389/fphar.2021.760671. eCollection 2021.

A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers

Johannes Reckweg  1 , Natasha L Mason  1 , Cees van Leeuwen  1 , Stefan W Toennes  2 , Theis H Terwey  3 , Johannes G Ramaekers  1
Affiliations

A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers

Johannes Reckweg et al. Front Pharmacol. .

Abstract

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels of a novel vaporized 5-MeO-DMT formulation (GH001) administered via inhalation as single doses of 2 (N = 4), 6 (N = 6), 12 (N = 4) and 18 mg (N = 4), and in an individualized dose escalation regimen (N = 4) on the safety, tolerability, and the dose-related psychoactive effects in healthy volunteers (N = 22). The psychedelic experience was assessed with a novel Peak Experience Scale (PES), the Mystical Experience Questionnaire (MEQ), the Ego Dissolution Inventory (EDI), the Challenging Experience Questionnaire (CEQ), and the 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Further aims were to assess the impact of 5-MeO-DMT on cognitive functioning, mood, and well-being. Higher doses of 5-MeO-DMT produced significant increments in the intensity of the psychedelic experience ratings as compared to the lowest 2 mg dose on all questionnaires, except the CEQ. Prominent effects were observed following single doses of 6, 12, and 18 mg on PES and MEQ ratings, while maximal effects on PES, MEQ, EDI, and 5D-ASC ratings were observed following individualized dose escalation of 5-MeO-DMT. Measures of cognition, mood, and well-being were not affected by 5-MeO-DMT. Vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously. Individualized dose escalation of 5-MeO-DMT may be preferable over single dose administration for clinical applications that aim to maximize the experience to elicit a strong therapeutic response.

Keywords: 5-MeO-DMT; cognition; dose finding; psychedelic agents; psychoactive.

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Conflict of interest statement

This study was funded by GH Research, Dublin, Ireland. JR and JGR are scientific consultants to GH Research. TT is an employee and shareholder of the company GH Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mean (SE) and individual retrospective ratings of the acute psychedelic experience (PES, EDI, MEQ, CEQ) per dose level.
FIGURE 2
FIGURE 2
Mean (SE) and individual retrospective ratings of the acute psychedelic experience per dose level for 5 key-dimensions on the 5D-ASC and the overall score.
FIGURE 3
FIGURE 3
Mean (SE) and individual CADSS and DASS ratings per dose level.
FIGURE 4
FIGURE 4
Mean (SE) and individual lapses of attention in the PVT, number of correct responses in the DSST, number of correct inhibitions in the PVT, ratings of satisfaction with life, mindfulness (FFMQ) and BPRS in every dose condition.
See this image and copyright information in PMC

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