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

This Phase I study assessed the safety and psychoactive effects of 5-MeO-DMT (GH001) in healthy volunteers (n=22). Single doses of 6, 12, and 18 mg of the inhaled GH001 formulation of 5-MeO-DMT were able to induce a peak experience in a minority of participants. An individualized dose escalation regimen produced a peak experience in every participant. Measures of cognition, mood, and well-being were not affected by 5-MeO-DMT. Adverse events were generally mild and resolved spontaneously.

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.”

Authors: Johannes Reckweg, Natasha L. Mason, Cees van Leeuwen, Stefan W. Toennes, Theis H. Terwey & Johannes G. Ramaekers

Notes

In the world of psychedelics, 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a somewhat controversial substance. Much of this controversy relates to Bufo alvarius, or the Sonoran Desert Toad, which secretes a venom rich in 5-MeO-DMT to keep predators at bay. The recent popularization of psychedelics on television and in the media has led to an increase in the practice of catching and “milking” these toads in order to extract the psychoactive venom. Perhaps unbeknownst to these curious psychonauts, such practices are pushing this species towards extinction.

Given the therapeutic potential of 5-MeO-DMT, researchers are exploring the possibility of utilizing lab-created synthetic alternatives of this molecule. Beckley Psytech is one such company that is currently conducting a Phase I study exploring the safety and tolerability of a novel formulation of intranasal 5-MeO-DMT. Another company in this area of psychedelic science is GH Research who have just published the findings from their Phase I study investigating GH001, their proprietary inhalable 5-MeO-DMT formulation.

The present study assessed the safety, tolerability and impact of four different doses of GH001 in 22 healthy volunteers. Doses included 2 (n=4), 6 (n=6), 12 (n=4) and 18 mg (n=4), as well as an individualized dose escalation regimen (n=4).

Main findings:

• Higher doses of 5-MeO-DMT produced significant increments in the mean intensity of the psychedelic experience as compared to the lowest 2 mg dose across all questionnaires used, bar the Challenging Experience Questionnaire.
• Measures of cognition, mood, and wellbeing were not affected by 5-MeO-DMT.
• 5-MeO-DMT was generally well tolerated as vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously,
• The 5-MeO-DMT dose needed to achieve a peak experience largely varies between individuals suggesting that 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.

Overall, the findings of the present study show that the novel formulation of 5-MeO-DMT, GH001, is safe and is well tolerated. Such findings are important for future therapeutic applications of any 5-MeO-DMT formulation as well as ensuring the conservation of Bufo alvarius.