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.

Summary

INTRODUCTION

Psychedelic drugs were extensively used in psychiatry before they were placed in Schedule I of the UN Convention on Psychotropic Substances in 1971. There is now a major revival of human psychedelic research.

5-MeO-DMT is a naturally-occurring tryptamine that works as a selective serotonin receptor agonist at the 5-HT1A and 5-HT2A receptors, whereby functional dominance of the 5-HT1A subtype has been suggested.

5-MeO-DMT has been used in spiritual or self-exploratory contexts for its ability to induce so called peak experiences (PEs), which have been shown to be correlated with therapeutic effects in many prior studies with other psychedelic agents, including tryptamines. Observational studies have shown that 5-MeO-DMT induces mystical experiences that are associated with improvements in subjective measures of satisfaction with life and reduction of psychological distress in participants without an underlying mental health condition.

This study is the first formal prospective clinical study to investigate the safety profile of 5-MeO-DMT and its dose-related effects on states of consciousness. The study suggests that 5-MeO-DMT is non-addictive, and with a low potential for abuse.

This study evaluated the safety and tolerability of a novel vaporized 5-MeO-DMT formulation in healthy volunteers and assessed the impact of 5-MeO-DMT on cognitive functioning, mood, and well-being. The study aimed to determine the optimal dosing regimen of 5-MeO-DMT for achieving a peak experience.

Design

A phase 1 study was conducted with 5-MeO-DMT, where four different volunteers were given a dose of 2, 6, 12, and 18 mg. A Study Safety Group evaluated all available safety data, data on cognitive tests, and data on whether the participants achieved a PE. In part B, participants were given 6,12,18mg of 5-MeO-DMT interspaced at 3 h on a single day, and were informed that all doses were active (part A and B). They were also informed on the subjective effects of treatment, the duration of the effects, and potential adverse events.

The study was comprised of four visits: medical screenings, baseline measurements, administration day, and contact day. After completion of the study, participants were informed about the study drug.

Study Drug Administration

GH001 is a proprietary formulation of highly pure, GMP pharmaceutical grade 5-MeO-DMT for administration via inhalation. The product was administered after a standardized vaporization procedure using the Volcano Medic Vaporization System.

Subjective Ratings of Psychedelic Effects

Subjective psychedelic effects were retrospectively rated at 2 h after the administration representing the participant’s experience during acute 5-MeO-DMT exposure.

Subjective Measures of Mood and Well-Being

Subjective measures of mood and well-being included the DASS-21, SWL, FFMQ, CADSS and BPRS.

Cognitive Tests

A battery of cognitive tests was conducted including the Psychomotor Vigilance Task, Prospective Memory Task and Digit Symbol Substitution Task.

Vital Signs and Blood Samples

The Caretaker 4 monitored vital signs of the participant throughout the test day. Manual cuff-based measurements of blood pressure and heart rate were added for the 12, 18 mg, and IDE groups after 30 min and 1 and 3 h of 5-MeO-DMT exposure.

Blood and urine samples were collected for laboratory safety measures, and 1- and 3-hour post administration samples were taken to assess the elimination of 5-MeO-DMT and its metabolite bufotenine.

Psychedelic Experience

One participant achieved a PE with 6 mg, two participants achieved a PE with 12 mg, and one participant achieved a PE with 18 mg. The mean duration of the psychedelic experience was 13.5 min according to observations and 17.7 min according to subjective estimation.

DISCUSSION

A Phase 1 study was conducted to assess the safety and tolerability of a novel vaporized 5-MeO-DMT formulation administered via inhalation as single doses and in an individualized dose escalation. The study also aimed to quantify the altered state of consciousness as a function of the 5-MeO-DMT dose.

5-MeO-DMT administered as the inhaled GH001 formulation caused little distress to participants, and did not significantly correlate to the total dose of 5-MeO-DMT that participants received.

The current study used the PES, a short scale that integrates central aspects of the MEQ, EDI and 5D-ASC, to monitor the magnitude of psychoactive effects after administration of 5-MeO-DMT. It appeared to be a relevant indicator of the occurrence of peak experiences in eight individuals. The MEQ, EDI and 5D-ASC scales may capture aspects of a psychedelic experience that are not typical of clinical use of 5-MeO-DMT. The PES may provide a more selective and distinct addition to existing questionnaires.

5-MeO-DMT did not elicit any short-term or long-term changes in memory, attention, or cognitive function in healthy volunteers. The concentration of 5-MeO-DMT in the blood was low already 1 hour after administration, and was barely measurable at 3 hours after administration.

The present study did not find any improvement in measures of mood and wellbeing after the administration of 5-MeO-DMT, however, many participants in previous studies reported improved mental health following 5-MeO-DMT use.

The present study demonstrates that a dose range of 6, 12, and 18 mg of the inhaled GH001 formulation of 5-MeO-DMT can induce a peak experience in a minority of healthy participants. An individualized dose escalation regimen produced a peak experience in every participant.

ACKNOWLEDGMENTS

The authors thank the Study Safety Group, Beatrice de Rios, and the participants for their assistance.