Medicinal Chemistry & Drug Development5-MeO-DMT

A narrative synthesis of research with 5-MeO-DMT

This narrative review synthesises preclinical, epidemiological and pharmacological literature on 5‑MeO‑DMT, identifying it as a short‑acting serotonergic agonist with highest affinity for 5‑HT1A that produces profound alterations of consciousness (including mystical experiences) but lacks controlled clinical human studies. Given its short duration, relative paucity of visual effects and reportedly high rates of ego‑dissolution, the authors conclude 5‑MeO‑DMT merits further clinical investigation with the same safeguards used for other classic psychedelics.

Authors

  • James Rucker
  • Matthew Johnson
  • Fiona Dunbar

Published

Journal of Psychopharmacology
meta Study

Abstract

Background

5-Methoxy- N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring, short-acting psychedelic tryptamine, produced by a variety of plant and animal species. Plants containing 5-MeO-DMT have been used throughout history for ritual and spiritual purposes. The aim of this article is to review the available literature about 5-MeO-DMT and inform subsequent clinical development.

Methods

We searched PubMed database for articles about 5-MeO-DMT. Search results were cross-checked against earlier reviews and reference lists were hand searched. Findings were synthesised using a narrative synthesis approach. This review covers the pharmacology, chemistry and metabolism of 5-MeO-DMT, as well epidemiological studies, and reported adverse and beneficial effects.

Results

5-MeO-DMT is serotonergic agonist, with highest affinity for 5-HT1A receptors. It was studied in a variety of animal models, but clinical studies with humans are lacking. Epidemiological studies indicate that, like other psychedelics, 5-MeO-DMT induces profound alterations in consciousness (including mystical experiences), with potential beneficial long-term effects on mental health and well-being.

Conclusion

5-MeO-DMT is a potentially useful addition to the psychedelic pharmacopoeia because of its short duration of action, relative lack of visual effects and putatively higher rates of ego-dissolution and mystical experiences. We conclude that further clinical exploration is warranted, using similar precautions as with other classic psychedelics.

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Research Summary of 'A narrative synthesis of research with 5-MeO-DMT'

Introduction

Plant- and fungi-derived classical psychedelics have long histories of ritual and therapeutic use, and in recent decades clinical research into compounds such as psilocybin and LSD has resumed after earlier regulatory restrictions. A recurrent practical issue is that classical psychedelics vary substantially in duration of action: LSD can last about 12 hours after oral ingestion, psilocybin about 6 hours, while shorter-acting substances may offer logistical and cost advantages for therapeutic delivery. Earlier observational literature and survey studies have suggested potential therapeutic benefits from short-acting tryptamines, but controlled human data are sparse. This narrative review set out to synthesise the available preclinical, epidemiological and human-use literature on 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) to inform clinical development. The authors aimed to collate evidence on chemistry, pharmacology, metabolism, safety and reported beneficial and adverse effects, with an explicit view to identifying knowledge gaps relevant to initiating controlled clinical trials of 5-MeO-DMT in humans.

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Study Details

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