The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)

J. T. Reckweg, M. V. Uthaug, A. Szabo, A. K. Davis, R. Lancelotta, N. L. Mason, J. G. Ramaekers*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine that primarily acts as an agonist at the 5-HT1A and 5-HT2A receptors, whereby affinity for the 5-HT1A subtype is highest. Subjective effects following 5-MeO-DMT administration include distortions in auditory and time perception, amplification of emotional states and feelings of ego dissolution that usually are short lasting, depending on the route of administration. Individual dose escalation of 5-MeO-DMT reliably induces a "peak" experience, a state thought to be a core predictor of the therapeutic efficacy of psychedelics. Observational studies and surveys have suggested that single exposure to 5-MeO-DMT can cause rapid and sustained reductions in symptoms of depression, anxiety and stress. 5-MeO-DMT also stimulates neuroendocrine function, immunoregulation and anti-inflammatory processes, which may contribute to changes in mental health outcomes. To date, only one clinical trial has been published on 5-MeO-DMT, demonstrating safety of vaporised dosing up to 18mg. Importantly, the rapid onset and short duration of the 5-MeO-DMT experience may render it more suitable for individual dose finding strategies as compared to longer acting psychedelics. A range of biotech companies have shown an interest in the development of 5-MeO-DMT formulations for a range of medical indications, most notably depression. Commercial development will therefore be the most important resource for bringing 5-MeO-DMT to the clinic. However fundamental research will also be needed to increase understanding of the neurophysical and neural mechanisms that contribute to the potential clinical effects of 5-MeO-DMT and its sustainability and dissemination over time. Such studies are less likely to be conducted as part of drug development programs and are more likely to rely on independent, academic initiatives.

Original languageEnglish
Number of pages19
JournalJournal of Neurochemistry
DOIs
Publication statusE-pub ahead of print - 11 Feb 2022

Keywords

  • 3,4-METHYLENEDIOXYMETHAMPHETAMINE-ASSISTED PSYCHOTHERAPY
  • 5-HT1A RECEPTOR
  • 5-MeO-DMT
  • ASSISTED PSYCHOTHERAPY
  • CENTRAL-NERVOUS-SYSTEM
  • LIFE-THREATENING CANCER
  • MASS SPECTROMETRIC IDENTIFICATION
  • POSTTRAUMATIC-STRESS-DISORDER
  • PROLACTIN SECRETION
  • RECURRENT DEPRESSION
  • SCHIZOPHRENIC-PATIENTS
  • clinical development
  • mental health
  • neuroinflammation

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