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

Johannes T. Reckweg, Malin V. Uthaug, Attila Szabo, Alan K. Davis, Rafael Lancelotta, Natasha L. Mason, Johannes G. Ramaekers

Journal of Neurochemistry February 12, 2022 DOI: 10.1111/jnc.15587 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Topics Anxiety 5-MeO-DMT DMT
Keywords Agonist Depression economics Pharmacology Receptor
Citations 108
Key findings 5-MeO-DMT shows potential for rapid and sustained reductions in depression, anxiety, and stress symptoms based on observational studies and surveys, with one clinical trial confirming safety of vaporized dosing up to 18 mg.

Abstract

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 the safety of vaporized dosing up to 18 mg. Importantly, the rapid onset and short duration of the 5‐MeO‐DMT experience may render it more suitable for individual dose‐finding strategies compared with longer‐acting psychedelics. A range of biotech companies has 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 neurophysiological 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. image

Comparable studies

Other narrative reviews on DMT, most cited first.

Study Year Design Participants
Neuropharmacology of N,N-dimethyltryptamine 2016 Review
N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) 2018 Review
Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Humans (pharmacokinetics) 2010 Review
Pharmahuasca: Human Pharmacology of Oral DMT Plus Harmine Human self-experimenters 1999 Review n = 8
The psychedelic model of schizophrenia: the case of N,N- dimethyltryptamine 1976 Review

Citations in the library

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Anxiety 5-MeO-DMT DMT Addiction Depression Ego dissolution Mystical experience Serotonin