The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
This review (2022) explores the current state of research surrounding 5-MeO-DMT. The authors provide food for thought on its therapeutic potential as well as the commercialization of the substance.
Authors
- Johannes Ramaekers
- Nathalie Mason
- Alan Davis
Published
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.
Research Summary of 'The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)'
Introduction
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine found in various plants and in the parotoid gland secretion of the Sonoran Desert toad (Incilius alvarius). The Introduction summarises ethnobotanical reports and biochemical traces that have prompted interest in 5-MeO-DMT, while noting that strong evidence for longstanding indigenous use is limited. The compound has been detected alongside other indole alkaloids such as DMT in plant materials, and its presence in toad venom has driven recreational and experimental use in Western contexts. The authors also review suggestions, and conflicting data, about possible endogenous production of 5-MeO-DMT in mammals and humans, concluding that further evidence is needed to support any physiological role. This paper sets out to survey the clinical pharmacology, subjective effects, neurophysiological actions, and potential therapeutic applications of 5-MeO-DMT, drawing on receptor binding and preclinical studies, observational and survey data, and the limited clinical research to date. The review aims to identify mechanistic pathways (serotonergic, neuroendocrine, immunological, and neuroplasticity-related) that could plausibly underlie reported mental health effects and to highlight gaps that need addressing before clinical development can proceed safely and effectively.
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Reckweg, J. T., Uthaug, M. V., Szabo, A., Davis, A. K., Lancelotta, R., Mason, N. L., & Ramaekers, J. G. (2022). The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Journal of Neurochemistry, 162(1), 128-146. https://doi.org/10.1111/jnc.15587
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