A narrative synthesis of research with 5-MeO-DMT

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.

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

“…However, systematic evidence of the therapeutic utility of 5‐MeO‐DMT is currently limited to anecdotal reports and observational studies in self‐selected healthy and clinical populations, who are using the drug in a natural environment (Lancelotta & Davis, 2020). As such, the current therapeutic potential of 5‐MeO‐DMT is mainly hypothetical (Ermakova et al, 2021) and based on preliminary evidence. As reviewed above, current therapeutic evidence stems from a small number of prospective observational studies and cross‐sectional surveys on the naturalistic use of synthetic 5‐MeO‐DMT and toad secretion containing 5‐MeO‐DMT in self‐selected samples.…”

Expectancy in placebo-controlled trials of psychedelics: if so, so what?

“…Psychedelics used in clinical trials, ranging from the short acting 5-methoxy-N,N-dimethyltryptamine (5-MEO-DMT), to longer acting psilocybin, are united in eliciting recognisable subjective effects ('trips') at common doses (Ermakova et al 2021;Nichols 2016). In other words, psychedelics are psychoactive, a property they share with several other medications currently under investigation for neuropsychiatric disorders, such as 3,4-methylenedioxymethamphetamine (MDMA), cannabis and (es)ketamine, as well as several licenced medications, such as benzodiazepines, gabapentinoids (gabapentin, pregabalin), opiates and stimulants (e.g.…”

Classic psychedelics: past uses, present trends, future possibilities

“…Such "flash backs" are more formally given a diagnosis of hallucinogen persisting perception disorder (HPPD). However, such enduring perceptual disturbances are rare (Ermakova et al, 2021), and are also not necessarily harmful. Further, such side effects (or potential active ingredients for catalyzing other kinds of change) are not exclusive to psychedelics, with both benzodiazepines and tobacco having been noted as potential causes of HPPD (Halpern et al, 2018).…”