A narrative synthesis of research with 5-MeO-DMT

In this review article (2021) researchers combined the evidence from articles about 5-MeO-DMT to enhance our understanding of its potential clinical applications. It was found that although studies in humans are lacking, 5-MeO-DMT has the potential to produce long-term beneficial effects on mental health.


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.”

Authors: Anna O. Ermakova, Fiona Dunbar, James Rucker & Matthew W. Johnson


As we progress through the psychedelic renaissance, researchers are continuously striving to enhance our understanding of psychedelic substances and the therapeutic potential they may possess. One substance that continues to remain somewhat of a mystery is 5-MeO-DMT. This particular substance is best known for being found in the glandular secretion of the Sonoran Desert Toad as well as a wide variety of plant species. While this particular psychedelic has been used throughout history for ritualistic purposes, modern clinical evidence is only beginning to emerge.

The present study seeks to enhance our understanding of 5-MeO-DMT in order to better inform the clinical development of this substance. To do so, researchers reviewed the current literature available on 5-MeO-DMT. The evidence from the literature was then compiled and analyzed using narrative synthesis, covering aspects of the pharmacology, chemistry and metabolism of 5-MeO-DMT, as well epidemiological studies, and reported adverse and beneficial effects.

The main findings:

  • There have been no published clinical trials exploring the effects of 5-MeO-DMT in humans bar one case study investigating the effects of ibogaine and 5-MeO-DMT in a veteran with alcohol use disorder.
  • The majority of research on 5-MeO-DMT has been conducted in animal models, establishing effects of the substance on pharmacokinetics, thermoregulation, nociception, heart rate and blood pressure in these models.
  • Surveys from recreational users imply that 5-MeO-DMT has rapid anxiolytic and antidepressant effects which are not dissimilar to the findings of early psilocybin and LSD studies.
  • Given its short-lasting effects (10-20 minutes) and its ability to induce higher rates of ego-dissolution and mystical experiences, 5-MeO-DMT may be particularly useful psychedelic substance when used in tandem with psychotherapy.

The results of this narrative synthesis indicate that 5-MeO-DMT possess significant therapeutic potential and warrants further clinical investigation. Research is needed to develop the appropriate dose rate in humans and develop the safety profile of 5-MeO-DMT. If these challenges can be overcome, 5-MeO-DMT may be the psychedelic that best fits within the current (or future) medical system.

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