This review (2023) of 5-MeO-DMT, a tryptamine with unique antidepressant potential, notes its distinct effects compared to typical psychedelics. It draws parallels between 5-MeO-DMT’s effects and epileptiform activity, particularly through 5-HT1A receptor interactions, suggesting its therapeutic action may resemble electroconvulsive therapy (ECT).

Abstract of 5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk?

“5-MeO-DMT is a tryptamine being developed as a potential antidepressant that may display a distinct therapeutic mecha-nism due to its unique pharmacology and subjective effects compared to typical psychedelics. In this article, we parallel the relatively distinct phenomenology and behavioral effects of the acute and post-acute effects of 5-MeO-DMT to those induced by epileptiform activity, particularly in instances within epileptogenic zones of the temporal lobes. This is done by reviewing aberrant 5-HT1A receptor functioning in epilepsy, noting that 5-MeO-DMT has notable 5-HT1A receptor agonist properties—and then comparing the acute behavioral and subjective effects induced by 5-MeO-DMT to those that occur in seizures. It might be that 5-MeO-DMT’s therapeutic mechanism is partly mediated by evoking temporary epileptiform activity, suggesting a similarity to electroconvulsive therapy. It is also noted that “reactivations,” the sudden re-experiencing of drug effects common after 5-MeO-DMT but not after typical psychedelics, may suggest that 5-MeO-DMT produces recurrent epileptiform activity. Overall, this review indicates that further evaluation of 5-MeO-DMT’s unique mechanisms in research settings and among naturalistic users are warranted.“

Authors: Haley M. Dourron, Charles D. Nichols, Otto Simonsson, Melissa Bradley, Robin L. Carhart‑Harris & Peter S. Hendricks

Summary of 5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk?

5-MeO-DMT is a tryptamine found in several plant species as well as in the defence secretions of the Incilius alvarius (Colorado River toad). It is unclear whether the principal pharmacological action of 5-MeO-DMT is via 5-HT2A receptor agonism.

Humans have not used 5-MeO-DMT for a long time. It has only recently been studied in humans, and there is no long-term history of human use of 5-MeO-DMT. 5-MeO-DMT is relatively rarely used recreationally today, but interest in the compound is increasing online, and researchers are beginning to examine the effects of naturalistic use of the compound.

Research suggests that 5-MeO-DMT has the potential to decrease anxiety and depressive symptoms, and a recent open-label trial suggests that it may reduce symptoms of treatment-resistant depression for at least one week. However, any advantage over the short-acting typical psychedelic, DMT, is unclear.

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