5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk?
Bradley, M. K., Carhart-Harris, R. L., Dourron, H. M., Hendricks, P. S., Nichols, C. D., Simonsson, O.
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
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.