5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk?
Haley Maria Dourron, Charles D Nichols, Otto Simonsson, Melissa Bradley, Robin Carhart-Harris, Peter S Hendricks
Psychopharmacology December 11, 2023 DOI: 10.1007/s00213-023-06517-1 via PubMed
Summary
AI-generated from the abstract5-MeO-DMT, a tryptamine being developed as an antidepressant, may work through a mechanism distinct from typical psychedelics. This review compares the acute and post-acute effects of 5-MeO-DMT to epileptiform activity, particularly in temporal lobe epileptogenic zones. The authors note that 5-MeO-DMT has notable 5-HT1A receptor agonist properties and that aberrant 5-HT1A receptor functioning occurs in epilepsy. They suggest that 5-MeO-DMT's therapeutic mechanism might be partly mediated by evoking temporary epileptiform activity, similar to electroconvulsive therapy. The phenomenon of 'reactivations'—sudden re-experiencing of drug effects common after 5-MeO-DMT but not typical psychedelics—may indicate recurrent epileptiform activity. The review concludes that further evaluation of 5-MeO-DMT's unique mechanisms is warranted.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | 5-MeO-DMT |
| Keywords | 5-ht1a receptors Flashbacks Seizures Psychedelics hallucinogens Psychedelic drugs |
| Citations | 23 |
| Key finding | 5-MeO-DMT's therapeutic mechanism may be partly mediated by evoking temporary epileptiform activity, suggesting a similarity to electroconvulsive therapy. |
Abstract
5-MeO-DMT is a tryptamine being developed as a potential antidepressant that may display a distinct therapeutic mechanism 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.