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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | 5-MeO-DMT DMT Philosophy of mind |
| Keywords | 5-ht1a receptors Flashbacks Seizures Psychedelics hallucinogens Psychedelic drugs 5-MEO-DMT Tryptamines Dimethy Entheogens Neuroscience brain science Neural activity Neurology |
| Citations | 23 |
| Key findings | 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.
Comparable studies
Other narrative reviews on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuropharmacology of N,N-dimethyltryptamine | 2016 | Review | |
| N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) | 2018 | Review | |
| Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Humans (pharmacokinetics) | 2010 | Review | |
| Dark Classics in Chemical Neuroscience:N,N-Dimethyltryptamine (DMT) | 2018 | Review | |
| A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. | 2013 | Review |
Citations in the library
Cited by 25
- Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression American Journal of Psychiatry 2025
- Why N,N-dimethyltryptamine matters: unique features and therapeutic potential beyond classical psychedelics. Frontiers in Psychiatry November 6, 2024
- Complex slow waves in the human brain under 5-MeO-DMT. Cell Reports July 22, 2025
- Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine in human subjects: a systematic review of clinical trials. Frontiers in Psychiatry 2024
- Psychedelics, entactogens and psychoplastogens for depression and related disorders British Journal of Pharmacology June 15, 2025
and 20 more in the library
Cites 96
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