N, N-dimethyltryptamine (DMT) in rodent brain: Concentrations, distribution, and recent pharmacological data.
Progress in Neuro-Psychopharmacology and Biological Psychiatry March 20, 2025 DOI: 10.1016/j.pnpbp.2025.111259 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Rat brain neurons |
| Topics | DMT Neuroplasticity 5-MeO-DMT |
| Keywords | Stress response Developmental biology Golgi Neurodevelopment Receptor Psychopharmacology Brain chemistry |
| Citations | 3 |
| Key findings | DMT is proposed as the missing endogenous ligand for intracellular 5-HT2a receptors in the Golgi apparatus, and its brain levels are elevated by stress in rats, suggesting involvement in brain development and adaptive regulation. |
Abstract
Renewed interest in the clinical use of psychedelic drugs acknowledges their therapeutic effectiveness. It has also provided a changing frame of reference for older psychedelic drug study data, especially regarding concentrations of N, N-dimethyltryptamine (DMT) reported in rodent brains and recent discoveries in DMT receptor interactions in rat brain neurons and select brain areas. The mode of action of DMT in its newly defined role as a neuroplastogen, its effectiveness in treating neuropsychiatric disorders, and its binding to intracellular sigma-1 and 5HT2a receptors may define these possible roles. Recent data also show psychedelics promote neuroplasticity via activation of sigma-1 receptors associated with the endoplasmic reticulum and binding to 5-HT2a receptors predominantly related to the intracellular membrane of the Golgi apparatus in cortical neurons and the failure of DMT to occupy cell surface 5-HT2a receptors. While DMT has been proposed as the endogenous ligand for sigma-1, there is no identified ligand for intracellular 5-HT2a receptors, which serotonin cannot acquire. DMT is proposed to be the missing endogenous ligand. These data further suggest that DMT may be involved in brain development in rat pups. Brain levels of DMT have also been shown to be elevated by stress in the rat and appear to be under an inducible, adaptive, physiological regulatory system control. With DMT acting as the natural ligand for intracellular 5HT2a receptors in the Golgi, it may also explain the subjective effects observed from the administration of psychedelics in general and define some of the natural roles for DMT in particular.
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 4
- Antinociceptive effect of N,N-dimethyltryptamine (DMT) involving serotonergic, opioidergic, cannabinoidergic, and nitrergic systems in PGE2-induced hyperalgesia in rats Journal of Pain Research and Management February 14, 2026
- N,N-dimethyltryptamine (DMT) is neither formed nor retained in serotonin terminals in the rat brain Neuropharmacology February 9, 2026
- Indolethylamine N-Methyltransferase Deletion Impacts Mouse Behavior without Disrupting Endogenous Psychedelic Tryptamine Production. ACS Chemical Neuroscience October 15, 2025
- From molecules to meaning: unpacking the antidepressant mechanisms of psychedelic drugs. Expert Review of Clinical Pharmacology June 11, 2025
Cites 58
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- The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacology & Translational Science December 10, 2020
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
and 53 more in the library