N,N-dimethyltryptamine mitigates experimental stroke by stabilizing the blood-brain barrier and reducing neuroinflammation.
Marcell J László, Judit P Vigh, Anna E Kocsis, Gergő Porkoláb, Zsófia Hoyk, Tamás Polgár, Fruzsina R Walter, Attila Szabo, Srdjan Djurovic, Béla Merkely, Alán Alpár, Ede Frecska, Zoltán Nagy, Mária A Deli, Sándor Nardai
Science Advances August 15, 2025 DOI: 10.1126/sciadv.adx5958 (opens in new tab)
Study at a glance
AI-extracted from the abstractAbstract
N,N-dimethyltryptamine (DMT) is a psychoactive molecule present in the human brain. DMT is under clinical evaluation as a neuroprotective agent in poststroke recovery. Yet, its mechanism of action remains poorly understood. In a rat transient middle cerebral artery occlusion stroke model, we previously showed that DMT reduces infarct volume. Here, we demonstrate that this effect is accompanied by reduction of cerebral edema, attenuated astrocyte dysfunction, and a shift in serum protein composition toward an anti-inflammatory, neuroprotective state. DMT restored tight junction integrity and blood-brain barrier (BBB) function in vitro and in vivo. DMT suppressed the release of proinflammatory cytokines and chemokines in brain endothelial cells and peripheral immune cells and reduced microglial activation via the sigma-1 receptor. Our findings prove that DMT mitigates a poststroke effect by stabilizing the BBB and reducing neuroinflammation. Such interactions of DMT with the vascular and immune systems can be leveraged to complement current, insufficient, stroke therapy.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 7
- Psychoplastogens to Reduce Persistent Cognitive Symptoms for Traumatic Brain Injury as a Chronic Condition Journal of Neurotrauma October 19, 2026
- Direct anti-inflammatory actions of N,N -dimethyltryptamine on microglia are revealed by proteomic profiling and receptor pharmacology bioRxiv (Cold Spring Harbor Laboratory) August 11, 2026
- Proliferative Effects of the Psychedelic N,N-Dimethyltryptamine (DMT) in Human Neural Stem Cells. ACS Chemical Neuroscience July 9, 2026
- Therapeutic properties of ayahuasca component N,N-Dimethyltryptamine in a pre-clinical model of Parkinson's disease. Experimental Neurology May 12, 2026
- Pretreatment with the psychedelic DOI mitigates LPS-induced hippocampal inflammation and behavioral impairments in mice BMC Neuroscience March 24, 2026
and 2 more in the library
Cites 7
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain. Scientific Reports June 27, 2019
- A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. Journal of Neural Transmission April 26, 2013
- N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats Experimental Neurology February 14, 2020
and 2 more in the library