N,N-dimethyltryptamine reduces infarct size and improves functional recovery following transient focal brain ischemia in rats
Sándor Nardai, Marcell J László, Attila Szabo, Alán Alpár, János Hanics, Péter Zahola, Béla Merkely, Ede Frecska, Zoltán Nagy
Experimental Neurology February 14, 2020 DOI: 10.1016/j.expneurol.2020.113245 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 38 |
| Population | Male Wistar rats |
| Interventions | N N-dimethyltryptamine (DMT) |
| Dose | 1 mg/kg bolus + 2 mg/kg/h maintenance for DMT; 1 mg/kg bolus + 2 mg/kg/h maintenance for BD1063 |
| Duration | 24-hour infusion; functional recovery assessed over 30 days |
| Topics | 5-MeO-DMT DMT |
| Citations | 91 |
| Key findings | DMT treatment reduced ischemic lesion volume and improved functional recovery in a rat model of stroke, an effect dependent on Sigma-1 receptor activation. |
Abstract
Background and purposeN,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 receptor (Sig-1R) with documented in vitro cytoprotective properties against hypoxia. Our aim was to demonstrate the in vivo neuroprotective effect of DMT following ischemia-reperfusion injury in the rat brain.MethodsTransient middle cerebral occlusion (MCAO) was induced for 60 min in male Wistar rats using the filament occlusion model under general anaesthesia. Before the removal of the filament the treatment group (n = 10) received an intra-peritoneal (IP) bolus of 1 mg/kg-body weight (bw) DMT dissolved in 1 ml 7% ethanol/saline vehicle, followed by a maintenance dose of 2 mg/Kg-bw/h delivered over 24 h via osmotic minipumps. Controls (n = 10) received a vehicle bolus only. A third group (n = 10) received a Sig-1R antagonist (BD1063, 1 mg/kg-bw bolus +2 mg/kg-bw/h maintenance) in parallel with the DMT. Lesion volume was measured by MRI 24 h following the MCAO. Shortly after imaging the animals were terminated, and the native brains and sera were removed. Four rats were perfusion fixed. Functional recovery was studied in two separate group of pre-trained animals (n = 8-8) using the staircase method for 30 days. The expression levels of proteins involved in apoptosis, neuroplasticity and inflammatory regulation were assessed by real-time qPCR and ELISA.ResultsDMT treated rats were characterized by lower ischemic lesion volume (p = .0373), and better functional recovery (p = .0084) compared to the controls. Sig-1R was expressed both in neurons and in microglia in the peri-infarct cortex, and the DMT induced change in the lesion volume was hindered by BD1063. Lower APAF1 expression (mRNA and protein) and higher BNDF levels were documented on DTM, while decreased TNF-α, IL1-β, IL-6 and increased IL-10 expressions indicated the compound's anti-inflammatory potential.ConclusionOur results indicate a Sig-1R dependent reduction of the ischemic brain injury following exogenous DMT administration in rats, presumably through a combined anti-apoptotic, pro-neurotrophic and anti-inflammatory treatment effect.
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 72
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Frontiers in Psychiatry September 10, 2021
- Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study Brain, Behavior, and Immunity September 7, 2023
- From psychiatry to neurology: Psychedelics as prospective therapeutics for neurodegenerative disorders Journal of Neurochemistry September 14, 2021
- Psychedelics as a novel approach to treating autoimmune conditions Immunology Letters October 6, 2020
- N,N-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain. Neuropharmacology July 1, 2021
and 67 more in the library
Cites 7
- The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Science February 13, 2009
- Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Journal of Ethnopharmacology April 1, 1984
- 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. PLoS One 2014
- 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 Prevents Renal Ischemia-Reperfusion Injury in a Rat Model. Transplantation Proceedings May 1, 2019
and 2 more in the library