DMT might protect your brain post-stroke!

To the surprise of many, the compound allows many users across all social media platforms to communicate with alien beings. To become jaguars, or in the mouth of many, the “Strongest Psychedelic”, DMT, is not only found in hundreds of plant species, from Mimosa Hostilis to the leaves of a simple citrus tree, like a lemon tree, for example. It is also found within the human body. While this statement alone has various back-and-forths about its veracity, we must clear the claim. Typically, when we read/hear people claiming that we have DMT in our bodies, they are following the ideology brought to us by Rick Strassman, who claimed that DMT was produced by our pineal gland. As a result, we would release DMT in near-death experiences, allowing the so-called “life flashing before our eyes”.

DMT: Consciousness Expedition

While Strassman found evidence of endogenous DMT in the pineal glands of rats, the same cannot be said about the human brain. However, the idea that we DO have endogenous DMT is not entirely wrong, as early as 1965, FR. FRANZEN & H. Gross have found evidence of endogenous DMT in various tissues (for example, the liver and lungs) using techniques as gas chromatography and mass spectrometry.

How we biosynthesize DMT:

Pathways for the biosynthesis and metabolism of DMT, 1. Biosynthesis: Tryptophan (2) is converted to tryptamine (TA, 3) by aromatic amino acid decarboxylase (AADC). TA is dimethylated to first yield N-methyltryptamine (NMT, 4) and then DMT (1) by indole-N-methyltransferase (INMT), using S-adenosyl-methionine (SAM) as the methyl source. Metabolism: TA, NMT, and DMT are all substrates for monoamine oxidase, yielding indole-3-acetic acid (5, IAA) as both a common precursor metabolite and the most abundant metabolite of DMT itself. DMT is also converted to DMT-N-oxide (6) as the second-most abundant metabolite. Two 1,2,3,4-tetrahydro-beta-carbolines (THBCs) have also been identified as metabolites: 2-methyl-THBC (7, MTHBC) and THBC (8). –Source: Barker SA. N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function. Front Neurosci. 2018 Aug 6;12:536. doi: 10.3389/fnins.2018.00536. PMID: 30127713; PMCID: PMC6088236.

 

DMT acts as a natural endogenous agonist of the Sigma-1 receptor, thus demonstrating its versatility in modulating multiple physiological systems (such as mitochondrial function, cell survival, and proliferation). When administered exogenously (whether consumed in the Ayahuasca tea, or boofing/smoking, or even IV the extracted/synthetic compound), it has a complex and profound impact on human consciousness due to its interaction with serotonin, glutamate, and sigma receptors, each with varying affinities (you can read more about the depths of DMT pharmacokinetics here!)

 

We will focus on the Sigma-1 interaction to understand how DMT could protect your brain after a stroke.

 

Upon administering DMT in rats with ischemic brain injury, the team of Marcell J. László et al. observed reduced apoptosis, increased neurotrophic activity, and decreased inflammation, which could be potential contributory mechanisms behind the treatment effect. While the study mainly focuses on the mechanism of Sigma-1 receptors, we must include that the 5-HT1A may also have contributed to these changes.

 

Such a mechanism was somewhat misunderstood until fairly recently.

 

Effect of DMT on infarct size and barrier integrity in a rat model of stroke. (A) Representative images of coronal brain sections from a DMT-treated rat, stained with cresyl violet, are shown sequentially from cranial to caudal sections. The infarct area is delineated by a yellow dotted line. (B and C) Comparison of brain infarct volumes and edema between the stroke group (n = 10) and the DMT-treated stroke group (n = 9). DMT treatment reduced both infarct volume (**P = 0.0327) and associated edema (**P = 0.0135); mean ± SD, unpaired t test. (D) Treatment and procedure timeline. (E) Representative magnetic resonance imaging (MRI) images of rats from the stroke group, DMT-treated stroke group, and DMT + BD1063 cotreated group (n = 10 rats per group) are shown in sagittal, axial, and coronal planes. (F) Representative images show green fluorescence, indicating FITC-albumin extravasation into the brain parenchyma. (G) Quantification of FITC-albumin extravasation in the control and injured brain hemispheres in the stroke, DMT-treated stroke, and DMT + BD1063–treated stroke groups (n = 7 rats per group). DMT reduced FITC intensity compared to the stroke group (***P = 0.0093). Cotreatment with DMT + BD1063 also decreased intensity relative to stroke (*P = 0.011) and showed no difference from the DMT treatment group (P = 0.4254); mean ± SD, two-way analysis of variance (ANOVA) with Bonferroni’s post hoc test. No change was observed in the noninjured hemispheres. AU, arbitrary units. (H) Quantification of FITC-albumin extravasation to the CSF by fluorescence spectroscopy (n = 5 rats per group). FITC intensity was lower in the DMT-treated group (*P = 0.0454) but not in the DMT + BD1063 cotreatment group compared to the stroke group (P = 0.3821).

 

The team followed up on the previous research to better understand the underlying mechanisms, leading to evidence that the reduction of infarct volume is accompanied by a reduction of cerebral edema, attenuated astrocyte dysfunction, and a shift in serum protein composition toward an anti-inflammatory, neuroprotective state.

 

DMT restored the tight junction integrity and blood-brain barrier function both in vitro and in vivo.  The compound suppressed the release of pro-inflammatory cytokines and chemokines in brain endothelial cells and peripheral immune cells while reducing microglial activation via sigma-1 receptor. Proving that DMT mitigates poststroke effects by stabilizing the blood-brain barrier and reducing neuroinflammation.

 

Thus making DMT a potential candidate for future stroke therapy.

 

References:

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