Dimethyltryptamine (DMT): a biochemical Swiss Army knife in neuroinflammation and neuroprotection?

This commentary (2016) reviews the role of DMT as an endogenous ligand of the Sigma-1 receptor, and although the exact physiological role of endogenous DMT is yet to be identified, there is evidence that suggests that it can modulate immune responses through the suppression of inflammatory cytokines. These neuroprotective and neuroregenerative effects may render DMT a potentially useful therapeutic tool in a broad range of chronic inflammatory and autoimmune diseases.


“The inflammatory theory of many neuropsychiatric illnesses has become an emerging trend in modern medicine. Various immune mechanisms – mainly via the activity of microglia – may contribute to the etiology and symptomatology of diseases, such as schizophrenia, bipolar disorder, depression, or Alzheimer’s disease (Deleidi et al., 2015; Khandaker et al., 2015). Unwanted and excess inflammation is most typically the result of dysregulated innate immune responses. Recognition of self-derived damage-associated molecular patterns (DAMPs) or pathogen-associated molecular pattern molecules (PAMPs) is usually leading to the activation of tissue resident immune cells including macrophages (microglia) and dendritic cells. They act as ‘gatekeepers’ continuously monitoring the tissue microenvironment for potential ‘danger signals’ by means of their pattern recognition receptors, such as Toll-like receptors or RIG-I-like receptors. Once a DAMP or PAMP has been recognized by a pattern recognition receptor various downstream signaling pathways are initiated, which eventually leads to the secretion of inflammatory cytokines and many other soluble factors important in the elimination of e.g. invading microbes. Pattern recognition receptors couple to nuclear factor kappaB (NF-κB), the master transcription regulator of inflammatory cytokines (e.g., IL-1β, IL-6, TNFα) and chemokines (e.g., IL-8/CXCL8) (Szabo and Rajnavolgyi, 2013). Macrophages and dendritic cells are also capable of antigen-presentation so they can initiate adaptive immune responses by priming naive T-cells. During inflammation of the central nervous system, polarization towards the T helper 1 and 17 (Th1, Th17) subsets is especially important as these T cells play a major role in the development of chronic inflammation and brain tissue damage in infectious diseases and autoimmunity (Kothur et al., 2016).”

Authors: Atilla Szabó & Ede Frecska

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Literature Review Bio/Neuro

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