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A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity


N,N-dimethyltryptamine (DMT) is classified as a naturally occurring serotonergic hallucinogen of plant origin. It has also been found in animal tissues and regarded as an endogenous trace amine transmitter. The vast majority of research on DMT has targeted its psychotropic/psychedelic properties with less focus on its effects beyond the nervous system. The recent discovery that DMT is an endogenous ligand of the sigma-1 receptor may shed light on yet undiscovered physiological mechanisms of DMT activity and reveal some of its putative biological functions. A three-step active uptake process of DMT from peripheral sources to neurons underscores a presumed physiological significance of this endogenous hallucinogen. In this paper, we overview the literature on the effects of sigma-1 receptor ligands on cellular bioenergetics, the role of serotonin, and serotoninergic analogues in immunoregulation and the data regarding gene expression of the DMT synthesizing enzyme indolethylamine-N-methyltransferase in carcinogenesis. We conclude that the function of DMT may extend central nervous activity and involve a more universal role in cellular protective mechanisms. Suggestions are offered for future directions of indole alkaloid research in the general medical field. We provide converging evidence that while DMT is a substance which produces powerful psychedelic experiences, it is better understood not as a hallucinogenic drug of abuse, but rather an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies.

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The authors acknowledge the assistance of Eszter Acs in the preparation of the manuscript.

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No financial support was necessary for the preparation of this paper. All authors contributed in a significant way to the manuscript and all authors have read and approved the final manuscript. The authors declare that they have no conflicts of interest in the research.

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Correspondence to Ede Frecska.

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Frecska, E., Szabo, A., Winkelman, M.J. et al. A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. J Neural Transm 120, 1295–1303 (2013). https://doi.org/10.1007/s00702-013-1024-y

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  • N,N-dimethyltryptamine
  • Indolethylamine-N-methyltransferase
  • Sigma receptors
  • Oxidative stress
  • Immunoregulation
  • Carcinogenesis