A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity
This review (2012) postulates that DMT may play a role in cell protection, regeneration, and immunity by activating a cell-endogenous sigma-1 receptor pathway which regulates oxidative stress-induced changes at the endoplasmic reticulum-mitochondria interface. Supportive experimental data are still necessary for advancing the outlined concepts, such as the endogenous role of DMT or the immunoprotective benefits of exogenous DMT ingested in larger quantities.
Authors
- Attila Szabo
- Ede Ottó Frecska
- Michael Winkelman
Published
Abstract
Introduction
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.
Methods
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.
Results
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.
Discussion
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.
Research Summary of 'A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity'
Introduction
N,N-dimethyltryptamine (DMT) is a methylated indolealkylamine found widely in plants and detected in animal tissues, where it is considered an endogenous trace amine. Earlier research has focused predominantly on DMT's potent psychotropic and hallucinogenic effects, leaving its potential physiological roles poorly understood. The enzyme indolethylamine-N-methyltransferase (INMT), which synthesises DMT from tryptamine, is expressed most strongly in peripheral tissues (lungs, thyroid, adrenal gland) and only sparsely in the brain; nonetheless, evidence for active uptake mechanisms across the blood–brain barrier suggests peripheral synthesis could influence central nervous system function. Overall, the ubiquity of DMT across species and the specialised transport and storage processes that have been reported raise questions about functions beyond hallucination or toxicity. Frecska and colleagues set out to review and integrate literature bearing on non-psychedelic roles of DMT, emphasising its recently reported activity at the sigma-1 receptor (Sig-1R). The paper surveys evidence on DMT biosynthesis and biodistribution, Sig-1R biology and cellular bioenergetics, serotonergic mechanisms in immunoregulation, and data on INMT expression in cancer. The stated aim is to propose that DMT may participate in adaptive cellular protective mechanisms—such as protection from hypoxia, modulation of immunity, and effects on tissue regeneration—and to suggest directions for further experimental research and potential medical applications.
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Frecska, E., Szabo, A., Winkelman, M. J., Luna, L. E., & McKenna, D. J. (2013). A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. Journal of Neural Transmission, 120(9), 1295-1303. https://doi.org/10.1007/s00702-013-1024-y
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Dakic, V., Nascimento, J. M., Sartore, R. C. et al. · Scientific Reports (2017)
Dos Santos, R. G., Hallak, J. E., Bouso, J. C. · Therapeutic Advances in Psychopharmacology (2017)
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van Waarde, A., Rybczynska, A. A., Ramakrishnan, N. et al. · Biochimica et Biophysica Acta (BBA) - Biomembranes (2014)
Schenberg, E. E. · Sage Open Medicine (2013)
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