Journal of Neural Transmission

, Volume 120, Issue 9, pp 1295–1303 | Cite as

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

  • Ede Frecska
  • Attila Szabo
  • Michael J. Winkelman
  • Luis E. Luna
  • Dennis J. McKenna
Translational Neurosciences - Review article


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.


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



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

Conflict of interest

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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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Ede Frecska
    • 1
  • Attila Szabo
    • 2
  • Michael J. Winkelman
    • 3
  • Luis E. Luna
    • 4
  • Dennis J. McKenna
    • 5
  1. 1.Department of Psychiatry, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  2. 2.Department of Immunology, Medical and Health Science CenterUniversity of DebrecenDebrecenHungary
  3. 3.School of Human Evolution and Social ChangeArizona State UniversityTempeUSA
  4. 4.Wasiwaska Research Center for the Study of Psychointegrator PlantsVisionary Art and ConsciousnessFlorianopolisBrazil
  5. 5.Center for Spirituality and Healing, Academic Health CenterUniversity of MinnesotaMinneapolisUSA

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