When the Endogenous Hallucinogenic Trace Amine N,N-Dimethyltryptamine Meets the Sigma-1 Receptor

Tsung-Ping Su^*1, Teruo Hayashi¹, and D. Bruce Vaupel²

¹ Cellular Pathobiology Section, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 333 Cassell Drive, Baltimore, MD 21224, USA.
² Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 333 Cassell Drive, Baltimore, MD 21224, USA.

Abstract: N,N-dimethyltryptamine (DMT) is a hallucinogen found endogenously in human brain that is commonly recognized to target the 5-hydroxytryptamine 2A receptor or the trace amine–associated receptor to exert its psychedelic effect. DMT has been recently shown to bind sigma-1 receptors, which are ligand-regulated molecular chaperones whose function includes inhibiting various voltage-sensitive ion channels. Thus, it is possible that the psychedelic action of DMT might be mediated in part through sigma-1 receptors. Here, we present a hypothetical signaling scheme that might be triggered by the binding of DMT to sigma-1 receptors.

* Corresponding author. Cellular Pathobiology Section, IRP, NIDA, NIH Suite 3304, 333 Cassell Drive, Baltimore, MD 21224, USA. Telephone: 443-740-2804; fax: 443-740-2142; e-mail: TSU{at}intra.nida.nih.gov.

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