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

DMT, a hallucinogen naturally found in the human brain, is known to act through serotonin and trace amine receptors to produce its psychedelic effects. Recent evidence shows DMT also binds to sigma-1 receptors, which are molecular chaperones that regulate ion channels. This suggests sigma-1 receptors may partially mediate DMT's psychedelic action. The authors propose a hypothetical signaling pathway triggered by DMT binding to sigma-1 receptors.

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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.