The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator
Dominique Fontanilla, Molly Johannessen, Abdol R. Hajipour, Nicholas V. Cozzi, Meyer B. Jackson, Arnold E. Ruoho
Science February 13, 2009 DOI: 10.1126/science.1166127 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice and cell lines |
| Intervention | DMT |
| Topics | 5-MeO-DMT DMT |
| Keywords | Sigma-1 receptor Sigma receptor Hallucinogen Pharmacology Agonist Endogeny Allosteric modulator Knockout mouse Opioid receptor Biochemistry |
| Citations | 528 |
| Key findings | DMT is an endogenous agonist for the sigma-1 receptor. |
Abstract
The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.