The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells
Frontiers in Neuroscience September 14, 2016 Attila Szabó, A. Kovács, Jordi Riba et al. 18 citations
N,N-dimethyltryptamine (DMT), an endogenous hallucinogen found in the human brain, activates the sigma-1 receptor (Sig-1R), an intracellular chaperone that helps manage cellular stress. This study tested whether DMT protects brain cells from hypoxia by activating Sig-1R. In cultured human cortical neurons, macrophages, and dendritic cells exposed to severe hypoxia (0.5% O2), DMT robustly increased cell survival through Sig-1R activation. This effect was linked to decreased expression and function of hypoxia-inducible factor 1 alpha (HIF-1α), suggesting DMT alleviates hypoxic stress independently of HIF-1. The results indicate DMT may be endogenously produced during stress to protect the brain from hypoxic or ischemic damage.