The sigma-1 receptor, a protein found in the central nervous system and immune cells, can be activated by the psychedelic compounds N,N-dimethyltryptamine (NN-DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) to dampen inflammatory responses in human immune cells. When human dendritic cells were exposed to inflammatory triggers along with these compounds, production of pro-inflammatory cytokines IL-1β, IL-6, TNFα, and chemokine IL-8 decreased, while the anti-inflammatory cytokine IL-10 increased. The compounds also reduced the cells' ability to activate inflammatory T-cells. This suggests dimethyltryptamines may act as endogenous regulators of inflammation and immune balance, pointing toward potential treatments for autoimmune and chronic inflammatory conditions.
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.