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.
A study tested whether N’N-dimethyltryptamine (DMT), a psychedelic compound, could protect the retina from damage caused by ischemia (restricted blood flow) followed by reperfusion. Because DMT is rapidly broken down by monoamine oxidase A (MAO-A), it was given alongside harmaline (a MAO-A inhibitor found in the Amazonian brew ayahuasca). In rats whose eye blood flow was blocked for 60 minutes and then restored for 7 days, harmaline alone protected the retina from injury. Surprisingly, adding DMT counteracted that protection. The two drugs had opposing effects on proteins involved in cell death, inflammation, tissue breakdown, and oxidative stress. The results suggest harmaline may have therapeutic potential for ischemic eye diseases, while DMT's effects on eye ischemia warrant caution.