Dimethyltryptamine (DMT), a natural compound that activates sigma-1 receptors, reduced spreading depolarizations—waves of electrical disruption in the brain that worsen stroke injury—in rats subjected to global forebrain ischemia. DMT also decreased the number of dying cells and supported astrocyte survival. The protective effects were shared by a selective sigma-1 receptor agonist and were blocked by a sigma-1 receptor antagonist, indicating the receptor mediates the protection. DMT remained effective even when serotonin receptors were blocked. These results suggest DMT could be an additional treatment for acute stroke.
A new two-dimensional liquid chromatography method coupled to high-resolution tandem mass spectrometry was developed to measure the level of N,N-dimethyltriptamine (DMT) in rat plasma and brain tissue. The method achieved high recovery (90% in plasma, 88% in brain) and sensitivity (limit of detection 0.108 ng/mL in plasma, 0.212 ng/g in brain) within a 10-minute run. In an experimental model of cerebral ischemia/reperfusion, DMT concentration in rat plasma before hypoxia (49.3–114.3 ng/mL) was generally higher than after hypoxia (10.6–96.1 ng/mL). After treatment, brain DMT levels rose to 2–6.1 ng/g. The approach reliably detects and confirms DMT administered therapeutically.