DMT, a hallucinogen naturally found in the human brain, is known to act through serotonin and trace amine receptors to produce its psychedelic effects. Recent evidence shows DMT also binds to sigma-1 receptors, which are molecular chaperones that regulate ion channels. This suggests sigma-1 receptors may partially mediate DMT's psychedelic action. The authors propose a hypothetical signaling pathway triggered by DMT binding to sigma-1 receptors.
The stress hormone corticosterone is required for ketamine to produce its rapid antidepressant effects. Blocking the hormone's action prevented the drug from working in animal models, suggesting that the body's stress response system plays a necessary role in ketamine's therapeutic mechanism.