Advancements in psychedelic research: Effects, mechanisms, and therapeutic potential as emerging antidepressants

Major depressive disorder (MDD) causes great physical and mental suffering to patients while also imposing a tremendous economic burden on the global economy. Psychedelics, also known as serotonergic hallucinogens, are potent psychoactive compounds known for their ability to alter mood, perception, and a range of cognitive functions. Increasing evidence suggests that some psychedelics positively facilitate individual social functions, with rapid and sustained improvement in symptoms associated with MDD. Consequently, the application of psychedelics in the treatment of MDD has garnered considerable attention from researchers in recent years. This review examines recent advancements in evaluating the behavioral and physiological effects of psychedelics in both preclinical animal models and clinical trials focused on MDD. Additionally, we summarize and discuss the cellular, brain region, and circuit-level mechanisms, as well as potential intracellular signaling pathways, that may contribute to the antidepressant effects of psychedelics. Based on current evidence, we conclude that psychedelics hold significant promise as therapeutic agents for MDD.