Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT2A receptor the unique player?
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology March 1, 2024 Mehdi Sekssaoui, Joël Bockaert, Philippe Marin et al. 76 citations
A single injection of psychedelic or non-hallucinogenic drugs that activate the serotonin 5-HT2A receptor can produce antidepressant- and anxiety-reducing effects in mice with a depression-like condition, lasting up to 15 days. The non-hallucinogenic drug lisuride was effective, suggesting hallucinogenic properties are not required for antidepressant action. In mice lacking the 5-HT2A receptor, the psychedelic DOI was ineffective, but psilocybin still worked, indicating psilocybin's effects can occur through other mechanisms. Blocking other serotonin or dopamine receptors did not stop psilocybin's effects in these mice. These results suggest that 5-HT2A receptor agonists can relieve depression through multiple pathways, independent of whether they cause hallucinations.