Through what mechanism is psilocybin thought to exhibit antidepressant effects?
Psilocybin is thought to exhibit antidepressant effects through agonism at the serotonin 5-HT2A receptors. When ingested, psilocybin is in a prodrug form that is metabolized in-vivo to the active form, psilocin, which is structurally similar to serotonin. Although the antidepressant effects are thought to be exhibited via the serotonin 5-HT2A receptors, the psychedelic effects are demonstrated to be via alternative receptor pathways.
Susan L, Ceban F, Lui LMW, et al. Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. CNS Drugs. 2022;36(1):17-30. DOI: 10.1007/s40263-021-00877-y.