Aiming to understand physiological consequences of drug consumption on synaptic plasticity and neuronal circuits, we investigate the mode of action of psychoactive substances. Our research focus is currently on the psychedelic compound psilocybin which may be clinically used for the treatment of psychiatric disorders, including major depressive disorder. Psilocybin induces hallucinations through its active metabolite psilocin, a serotonin 5-HT2A receptor agonist. Using mouse models, we investigate neuronal circuits and synapses that may be persistently changed after a single psilocybin administration and test for causality to psilocybin’s antidepressant effects. Our research also aims to provide mechanistic rationale for improving treatment strategies with psychedelics in psychiatric disorders.