Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms.
Psychopharmacology January 1, 2023 Juliet Meccia, Joëlle Lopez, Rosemary C Bagot 14 citations
Psilocybin, a serotonergic psychedelic, shows promise as a rapid and lasting antidepressant in human clinical research, but its acute mechanisms leading to enduring cognitive and behavioral changes remain poorly understood. Human neuroimaging reveals both immediate and sustained changes in functional connectivity within key cortical brain networks. Preclinical evidence emphasizes psilocybin-induced neuroplasticity and alterations in the prefrontal cortex (PFC). This review examines how acute modulation of PFC circuits may drive long-term structural and functional changes underlying antidepressant effects, highlighting the need for preclinical circuit and behavioral approaches to clarify how psilocybin affects cognitive and affective neural circuits and support its development as a depression treatment.