Emerging mechanisms of psilocybin-induced neuroplasticity
Trends in Pharmacological Sciences September 16, 2025 Sonia Sonda, Diana Pendin, Stefano Comai et al. 11 citations
Psilocybin, a serotonergic psychedelic, shows rapid and lasting therapeutic effects for depression and other hard-to-treat neuropsychiatric conditions, likely due to its ability to enhance neuronal plasticity. While these effects are often attributed to activation of the serotonin 2A (5-HT2A) receptor, emerging evidence indicates a more complex pharmacological profile involving multiple serotonin receptor subtypes and non-serotonergic targets like TrkB. This review integrates current findings on the molecular interactome of psilocin, the active metabolite of psilocybin, focusing on receptor selectivity, biased agonism, and intracellular receptor localization. These insights provide a refined framework for understanding psilocybin's enduring effects and guiding the development of next-generation neuroplastogens with improved specificity and safety.