Emerging mechanisms of psilocybin-induced neuroplasticity
Sonia Sonda, Diana Pendin, Stefano Comai, Sara de Martin, Paolo L. Manfredi, Andrea Mattarei
Trends in Pharmacological Sciences September 16, 2025 DOI: 10.1016/j.tips.2025.08.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Neuroplasticity Psilocybin |
| Citations | 11 |
| Key findings | Psilocybin's therapeutic and neuroplastic effects involve a complex molecular interactome beyond just 5-HT2A receptor activation, including multiple serotonin receptor subtypes and non-serotonergic targets such as TrkB. |
Abstract
Psilocybin, a serotonergic psychedelic, is gaining attention for its rapid and sustained therapeutic effects in depression and other hard-to-treat neuropsychiatric conditions, potentially through its capacity to enhance neuronal plasticity. While its neuroplastic and therapeutic effects are commonly attributed to serotonin 2A (5-HT 2A ) receptor activation, emerging evidence reveals a more nuanced pharmacological profile involving multiple serotonin receptor subtypes and nonserotonergic targets such as TrkB. This review integrates current findings on the molecular interactome of psilocin (psilocybin active metabolite), emphasizing receptor selectivity, biased agonism, and intracellular receptor localization. Together, these insights offer a refined framework for understanding psilocybin's enduring effects and guiding the development of next-generation neuroplastogens with improved specificity and safety.