Sonda Sonia, Pendin Diana, Comai Stefano, De Martin Sara, Manfredi Paolo, Mattarei Andrea
Neuroscience Institute, National Research Council (CNR), Padua, Italy; Department of Biomedical Sciences, University of Padua, Padua, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy; Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Trends Pharmacol Sci. 2025 Nov;46(11):1130-1143. doi: 10.1016/j.tips.2025.08.012. Epub 2025 Sep 15.
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) 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.
裸盖菇素是一种血清素能致幻剂，因其在抑郁症和其他难以治疗的神经精神疾病中具有快速且持久的治疗效果而受到关注，这可能是通过其增强神经元可塑性的能力实现的。虽然其神经可塑性和治疗效果通常归因于血清素2A（5-HT）受体激活，但新出现的证据揭示了一种更细致入微的药理学特征，涉及多种血清素受体亚型和诸如TrkB等非血清素能靶点。本综述整合了关于裸盖菇素（裸盖菇素的活性代谢物）分子相互作用组的当前研究结果，强调受体选择性、偏向性激动作用以及细胞内受体定位。这些见解共同为理解裸盖菇素的持久效果以及指导开发具有更高特异性和安全性的下一代神经可塑性增强剂提供了一个完善的框架。
