Meshkat Shakila, Al-Shamali Huda, Perivolaris Argyrios, Tullu Trusha, Zeifman Richard J, Zhang Yanbo, Burback Lisa, Winkler Olga, Greenshaw Andrew, Husain Muhammad Ishrat, C Reichelt Amy, Vermetten Eric, Jha Manish K, Jetly Rakesh, Loebenberg Raimar, Bhat Venkat
Interventional Psychiatry Program, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
NYU Center for Psychedelic Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Pharmaceutics. 2025 Mar 25;17(4):411. doi: 10.3390/pharmaceutics17040411.
Psilocybin has shown promise in therapeutic applications for mental disorders. Understanding the pharmacokinetics of psilocybin and its active metabolite psilocin is crucial for optimizing its clinical use and minimizing adverse effects. This systematic review involved a comprehensive search across MEDLINE, APA PsycINFO, and Embase databases, from inception to December 2024, identifying original studies that investigated the pharmacokinetics of psilocybin. Fourteen studies met the inclusion criteria: eight laboratory-based and six clinical studies. Laboratory studies used animal models or in vitro systems, while clinical studies included 112 healthy human participants. Psilocybin is rapidly dephosphorylated to psilocin, which is absorbed with Tmax values ranging from 1.8 to 4 h following oral administration. Cmax varied dose-dependently, from 8.2 ± 2.8 ng/mL (plasma) to 871 ng/mL (urine). One study reported psilocin bioavailability at 52.7 ± 20%. The volume of distribution was extensive, ranging from 277 ± 92 L to 1016 L, suggesting significant tissue distribution. Psilocin metabolism is primarily mediated by CYP2D6 and CYP3A4, with secondary contributions from monoamine oxidase A. It undergoes further hepatic biotransformation into 4-hydroxyindole-3-acetic acid and 4-hydroxytryptophol. Elimination half-life varied across studies, ranging from 1.5 to 4 h. Psilocybin pharmacokinetics demonstrate significant variability based on dosage, route, and species. CYP enzymes play a critical role in its metabolism, highlighting the potential for drug-drug interactions. These findings underscore the importance of further research to elucidate psilocybin's pharmacokinetic profile, which is assessed in vivo by its active metabolite psilocin.
裸盖菇素在精神障碍的治疗应用中已显示出前景。了解裸盖菇素及其活性代谢物脱磷酸裸盖菇素的药代动力学对于优化其临床应用和最小化不良反应至关重要。本系统评价涉及从数据库创建到2024年12月对MEDLINE、美国心理学会心理学文摘数据库（APA PsycINFO）和Embase数据库进行全面检索，以识别研究裸盖菇素药代动力学的原始研究。十四项研究符合纳入标准：八项基于实验室的研究和六项临床研究。实验室研究使用动物模型或体外系统，而临床研究包括112名健康人类参与者。裸盖菇素迅速脱磷酸化为脱磷酸裸盖菇素，口服给药后，脱磷酸裸盖菇素的吸收Tmax值范围为1.8至4小时。Cmax呈剂量依赖性变化，血浆中为8.2±2.8 ng/mL，尿液中为871 ng/mL。一项研究报告脱磷酸裸盖菇素的生物利用度为52.7±20%。分布容积广泛，范围为277±92 L至1016 L，表明有显著的组织分布。脱磷酸裸盖菇素的代谢主要由CYP2D6和CYP3A4介导，单胺氧化酶A也有次要作用。它在肝脏中进一步生物转化为4-羟基吲哚-3-乙酸和4-羟基色醇。消除半衰期在不同研究中有所不同，范围为1.5至4小时。裸盖菇素的药代动力学因剂量、给药途径和物种而异。CYP酶在其代谢中起关键作用，突出了药物相互作用的可能性。这些发现强调了进一步研究以阐明裸盖菇素药代动力学特征的重要性，其药代动力学特征通过其活性代谢物脱磷酸裸盖菇素在体内进行评估。
