Pharmacokinetics of Psilocybin: A Systematic Review
<b>Background:</b> 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. <b>Methods:</b> Thi...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/1999-4923/17/4/411 |
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| author | Shakila Meshkat Huda Al-Shamali Argyrios Perivolaris Trusha Tullu Richard J. Zeifman Yanbo Zhang Lisa Burback Olga Winkler Andrew Greenshaw Muhammad Ishrat Husain Amy C. Reichelt Eric Vermetten Manish K. Jha Rakesh Jetly Raimar Loebenberg Venkat Bhat |
| author_facet | Shakila Meshkat Huda Al-Shamali Argyrios Perivolaris Trusha Tullu Richard J. Zeifman Yanbo Zhang Lisa Burback Olga Winkler Andrew Greenshaw Muhammad Ishrat Husain Amy C. Reichelt Eric Vermetten Manish K. Jha Rakesh Jetly Raimar Loebenberg Venkat Bhat |
| author_sort | Shakila Meshkat |
| collection | DOAJ |
| description | <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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. |
| format | Article |
| id | doaj-art-ea5bdd9600b24db08f2df19c1f27b00e |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-ea5bdd9600b24db08f2df19c1f27b00e2025-08-20T02:28:28ZengMDPI AGPharmaceutics1999-49232025-03-0117441110.3390/pharmaceutics17040411Pharmacokinetics of Psilocybin: A Systematic ReviewShakila Meshkat0Huda Al-Shamali1Argyrios Perivolaris2Trusha Tullu3Richard J. Zeifman4Yanbo Zhang5Lisa Burback6Olga Winkler7Andrew Greenshaw8Muhammad Ishrat Husain9Amy C. Reichelt10Eric Vermetten11Manish K. Jha12Rakesh Jetly13Raimar Loebenberg14Venkat Bhat15Interventional Psychiatry Program, St. Michael’s Hospital, Toronto, ON M5B 1W8, CanadaInterventional Psychiatry Program, St. Michael’s Hospital, Toronto, ON M5B 1W8, CanadaInterventional Psychiatry Program, St. Michael’s Hospital, Toronto, ON M5B 1W8, CanadaInterventional Psychiatry Program, St. Michael’s Hospital, Toronto, ON M5B 1W8, CanadaNYU Center for Psychedelic Medicine, NYU Grossman School of Medicine, New York, NY 10016, USADepartment of Psychiatry, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Psychiatry, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Psychiatry, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Psychiatry, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Psychiatry, University of Toronto, Toronto, ON M5S 1A1, CanadaDepartment of Physiology and Pharmacology, Western University, London, ON N6A 3K7, CanadaDepartment of Psychiatry, Leiden University Medical Center, 2333 ZG Leiden, The NetherlandsDepartment of Psychiatry, O’Donnell Brain Institute, UT Southwestern Medical Center, Dallas, TX 75390, USAInstitute of Mental Health Research, University of Ottawa, Royal Ottawa Hospital, Ontario, ON K1Z 7K4, CanadaFaculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, CanadaInterventional Psychiatry Program, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.https://www.mdpi.com/1999-4923/17/4/411psilocybinpharmacokineticsmetabolismCYP450 |
| spellingShingle | Shakila Meshkat Huda Al-Shamali Argyrios Perivolaris Trusha Tullu Richard J. Zeifman Yanbo Zhang Lisa Burback Olga Winkler Andrew Greenshaw Muhammad Ishrat Husain Amy C. Reichelt Eric Vermetten Manish K. Jha Rakesh Jetly Raimar Loebenberg Venkat Bhat Pharmacokinetics of Psilocybin: A Systematic Review Pharmaceutics psilocybin pharmacokinetics metabolism CYP450 |
| title | Pharmacokinetics of Psilocybin: A Systematic Review |
| title_full | Pharmacokinetics of Psilocybin: A Systematic Review |
| title_fullStr | Pharmacokinetics of Psilocybin: A Systematic Review |
| title_full_unstemmed | Pharmacokinetics of Psilocybin: A Systematic Review |
| title_short | Pharmacokinetics of Psilocybin: A Systematic Review |
| title_sort | pharmacokinetics of psilocybin a systematic review |
| topic | psilocybin pharmacokinetics metabolism CYP450 |
| url | https://www.mdpi.com/1999-4923/17/4/411 |
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