{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:37:34Z","timestamp":1791859054282,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>One in six Americans uses cannabidiol\u2010based or cannabis\u2010derived products. Cannabidiol is a substrate of CYP3A, but its role as a potential CYP3A inhibitor remains unclear. We hypothesized that cannabidiol would inhibit CYP3A\u2010mediated metabolism of tacrolimus. This report is an interim analysis of an open\u2010label, three\u2010period, fixed\u2010sequence, crossover study in healthy participants. Participants first received a single dose of tacrolimus 5\u2009mg orally. After washout, participants later received cannabidiol titrated to 5\u2009mg\/kg twice daily for 14\u2009days to reach a steady state, followed by a second single dose of tacrolimus 5\u2009mg orally. Tacrolimus concentrations in whole blood were measured by UHPLC\u2013MS\/MS method. Pharmacokinetic parameters were calculated by noncompartmental analysis. Twelve participants completed all periods of the study. The maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) of tacrolimus increased 4.2\u2010fold (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001) with cannabidiol (40.2\u2009\u00b1\u200913.5\u2009ng\/mL) compared with without cannabidiol (9.85\u2009\u00b1\u20094.63\u2009ng\/mL). The area under the concentration\u2010vs.\u2010time curve (AUC<jats:sub>0\u2010\u221e<\/jats:sub>) increased 3.1\u2010fold (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). No change in half\u2010life (<jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub>) was observed. This study demonstrates that cannabidiol increases tacrolimus exposure. Our data suggest the need for dose reduction in tacrolimus and frequent therapeutic dose monitoring in transplant patients taking cannabidiol concomitantly. Whether this observed interaction occurred due to the inhibition of CYP3A4 and\/or CYP3A5 in the liver, intestine, or both, or intestinal drug transporters (e.g., p\u2010glycoprotein) during the first\u2010pass elimination remains to be elucidated.<\/jats:p>","DOI":"10.1002\/cpt.3504","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T09:50:39Z","timestamp":1732701039000},"page":"716-723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Phase I Trial of the Pharmacokinetic Interaction Between Cannabidiol and Tacrolimus"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-5116","authenticated-orcid":false,"given":"Gerald C.","family":"So","sequence":"first","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Bo Li","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Hua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-4585","authenticated-orcid":false,"given":"Debora L.","family":"Gisch","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"McClara","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Dexter","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif A.","family":"Sharfuddin","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumar","family":"Etkins","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-9811","authenticated-orcid":false,"given":"Emma M.","family":"Tillman","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis R.","family":"Beamon","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Cowsert","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Stuart","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1513-1295","authenticated-orcid":false,"given":"Zeruesenay","family":"Desta","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-2876","authenticated-orcid":false,"given":"Michael T.","family":"Eadon","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"crossref","unstructured":"OPTN\/SRTR 2022 Annual Data Report.Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR)<http:\/\/srtr.transplant.hrsa.gov\/annual_reports\/Default.aspx> (2024). Accessed March 1 2024.","DOI":"10.1016\/j.ajt.2024.01.010"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-017-0553-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32835fcbb6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2015.01.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200403000-00002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.04800908"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2019.08.006"},{"key":"e_1_2_9_8_1","unstructured":"Online World Drug Report 2023\u2014Latest Data and Trend AnalysisUnited Nations Office on Drugs and Crime <https:\/\/www.unodc.org\/unodc\/en\/data\u2010and\u2010analysis\/wdr\u20102023\u2010online\u2010segment.html>. 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