{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:37:37Z","timestamp":1791859057452,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["U54 AT008909"],"award-info":[{"award-number":["U54 AT008909"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["T32DA07209"],"award-info":[{"award-number":["T32DA07209"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["P01 DA032507"],"award-info":[{"award-number":["P01 DA032507"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:p>\n                    Understanding cannabis\u2010drug interactions is critical given regulatory changes that have increased access to and use of cannabis. Cannabidiol (CBD) and \u0394\u20109\u2010tetrahydrocannabinol (\u03949\u2010THC), the most abundant phytocannabinoids, are\n                    <jats:italic>in vitro<\/jats:italic>\n                    reversible and time\u2010dependent (CBD only) inhibitors of several cytochrome P450 (CYP) enzymes. Cannabis extracts were used to evaluate quantitatively potential pharmacokinetic cannabinoid\u2010drug interactions in 18 healthy adults. Participant received, in a randomized cross\u2010over manner (separated by \u2265\u20091\u2009week), a brownie containing (i) no cannabis extract (ethanol\/placebo), (ii) CBD\u2010dominant cannabis extract (640\u2009mg CBD\u2009+\u200920\u2009mg \u03949\u2010THC), or (iii) \u03949\u2010THC\u2010dominant cannabis extract (20\u2009mg \u03949\u2010THC and no CBD). After 30\u2009minutes, participants consumed a cytochrome P450 (CYP) drug cocktail consisting of caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A). Plasma and urine samples were collected (0\u201324\u2009hours). The CBD\u2009+\u2009\u03949\u2010THC brownie inhibited CYP2C19\u2009&gt;\u2009CYP2C9\u2009&gt;\u2009CYP3A\u2009&gt;\u2009CYP1A2 (but not CYP2D6) activity, as evidenced by an increase in the geometric mean ratio of probe drug area under the plasma concentration\u2010time curve (AUC) relative to placebo (AUC\n                    <jats:sub>GMR<\/jats:sub>\n                    ) of omeprazole, losartan, midazolam, and caffeine by 207%, 77%, 56%, and 39%, respectively. In contrast, the \u03949\u2010THC brownie did not inhibit any of the CYPs. The CBD\u2009+\u2009\u03949\u2010THC brownie increased \u03949\u2010THC AUC\n                    <jats:sub>GMR<\/jats:sub>\n                    by 161%, consistent with CBD inhibiting CYP2C9\u2010mediated oral \u03949\u2010THC clearance. Except for caffeine, these interactions were well\u2010predicted by our physiologically\u2010based pharmacokinetic model (within 26% of observed interactions). Results can be used to help guide dose adjustment of drugs co\u2010consumed with cannabis products and the dose of CBD in cannabis products to reduce interaction risk with \u03949\u2010THC.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2973","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T06:21:36Z","timestamp":1686723696000},"page":"693-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Evaluation of Cytochrome\n                    <scp>P450\u2010Mediated Cannabinoid\u2010Drug<\/scp>\n                    Interactions in Healthy Adult Participants"],"prefix":"10.1111","volume":"114","author":[{"given":"Sumit","family":"Bansal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Austin","family":"Zamarripa","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tory R.","family":"Spindle","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise M.","family":"Weerts","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Thummel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Vandrey","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3331-1839","authenticated-orcid":false,"given":"Mary F.","family":"Paine","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"},{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4820-8455","authenticated-orcid":false,"given":"Jashvant D.","family":"Unadkat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy University of Washington  Seattle Washington USA"},{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"Key Substance Use and Mental Health Indicators in the United States: Results from the 2020 National Survey on Drug Use and Health. <https:\/\/www.samhsa.gov\/data\/sites\/default\/files\/reports\/rpt35325\/NSDUHFFRPDFWHTMLFiles2020\/2020NSDUHFFR1PDFW102121.pdf> (2020). 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