{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:40:39Z","timestamp":1786977639537,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"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":[[2023,6]]},"abstract":"<jats:p>\n                    Oral formulations prepared from the leaves of the kratom (\n                    <jats:italic>Mitragyna speciosa<\/jats:italic>\n                    ) plant are increasingly used for their opioid\u2010like effects to self\u2010manage opioid withdrawal and pain. Calls to US poison centers involving kratom exposures increased &gt;50\u2010fold from 2011\u20132017, one\u2010third of which reported concomitant use of kratom with drugs of abuse. Many of these drugs are eliminated primarily\n                    <jats:italic>via<\/jats:italic>\n                    cytochrome P450 (CYP) 3A and CYP2D6, raising concerns for potential adverse pharmacokinetic kratom\u2010drug interactions. The impact of a single low dose of kratom tea (2\u2009g) on the pharmacokinetics of the CYP3A probe midazolam (2.5\u2009mg) and CYP2D6 probe dextromethorphan (30\u2009mg) were assessed in 12 healthy adult participants after oral administration. Kratom showed no effect on dextromethorphan area under the plasma concentration time\u2010curve (AUC) and maximum concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ; geometric mean ratio (90% confidence interval) 0.99 (0.83\u20131.19) and 0.96 (0.78\u20131.19), respectively) but a modest increase in midazolam AUC and\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (1.39 (1.23\u20131.57) and 1.50 (1.32\u20131.70), respectively). Lack of change in midazolam half\u2010life (1.07 (0.98\u20131.17)) suggested that kratom primarily inhibited intestinal CYP3A. This inference was further supported by a physiologically based pharmacokinetic drug interaction model using the abundant alkaloid mitragynine, a relatively potent CYP3A time\u2010dependent inhibitor\n                    <jats:italic>in vitro<\/jats:italic>\n                    (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>I<\/jats:italic>\n                    <\/jats:sub>\n                    , ~4\u2009\u03bcM;\n                    <jats:italic>k<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>inact<\/jats:italic>\n                    <\/jats:sub>\n                    , ~0.07\u2009min\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). This work is the first to clinically evaluate the pharmacokinetic drug interaction potential of kratom. Co\u2010consuming kratom with certain drugs extensively metabolized by CYP3A may precipitate serious interactions. These data fill critical knowledge gaps about the safe use of this increasingly popular natural product, thereby addressing ongoing public health concerns.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2891","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T05:39:20Z","timestamp":1678945160000},"page":"1315-1325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom"],"prefix":"10.1111","volume":"113","author":[{"given":"Rakshit S.","family":"Tanna","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-7882","authenticated-orcid":false,"given":"James T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deena L.","family":"Hadi","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"}]},{"given":"Matthew E.","family":"Layton","sequence":"additional","affiliation":[{"name":"Elson S. Floyd College of Medicine Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja B.","family":"Cech","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"},{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro  Greensboro North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0354-8464","authenticated-orcid":false,"given":"Nicholas H.","family":"Oberlies","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"},{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro  Greensboro North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan E.","family":"Rettie","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"},{"name":"Department of Medicinal Chemistry School of Pharmacy, University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Thummel","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"},{"name":"Department of Pharmaceutics School of Pharmacy, University of Washington  Seattle Washington 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"}]}],"member":"311","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.801855"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.05.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.0c00257"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76119-w"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1795-5876"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(96)00432-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2003.09.054"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01465"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00726"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugpo.2020.102715"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650.2019.1569236"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1811055"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6814a2"},{"key":"e_1_2_10_14_1","unstructured":"DEA announces intent to schedule kratom. Drug Enforcement Administration<https:\/\/www.dea.gov\/press\u2010releases\/2016\/08\/30\/dea\u2010announces\u2010intent\u2010schedule\u2010kratom>(2016). Accessed January 10 2023."},{"key":"e_1_2_10_15_1","unstructured":"Statement from FDA Commissioner Scott Gottlieb M.D. On the agency's Scientific Evidence on the Presence of Opioid Compounds in Kratom Underscoring its Potential for Abuse<https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/statement\u2010fda\u2010commissioner\u2010scott\u2010gottlieb\u2010md\u2010agencys\u2010scientific\u2010evidence\u2010presence\u2010opioid\u2010compounds>(2018). Accessed January 10 2023."},{"key":"e_1_2_10_16_1","unstructured":"FDA and Kratom.U.S. Food and Drug Administration<https:\/\/www.fda.gov\/news\u2010events\/public\u2010health\u2010focus\/fda\u2010and\u2010kratom>(2019). 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