{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:04:53Z","timestamp":1770455093991,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM109005"],"award-info":[{"award-number":["P20 GM109005"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury\u2013acetaminophen (APAP)\u2013in aged female CD-1 mice. Gavaging mice with 116 mg\/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg\/kg of CBD] in CRCE delivered with sesame oil for three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg\/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated with 290 mg\/kg of CBD+APAP (MED of 25 mg\/kg of CBD) or APAP alone. Following CRCE\/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury\u2013the severity of which correlated with the degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg\/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD\/drug interactions, and reveal an interesting paradoxical effect of CBD\/APAP-induced hepatotoxicity.<\/jats:p>","DOI":"10.3390\/molecules24122256","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T11:24:45Z","timestamp":1560770685000},"page":"2256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8496-8518","authenticated-orcid":false,"given":"Laura E.","family":"Ewing","sequence":"first","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell R.","family":"McGill","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Center for Dietary Supplements Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9643-6439","authenticated-orcid":false,"given":"Eric U.","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Quick","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Center for Dietary Supplements Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Kennon-McGill","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Clemens","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel H.","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra S.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Keith","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristy R.","family":"Kutanzi","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry A.","family":"Walker","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA"},{"name":"ElSohly Laboratories, Inc. (ELI), Oxford, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud A.","family":"ElSohly","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA"},{"name":"ElSohly Laboratories, Inc. (ELI), Oxford, MS 38677, USA"},{"name":"Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura P.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bill J.","family":"Gurley","sequence":"additional","affiliation":[{"name":"Center for Dietary Supplements Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4090-7008","authenticated-orcid":false,"given":"Igor","family":"Koturbash","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"Center for Dietary Supplements Research, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMc1708349","article-title":"Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome","volume":"377","author":"Devinsky","year":"2017","journal-title":"N. 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