{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T23:42:45Z","timestamp":1782171765109,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      This study evaluated long\u2010term plasma concentrations of cannabidiol (CBD) and \u03949\u2010tetrahydrocannabinol (THC) in children receiving highly purified cannabidiol (hpCBD; Epidyolex\u00ae) therapy for drug\u2010resistant epilepsy. A retrospective analysis was performed on 38 patients with a median age of 11\u2009years (IQR, 5) treated in a single center from 2019 to 2024. Incremental doses of Epidyolex\u00ae (mean dose: 13.6\u2009mg\/kg\/day) were administered, and plasma levels of CBD and THC were measured using liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS). THC remained consistently undetectable (&lt;0.2\u2009\u03bcg\/L) at all time points, confirming the negligible systemic exposure. CBD levels increased dose\u2010dependently, reaching a median concentration of 89.8\u2009\u03bcg\/L (IQR, 112.2) at final follow\u2010up, demonstrating a significant positive correlation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) between dosage and plasma concentration. Epidyolex\u00ae treatment effectively maintains therapeutic CBD levels without detectable THC, supporting the safety and suitability of this therapy. These results highlight the value of plasma CBD monitoring to verify dose\u2010dependent exposure and support safe, individualized treatment with CBD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>This study examined blood levels of cannabidiol (CBD) and tetrahydrocannabinol (THC) in children with drug\u2010resistant epilepsy treated with highly purified CBD (Epidyolex). CBD levels increased proportionally with the dose, while THC levels remained undetectable. The consistent lack of THC detection across all measured time points and dose levels suggests that systemic exposure to THC remains negligible, even with prolonged administration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70112","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T15:01:53Z","timestamp":1757689313000},"page":"1699-1704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long\u2010term plasma monitoring of\n                    <scp>THC<\/scp>\n                    and\n                    <scp>CBD<\/scp>\n                    in pediatric drug\u2010resistant epilepsy: Implications for cannabidiol therapy with Epidyolex\u00ae"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1132-1267","authenticated-orcid":false,"given":"Alessia","family":"Cafaro","sequence":"first","affiliation":[{"name":"Biochemistry, Pharmacology and Newborn Screening Unit, Central Laboratory of Analysis IRCCS Istituto Giannina, Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-8610","authenticated-orcid":false,"given":"Federica","family":"Pigliasco","sequence":"additional","affiliation":[{"name":"Biochemistry, Pharmacology and Newborn Screening Unit, Central Laboratory of Analysis IRCCS Istituto Giannina, Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-427X","authenticated-orcid":false,"given":"Sebastiano","family":"Barco","sequence":"additional","affiliation":[{"name":"Biochemistry, Pharmacology and Newborn Screening Unit, Central Laboratory of Analysis IRCCS Istituto Giannina, Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Manca","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Stella Vari","sequence":"additional","affiliation":[{"name":"Paediatric Neurology and Muscular Disease Unit IRCCS Istituto Giannina Gaslini, full member of ERN EpiCARE  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5122-4029","authenticated-orcid":false,"given":"Maria Margherita","family":"Mancardi","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry IRCCS Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Nobili","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"Unit of Child Neuropsychiatry IRCCS Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Pichini","sequence":"additional","affiliation":[{"name":"National Centre on Addiction and Doping, Istituto Superiore di Sanit\u00e0  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Paolo","family":"Busard\u00f2","sequence":"additional","affiliation":[{"name":"Department of Excellence\u2010Biomedical Sciences and Public Health Universit\u00e0 Politecnica delle Marche  Ancona 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