{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:54:32Z","timestamp":1786366472549,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:00:00Z","timestamp":1590451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Four pivotal randomized placebo\u2010controlled trials have demonstrated that adjunctive therapy with cannabidiol (CBD) improves seizure control in patients with Dravet syndrome (DS) and Lennox\u2010Gastaut syndrome (LGS). Between 47% and 68% of patients allocated to CBD treatment in these trials were receiving clobazam (CLB), which shows complex interactions with CBD resulting, in particular, in a 3.4\u2010 to 5\u2010fold increase in plasma concentration of the active metabolite norclobazam. This raises concern as to the role played by these interactions in determining the reduction in seizure frequency in CBD\u2010treated patients, and the question of whether CBD per se has clinically evident antiseizure effects. We appraised available evidence on the clinical consequences of the CBD\u2010CLB interaction, focusing on subgroup analyses of seizure outcomes in patients on and off CLB comedication in the pivotal CBD trials, as provided by the European Medicines Agency Public Assessment Report. Evaluation of the results of individual trials clearly showed that improvement in seizure control over placebo was greater when CBD was added on to CLB than when it was added on to other medications. However, seizure control was also improved in patients off CLB, and despite the small sample size the difference vs placebo was statistically significant for the 10\u00a0mg\/kg\/d dose in one of the two LGS trials. Stronger evidence for an antiseizure effect of CBD independent of an interaction with CLB emerges from meta\u2010analyses of seizure outcomes in the pooled population of LGS and DS patients not receiving CLB comedication. Although these results need to be interpreted taking into account methodological limitations, they provide the best clinical evidence to date that CBD exerts therapeutic effects in patients with epilepsy that are independent of its interaction with CLB. Greater antiseizure effects, and a greater burden of adverse effects, are observed when CBD is combined with CLB.<\/jats:p>","DOI":"10.1111\/epi.16542","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T11:42:43Z","timestamp":1590493363000},"page":"1082-1089","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-4171","authenticated-orcid":false,"given":"Meir","family":"Bialer","sequence":"first","affiliation":[{"name":"Faculty of Medicine School of Pharmacy Institute of Drug Research The Hebrew University of Jerusalem Jerusalem Israel"},{"name":"David R. Bloom Center for Pharmacy The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8703-223X","authenticated-orcid":false,"given":"Emilio","family":"Perucca","sequence":"additional","affiliation":[{"name":"Division of Clinical and Experimental Pharmacology Department of Internal Medicine and Therapeutics University of Pavia Pavia Italy"},{"name":"IRCCS Mondino Foundation Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Epidiolex.Full Prescribing Information. Greenwich Biosciences Inc.2018[accessed April 1 2018]. Available fromhttps:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/210365lbl.pdf"},{"key":"e_1_2_8_3_1","unstructured":"Epidyolex.Summary of Product Characteristics. [cited 2020 April 2]. 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