{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:44:51Z","timestamp":1784616291576,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004856","name":"New York State Department of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cannabidiol (CBD) expanded access program, initiated in 2014, provided add\u2010on CBD to patients with treatment\u2010resistant epilepsies (TREs) at 35 US epilepsy centers. Prior publications reported results through December 2016; herein, we present efficacy and safety results through January 2019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received plant\u2010derived highly purified CBD (Epidiolex\u00ae; 100\u2009mg\/ml oral solution), increasing from 2 to 10\u2009mg\/kg\/day to tolerance or maximum 25\u201350\u2009mg\/kg\/day dose, depending on the study site. Efficacy endpoints included percentage change from baseline in median monthly convulsive and total seizure frequency and\u2009\u226550%, \u226575%, and 100% responder rates across 12\u2010week visit windows for up to 192\u2009weeks. Adverse events (AEs) were documented at each visit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 892 patients in the safety analysis set, 322 (36%) withdrew; lack of efficacy (19%) and AEs (7%) were the most commonly reported primary reasons for withdrawal. Median (range) age was 11.8\u2009years (range\u00a0=\u00a00\u201374.5), and patients were taking a median of three (range\u00a0=\u00a00\u201310) antiseizure medications (ASMs) at baseline; the most common ASMs were clobazam (47%), levetiracetam (34%), and valproate (28%). Median top CBD dose was 25\u2009mg\/kg\/day; median exposure duration was 694\u2009days. Median percentage reduction from baseline ranged 50%\u201367% for convulsive seizures and 46%\u201366% for total seizures. Convulsive seizure responder rates (\u226550%, \u226575%, and 100% reduction) ranged 51%\u201359%, 33%\u201342%, and 11%\u201317% of patients across visit windows, respectively. AEs were reported in 88% of patients and serious AEs in 41%; 8% withdrew because of an AE. There were 20 deaths during the study deemed unrelated to treatment by the investigator. The most common AEs (\u226520% of patients) were diarrhea (33%), seizure (24%), and somnolence (23%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Add\u2010on CBD was associated with sustained seizure reduction up to 192\u2009weeks with an acceptable safety profile and can be used for long\u2010term treatment of TREs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17496","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T13:47:47Z","timestamp":1671544067000},"page":"619-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Long\u2010term efficacy and safety of cannabidiol in patients with treatment\u2010resistant epilepsies: Four\u2010year results from the expanded access program"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5936-6627","authenticated-orcid":false,"given":"Jerzy P.","family":"Szaflarski","sequence":"first","affiliation":[{"name":"Department of Neurology, UAB Epilepsy Center, Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center NYU Langone Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merrick","family":"Lopez","sequence":"additional","affiliation":[{"name":"Pediatric Critical Care Medicine Loma Linda University Children's Hospital  Loma Linda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong D.","family":"Park","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Medical College of Georgia, Augusta University  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar Pichon","family":"Zentil","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Loma Linda University Children's Hospital  Loma Linda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9313-1541","authenticated-orcid":false,"given":"Anup D.","family":"Patel","sequence":"additional","affiliation":[{"name":"Neurology and Pediatrics Nationwide Children's Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3431-4713","authenticated-orcid":false,"given":"Elizabeth A.","family":"Thiele","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Wechsler","sequence":"additional","affiliation":[{"name":"Consultants in Epilepsy &amp; Neurology and Idaho Comprehensive Epilepsy Center  Boise Idaho USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Checketts","sequence":"additional","affiliation":[{"name":"Biostatistics Jazz Pharmaceuticals, Inc.  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7748-7836","authenticated-orcid":false,"given":"Farhad","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Clinical Development Jazz Pharmaceuticals, Inc.  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