{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:34:57Z","timestamp":1782538497922,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo\u2010controlled, phase 3 trial in patients with drug\u2010resistant epilepsy associated with tuberous sclerosis complex (TSC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received plant\u2010derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100\u00a0mg\/ml oral solution) at 25\u00a0mg\/kg\/day (CBD25) or 50\u00a0mg\/kg\/day (CBD50) or placebo for 16\u00a0weeks (4\u2010week titration, 12\u2010week maintenance). Treatment started at 5\u00a0mg\/kg\/day for all groups and reached 25\u00a0mg\/kg\/day on Day 9 and 50\u00a0mg\/kg\/day on Day 29. Percentage change from baseline in TSC\u2010associated seizure (countable focal or generalized) count was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 224 patients, 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo. Median (range) age was 11.3 (1.1\u201356.8)\u00a0years. Patients had discontinued a median (range) of 4 (0\u201315) antiseizure medications and were currently taking 3 (0\u20135). Difference in seizure reduction between CBD and placebo emerged on Day 6 (titrated dose, 15\u00a0mg\/kg\/day) and became nominally significant (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.049) by Day 10. Separation between placebo and CBD in \u226550% responder rate also emerged by Day 10. Onset of AEs occurred during the first 2\u00a0weeks of the titration period in 61% of patients (CBD25, 61%; CBD50, 67%; placebo, 54%). In patients with an AE, resolution occurred within 4\u00a0weeks of onset in 42% of placebo and 27% of CBD patients and by end of trial in 78% of placebo and 51% of CBD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Onset of treatment effect occurred within 6\u201310\u00a0days. AEs lasted longer for CBD than placebo, but the most common (diarrhea, decreased appetite, and somnolence) resolved during the 16\u2010week trial in most patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17199","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T16:44:49Z","timestamp":1645116289000},"page":"1189-1199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Time to onset of cannabidiol treatment effect and resolution of adverse events in tuberous sclerosis complex: Post hoc analysis of randomized controlled phase 3 trial GWPCARE6"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-788X","authenticated-orcid":false,"given":"Joyce Y.","family":"Wu","sequence":"first","affiliation":[{"name":"Ann and Robert H. Lurie Children's Hospital of Chicago Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-0141","authenticated-orcid":false,"given":"Hannah R.","family":"Cock","sequence":"additional","affiliation":[{"name":"St George's University Hospitals National Health Service Foundation Trust St George's University of London  London UK"}],"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4502-7242","authenticated-orcid":false,"given":"Charuta","family":"Joshi","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0416-1015","authenticated-orcid":false,"given":"Ian","family":"Miller","sequence":"additional","affiliation":[{"name":"Nicklaus Children's Hospital  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin M.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-0686","authenticated-orcid":false,"given":"Rocio","family":"Sanchez\u2010Carpintero","sequence":"additional","affiliation":[{"name":"University of Navarra Clinic  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Checketts","sequence":"additional","affiliation":[{"name":"GW Research  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Greenwich Biosciences  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"issue":"49","key":"e_1_2_10_2_1","first-page":"243","article-title":"Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference","volume":"2013","author":"Northrup H","year":"2012","journal-title":"Pediatr Neurol"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61279-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra055323"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.12.1236"},{"key":"e_1_2_10_6_1","first-page":"2021","article-title":"Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options","volume":"10","author":"Wang S","year":"2014","journal-title":"Neuropsychiatr Dis Treat"},{"key":"e_1_2_10_7_1","unstructured":"Tuberous Sclerosis Alliance.Diagnosis surveillance and management for healthcare professionals. 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