{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:01:09Z","timestamp":1783814469462,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,10,3]],"date-time":"2016-10-03T00:00:00Z","timestamp":1475452800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Herscot Center for Tuberous Sclerosis Complex"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Tuberous sclerosis complex (<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>) is an autosomal\u2010dominant genetic disorder with highly variable expression. The most common neurologic manifestation of <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment\u2010resistant epilepsy. Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol (<jats:styled-content style=\"fixed-case\">CBD<\/jats:styled-content>), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen of the 56 patients who have enrolled in our current expanded\u2010access study of cannabidiol for patients with treatment\u2010resistant epilepsy carry a diagnosis of <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>. After an initial baseline period of 1\u00a0month, patients began treatment with <jats:styled-content style=\"fixed-case\">CBD<\/jats:styled-content>. The initial dose of 5\u00a0mg\/kg\/day was increased by 5\u00a0mg\/kg\/day every week up to a maximum dose of 50\u00a0mg\/kg\/day, if tolerated. Weekly seizure frequencies, percent change in seizure frequencies, and responder rates were calculated during the 2nd, 3rd, 6th, 9th, and 12th month of treatment with <jats:styled-content style=\"fixed-case\">CBD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median weekly seizure frequency during the baseline period was 22.0 (interquartile range [<jats:styled-content style=\"fixed-case\">IQR<\/jats:styled-content>] 14.8\u201357.4), which decreased to 13.3 (<jats:styled-content style=\"fixed-case\">IQR<\/jats:styled-content> 5.1\u201322.1) after 3\u00a0months of treatment with cannabidiol. The median percent change in total weekly seizure frequency was \u221248.8% (<jats:styled-content style=\"fixed-case\">IQR<\/jats:styled-content> \u221269.1% to \u221211.1%) after 3\u00a0months of treatment. The 50% responder rates over the course of the study were 50%, 50%, 38.9%, 50%, and 50% after 2, 3, 6, 9, and 12\u00a0months of treatment with <jats:styled-content style=\"fixed-case\">CBD<\/jats:styled-content>, respectively. In patients taking clobazam concurrently with <jats:styled-content style=\"fixed-case\">CBD<\/jats:styled-content> (n\u00a0=\u00a012), the responder rate after 3\u00a0months of treatment was 58.3%, compared to 33.3% in patients not taking clobazam (n\u00a0=\u00a06). Twelve (66.7%) of 18 patients in this study experienced at least one adverse event thought possibly related to <jats:styled-content style=\"fixed-case\">CBD<\/jats:styled-content>; the most common adverse events were drowsiness (n\u00a0=\u00a08, 44.4%), ataxia (n\u00a0=\u00a05, 27.8%), and diarrhea (n\u00a0=\u00a04, 22.2%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Although double\u2010blind, placebo\u2010controlled trials are still necessary, these findings suggest that cannabidiol may be an effective and well\u2010tolerated treatment option for patients with refractory seizures in <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13499","type":"journal-article","created":{"date-parts":[[2016,10,11]],"date-time":"2016-10-11T20:05:53Z","timestamp":1476216353000},"page":"1617-1624","source":"Crossref","is-referenced-by-count":174,"title":["Cannabidiol as a new treatment for drug\u2010resistant epilepsy in tuberous sclerosis complex"],"prefix":"10.1111","volume":"57","author":[{"given":"Evan J.","family":"Hess","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten A.","family":"Moody","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra L.","family":"Geffrey","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F.","family":"Pollack","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Skirvin","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Bruno","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan L.","family":"Paolini","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Thiele","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00069-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.35"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02474.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12635"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12631"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00379-8"},{"key":"e_1_2_8_8_1","first-page":"271","article-title":"Cannabinoids for pediatric epilepsy? Up in smoke or real science?","volume":"4","author":"Francis FM","year":"2015","journal-title":"Transl Pediatr"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1407304"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535-7597-14.5.250"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00421539"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1975.tb09515.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1977.tb11378.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(82)90264-3"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1973.tb09976.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.159145"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2012.03.001"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1979.tb04815.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000137430"},{"key":"e_1_2_8_20_1","first-page":"CD009270","article-title":"Cannabinoids for epilepsy","volume":"6","author":"Gloss D","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13060"},{"key":"e_1_2_8_22_1","volume-title":"GW pharmaceuticals announces positive phase 3 pivotal study results for epidiolex (cannabidiol)","year":"2016"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S2937"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000217916.00225.3a"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.13499","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.13499","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.13499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T12:38:11Z","timestamp":1695559091000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.13499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1111\/epi.13499"],"URL":"https:\/\/doi.org\/10.1111\/epi.13499","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]}}}