{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T11:07:28Z","timestamp":1794049648207,"version":"4.8.0"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"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"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Rett syndrome (RTT), commonly caused by methyl\u2010CpG\u2010binding protein 2 (<jats:italic>MECP2<\/jats:italic>) pathogenic variants, has many comorbidities. Fifty to ninety percent of children with RTT have epilepsy, which is often drug\u2010resistant. Cannabidivarin (CBDV), a non\u2010hallucinogenic phytocannabinoid, has shown benefit in <jats:italic>MECP2<\/jats:italic> animal models. This phase 1 trial assessed the safety and tolerability of CBDV in female children with RTT and drug\u2010resistant epilepsy, as well as the effect on mean monthly seizure frequency (MMSF), the electroencephalogram (EEG), and non\u2010epilepsy comorbid symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five female children with drug\u2010resistant epilepsy and a pathogenic <jats:italic>MECP2<\/jats:italic> variant were enrolled. Baseline clinical and laboratory assessments, including monthly seizure frequency, were recorded. CBDV oral solution (50\u00a0mg\/ml) was prescribed and titrated to 10\u00a0mg\/kg\/day. Data collected included pharmacokinetics, seizure type and frequency, adverse events, EEG, and responses to the Rett Syndrome Behaviour Questionnaire and Rett Syndrome Symptom Severity Index, and were compared to baseline data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All five children reached the maximum CBDV dose of 10\u00a0mg\/kg\/day and had a reduction in MMSF (median = 79% reduction). Three children had MMSF reduction &gt; 75%. This corresponded to an overall reduction in seizure frequency from 32 to 7.2 seizures per month. Ninety\u2010one percent of adverse events were mild or moderate, and none required drug withdrawal. Sixty\u2010two percent were judged to be unrelated to CBDV. Thirty\u2010one percent of adverse events were identified as possibly related, of which nearly all were mild, and the remainder were later assessed as RTT symptoms. Hypersomnolence and drooling were identified as related to CBDV. No serious adverse events reported were related to CBDV. No significant change was noted in EEG or non\u2010epilepsy\u2010related symptoms of RTT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>A dose of 10\u00a0mg\/kg\/day of CBDV is safe and well tolerated in a pediatric RTT cohort and suggests improved seizure control in children with <jats:italic>MECP2<\/jats:italic>\u2010related RTT.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17247","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T21:15:37Z","timestamp":1648847737000},"page":"1736-1747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Efficacy and safety of cannabidivarin treatment of epilepsy in girls with Rett syndrome: A phase 1 clinical trial"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9808-194X","authenticated-orcid":false,"given":"Ellen 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Health UNSW Medicine and Health University of New South Wales  Randwick New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Neurology Sydney Children\u2019s Hospital Randwick  Sydney New South Wales Australia"},{"name":"School of Women\u2019s and Children\u2019s Health UNSW Medicine and Health University of New South Wales  Randwick New South Wales Australia"},{"name":"National Health and Medical Research Council Australian Centre for Cannabinoid Clinical and Research Excellence University of Newcastle  Callaghan New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Gordon","sequence":"additional","affiliation":[{"name":"National Health and Medical Research Council Australian Centre for Cannabinoid Clinical and Research Excellence University of Newcastle  Callaghan New South Wales 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