{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:42:44Z","timestamp":1792154564157,"version":"4.4.0"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011096","name":"Jazz Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011096","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>CDKL5 deficiency disorder (CDD) is an early\u2010onset developmental and epileptic encephalopathy characterized by frequent drug\u2010resistant seizures, cerebral visual impairment, motor dysfunction, and sleep and gastrointestinal disturbances. Preliminary evidence suggests that highly purified cannabidiol (CBD) may reduce seizure frequency, but data on its effects on comorbidities are lacking. This study aimed to evaluate the efficacy and safety of CBD in individuals with CDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective, open\u2010label, single\u2010center study including patients with CDD aged &gt;1\u2009year. Outcomes included motor seizure frequency, caregiver\u2010 and clinician\u2010rated Clinical Global Impression (CGI), and changes in sleep, motor abilities, and EEG at 3, 6, and 12\u2009months. CBD plasma levels were measured with High\u2010Performance Liquid chromatography\u2013Mass Spectrometry (HPLC\u2010MS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight of nine patients (all females; median age 10\u2009years, range 1\u201324) completed the study, with a retention rate at 12\u2009months of 8\/9 (89%). One discontinued at 6\u2009months due to a skin rash. A\u2009&gt;\u200950% seizure reduction was observed in 8\/9 patients at 3\u2009months, 6\/9 at 6\u2009months, and 1\/8 at 12\u2009months. Seven patients showed some degree of vigilance improvements, three in motor performance, and two in sleep and constipation. All caregivers reported at least minimal overall improvement (CGI score 3) at 3 months, and three reported marked improvement (CGI score 2), with a peak at 3\u2009months. Five patients showed adverse events during the trial, but none were considered serious. The median CBD dose at all time\u2010points was 15.6\u2009mg\/kg\/day (IQR 10.0\u201318.9) corresponding to a plasma dose of 69.9\u2009ng\/mL (IQR 29.8\u2013114.6) and the median concentration\/dose ratio was 4.7 (IQR 2.7\u20136.8).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The safety and efficacy of highly purified CBD in CDD were consistent with previous reports in the literature, with possible benefits beyond seizure control. Further studies are warranted to assess non\u2010seizure outcomes and compare long\u2010term efficacy across treatment options.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>We studied nine girls with CDKL5 deficiency disorder who had frequent, hard\u2010to\u2010treat seizures. They received cannabidiol for up to 1 year, added to their usual medicines. Most children had fewer seizures in the first months of treatment. Some families also noticed better alertness, eye contact, movement, sleep, or constipation. Side effects were usually mild and manageable. Although seizure frequency often returned to baseline by the end of the study, most families chose to continue cannabidiol. Because this was a small study without a placebo group, these results are preliminary, and larger controlled trials are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70213","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:41:48Z","timestamp":1770900108000},"page":"466-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Highly purified cannabidiol (\n                    <scp>CBD<\/scp>\n                    ) in\n                    <scp>CDKL5<\/scp>\n                    deficiency disorder (\n                    <scp>CDD<\/scp>\n                    ): Open\u2010label prospective study"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3311-2765","authenticated-orcid":false,"given":"Marco","family":"Perulli","sequence":"first","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7330-1030","authenticated-orcid":false,"given":"Alessia","family":"De Gioia","sequence":"additional","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5841-6409","authenticated-orcid":false,"given":"Federica","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0218-9748","authenticated-orcid":false,"given":"Federica","family":"Ascione","sequence":"additional","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0038-0151","authenticated-orcid":false,"given":"Chiara","family":"Porto","sequence":"additional","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3298-2390","authenticated-orcid":false,"given":"Elisa","family":"Musto","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-4961","authenticated-orcid":false,"given":"Valentina","family":"Massaroni","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2300-1514","authenticated-orcid":false,"given":"Maria","family":"Picilli","sequence":"additional","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-6221","authenticated-orcid":false,"given":"Maria Luigia","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8278-6953","authenticated-orcid":false,"given":"Michela","family":"Quintiliani","sequence":"additional","affiliation":[{"name":"Neuropsichiatria Infantile Fondazione Policlinico Universitario A. 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