Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?
Abstract Objective This study aimed to evaluate the efficacy and safety of adjunctive, highly purified Cannabidiol (Epidiolex®) in individuals with drug‐resistant epilepsy (DRE) due to genetically determined typical Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD). Methods We recruited subjec...
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| Language: | English |
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Wiley
2025-08-01
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| Series: | Epilepsia Open |
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| Online Access: | https://doi.org/10.1002/epi4.70078 |
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| author | Aglaia Vignoli Giulia Prato Enrico Alfei Irene Bagnasco Alberto Danieli Massimiliano Celario Jacopo Favaro Sara Matricardi Francesca Felicia Operto Alessandro Orsini Davide Paolo Bernasconi Nicola Pietrafusa Emilia Ricci Luca Manfredini Giulia Balletto Paolo Bonanni Maria Paola Canevini Valentina De Giorgis Lino Nobili Stefano Sartori Miriam Nella Savini Ilaria Viganò Nicola Specchio |
| author_facet | Aglaia Vignoli Giulia Prato Enrico Alfei Irene Bagnasco Alberto Danieli Massimiliano Celario Jacopo Favaro Sara Matricardi Francesca Felicia Operto Alessandro Orsini Davide Paolo Bernasconi Nicola Pietrafusa Emilia Ricci Luca Manfredini Giulia Balletto Paolo Bonanni Maria Paola Canevini Valentina De Giorgis Lino Nobili Stefano Sartori Miriam Nella Savini Ilaria Viganò Nicola Specchio |
| author_sort | Aglaia Vignoli |
| collection | DOAJ |
| description | Abstract Objective This study aimed to evaluate the efficacy and safety of adjunctive, highly purified Cannabidiol (Epidiolex®) in individuals with drug‐resistant epilepsy (DRE) due to genetically determined typical Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD). Methods We recruited subjects with genetically confirmed typical RTT and CDD with drug‐resistant seizures who received add‐on treatment with highly purified Cannabidiol (CBD) through a national collaboration group. CBD treatment was titrated from 5 to 20 mg/kg/day; concurrent antiseizure medications (ASMs) could have been adjusted as clinically indicated. Results We enrolled 27 subjects (26 females), carrying a MECP2 genetic variant (14 subjects, 51.9%) or a CDKL5 genetic variant (13 subjects, 48.1%). Median age [IRQ] of individuals was 10.5 [7.9, 18.5] years. The median dose of CBD [IRQ] at last follow‐up was 15 [11.12, 18.8] mg/kg/day, in association with a mean of 3 ASMs (range 2–4). The median duration of treatment was 14 [8.5, 20] months. Although not reaching a significant statistical effect, CBD reduced the incidence of seizures with respect to the baseline in 18/27 (66.6%) subjects, with 7 (25.9%) showing a seizure reduction >75%, and 11 (40.7%) >50%. The most relevant adverse events were somnolence seen in 3 subjects, irritability/agitation in 2 subjects, loss of appetite in 2 subjects, and insomnia in 1 individual. Caregivers reported an improvement in attention and reactivity in 12 subjects (44.4%), in sleep quality in 5 subjects (18.5%), and in motor aspects in 3 patients (11.1%). Significance CBD resulted effective in reducing seizure frequency in 66.6% of the study sample, regardless of the pathogenic variant; side effects were mild, and caregivers reported an improvement in behavioral and motor features. Plain Language Summary This study explored the use of highly purified Cannabidiol (CBD, Epidiolex®) as an add‐on therapy for individuals with drug‐resistant epilepsy due to Rett Syndrome (RTT) or CDKL5 Deficiency Disorder (CDD). Twenty‐seven participants received CBD alongside their usual ASMs. After a median treatment duration of 14 months, 66.6% experienced fewer seizures, with some showing over 75% reduction. Side effects were generally mild, mainly sleepiness or irritability. Notably, caregivers reported improvements in attention, responsiveness, sleep, and motor function. While results were not statistically significant, they suggest CBD may benefit seizure control and quality of life in RTT and CDD patients. |
| format | Article |
| id | doaj-art-e1cc8012e6cb4fc8a8fee682340f6bde |
| institution | Kabale University |
| issn | 2470-9239 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj-art-e1cc8012e6cb4fc8a8fee682340f6bde2025-08-20T03:44:18ZengWileyEpilepsia Open2470-92392025-08-011041111111910.1002/epi4.70078Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?Aglaia Vignoli0Giulia Prato1Enrico Alfei2Irene Bagnasco3Alberto Danieli4Massimiliano Celario5Jacopo Favaro6Sara Matricardi7Francesca Felicia Operto8Alessandro Orsini9Davide Paolo Bernasconi10Nicola Pietrafusa11Emilia Ricci12Luca Manfredini13Giulia Balletto14Paolo Bonanni15Maria Paola Canevini16Valentina De Giorgis17Lino Nobili18Stefano Sartori19Miriam Nella Savini20Ilaria Viganò21Nicola Specchio22Childhood and Adolescence Neuropsychiatry Unit Grande Ospedale Metropolitano Niguarda Milan ItalyUnit of Child Neuropsychiatry IRCCS Istituto Giannina Gaslini, Full Member of European Reference Network EpiCARE Genoa ItalyPediatric Neurology Unit Buzzi Children's Hospital Milan ItalyDivision of Child Neuropsychiatry Martini Hospital Torino ItalyEpilepsy Unit IRCCS E. Medea Scientific Institute Conegliano ItalyDepartment of Child Neurology and Psychiatry IRCCS Mondino Foundation Pavia ItalyDepartment of Women's and Child's Health University of Padua Padova ItalyDepartment of Pediatrics University of Chieti Chieti ItalyDepartment of Science of Health School of Medicine University Magna Greacia of Catanzaro Catanzaro ItalyPediatric Neurology, University Hospital of Pisa Azienda Ospedaliero Universitaria Pisana Pisa ItalyBicocca Bioinformatics Biostatistics and Bioimaging Center, School of Medicine and Surgery University of Milano‐Bicocca ItalyNeurology, Epilepsy and Movement Disorders Unit Bambino Gesù Children's Hospital IRCCS, Full Member of European Reference Network EpiCARE Rome ItalyHealth Sciences Department Università degli Studi di Milano Milan ItalyPaediatric Chronic Pain and Palliative Care Service IRCCS Istituto Giannina Gaslini Genoa ItalyUnit of Child Neuropsychiatry IRCCS Istituto Giannina Gaslini, Full Member of European Reference Network EpiCARE Genoa ItalyEpilepsy Unit IRCCS E. Medea Scientific Institute Conegliano ItalyHealth Sciences Department Università degli Studi di Milano Milan ItalyDepartment of Child Neurology and Psychiatry IRCCS Mondino Foundation Pavia ItalyUnit of Child Neuropsychiatry IRCCS Istituto Giannina Gaslini, Full Member of European Reference Network EpiCARE Genoa ItalyDepartment of Women's and Child's Health University of Padua Padova ItalyChild Neurology Unit, Epilepsy Center San Paolo Hospital, Member of European Reference Network EpiCARE Milan ItalyChild Neurology Unit, Epilepsy Center San Paolo Hospital, Member of European Reference Network EpiCARE Milan ItalyNeurology, Epilepsy and Movement Disorders Unit Bambino Gesù Children's Hospital IRCCS, Full Member of European Reference Network EpiCARE Rome ItalyAbstract Objective This study aimed to evaluate the efficacy and safety of adjunctive, highly purified Cannabidiol (Epidiolex®) in individuals with drug‐resistant epilepsy (DRE) due to genetically determined typical Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD). Methods We recruited subjects with genetically confirmed typical RTT and CDD with drug‐resistant seizures who received add‐on treatment with highly purified Cannabidiol (CBD) through a national collaboration group. CBD treatment was titrated from 5 to 20 mg/kg/day; concurrent antiseizure medications (ASMs) could have been adjusted as clinically indicated. Results We enrolled 27 subjects (26 females), carrying a MECP2 genetic variant (14 subjects, 51.9%) or a CDKL5 genetic variant (13 subjects, 48.1%). Median age [IRQ] of individuals was 10.5 [7.9, 18.5] years. The median dose of CBD [IRQ] at last follow‐up was 15 [11.12, 18.8] mg/kg/day, in association with a mean of 3 ASMs (range 2–4). The median duration of treatment was 14 [8.5, 20] months. Although not reaching a significant statistical effect, CBD reduced the incidence of seizures with respect to the baseline in 18/27 (66.6%) subjects, with 7 (25.9%) showing a seizure reduction >75%, and 11 (40.7%) >50%. The most relevant adverse events were somnolence seen in 3 subjects, irritability/agitation in 2 subjects, loss of appetite in 2 subjects, and insomnia in 1 individual. Caregivers reported an improvement in attention and reactivity in 12 subjects (44.4%), in sleep quality in 5 subjects (18.5%), and in motor aspects in 3 patients (11.1%). Significance CBD resulted effective in reducing seizure frequency in 66.6% of the study sample, regardless of the pathogenic variant; side effects were mild, and caregivers reported an improvement in behavioral and motor features. Plain Language Summary This study explored the use of highly purified Cannabidiol (CBD, Epidiolex®) as an add‐on therapy for individuals with drug‐resistant epilepsy due to Rett Syndrome (RTT) or CDKL5 Deficiency Disorder (CDD). Twenty‐seven participants received CBD alongside their usual ASMs. After a median treatment duration of 14 months, 66.6% experienced fewer seizures, with some showing over 75% reduction. Side effects were generally mild, mainly sleepiness or irritability. Notably, caregivers reported improvements in attention, responsiveness, sleep, and motor function. While results were not statistically significant, they suggest CBD may benefit seizure control and quality of life in RTT and CDD patients.https://doi.org/10.1002/epi4.70078cannabidiolCDKL5 deficiency disorderdrug‐resistant epilepsyRett syndrome |
| spellingShingle | Aglaia Vignoli Giulia Prato Enrico Alfei Irene Bagnasco Alberto Danieli Massimiliano Celario Jacopo Favaro Sara Matricardi Francesca Felicia Operto Alessandro Orsini Davide Paolo Bernasconi Nicola Pietrafusa Emilia Ricci Luca Manfredini Giulia Balletto Paolo Bonanni Maria Paola Canevini Valentina De Giorgis Lino Nobili Stefano Sartori Miriam Nella Savini Ilaria Viganò Nicola Specchio Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder? Epilepsia Open cannabidiol CDKL5 deficiency disorder drug‐resistant epilepsy Rett syndrome |
| title | Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder? |
| title_full | Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder? |
| title_fullStr | Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder? |
| title_full_unstemmed | Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder? |
| title_short | Is highly purified cannabidiol a treatment opportunity for drug‐resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder? |
| title_sort | is highly purified cannabidiol a treatment opportunity for drug resistant epilepsy in subjects with typical rett syndrome and cdkl5 deficiency disorder |
| topic | cannabidiol CDKL5 deficiency disorder drug‐resistant epilepsy Rett syndrome |
| url | https://doi.org/10.1002/epi4.70078 |
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