In 27 patients with drug-resistant epilepsy from Rett syndrome or CDKL5 deficiency disorder, add-on CBD (Epidiolex) reduced seizure frequency in 67% over a median of 14 months, with mild side effects and caregiver-reported improvements in attention and sleep.
Pediatric neurologists, families affected by Rett syndrome or CDKL5 deficiency, and epilepsy researchers.
What the researchers found
CBD reduced seizure frequency in 18 of 27 patients (66.6%) with drug-resistant epilepsy due to Rett syndrome or CDKL5 deficiency. Seven patients (25.9%) achieved >75% seizure reduction and 11 (40.7%) achieved >50% reduction. Caregivers reported improvements in attention/reactivity (44.4%), sleep quality (18.5%), and motor function (11.1%).
Why it matters
Rett syndrome and CDKL5 deficiency are devastating genetic conditions with limited treatment options for their drug-resistant seizures. These results suggest CBD may offer meaningful benefit beyond what current medications provide, including improvements in behavior and cognition.
The numbers in context
27 patients (26 female). Median age 10.5 years. Median CBD dose: 15 mg/kg/day. Median treatment duration: 14 months. 66.6% had reduced seizures. 25.9% had >75% reduction. Mean concurrent ASMs: 3 (range 2–4). Adverse events: somnolence (3), irritability (2), appetite loss (2), insomnia (1).
How the study worked
Multi-center observational study of 27 patients (26 female) with genetically confirmed Rett syndrome (14) or CDKL5 deficiency (13) receiving add-on CBD (Epidiolex, titrated 5–20 mg/kg/day) alongside existing anti-seizure medications, through a national Italian collaboration.
What this study cannot tell us
Small sample (n=27), no control group or randomization. Results did not reach statistical significance. Open-label design with potential placebo effect. Concurrent ASM adjustments complicate attribution. Only Italian centers.
How to read the evidence
Multi-center observational study with reasonable follow-up duration, but small sample without randomization or blinding.
When this study was published
Published 2025.
The bigger picture
CBD (Epidiolex) is already approved for Dravet and Lennox-Gastaut syndromes. These findings support expanding its use to other rare genetic epilepsies, with the added benefit of improvements in attention and behavior that may be equally important to families.
Questions still open
- Would a randomized controlled trial confirm these benefits? Are the attention and behavioral improvements direct CBD effects or secondary to seizure reduction? Is the optimal dose different for RTT vs. CDD patients?
Common questions
Is CBD approved for Rett syndrome epilepsy?
What side effects were seen?
Read the original research
Is highly purified cannabidiol a treatment opportunity for drug-resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?
Epilepsia open, 10(4), 1111-1119
Citation
Vignoli, Aglaia; Prato, Giulia; Alfei, Enrico; Bagnasco, Irene; Danieli, Alberto; Celario, Massimiliano; Favaro, Jacopo; Matricardi, Sara; Operto, Francesca Felicia; Orsini, Alessandro; Bernasconi, Davide Paolo; Pietrafusa, Nicola; Ricci, Emilia; Manfredini, Luca; Balletto, Giulia; Bonanni, Paolo; Canevini, Maria Paola; De Giorgis, Valentina; Nobili, Lino; Sartori, Stefano; Savini, Miriam Nella; Viganò, Ilaria; Specchio, Nicola. (2025). Is highly purified cannabidiol a treatment opportunity for drug-resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?. Epilepsia open, 10(4), 1111-1119. https://doi.org/10.1002/epi4.70078
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