CBD Reduced Seizures in Two-Thirds of Patients With Rett Syndrome and CDKL5 Deficiency
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.
Quick Facts
What This Study 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%).
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Evidence Grade:
- Multi-center observational study with reasonable follow-up duration, but small sample without randomization or blinding.
- Study Age:
- Published 2025.
- Original Title:
- Is highly purified cannabidiol a treatment opportunity for drug-resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?
- Published In:
- Epilepsia open, 10(4), 1111-1119 (2025)
- Authors:
- Vignoli, Aglaia, Prato, Giulia(2), 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
- Database ID:
- RTHC-07870
Evidence Hierarchy
Frequently Asked Questions
Is CBD approved for Rett syndrome epilepsy?
Not yet specifically. CBD (Epidiolex) is approved for Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. This study adds evidence that it may also help Rett syndrome and CDKL5 deficiency, but formal approval for these conditions would require larger trials.
What side effects were seen?
Side effects were generally mild: somnolence in 3 patients, irritability in 2, appetite loss in 2, and insomnia in 1. These are consistent with the known safety profile of Epidiolex.
Read More on RethinkTHC
- CBD-oil-quality-guide
- anxiety-medication-after-quitting-weed
- cannabis-chemotherapy-nausea
- cannabis-chronic-pain-research
- cannabis-epilepsy-CBD-Epidiolex
- cbd-anxiety-research-evidence
- cbd-for-weed-withdrawal
- cbd-vs-thc-difference
- medical-benefits-of-cannabis
- quitting-weed-before-surgery
- quitting-weed-medication-interactions
- quitting-weed-pregnancy
- quitting-weed-pregnant
- seniors-older-adults-cannabis-risks-medications
- weed-breastfeeding-THC-breast-milk
- cannabis-and-autism-families-research
Cite This Study
https://rethinkthc.com/research/RTHC-07870APA
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
MLA
Vignoli, Aglaia, et al. "Is highly purified cannabidiol a treatment opportunity for drug-resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?." Epilepsia open, 2025. https://doi.org/10.1002/epi4.70078
RethinkTHC
RethinkTHC Research Database. "Is highly purified cannabidiol a treatment opportunity for d..." RTHC-07870. Retrieved from https://rethinkthc.com/research/vignoli-2025-is-highly-purified-cannabidiol
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.