CBD showed similar effectiveness for rare genetic epilepsies whether used on-label or off-label | Research

The takeaway

In 266 patients with 77 different monogenic epilepsies, nearly half achieved 50% or greater seizure reduction with CBD, with no difference between approved and off-label uses.

Neurologists, epilepsy specialists, families of patients with rare genetic epilepsies

47.5% achieved 50%+ seizure reduction across 77 different monogenic epilepsies

What the researchers found

47.5% of patients achieved 50% or greater seizure reduction; 7.4% became seizure-free; no significant difference between approved indications and off-label use; shorter prior seizure-free periods and greater intellectual disability predicted lower effectiveness.

Why it matters

CBD is only approved for three specific epilepsy syndromes, but this large real-world study suggests comparable effectiveness across a much wider range of genetic epilepsies.

The numbers in context

266 patients (135 female); 77 different monogenic epilepsies; median age at CBD start 12 years; 47.5% achieved 50%+ seizure reduction; 7.4% seizure-free; 65.8% showed Clinical Global Impression improvement; median follow-up 17 months.

How the study worked

Retrospective multicenter study across 27 epilepsy centers; 266 patients with monogenic epilepsies treated with highly purified CBD for at least 3 months; median follow-up 17 months.

What this study cannot tell us

Retrospective design; no control group; variable dosing and co-medications across centers; potential selection bias toward patients expected to respond.

How to read the evidence

Large multicenter real-world study with meaningful follow-up, though retrospective design and lack of control group limit causal claims.

When this study was published

Published 2025

The bigger picture

This provides the strongest evidence yet that CBD's antiseizure effects extend well beyond Dravet, Lennox-Gastaut, and tuberous sclerosis syndromes.

Questions still open

Which specific genetic epilepsies respond best to CBD? Should regulatory approvals expand to include more monogenic epilepsies? Can genetic markers predict CBD response?

Common questions

Did CBD work as well for off-label epilepsies as for approved ones?

Yes. There was no significant difference in seizure outcomes between patients using CBD for its approved indications versus off-label genetic epilepsies.

What predicted poorer response to CBD?

Shorter maximum seizure-free periods before starting CBD and greater intellectual disability were both associated with lower effectiveness.

Read the original research

Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study.

Epilepsia, 66(7), 2253-2267

View on PubMed ↗Publisher’s paper ↗

Citation

Cerulli Irelli, Emanuele; Mazzeo, Adolfo; Caraballo, Roberto H; Perulli, Marco; Moloney, Patrick B; Peña-Ceballos, Javier; Rubino, Marica; Mieszczanek, Katarzyna M; Santangelo, Andrea; Licchetta, Laura; De Giorgis, Valentina; Reyes Valenzuela, Gabriela; Casellato, Susanna; Cesaroni, Elisabetta; Operto, Francesca F; Domínguez-Carral, Jana; Ramírez-Camacho, Alia; Ferretti, Alessandro; Santangelo, Giuseppe; Aledo-Serrano, Angel; Rüegger, Andrea; Mancardi, Maria M; Prato, Giulia; Riva, Antonella; Bergonzini, Luca; Cordelli, Duccio M; Bonanni, Paolo; Bisulli, Francesca; Di Gennaro, Giancarlo; Matricardi, Sara; Striano, Pasquale; Delanty, Norman; Marini, Carla; Battaglia, Domenica; Di Bonaventura, Carlo; Ramantani, Georgia; Gardella, Elena; Orsini, Alessandro; Coppola, Antonietta. (2025). Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study.. Epilepsia, 66(7), 2253-2267. https://doi.org/10.1111/epi.18378