In 107 patients with severe developmental epilepsy syndromes, 69% achieved at least a 50% seizure reduction with CBD—and patients with genetic causes responded best.
Neurologists prescribing CBD for severe epilepsy, families of children with DEEs, and researchers studying predictors of CBD response.
What the researchers found
Clinical trials establish whether a drug works under ideal conditions. Real-world studies reveal how it performs in actual clinical practice—with diverse patients, varied medication regimens, and imperfect adherence. This study fills that gap for CBD in severe epilepsy.
One hundred seven patients with developmental and epileptic encephalopathies (DEEs) were treated with pharmaceutical CBD for at least 3 months between 2020 and 2024. The cohort included approved indications (Lennox-Gastaut, Dravet, tuberous sclerosis complex) and off-label uses in other DEEs.
At a median follow-up of 20 months, 69% achieved at least 50% seizure reduction—a strong real-world result. Twenty-one percent achieved 75% or greater reduction. These numbers are encouraging given that all patients were, by definition, treatment-resistant (having failed multiple prior medications).
Two findings stood out for personalizing treatment. First, patients with LGS, TSC, and other DEEs showed higher efficacy and retention than Dravet syndrome patients—surprising given that Dravet was one of the original FDA-approved indications. Second, genetic or unknown etiology predicted better outcomes (p = 0.011), suggesting that the underlying cause of epilepsy matters for CBD response.
The combination of CBD with valproate was associated with specific side effect considerations that required clinical management.
Why it matters
Real-world data like this helps clinicians set realistic expectations. The 69% responder rate is strong but also means 31% didn't achieve meaningful seizure reduction—knowing who is most likely to respond (genetic etiology, LGS/TSC) can inform treatment decisions. The off-label data in "other DEEs" also expands the evidence base beyond the three FDA-approved syndromes.
The numbers in context
N = 107. Median follow-up: 20 months. 69% achieved ≥50% seizure reduction. 21% achieved ≥75% reduction. LGS: 55.1%, Dravet: 16.8%, TSC: 8.4%, other DEEs: 19.6%. Genetic etiology: 56.1%. Genetic/unknown etiology associated with better outcomes (p = 0.011).
How the study worked
Retrospective study of 107 patients with DEEs treated with CBD for ≥3 months (2020–2024). Diagnoses: LGS (55.1%), Dravet (16.8%), TSC (8.4%), other DEEs (19.6%). Genetic etiology in 56.1%. Data on seizure frequency, tolerability, retention, and non-seizure outcomes. Efficacy defined as ≥50% or ≥75% seizure reduction. Statistical analysis of predictors of response.
Who was studied
N=107 patients with developmental and epileptic encephalopathies, treated with CBD for ≥3 months, from 2020 to 2024.
What this study cannot tell us
Retrospective design with inherent biases (treatment decisions weren't randomized). No control group—some improvement may reflect natural seizure fluctuation. Single-center experience. The 3-month minimum treatment duration excludes early discontinuations (potentially biasing toward responders). Seizure counting relies on caregiver observation, which can be imprecise.
How to read the evidence
Retrospective real-world cohort with 20-month median follow-up—valuable for clinical practice but limited by lack of randomization and control group.
When this study was published
Published in 2025 with data from 2020–2024, reflecting current clinical CBD use patterns.
The bigger picture
This real-world evidence complements RTHC-00186's prescribing guide and RTHC-00165's evidence review. While RTHC-00160 and RTHC-00179 explore next-generation CBD formulations in animals, this study shows what currently available pharmaceutical CBD is achieving in clinical practice. The finding that Dravet patients responded less well than LGS/TSC is clinically important and somewhat counterintuitive given Dravet's prominence in the CBD-epilepsy narrative.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Why do Dravet patients show lower response rates than other DEEs in real-world use? Could genetic testing identify CBD responders before starting treatment? Would the off-label DEE patients have been eligible for approval trials, and should indications be expanded?
Read the original research
Real-world efficacy and safety of cannabidiol in developmental and epileptic encephalopathies.
Epilepsia open, 10(6), 1806-1813
Epilepsia Open is a reputable journal focusing on epilepsy research and treatment.
Citation
Perulli, Marco; Bianchetti, Maddalena; Pantalone, Gloria; Quintiliani, Michela; Gambardella, Maria Luigia; Picilli, Maria; Marini, Carla; Cesaroni, Elisabetta; Battaglia, Domenica Immacolata. (2025). Real-world efficacy and safety of cannabidiol in developmental and epileptic encephalopathies.. Epilepsia open, 10(6), 1806-1813. https://doi.org/10.1002/epi4.70149
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