Researchers have found that cannabidiol (CBD) significantly reduces seizures and extends survival in a mouse model of developmental and epileptic encephalopathy type 1 (DEE1), a rare and drug-resistant pediatric epilepsy.
The study, published in Epilepsia, involved a collaboration between researchers from the National Research Council of Italy, the University of Cassino and Southern Lazio, the University of Naples “Federico II”, and Université Laval.
DEE1 is caused by trinucleotide repeat expansions in the ARX gene, leading to elongation of the first polyalanine tract. This condition results in early-onset tonic seizures or spasms, cognitive impairment, and a high risk of premature death. Using a DEE1 mouse model (Arx(GCG)7/Y), the researchers administered daily doses of highly purified CBD at 100 mg/kg for seven days.
“CBD reduced the severity and frequency of spontaneous recurrent seizures and significantly extended the lifespan of epileptic mice,” the study found. Researchers noted that CBD activated peroxisome Pparg expression while desensitizing TRPV1 channels. It also counteracted elevated levels of proinflammatory genes like Ptgs2, Mmp9, Il12, and Cd68, and helped normalize microglial morphology in the cortex of affected mice.
Importantly, CBD corrected abnormal alternative splicing of key presynaptic receptor genes (Nrnx1 and Nrnx3) and improved neuronal function by reducing excitability. It achieved this by inducing hyperpolarization and increasing the action potential threshold, ultimately restoring healthier neuronal signaling.
These results offer the first preclinical evidence that CBD may hold therapeutic value for treating DEE1 and highlight molecular pathways that could serve as future drug targets.
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