Posted by Developmental epilepsy syndromes are characterized by recurrent seizures and developmental delays. Current anticonvulsants target γ-aminobutyric acid type A receptor signaling to decrease neuronal excitability, however, there are adverse effects for the developing brain, and many patients are refractory. The major non-psychotropic phytocannabinoid cannabidiol (CBD) has emerged as an anti-seizure medication effective in select developmental epilepsy syndromes, but its overall applicability in treating seizure disorders is limited. In the present study, we characterize a small library of non-Cannabis carvone derived CBD (+) enantiomers, with the larger goal of identifying novel therapeutics for developmental epilepsy syndromes.
This study presents a comprehensive analysis of synthetic carvone-derived CBD enantiomers, highlighting (+)-CBD-oct—the derivative with the longest alkyl chain—as a promising candidate for treating intractable developmental epilepsy. ( + )-CBD-oct significantly reduces seizure-related mortality in both C57Bl6 adults and a developmental epilepsy mouse model, supporting its potential for further preclinical and clinical development. EEG based structure activity relationship assessment supports that elongated alkyl chains increase the potency of the congeners, with (+)-CBD-oct displaying effects on both δ and θ frequency bands. Pre-treatment with (+)-CBD-oct promotes seizure resilience in both wildtype mice and the Gabra2-1 model of developmental epilepsy by influencing seizure characteristics, and reduces mortality. 5 days of (+)-CBD-oct oral gavage in wildtype and Gabra2-1 mice during postnatal development normalizes the aberrant dendritic spine phenotype of Gabra2-1 mice.
For tyhe animal studies CBD derivatives were dissolved in sesame oil. Why not to try a CD (HPBCD or SBECD) to improve the aqueous solubility and most probably also bioavailability?
Hines, R.M., Contreras, A., Carrillo, A. et al. Carvone derived cannabidiol enantiomers as novel anticonvulsants. Neuropsychopharmacol. (2025). https://doi.org/10.1038/s41386-025-02220-1