Charakterystyka behawioralna, elektrofizjologiczna i epigenetyczna ostrych dawek kannabinoidów podczas indukowanego pilokarpiną stanu padaczkowego u myszy

Abstract There is growing interest in using cannabis and its active ingredients for epilepsy treatment. The main components of cannabis are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), with some formulations of CBD approved for treating epilepsies refractory to traditional pharmacological treatments. However, it remains unclear whether the acute administration of THC or CBD can reverse a seizure once it has started. In this study, we used a temporal epilepsy model in mice induced by pilocarpine injection and analyzed the effects of CBD and THC during status epilepticus (SE) on behavior, cortical activity, and epigenetics. Behavioral analyses showed that CBD did not alter seizure severity, while THC only increased sedation. Regarding cortical electrical activity, neither CBD nor THC reverted the electroencephalographic changes induced by pilocarpine. Finally, we found that acute THC treatment prevented the seizure-induced homeostatic downregulation of neuroLSD1, maintaining it at physiological levels despite the insult. These results highlight that an acute dose of cannabinoid drugs is insufficient to reduce seizures and suggest that THC could promote the ongoing network excitability during seizures.