In mice, THC lowered observed seizure severity but caused marked sedation

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 analyzed the effects of CBD and THC during pilocarpine-induced status epilepticus (SE) on behavior, cortical activity, and on the transcriptional regulator neuroLSD1. Male C57BL/6 mice were injected with pilocarpine 300 mg/kg ip, followed by CBD 100 mg/kg ip or THC 10 mg/kg ip. Behavioral analysis, electrocorticogram and Rtf-PCR for LSD1/neuroLSD1 were performed. Behavioral analyses showed that CBD did not alter seizure severity. In contrast, THC reduced seizure severity although this reduction was accompanied by marked 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.