Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats

We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARy) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seven days after the induction of status epilepticus and the appearance of spontaneous recurrent seizures in all rats, CBD was dissolved in medium-chain triglyceride (MCT) oil and administered subcutaneously at 120 mg/kg (n = 10) or 12 mg/kg (n = 10), twice a day for three days. Similarly, the vehicle was administered to ten epileptic rats. Brain levels of PPAR gamma immunoreactivity were compared to those of six healthy controls. CBD at 120 mg/kg abolished the seizures in 50% of rats (p = 0.033 vs. pretreatment, Fisher's exact test) and reduced total seizure duration (p < 0.05, Tukey Test) and occurrence (p < 0.05). PPAR gamma levels increased with CBD in the hippocampal CA1 subfield and subiculum (p < 0.05 vs. controls, Holm-Sidak test), but only the highest dose increased the immunoreactivity in the hippocampal CA3 subfield (p < 0.001), perirhinal cortex, and amygdala (p < 0.05). Overall, these results suggest that the antiseizure effects of CBD are associated with upregulation of PPAR gamma in the hippocampal CA3 region.