Abstract
Objective: To evaluate the effects of transdermal administration of cannabidiol (CBD), either alone or in combination with phenobarbital, on behavioral, histopathological, and oxidative changes in an experimental model of pilocarpine-induced epilepsy. Methods: Seventy-two Wistar rats were divided into eight experimental groups, subjected to pilocarpine-induced epilepsy, and treated transdermally for 30 days with formulations containing CBD and/or phenobarbital. Behavioral tests were performed in an elevated plus maze and open field, along with histopathological and histomorphometric analyses of the hippocampus, as well as the evaluation of markers of oxidative stress. The nanostructured formulations were also characterized for physicochemical stability. Results: The groups treated with CBD showed reduced neuronal hyperexcitability, behavioral improvement, and decreased locomotor activity. Lower neuronal mortality, reduced gliosis, and partial preservation of hippocampal architecture were observed, especially in the CBD35 group. This group also demonstrated a better antioxidant response, with increased superoxide dismutase activity and partial maintenance of catalase. Conclusion: Transdermal administration of CBD, particularly in combination with phenobarbital, demonstrated neuroprotective and antioxidant potential in the experimental epilepsy model, proving to be a promising therapeutic strategy.
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