Evaluation of interactions between cannabinoid compounds and diazepam

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Several studies have shown that cannabinoids have anticonvulsant properties that are mediated through activation of the cannabinoid CB1 receptors. The present study was designed to evaluate the anticonvulsant effects of diazepam and WIN55212-2, a synthetic cannabinoid CB1 receptor agonist, and their interactions in the electroshock-induced seizure model in mice. Diazepam (0.25–2 mg/kg) and WIN55212-2 (0.5–4 mg/kg) dose dependently produced an antiepileptic effect evaluated in terms of increased percentage of protection against electroshock-induced seizure. Logistic regression analysis indicated synergistic interactions in anticonvulsant action after co-administration of diazepam and WIN55212-2 in fixed-ratio combination of 3:1 (diazepam:WIN55212-2). The results suggest that cannabinoids may offer a new class of therapeutic agents for the treatment of seizure disorders. The synergistic interaction between diazepam and WIN55212-2 supports the potential of cannabinoids in combination with traditional anticonvulsants to improve seizure control.