Antiseizure effects of the cannabinoids in the amygdala-kindling model.
Focal impaired awareness seizures (FIASs) are the most common seizure type in adults and are often refractory to medication. Management of FIASs is clinically challenging, and new interventions are needed for better seizure control. The amygdala-kindling model is a preclinical model of FIASs with secondary generalization. The present study assessed the efficacy of cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), and a combination of CBD and THC in a 151 ratio at suppressing focal and secondarily generalized seizures in the amygdala-kindled rat. Fully kindled, male Sprague Dawley rats, with bipolar electrodes implanted in the right amygdala, were given either CBD (0-320 mgkg), THC (0-40 mgkg), or a combination of CBD and THC (151 ratio, multiple doses) intraperitoneally. Suprathreshold kindling stimulation was administered 1 h (THC) or 2 h (CBD) after drug injection, and outcomes were assessed using focal electroencephalographic recording and the Racine seizure scale. CBD alone produced a partial suppression of both generalized seizures (median effective dose ED CBD and THC both have antiseizure properties in the amygdala-kindling model, although THC produces suppression of the amygdala focus only at doses that produce hypolocomotion. The addition of small amounts of THC greatly improves the effectiveness of CBD. A combination of CBD and THC might be useful for the management of FIASs.