A complex partial seizure also termed as focal impaired awareness seizures oral lobe origin (FIAS) is the most common seizures in adults and are normally drug-resistant. This kind of seizure occurs in a single region of the brain, generally the temporal lobe of the brain. It affects the consciousness of a person, as they are able to hear you but not completely understand your words or respond to you and would not react normally. Management of FIAS is clinically difficult and challenging, and new interventions may prove useful to achieve seizure freedom in such patients. The amygdala-kindling model is a pre-clinical model of FIAS with secondary generalization.
Kindling is an extensively studied animal model of temporal lobe epilepsy in which daily electrical stimulation of some regions of the brain results in the gradual progression and escalation of limbic motor seizures. Many investigators have found that short-term and partial kindling generates robust alterations in emotional behavior in both rats and cats.
The objective of this study is to examine the effectiveness and safety of cannabidiol (CBD) alone, 9-tetrahydrocannabinol (THC) alone, and a combination of CBD and THC (15:1) in restraining generalized and focal seizures in the amygdala-kindled rat.
Fully kindled, Sprague-Dawley rats with bipolar electrodes implanted in the right amygdala were administered intraperitoneal injections of either CBD (Dose: 0-320 mg/kg), THC (Dose: 0-80 mg/kg), or a combination of CBD and THC in the ratio of 15:1. Suprathreshold stimulation was applied after injection, and efficiency was evaluated using stereo-EEG and the Racine scale.
Suprathreshold refers to a stimulus that is huge in magnitude to produce an action potential in excitable cells.
CBD alone restrained generalized and focal seizures in the kindling model at sub-toxic doses. THC on its own also suppressed generalized and focal seizures, but only at doses that resulted in psychotoxic effects (present above 10 mg/kg). The inclusion of a low dose of THC to CBD (15:1) moved left the dose-response curve for CBD, producing lower ED50s for both generalized (ED 50: 40 + 2.66 mg/kg) and focal seizures (ED 40 + 2.66 mg/kg). No toxicity was observed at these doses of THC.
CBD and THC both contain anti-seizure properties in the amygdala kindling model, although THC works only at psychotoxic doses. The addition of small (subtoxic) amounts of THC immensely improves the effectiveness of CBD. A combination of CBD and THC may be beneficial in the clinical management of FIAS.