Anticonvulsant effects of cannabinoids in mice

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The anticonvulsant activity of orally administered δ9-tetrahydrocannabinol (δ9-THC), δ8-THC, cannabidiol (CBD) and cannabinol (CBN) was tested in mice utilizing electroshock and chemoshock methods. In doses tested δ9-THC afforded no protection to mice from chemoshock seizures and was effective against electroshock only in high doses (160–200 mg/kg). CBD and CBN (150–200 mg/kg) were without effect in both tests. An interaction between cannbinoids was apparent when all three were administered simultaneously (each at 50 mg/kg) because this combination produced a significant reduction in the duration of the hind-limb extensor phase of the electroshock seizures. The administration of δ9-THC significantly potentiated the anticonvulsant effectiveness of phenytoin against electroshock seizures and this effect was further potentiated by the concurrent administration of CBD. Whilst the potentiation of phenytoin by δ9-THC (50 mg/kg) was of the order of 1.5 times, the combination of δ-9THC and CBD (each 50 mg/kg) produced a four-fold potentiation.