The anticonvulsant activity of orally administered δ 9-tetrahydrocannabinol (δ 9-THC), δ 8-THC, cannabidiol (CBD) and cannabinol (CBN) was tested in mice utilizing electroshock and chemoshock methods. In doses tested δ 9-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 δ 9-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 δ 9-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.
Neither within-cannabinoid interaction nor cannabinoid potentiation of phenobarbitone effectiveness could be demonstrated in chemoshock tests.
The mechanism of the cannabinoid facilitation of phenytoin is unknown but it possibly involves activity at central nervous system level rather than being a metabolic interaction. This drug interaction may have potential clinical significance.
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Chesher, G.B., Jackson, D.M. Anticonvulsant effects of cannabinoids in mice: Drug interactions within cannabinoids and cannabinoid interactions with phenytoin. Psychopharmacologia 37, 255–264 (1974). https://doi.org/10.1007/BF00421539
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