• DOI:10.1111/j.2042-7158.1975.tb09515.x
• Corpus ID: 27241108

Interaction of Δ9‐tetrahydrocannabinol and cannabidiol with phenobarbitone in protecting mice from electrically induced convulsions

@article{Chesher1975InteractionO,
  title={Interaction of $\Delta$9‐tetrahydrocannabinol and cannabidiol with phenobarbitone in protecting mice from electrically induced convulsions},
  author={Gregory B. Chesher and David M. Jackson and Ron Malor},
  journal={Journal of Pharmacy and Pharmacology},
  year={1975},
  volume={27}
}

• G. Chesher, D. Jackson, R. Malor
• Published 1 August 1975
• Biology
• Journal of Pharmacy and Pharmacology

In a previous study (Chesher & Jackson, 1974) we reported that the protection against electrically-induced seizures afforded mice by phenytoin, was potentiated significantly by Ag-tetrahydrocannabinol (THC) and cannabidiol (CBD). In contrast, these cannabinoids failed to alter the effect of phenobarbitone on the convulsive threshold to leptazol induced seizures. Although TMC itself showed a weak anticonvulsant activity against electrically induced seizures, it failed to affect the convulsive threshold to leptazol. These findings suggested that the interaction between the cannabinoids and phenytoin possibly involved activity in the central nervous system rather than a metabolic interaction. This hypothesis is supported by the results of the present study which reports the potentiation by the cannabinoids of the effect of phenobarbitone on electrically-induced seizures. Random bred male mice (QS strain, 18-30 g) were used and allowed free access to food and water up to the time of the experiment. Maximum electroshock seizures (MES) were induced using a current of 50 mA, 50 Hz and 0.3 s duration applied by corneal electrodes moistened with 0.9 % saline (Swinyard, 1949; Swinyard, Brown & Goodman, 1952). Two endpoints were recorded; the abolition of the hind limb extensor component of the seizure was taken to represent protection and, in those animals where hind limb extension occurred, its duration was recorded by means of a stop-watch. Cannabinoids were prepared in a suspension in propylene glycol and Lissapol-Dispersol (Whittle, 1964) as described previously (Chesher, Dahl & others, 1973) and administered by gavage (1 ml100 g-1 body wt) 1 h before phenobarbitone (i.p.) and 2 h before MES. The data were analysed by probit analysis. The results (Table 1) show that THC (50 mg kg-l) significantly potentiated the protection afforded mice by phenobarbitone when determined both by protection from seizures and by the shortening of the duration of hind limb extension. CBD (50 mg kg-l) was much less active and whilst it significantly reduced the ED50 of phenobarbitone when assessed as protection from convulsions, it produced no significant change when effectiveness was assessed by the duration of hind limb extension.