A Comparison Of The Anticonvulsant Effects And Side Effect Profiles Of The Phytocannabinoids, Cannabidiol And Cannabidivarin
Epilepsy is characterised by spontaneous seizures, existing anti-epileptic drugs (AEDs) can cause adverse motor side effects and around 30% of epilepsy cases are pharmacoresistant. We have previously shown that cannabidiol (CBD) and cannabidivarin (CBDV) are anti-convulsant phytocannabinoids (Jones et al., 2010, Hill et al., 2010). Here the efficacy of their anticonvulsant properties are compared and motor side effects investigated.
Effects of CBDV and CBD (100 or 200mg/kg; IP; n = 15 per drug per dose) were examined in a pentylenetetrazole (PTZ) model of severe seizure in adult male Han Wistar rats (60-100g). CBD or CBDV were administered one hour prior to PTZ (85mg/kg; IP) administration. Seizure behaviour was recorded for 30 minutes in monitored tanks (21°C) before offline analysis. Compared to vehicle treatment, median seizure severity of the 200mg/kg CBDV group was significantly lower (ANOVA, p≤0.01). Mortality was significantly reduced by 100 and 200mg/kg CBDV compared to vehicle treatment (6.7, 6.7 and 46.7% respectively, Chi squared, p≤0.05). CBD had no significant effect.
Side effect profiles of CBDV, CBD (both 50-200mg/kg) and the AEDs, valproate (VPA; 250 and 350mg/kg), ethosuximide (ESM; 175 and 300mg/kg) and phenobarbital (PBL; 40 and 50mg/kg) were compared using static beam and grip strength assays. CBDV and CBD (n = 10) were administered 1 hour before testing whilst VPA, ESM or PBL were administered 30 minutes before testing. Both arms used a vehicle group and IP administration (male Han Wistar rats; starting weight 110-140g). AEDs caused significantly more severe side effects than CBD or CBDV (Table 1).
Table 1. VPA, ESM, PBL, CBD and CBDV effects on motor performance. Results are mean±SEM. * = p≤0.05, ** = p≤0.01 and *** = p≤0.001. Chi squared or ANOVA with post hoc Tukey where appropriate.
These results show CBDV is a well-tolerated and effective anti-convulsant in rat with significant clinical potential for the treatment of epilepsy.
Work funded, and phytocannabinoids provided, by GW Pharmaceuticals & Otsuka Pharmaceuticals.
JONES, N. A., HILL, A. J., SMITH, I., BEVAN, S. A., WILLIAMS, C. M., WHALLEY, B. J. & STEPHENS, G. J. (2010) Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. Journal of Pharmacology and Experimental Therapeutics, 332, 569.
HILL, A. J., JONES, N. A., STEPHENS, G. J., WILLIAMS, C. M. & WHALLEY, B. J. (2010) Anticonvulsant effects of GWP42006 in vitro and in vivo in rat. Proceedings Physiological Society, 19.