Hill, A. J., Mercier, M. S., Hill, T. D., Glyn, S. E., Jones, N. A., Yamasaki, Y., Futamura, T., Duncan, M., Stott, C.G., Stephens, G.J., Williams, C. M. and Whalley, B.J.
Cannabidivarin is anticonvulsant in mouse and rat in vitro and in seizure models.
British Journal of Pharmacology, 167 (8).
To link to this article DOI: 10.1111/j.1476-5381.2012.02207.x
Background and purpose: Phytocannabinoids in Cannabis sativa have diverse
pharmacological targets extending beyond cannabinoid receptors and several exert notable
anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the
phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models.
Experimental approach: The effect of CBDV (1-100μM) on epileptiform local field
potentials (LFPs) induced in rat hippocampal brain slices by 4-AP application or Mg2+-free
conditions was assessed by in vitro multi-electrode array recordings. Additionally, the
anticonvulsant profile of CBDV (50-200 mg kg-1) in vivo was investigated in four rodent
seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and
pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rat. CBDV effects in
combination with commonly-used antiepileptic drugs were investigated in rat seizures.
Finally, the motor side effect profile of CBDV was investigated using static beam and gripstrength
Key results: CDBV significantly attenuated status epilepticus-like epileptiform LFPs
induced by 4-AP and Mg2+-free conditions. CBDV had significant anticonvulsant effects in
mES (≥100 mg kg-1), audiogenic (≥50 mg kg-1) and PTZ-induced seizures (≥100 mg kg-1).
CBDV alone had no effect against pilocarpine-induced seizures, but significantly attenuated
these seizures when administered with valproate or phenobarbital at 200 mg kg-1 CBDV.
CBDV had no effect on motor function.
Conclusions and Implications: These results indicate that CBDV is an effective
anticonvulsant across a broad range of seizure models, does not significantly affect normal
motor function and therefore merits further investigation in chronic epilepsy models to justify
|GW Pharmaceuticals ||Potential anticonvulsant activity of candidate phytocannabionoids (internal code: H5111100 sponsor code: Otsuka Scientists)|
|Otsuka Pharmaceuticals||Potential anticonvulsant activity of candidate phytocannabionoids (2) (internal code: H5113900 sponsor code: Otsuka Scientists)|
|Date Deposited:||18 Sep 2012 13:38|
|Last Modified:||15 Feb 2014 09:01|
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