Cannabidivarin is anticonvulsant in mouse and rat

Background and PurposePhytocannabinoids inCannabis sativahave 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 vitroand inin vivoseizure models.Experimental ApproachThe effect ofCBDV(1–100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4‐aminopyridine (4‐AP) application orMg2+‐free conditions was assessed byin vitromulti‐electrode array recordings. Additionally, the anticonvulsant profile ofCBDV(50–200 mg·kg−1)in vivowas investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine‐induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile ofCBDVwas investigated using static beam and grip strength assays.Key ResultsCBDVsignificantly attenuatedstatus epilepticus‐like epileptiformLFPsinduced by 4‐APandMg2+‐free conditions.CBDVhad significant anticonvulsant effects on themES(≥100 mg·kg−1), audiogenic (≥50 mg·kg−1) andPTZ‐induced seizures (≥100 mg·kg−1).CBDV(200 mg·kg−1) alone had no effect against pilocarpine‐induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose.CBDVhad no effect on motor function.Conclusions and ImplicationsThese results indicate thatCBDVis an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti‐epileptic in chronic epilepsy models.Linked ArticlesThis article is part of a themed section on Cannabinoids. To view the other articles in this section visithttp://dx.doi.org/10.1111/bph.2012.167.issue‐8