title: Cannabidivarin is anticonvulsant in mouse and rat.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  The effect of CBDV (1-100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (4-AP) application or Mg(2+) -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 rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays.
  
  
  RESULTS
  CBDV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg(2+) -free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg(-1) ), audiogenic (≥50 mg·kg(-1) ) and PTZ-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. CBDV had no effect on motor function.
  
  
  CONCLUSIONS
  These results indicate that CBDV is 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.
  
  
  BACKGROUND
  This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8.
authors.affiliation: Reading School of Pharmacy, University of Reading, Whiteknights, Reading, UK. a.j.hill@reading.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Hill
authors.forename: M S
authors.initials: MS
authors.lastname: Mercier
authors.forename: T D M
authors.initials: TD
authors.lastname: Hill
authors.forename: S E
authors.initials: SE
authors.lastname: Glyn
authors.forename: N A
authors.initials: NA
authors.lastname: Jones
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Futamura
authors.forename: M
authors.initials: M
authors.lastname: Duncan
authors.forename: C G
authors.initials: CG
authors.lastname: Stott
authors.forename: G J
authors.initials: GJ
authors.lastname: Stephens
authors.forename: C M
authors.initials: CM
authors.lastname: Williams
authors.forename: B J
authors.initials: BJ
authors.lastname: Whalley
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use*; D002188:Cannabis; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D008517:Phytotherapy; D010862:Pilocarpine; D051381:Rats; D011921:Rats, Inbred WKY; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D002186:Cannabinoids; D010862:Pilocarpine; C580853:cannabidivarin; D010433:Pentylenetetrazole