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Cannabidivarin is anticonvulsant in mouse and rat

  1. AJ Hill1,2,*,
  2. MS Mercier1,†,
  3. TDM Hill1,
  4. SE Glyn1,
  5. NA Jones1,2,
  6. Y Yamasaki1,2,3,
  7. T Futamura3,
  8. M Duncan4,
  9. CG Stott4,
  10. GJ Stephens1,
  11. CM Williams2 and
  12. BJ Whalley1

Article first published online: 29 NOV 2012

DOI: 10.1111/j.1476-5381.2012.02207.x

Issue

British Journal of Pharmacology

British Journal of Pharmacology

Special Issue: Themed Section: Cannabinoids 2012. Guest Editor: Stephen PH Alexander

Volume 167, Issue 8, pages 1629–1642, December 2012


Additional Information

How to Cite

Hill, A., Mercier, M., Hill, T., Glyn, S., Jones, N., Yamasaki, Y., Futamura, T., Duncan, M., Stott, C., Stephens, G., Williams, C. and Whalley, B. (2012), Cannabidivarin is anticonvulsant in mouse and rat. British Journal of Pharmacology, 167: 1629–1642. doi: 10.1111/j.1476-5381.2012.02207.x

Author Information

  1. 1

    Reading School of Pharmacy, University of Reading, Reading, UK

  2. 2

    School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK

  3. 3

    Otsuka Pharmaceutical, Co. Ltd, Tokushima, Japan

  4. 4

    GW Pharmaceuticals plc, Porton Down Science Park, Salisbury, Wiltshire, UK

  1. †

    Present address: MRC Centre for Synaptic Plasticity, University of Bristol, Medical Sciences Building, University Walk, Bristol, BS8 1TD, UK.

* Correspondence
Andrew Hill, Reading School of Pharmacy and School of Psychology and Clinical Language Sciences, University of Reading, Whiteknights, Reading, RG6 6AJ, UK. E-mail: a.j.hill@reading.ac.uk

Publication History

  1. Issue published online: 29 NOV 2012
  2. Article first published online: 29 NOV 2012
  3. Accepted manuscript online: 12 SEP 2012 06:44AM EST
  4. Manuscript Accepted: 28 AUG 2012
  5. Manuscript Revised: 17 AUG 2012
  6. Manuscript Received: 23 APR 2012

Funded by

  • BJW
  • CMW
  • GJS
  • GW Pharmaceuticals and Otsuka Pharmaceuticals

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Keywords:

  • epilepsy;
  • cannabinoid;
  • cannabidivarin;
  • seizure;
  • side effect;
  • hippocampus

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 (1–100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (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 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.

Key Results

CBDV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg2+-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 and Implications

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.

Linked Articles

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

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