BACKGROUND AND PURPOSEPhytocannabinoids 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 APPROACHThe effect of CBDV (1-100 mM) 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. KEY 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 (Ն100 mg·kg ) 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 IMPLICATIONSThese 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 ARTICLESThis article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx

Petit mal status epilepticus was induced by high doses of thyroxine, confirming experimental evidence that thyroxine may lower the seizure threshold. This is another hazard of rapidly correcting the hypothyroid state.

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After d and l‐tryptophan (50 mg/kg) were given intravenously in the dog, the concentration of the amino acid was increased in ventricular cerebrospinal fluid (CSF) during the subsequent 4 h of sampling, although the concentrations were significantly lower following the administration of the d‐isomer. There was no evidence that d‐tryptophan increased the synthesis of 5‐hydroxytryptamine (5‐HT) in dog brain as judged by the failure to cause a change in 5‐hydroxyindoleacetic acid (5‐HIAA) concentrations in ventricular CSF different from that seen with controls. There was no appreciable conversion of d‐tryptophan to l‐tryptophan in the dog. d‐tryptophan was cleared more rapidly from plasma than l‐tryptophan. No difference in plasma binding between d and l‐tryptophan was detected.