Delta(9)-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats.

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Hill AJ, Weston SE, Jones NA, Smith I, Bevan SA, Williamson EM, Stephens GJ, Williams CM, Whalley BJ

Delta(9)-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats.

Epilepsia. 2010 Aug;51(8):1522-32. doi: 10.1111/j.1528-1167.2010.02523.x. Epub 2010 Feb 26.

PubMed ID
20196794 [ View in PubMed
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Abstract

PURPOSE: We assessed the anticonvulsant potential of the phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV) by investigating its effects in an in vitro piriform cortex (PC) brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand-binding assays and in a generalized seizure model in rats. METHODS: Delta(9)-THCV was applied before (10 mum Delta(9)-THCV) or during (10-50 mum Delta(9)-THCV) epileptiform activity induced by Mg(2)(+) -free extracellular media in adult rat PC slices and measured using multielectrode array (MEA) extracellular electrophysiologic techniques. The actions of Delta(9)-THCV on CB1 receptors were examined using [(3)H]SR141716A competition binding and [(3)(5)S]GTPgammaS assays in rat cortical membranes. Effects of Delta(9)-HCV (0.025-2.5 mg/kg) on pentylenetetrazole (PTZ)-induced seizures in adult rats were also assessed. RESULTS: After induction of stable spontaneous epileptiform activity, acute Delta(9) -THCV application (>/= 20 mum) significantly reduced burst complex incidence and the amplitude and frequency of paroxysmal depolarizing shifts (PDSs). Furthermore, slices pretreated with 10 mum Delta(9)-THCV prior to induction of epileptiform activity exhibited significantly reduced burst complex incidence and PDS peak amplitude. In radioligand-binding experiments, Delta(9)-THCV acted as a CB1 receptor ligand, displacing 0.5 nm [(3)H]SR141716A with a Ki approximately 290 nm, but exerted no agonist stimulation of [(3)(5)S]GTPgammaS binding. In PTZ-induced seizures in vivo, 0.25 mg/kg Delta(9)-THCV significantly reduced seizure incidence. DISCUSSION: These data demonstrate that Delta(9)-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.

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