Cannabidiolic acid exhibits entourage-like improvements of anticonvulsant activity in an acute rat model of seizures

Abstract

ObjectivesCannabidiolic acid (CBDa) is pharmacologically unique from cannabidiol (CBD), but its chemical instability poses challenges for potential clinical utility. Here, we used magnesium ions to stabilize two cannabidiolic acid-enriched hemp extracts (Mg-CBDa and Chylobinoid, the latter of which also contains minor cannabinoid constituents) and compared their anticonvulsant activities with CBD in the maximal electroshock seizure test (MES) in rats. MethodsSprague-Dawley rats received intraperitoneal (i.p.) injections of Chylobinoid, Mg-CBDa, or CBD at varying doses at discrete time points. Rats were challenged with a 0.2 s, 60 Hz, 150 mA corneal stimulation and evaluated for resultant hindlimb tonic extension. Dose-response relationships were calculated using Probit analysis and statistical significance was assessed with a two-sample z-test. ResultsMedian effective doses (ED50) and 95 % confidence intervals were calculated for each compound and adjusted according to percentage of CBDa (w/w): Chylobinoid: 76.7 (51.7–109.2) mg/kg. Mg-CBDa: 115.4 (98.8–140.9) mg/kg. CBD: 68.8 (56.6–80.0) mg/kg. SignificanceCBDa-enriched hemp extracts exhibited dose-dependent protection in the MES model at doses comparable, but not more effective than, CBD. Chylobinoid was more effective than Mg-CBDa despite lower CBDa content. Test compounds should be compared by sub-chronic dosing in the MES test in order to assess safety and pharmacokinetic profiles. CBDa should be evaluated in pharmacoresistant and chronic animal models of epilepsy.