Effects of cannabidiol and beta-caryophyllene alone or in combination in a mouse model of permanent ischemia

Current treatments for stroke, which account for 6.5 million global deaths annually, re-main insufficient for treatment of disability and mortality. One targetable hallmark of stroke is the inflammatory response following infarct, which leads to significant damage post-infarct. Canna-binoids and their endogenous targets within the CNS have emerged as potential treatments for neu-roinflammatory indications. We and others have previously shown that synthetic agonists of the cannabinoid CB2 receptor reduce infarct size and microglial activation in rodent models of stroke. The non-cannabinoid receptor mediated effects of the phytocannabinoid cannabidiol (CBD) have also shown effectiveness in these models. The present aim was to determine the single and com-bined effects of the cannabis-derived sesquiterpene and putative CB2 receptor agonist β-caryo-phyllene (BCP) and CBD on permanent ischemia without reperfusion using a mouse model of pho-tothrombosis. Because BCP and CBD likely work through different sites of action but share common mechanisms of action, we sought to determine whether combinations of BCP and CBD were more potent than either compound alone. Therefore we determined the effect of BCP (3–30 mg/kg IP) and CBD (3–30 mg/kg IP), given alone or in combination (30:3, 30:10, and 30:30 BCP:CBD), on infarct size, microglial activation, and motor performance.