A pharmacological characterization of Cannabis sativa chemovar extracts

Background: Cannabis contains Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol (CBD) as the primary constituents responsible for pharmacological activity. However, there are numerous additional chemically-related structures to Delta(9)-THC and CBD that are pharmacologically active and may influence the pharmacological properties of Delta(9)-THC and CBD. This study chemically characterized the cannabinoid constituents in a series of cannabis chemovar extracts and investigated the potential cannabinoid entourage effect in two behavioral assays. Methods: Six chemovar extracts were compared to pure Delta(9)-THC, CBD and morphine for effects on the following behavioral assays in mice: hot plate and tail suspension. The battery of behavioral tests was conducted post intravenous administration of cannabis chemovar extract. Cannabinoid profiles of extracts were analyzed using high performance liquid chromatography. Cannabis extracts were administered at equal doses of Delta(9)-THC to investigate the role of their cannabinoid profiles in modulating the effects of Delta(9)-THC. Dose response curves were fit using a log[inhibitor] vs response three parameter model and differences between group means were determined using a one-way ANOVA followed by a post hoc test. Results: Cannabis chemovars tested in this study exhibited substantially different cannabinoid profiles. All chemovars produced dose-dependent immobility in the tail suspension assay and dose-dependent antinociception in the hot plate assay. The maximum antinociceptive effect and ED50 was comparable between cannabis chemovars and Delta(9)-THC. Two cannabis chemovars produced significantly greater immobility in the tail suspension test, with no significant differences in ED50. Conclusions: Commercially available cannabis chemovars vary widely in cannabinoid content, but when equalized for Delta(9) -THC content, they produce similar behavioral effects with two exceptions. These findings provide only limited support for the entourage hypothesis. Further studies are necessary to characterize the nature of these pharmacological differences between cannabis chemovars and pure Delta(9)-THC.