Cannabinoid-like Activity of Minor Cannabinoid Constituents in the Mouse Tetrad Assay

Cannabis sativa L. is a widely used medicinal plant for both recreational as well as therapeutic purposes. The recent approval of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) for the therapeutic management of nausea and pain associated with chemotherapy has triggered further research on cannabinoids. Despite the identification of over 500 compounds from the Cannabis plant, most research efforts have focused on Δ⁹-THC [1]. Thus, the goal of this study was to evaluate the pharmacological actions of several poorly characterized cannabinoid constituents isolated from Cannabis. Given that the isolated compounds bear high structural similarity to Δ⁹-THC, the study could also provide insight into the structure activity relationship (SAR) of cannabinoids. The isolated compounds were evaluated using male Swiss Webster mice in the established tetrad assay. In this assay, the cannabinoid receptor agonists Δ⁹-THC and CP55,940 caused a dose dependent reduction in locomotor activity, catalepsy, hypothermia, as well as antinociception. Seven isolated cannabinoids were evaluated in the assay and four compounds showed significant cannabinoid-like activity comparable to that of Δ⁹-THC. All compounds were analogs of either Δ⁹-THC or Δ⁸-THC. The Δ⁹-THC analog SAA-52-38 demonstrated significant analgesic, cataleptic, as well as hypothermic actions at 10 and 20 mg/kg doses (p < 0.001). Similarly, the Δ⁸-THC analogs MRRoss-01-45-28-46 and SAA-53-20 showed significant cannabinoid-like activity (p < 0.001 and p < 0.01, respectively). Time course studies have shown that the actions of these compounds persist up to 120 min following administration suggesting possible in vivo metabolic activation. Studies are underway to further characterize the therapeutic potential of these as well as other cannabinoids. Acknowledgements: The project described was supported by Grant Number P20RR021929 from the National Center For Research Resources and by the National Institute of Drug Abuse, Contract Number N01DA-5-7746. References: [1] ElSohly M, Slade D (2005). Life Sci. 78: 539–548.