Background and Purpose Cannabichromene (CBC) is one of the most abundant phytocannabinoids in Cannabis spp . It has modest antinociceptive and anti‐inflammatory effects and potentiates some effects of Δ 9 ‐tetrahydrocannabinol in vivo. How CBC exerts these effects is poorly defined and there is little information about its efficacy at cannabinoid receptors. We sought to determine the functional activity of CBC at cannabinoid CB 1 and CB 2 receptors. Experimental Approach AtT20 cells stably expressing haemagglutinin‐tagged human CB 1 and CB 2 receptors were used. Assays of cellular membrane potential and loss of cell surface receptors were performed. Key Results CBC activated CB 2 but not CB 1 receptors to produce hyperpolarization of AtT20 cells. This activation was inhibited by a CB 2 receptor antagonist AM630, and sensitive to Pertussis toxin. Application of CBC reduced activation of CB 2 , but not CB 1 , receptors by subsequent co‐application of CP55,940, an efficacious CB 1 and CB 2 receptor agonist. Continuous CBC application induced loss of cell surface CB 2 receptors and desensitization of the CB 2 receptor‐induced hyperpolarization. Conclusions and Implications CBC is a selective CB 2 receptor agonist displaying higher efficacy than tetrahydrocannabinol in hyperpolarizing AtT20 cells. CBC can also recruit CB 2 receptor regulatory mechanisms. CBC may contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially through CB 2 receptor‐mediated modulation of inflammation.