Experimental Methods to Study the Role of the Peripheral Cannabinoid Receptor in Immune Function

Marijuana components, such as Δ-9-tetrahydrocannabinol, and endogenous cannabinoids, such as anandamide and 2-arachydonoylglycerol, alter diverse immune functions. Two cannabinoid receptors have been discovered to date, the central cannabinoid receptor (CB₁ R) and the peripheral cannabinoid receptor (CB₂ R). The CB₁ R is expressed predominantly in the central nervous system. The CB₂ R is expressed mainly in cells of the immune system, suggesting that the CB₂ R is involved in immunoregulatory events. Cannabinoids have been shown to modulate diverse immune functions including cytokine production, lymphocyte proliferation, and humoral and cell-mediated immune responses. In addition, cannabinoids have been shown to induce different signal transduction pathways. However, the role of cannabinoids and their receptors in the immune system remains unclear. The objective of the experimental methods described herein is to investigate the role of CB₂ R activation in specific splenocyte and macrophage functions using a mouse lacking the CB₂ R. Interestingly, our findings, thus far suggest that basal CB₂ R activation modulates lymphocyte proliferation and cytokine secretion and macrophage phagocytic activity. Therefore, data obtained using the methodology described in this chapter will help us elucidate the role of cannabinoids and the CB₂ R in the immune system.