A synthetic cannabinoid JWH-210 reduces lymphoid organ weights and T-cell activator levels in mice via CB2 receptors.

The problem of new psychoactive substances (NPS) is emerging globally. However, the immunotoxicity of synthetic cannabinoids is not evaluated extensively yet. The purpose of the present study was to investigate whether synthetic cannabinoids (JWH-210 and JWH-030) induce adverse effects on lymphoid organs, viability of splenocytes and thymocytes, and immune cell activator and cytokines in mice. JWH-210 (10 mg/kg, 3 days, i.p.) is more likely to have cytotoxicity and reduce lymphoid organ weight than JWH-030 of ICR mice in vivo. We also demonstrated that JWH-210 administration resulted in the decrease of expression levels of T-cell activator including Cd3e, Cd3g, Cd74p31, and Cd74p41, while JWH-030 increased Cd3g levels. In addition, JWH-210 reduced expression levels of cytokines, such as interleukin-3, interleukin-5, and interleukin-6. Furthermore, we demonstrated that a CB2 receptor antagonist, AM630 inhibited JWH-210-induced cytotoxicity, whereas a CB1 receptor antagonist, rimonabant did not in primary cultured splenocytes. These results suggest that JWH-210 has a cytotoxicity via CB2 receptor action and results in decrement of lymphoid organ weights, T-cell activator, and cytokine mRNA expression levels.