Repeated administration of cannabidiol decreases splenic lymphocyte subset numbers in rats

Objective: Cannabidiol (CBD) administration (5 mg/kg) in healthy rats has been shown to significantly decrease lymphocyte subset numbers in peripheral blood without involvement of natural killer cells. The aim was to evaluate whether lymphocyte numbers also decrease in the spleen. Introduction: CBD, the major non-psychotropic compound of Cannabis sp., is an effective treatment for inflammatory and autoimmune diseases with various anti-tumor effects, but the mechanisms of its long-term actions in vivo remain unclear. Methods: To examine the effects of CBD on lymphocyte subsets in the spleen and NK cellular cytotoxicity (NKCC), adult male Wistar rats (n = 63) were administered intraperitoneal injections of CBD (2.5 or 5 mg/kg/day) for 14 consecutive days, and lymphocyte counts were obtained using flow cytometry. NKCC in the peripheral blood and spleen was quantified using a Chromium-51 release assay. Furthermore, the effect was similar to a decrease in lymphocytes caused by treatment with the selective receptor antagonist AM630 (1 mg/kg). Results: The results indicate that repeated administration of CBD at a dose of 5 mg/kg/day decreased splenic lymphocyte numbers, involving T and non-T/NK CD45RA+ lymphocytes but not NK cells. The effects of CB₂ receptor antagonist were not significant, but it had a significant interaction with CBD. No changes in NKCC were observed following CBD administration. Conclusion: These results reveal that in healthy rats, CBD produces similar lymphopenic effects in the spleen as it does in peripheral blood without affecting NK cell counts or cytotoxicity.