Cannabidiol Enhances Intestinal Cannabinoid Receptor Type 2 Receptor Expression and Activation Increasing Regulatory T Cells and Reduces Murine Acute Graft-versus-Host Disease without Interfering with the Graft-versus-Leukemia Response

Cannabidiol (CBD) is a highly lipidic phytocannabinoid with remarkable anti-inflammatory effects. The aim of this study was to evaluate CBD’s effects and mechanisms action in the treatment mice subjected acute graft-versus-host disease (aGVHD). aGVHD induced by transplantation bone marrow cells splenocytes from C57BL-6j Balb-c mice. recipient were treated daily CBD, reduced mouse mortality decreasing inflammation injury promoting immune regulation jejunum, ileum, liver. Analysis jejunum ileum showed that CBD levels C-C motif chemokine ligand (CCL) 2, CCL3, CCL5, tumor necrosis factor α, interferon γ (IFNγ). CCL3 IFNγ also decreased Mechanistically, increased number cannabinoid receptor type 2 (CB2) receptors on CD4+ forkhead box P3+ intestine, which may explain reduction proinflammatory cytokines chemokines. Antagonists CB2 survival rates CBD-treated mice, suggesting participation CBD. Furthermore, did not interfere graft-versus-leukemia response. appears protect immunomodulatory partially mediated interaction. Altogether, our suggests represents an interesting approach aGVHD, potential therapeutic applications patients undergoing transplantation. SIGNIFICANCE STATEMENT This provides for first time mechanism cannabidiol, no psychoactive effect, induces immunomodulation disease. Enhancing intestinal expression increasing these regulatory cells, cannabidiol decreases increases survival. effect dependent activation. Besides, response, central response avoid primary relapse.