CNR2 and Cowden disease: To assess the role of M1 macrophages derived from CD patients in compromising intestinal barrier integrity, and to further validate the protective potential of CB2 activation, we employed an ‘immunocompetent gut’ model [19,48], consisting of IBD-derived macrophages and the human epithelial cell line Caco-2, used as a representative model of the intestinal epithelial barrier.