A Crosstalk between the Cannabinoid Receptors and Nociceptin Receptors in Colitis—Clinical Implications

Inflammatory bowel diseases (IBD) refer to a group of gastrointestinal (GI) disorders with complex pathogenesis characterized by chronic intestinal inflammation with a variety of symptoms. Cannabinoid and nociceptin opioid receptors (NOPs) and their ligands are widely distributed in the GI tract. The nociceptin opioid receptor is a newly discovered member of the opioid receptor family with unique characteristics. Both cannabinoid and NOP systems exhibit antinociceptive and anti-inflammatory activity and contribute to maintaining proper motility, secretion and absorption in the GI tract. Furthermore, they influence high and low voltage calcium channels, which play a crucial role in the processing of pain, and share at least two kinases mediating their action. Among them there is NF-κB, a key factor in the regulation of inflammatory processes. Therefore, based on functional similarities between cannabinoid and nociceptin receptors and the anti-inflammatory effects exerted by their ligands, there is a high likelihood that there is an interaction between cannabinoid receptors 1 and 2 and the nociceptin receptor in colitis. In this review, we discuss potential overlaps between these two systems on a molecular and functional level in intestinal inflammation to create the basis for novel treatments of IBD.