Lay Summary

The body’s cannabinoid (endocannabinoid) system may play an important role in gastrointestinal immune function, motility, secretion and sensation. There is evidence in experimental models of gut inflammation that manipulation of the endocannabinoid system can dramatically alter the extent of inflammation. Precisely how the endocannabinoid system works to do this is not presently known, but recent research has revealed a link between endocannabinoid molecules in the body and a key enzyme associated with inflammation, COX-2. COX-2 acts on these molecules to produce a novel class of compounds known as prostamides. It is not clear yet what effects such prostamides may have in the human bowel, either in health or in diseases such as Crohn’s disease and ulcerative colitis.

 

We will explore the role of the body’s natural cannabinoid (endocannabinoid) system in the human colon, to determine if this system is altered in colitis. We will directly measure markers of the endocannabinoid system and correlate these with inflammation in the bowel. We will also attempt to induce or stimulate inflammation in healthy human colonic tissue and test the effects that novel prostamide drugs have on this process, in order to gain a better understanding of the role of these novel compounds on the inflammatory process in human bowel tissue.

There are novel molecules produced from this interaction and is not clear what role they play in normal bowel function and in clinical colitis. Ultimately, drugs targeting either the endocannabinoid system or, more selectively, prostamide pathways may afford new drug treatments for inflammatory bowel disease (IBD).