Grant: Operating Grant

Precise patterns of gastrointestinal (GI) motility are required for the optimal digestion of food, absorption of nutrients and expulsion of waste. There are serious health consequences when GI motility is disturbed in diseases such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Disordered motility causes impaired swallowing, heartburn, vomiting, early fullness, bloating, constipation, or diarrhea. Both slowed and accelerated GI motility are frequently accompanied by abdominal pain and discomfort. GI motility disorders affect millions of Canadians by negatively impact their quality of life and limiting daily activities. Cannabis and its extracts (cannabinoids) have been used for centuries to alleviate the symptoms of GI motility disease by improving appetite, and reducing diarrhea, cramping and pain. The body makes molecules whose actions resemble cannabinoids which were discovered relatively recently and are called endocannabinoids. Endocannabinoids are found in the GI tract and regulate gut motility in health. Their role in GI motility disorders is not well understood. We propose to explore the idea that by manipulating the levels of endocannabinoids can be used to treat disordered gut motility. We will examine how endocannabinoids are involved in motility control in mouse models of GI disease. Then using newly developed chemicals that increase or reduce the levels of endocannabinoids we will develop approaches to normalize disordered gut motility. Cannabinoids represent powerful potential therapeutics for disorders of gut motility. We will be able to make advances that could be translated to clinical applications for the treatment of motor disorders of the gut, including IBS and IBD, for which currently there are few effective therapies.