Endocannabinoid-related compounds in gastrointestinal diseases
The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at
both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and
sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting
their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS)
or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid
receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the
achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data
in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More
recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabinomimetics
has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI
disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases.