Endocannabinoids in the Gut

Cannabis has been used medicinally for centuries to treat a variety of disorders, including those associated with the gastrointestinal tract. The discovery of our bodies' own “cannabis-like molecules” and associated receptors and metabolic machinery—collectively called the endocannabinoid system—enabled investigations into the physiological relevance for the system and provided the field with evidence of a critical function for this endogenous signaling pathway in health and disease. Recent investigations yield insight into a significant participation for the endocannabinoid system in the normal physiology of gastrointestinal function and its possible dysfunction in gastrointestinal pathology. Many gaps, however, remain in our understanding of the precise neural and molecular mechanisms across tissue departments that are under the regulatory control of the endocannabinoid system. This review highlights research that reveals an important—and at times surprising—role for the endocannabinoid system in the control of a variety of gastrointestinal functions, including motility, gut–brain-mediated fat intake and hunger signaling, inflammation and gut permeability, and dynamic interactions with gut microbiota.