Cannabinoid receptors are present in gastric and intestinal lining cells, intestinal smooth muscle cells, and adjacent immune and nerve cells as well as blood vessels. They are vital for the normal functioning of the GI tract. CB1 activation decreases salivation peripherally and centrally. CB receptor activation slows GI contractions and transits both by relaxing smooth muscles but also by interrupting the normal peristaltic reflex. Activation of the ECS also decreases visceral sensitivity, and this along with alterations in the GI transit time is the hallmark of irritable bowel syndrome. Human polymorphisms and experimental studies further strengthen the connection between ECS dysfunction and IBS. As in other parts of the body, the ECS is also important for the control of inflammation in the bowels. Polymorphisms in components of the ECS have also been linked to inflammatory bowel diseases and celiac diseases. The ECS also appears to play a role in gut permeability and affects the composition of bowel flora, although in both cases, the mechanism and sequelae are still not well understood. CB1 activation decreases stomach acid production and ulcer formation as well as being vital to controlled nausea and vomiting. Dysregulation of the ECS appears to play a role in both cyclical vomiting syndrome and cannabis hyperemesis syndrome as well as certain liver disease states such as fibrosis.