Review: The Role of Cannabinoids on Esophageal Function—What We Know Thus Far

Abstract

The endocannabinoid system (ECS) primarily consists of cannabinoid receptors (CBRs), endogenous ligands, and enzymes for endocannabinoid biosynthesis and inactivation. Although the presence of CBRs, both CB1 and CB2, as well as a third receptor (G-protein receptor 55 [GPR55]), has been established in the gastrointestinal (GI) tract, few studies have focused on the role of cannabinoids on esophageal function. To date, studies have shown their effect on GI motility, inflammation and immunity, intestinal and gastric acid secretion, nociception and emesis pathways, and appetite control. Given the varying and sometimes limited efficacy of current medical therapies for diseases of the esophagus, further understanding and investigation into the interplay of the ECS on esophageal health and disease may present new therapeutic modalities that may help advance current treatment options. In this brief review, the current understanding of the ECS role in various esophageal functions and disorders is presented.

Cannabidiol and Other Non-Psychoactive Cannabinoids for Prevention and Treatment of Gastrointestinal Disorders: Useful Nutraceuticals?

“…In dogs and ferrets, cannabinoids inhibited transient LES relaxations through a CB1-dependent mechanism. These observations are of interest because transient LES relaxations are the predominant mechanism of gastroesophageal reflux disease [218]. In line with these preclinical observations, positive effects of THC have been observed in humans, although with issues related to the safety profile (central psychotropic activity) [219].…”

“…The lower esophageal sphincter (LES), a specialized region of the esophageal circular smooth muscle, allows the passage of a swallowed bolus to the stomach and prevents the reflux of gastric contents into the esophagus. The cannabinoid system has been implicated in the mechanisms regulating LES relaxation [218]. In dogs and ferrets, cannabinoids inhibited transient LES relaxations through a CB1-dependent mechanism.…”

Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in gastroparesis: A sex‐ and subtype‐dependent observation

“…The plant Cannabis has two major active components, tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been used for the treatment of GI disorders presenting with nausea, vomiting, abdominal pain, and inflammation 5,7,30‐36 . Based on recent studies, 11.7%‐46.7% of GP patients reported current or past use of cannabinoids including THC, dronabinol, and/or CBD.…”

Cannabinoids in disorders of gut-brain interaction and gastrointestinal motility

“…Conversely, chronic cannabis users have a high prevalence of hypertensive LES pressure. The administration of THC transiently reduces rates of transient LES relaxation 54 . Dronabinol, as a partial agonist of CB1, has been shown to increase pain thresholds and reduces pain intensity and odynophagia in patients with chronic chest pain of esophageal origin 55 .…”