Human esophageal epithelial cells express CB1 receptors and these receptors are downregulated in Gastro-Esophageal Reflux Disease (Calabrese et al., 2010).
CB2 receptors are present in the gastro-intestinal tract (Salaga et al., 2017) although they were not found in human esophageal epithelial cells (Calabrese et al., 2010). In mice, CB2 agonists dose-dependently protect against ethanol and diclofenac-induced gastric ulcers. This effect was reversed by CB2 antagonists (Salaga et al., 2017).
In humans, CB1 and CB2 are abundantly expressed in the myenteric plexus of the esophagus (Rohof et al., 2012).
In mice, blocking MAGL, thus increasing ambient endocannabinoid levels, reduced gastic acidity and ulceration (Crowe and Kinsey, 2017).
In dogs and human volunteers, THC reduced the number of Transient Lower Esophageal Sphincter Relaxations. This effect was blocked by CB1 antagonist SR141716A, suggesting involvement of CB1 (Beaumont et al., 2009).
Beaumont, H., Jensen, J., Carlsson, A., Ruth, M., Lehmann, A., and Boeckxstaens, G. (2009). Effect of delta9-tetrahydrocannabinol, a Cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans. Br. J. Pharmacol. 156, 153–162.
Calabrese, C., Spisni, E., Liguori, G., Lazzarini, G., Valerii, M.C., Strillacci, A., Gionchetti, P., Pagotto, U., Campieri, M., and Rizzello, F. (2010). Potential role of the Cannabinoid receptor CB in the pathogenesis of erosive and non-erosive gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther. 32, 603–611.
Crowe, M.S., and Kinsey, S.G. (2017). MAGL inhibition modulates gastric secretion and motility following NSAID exposure in mice. Eur. J. Pharmacol.
Rohof, W.O., Aronica, E., Beaumont, H., Troost, D., and Boeckxstaens, G.E. (2012). Localization of mGluR5, GABAB, GABAA, and Cannabinoid receptors on the vago-vagal reflex pathway responsible for transient lower esophageal sphincter relaxation in humans: an immunohistochemical study. Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc. 24, 383-e173.
Salaga, M., Zatorski, H., Zielińska, M., Mosinska, P., Timmermans, J.-P., Kordek, R., Storr, M., and Fichna, J. (2017). Highly selective CB2 receptor agonist A836339 has gastroprotective effect on experimentally induced gastric ulcers in mice. Naunyn. Schmiedebergs Arch. Pharmacol.