Nat Rev Gastroenterol Hepatol. 2022 Sep 27. doi: 10.1038/s41575-022-00682-y.Online ahead of print.

Stuart M Brierley ^1 2, Beverley Greenwood-Van Meerveld ³, Giovanni Sarnelli ⁴, Keith A Sharkey ^5 6 7, Martin Storr ^8 9, Jan Tack ¹⁰

Author information

¹Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia.

²Hopwood Centre for Neurobiology, Lifelong Health, South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, Australia.

³Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

⁴Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.

⁵Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. ksharkey@ucalgary.ca.

⁶Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. ksharkey@ucalgary.ca.

⁷Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. ksharkey@ucalgary.ca.

⁸Department of Medicine, Ludwig-Maximilians University, Munich, Germany.

⁹Zentrum für Endoskopie, Starnberg, Germany.

¹⁰Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.

Abstract

The management of visceral pain in patients with disorders of gut-brain interaction, notably irritable bowel syndrome, presents a considerable clinical challenge, with few available treatment options. Patients are increasingly using cannabis and cannabinoids to control abdominal pain. Cannabis acts on receptors of the endocannabinoid system, an endogenous system of lipid mediators that regulates gastrointestinal function and pain processing pathways in health and disease. The endocannabinoid system represents a logical molecular therapeutic target for the treatment of pain in irritable bowel syndrome. Here, we review the physiological and pathophysiological functions of the endocannabinoid system with a focus on the peripheral and central regulation of gastrointestinal function and visceral nociception. We address the use of cannabinoids in pain management, comparing them to other treatment modalities, including opioids and neuromodulators. Finally, we discuss emerging therapeutic candidates targeting the endocannabinoid system for the treatment of pain in irritable bowel syndrome.