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Cannabinoids and Digestive Disorders
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Jami A. Kinnucan, MD, AGAF, FACG

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References
  1. Leung J, Chan G, Stjepanović D, Chung JYC, Hall W, Hammond D. Prevalence and self-reported reasons of cannabis use for medical purposes in USA and Canada. Psychopharmacology (Berl). 2022;239(5):1509-1519. doi:10.1007/s00213-021-06047-8
  2. Ahmed W, Katz S. Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12(11):668-679.
  3. Ravikoff Allegretti J, Courtwright A, Lucci M, Korzenik JR, Levine J. Marijuana use patterns among patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(13):2809-2814. doi:10.1097/01.MIB.0000435851.94391.37
  4. Marijuana legality by state - updated February 1, 2024. DISA. Accessed March 1, 2024. https://disa.com/marijuana-legality-by-state
  5. The Cannigma Staff. Where is weed legal around the globe? The Cannigma. Updated July 3, 2022. Accessed March 1, 2024. https://cannigma.com/regulation/cannabis-regulation-around-the-world/
  6. Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19(3):833. doi:10.3390/ijms19030833
  7. Maselli DB, Camilleri M. Pharmacology, clinical effects, and therapeutic potential of cannabinoids for gastrointestinal and liver diseases. Clin Gastroenterol Hepatol. 2021;19(9):1748-1758.e2. doi:10.1016/j.cgh.2020.04.020
  8. Buckley MC, Kumar A, Swaminath A. Inflammatory bowel disease and cannabis: a practical approach for clinicians. Adv Ther. 2021;38(7):4152- 4161. doi:10.1007/s12325-021-01805-8
  9. Chang L, Cash BD, Lembo A, et al. Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: results from a phase 2b randomized placebo-controlled trial (CAPTIVATE). Neurogastroenterol Motil. 2023;35(5):e14539. doi:10.1111/nmo.14539
  10. Doeve BH, van de Meeberg MM, van Schaik FDM, Fidder HH. A systematic review with meta-analysis of the efficacy of cannabis and cannabinoids for inflammatory bowel disease: what can we learn from randomized and nonrandomized studies? J Clin Gastroenterol. 2021;55(9):798-809. doi:10.1097/MCG.0000000000001393
  11. Gotfried J, Naftali T, Schey R. Role of cannabis and its derivatives in gastrointestinal and hepatic disease [published correction appears in Gastroenterology. 2021;160(5):1904]. Gastroenterology. 2020;159(1):62-80. doi:10.1053/j.gastro.2020.03.087
  12. Goyal H, Singla U, Gupta U, May E. Role of cannabis in digestive disorders. Eur J Gastroenterol Hepatol. 2017;29(2):135-143. doi:10.1097/MEG.0000000000000779
  13. van Orten-Luiten AB, de Roos NM, Majait S, Witteman BJM, Witkamp RF. Effects of cannabidiol chewing gum on perceived pain and well-being of irritable bowel syndrome patients: a placebo-controlled crossover exploratory intervention study with symptom-driven dosing. Cannabis Cannabinoid Res. 2022;7(4):436-444. doi:10.1089/can.2020.0087
  14. Adejumo AC, Ajayi TO, Adegbala OM, Bukong TN. Higher odds of irritable bowel syndrome among hospitalized patients using cannabis: a propensity matched analysis. Eur J Gastroenterol Hepatol. 2019;31(7):756-765. doi:10.1097/MEG.0000000000001382
  15. Antoniou T, Bodkin J, Ho JM. Drug interactions with cannabinoids. CMAJ. 2020;192(9):E206. doi:10.1503/cmaj.191097
  16. Karila L, Roux P, Rolland B, et al. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014;20(25):4112-4118. doi:10.2174/13816128113199990620
  17. Venkatesan T, Levinthal DJ, Li BUK, et al. Role of chronic cannabis use: cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome. Neurogastroenterol Motil. 2019;31(suppl 2):e13606. doi:10.1111/nmo.13606
Author and Disclosure Information

Jami A. Kinnucan, MD, AGAF, FACG
Senior Associate Consultant
GI Practice Chair
Director of Digital Health and Practice Integration
Division of Gastroenterology and Hepatology
Department of Medicine
Mayo Clinic
Jacksonville, Florida

Disclosures:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbvie (Advisor, consultant); BMS (Advisor); Fresenius kabi (Advisor, consultant); Janssen (Advisor); Takeda (Advisor, consultant); Pfizer (Consultant)

Publications
GI and Hepatology News
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IBD & Intestinal Disorders
Author(s)
Jami A. Kinnucan, MD, AGAF, FACG
Author(s)
Jami A. Kinnucan, MD, AGAF, FACG
Author and Disclosure Information

Jami A. Kinnucan, MD, AGAF, FACG
Senior Associate Consultant
GI Practice Chair
Director of Digital Health and Practice Integration
Division of Gastroenterology and Hepatology
Department of Medicine
Mayo Clinic
Jacksonville, Florida

Disclosures:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbvie (Advisor, consultant); BMS (Advisor); Fresenius kabi (Advisor, consultant); Janssen (Advisor); Takeda (Advisor, consultant); Pfizer (Consultant)

Author and Disclosure Information

Jami A. Kinnucan, MD, AGAF, FACG
Senior Associate Consultant
GI Practice Chair
Director of Digital Health and Practice Integration
Division of Gastroenterology and Hepatology
Department of Medicine
Mayo Clinic
Jacksonville, Florida

Disclosures:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbvie (Advisor, consultant); BMS (Advisor); Fresenius kabi (Advisor, consultant); Janssen (Advisor); Takeda (Advisor, consultant); Pfizer (Consultant)

Click here to view more from Gastroenterology Data Trends 2024

Click here to view more from Gastroenterology Data Trends 2024

References
  1. Leung J, Chan G, Stjepanović D, Chung JYC, Hall W, Hammond D. Prevalence and self-reported reasons of cannabis use for medical purposes in USA and Canada. Psychopharmacology (Berl). 2022;239(5):1509-1519. doi:10.1007/s00213-021-06047-8
  2. Ahmed W, Katz S. Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12(11):668-679.
  3. Ravikoff Allegretti J, Courtwright A, Lucci M, Korzenik JR, Levine J. Marijuana use patterns among patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(13):2809-2814. doi:10.1097/01.MIB.0000435851.94391.37
  4. Marijuana legality by state - updated February 1, 2024. DISA. Accessed March 1, 2024. https://disa.com/marijuana-legality-by-state
  5. The Cannigma Staff. Where is weed legal around the globe? The Cannigma. Updated July 3, 2022. Accessed March 1, 2024. https://cannigma.com/regulation/cannabis-regulation-around-the-world/
  6. Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19(3):833. doi:10.3390/ijms19030833
  7. Maselli DB, Camilleri M. Pharmacology, clinical effects, and therapeutic potential of cannabinoids for gastrointestinal and liver diseases. Clin Gastroenterol Hepatol. 2021;19(9):1748-1758.e2. doi:10.1016/j.cgh.2020.04.020
  8. Buckley MC, Kumar A, Swaminath A. Inflammatory bowel disease and cannabis: a practical approach for clinicians. Adv Ther. 2021;38(7):4152- 4161. doi:10.1007/s12325-021-01805-8
  9. Chang L, Cash BD, Lembo A, et al. Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: results from a phase 2b randomized placebo-controlled trial (CAPTIVATE). Neurogastroenterol Motil. 2023;35(5):e14539. doi:10.1111/nmo.14539
  10. Doeve BH, van de Meeberg MM, van Schaik FDM, Fidder HH. A systematic review with meta-analysis of the efficacy of cannabis and cannabinoids for inflammatory bowel disease: what can we learn from randomized and nonrandomized studies? J Clin Gastroenterol. 2021;55(9):798-809. doi:10.1097/MCG.0000000000001393
  11. Gotfried J, Naftali T, Schey R. Role of cannabis and its derivatives in gastrointestinal and hepatic disease [published correction appears in Gastroenterology. 2021;160(5):1904]. Gastroenterology. 2020;159(1):62-80. doi:10.1053/j.gastro.2020.03.087
  12. Goyal H, Singla U, Gupta U, May E. Role of cannabis in digestive disorders. Eur J Gastroenterol Hepatol. 2017;29(2):135-143. doi:10.1097/MEG.0000000000000779
  13. van Orten-Luiten AB, de Roos NM, Majait S, Witteman BJM, Witkamp RF. Effects of cannabidiol chewing gum on perceived pain and well-being of irritable bowel syndrome patients: a placebo-controlled crossover exploratory intervention study with symptom-driven dosing. Cannabis Cannabinoid Res. 2022;7(4):436-444. doi:10.1089/can.2020.0087
  14. Adejumo AC, Ajayi TO, Adegbala OM, Bukong TN. Higher odds of irritable bowel syndrome among hospitalized patients using cannabis: a propensity matched analysis. Eur J Gastroenterol Hepatol. 2019;31(7):756-765. doi:10.1097/MEG.0000000000001382
  15. Antoniou T, Bodkin J, Ho JM. Drug interactions with cannabinoids. CMAJ. 2020;192(9):E206. doi:10.1503/cmaj.191097
  16. Karila L, Roux P, Rolland B, et al. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014;20(25):4112-4118. doi:10.2174/13816128113199990620
  17. Venkatesan T, Levinthal DJ, Li BUK, et al. Role of chronic cannabis use: cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome. Neurogastroenterol Motil. 2019;31(suppl 2):e13606. doi:10.1111/nmo.13606
References
  1. Leung J, Chan G, Stjepanović D, Chung JYC, Hall W, Hammond D. Prevalence and self-reported reasons of cannabis use for medical purposes in USA and Canada. Psychopharmacology (Berl). 2022;239(5):1509-1519. doi:10.1007/s00213-021-06047-8
  2. Ahmed W, Katz S. Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12(11):668-679.
  3. Ravikoff Allegretti J, Courtwright A, Lucci M, Korzenik JR, Levine J. Marijuana use patterns among patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(13):2809-2814. doi:10.1097/01.MIB.0000435851.94391.37
  4. Marijuana legality by state - updated February 1, 2024. DISA. Accessed March 1, 2024. https://disa.com/marijuana-legality-by-state
  5. The Cannigma Staff. Where is weed legal around the globe? The Cannigma. Updated July 3, 2022. Accessed March 1, 2024. https://cannigma.com/regulation/cannabis-regulation-around-the-world/
  6. Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci. 2018;19(3):833. doi:10.3390/ijms19030833
  7. Maselli DB, Camilleri M. Pharmacology, clinical effects, and therapeutic potential of cannabinoids for gastrointestinal and liver diseases. Clin Gastroenterol Hepatol. 2021;19(9):1748-1758.e2. doi:10.1016/j.cgh.2020.04.020
  8. Buckley MC, Kumar A, Swaminath A. Inflammatory bowel disease and cannabis: a practical approach for clinicians. Adv Ther. 2021;38(7):4152- 4161. doi:10.1007/s12325-021-01805-8
  9. Chang L, Cash BD, Lembo A, et al. Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: results from a phase 2b randomized placebo-controlled trial (CAPTIVATE). Neurogastroenterol Motil. 2023;35(5):e14539. doi:10.1111/nmo.14539
  10. Doeve BH, van de Meeberg MM, van Schaik FDM, Fidder HH. A systematic review with meta-analysis of the efficacy of cannabis and cannabinoids for inflammatory bowel disease: what can we learn from randomized and nonrandomized studies? J Clin Gastroenterol. 2021;55(9):798-809. doi:10.1097/MCG.0000000000001393
  11. Gotfried J, Naftali T, Schey R. Role of cannabis and its derivatives in gastrointestinal and hepatic disease [published correction appears in Gastroenterology. 2021;160(5):1904]. Gastroenterology. 2020;159(1):62-80. doi:10.1053/j.gastro.2020.03.087
  12. Goyal H, Singla U, Gupta U, May E. Role of cannabis in digestive disorders. Eur J Gastroenterol Hepatol. 2017;29(2):135-143. doi:10.1097/MEG.0000000000000779
  13. van Orten-Luiten AB, de Roos NM, Majait S, Witteman BJM, Witkamp RF. Effects of cannabidiol chewing gum on perceived pain and well-being of irritable bowel syndrome patients: a placebo-controlled crossover exploratory intervention study with symptom-driven dosing. Cannabis Cannabinoid Res. 2022;7(4):436-444. doi:10.1089/can.2020.0087
  14. Adejumo AC, Ajayi TO, Adegbala OM, Bukong TN. Higher odds of irritable bowel syndrome among hospitalized patients using cannabis: a propensity matched analysis. Eur J Gastroenterol Hepatol. 2019;31(7):756-765. doi:10.1097/MEG.0000000000001382
  15. Antoniou T, Bodkin J, Ho JM. Drug interactions with cannabinoids. CMAJ. 2020;192(9):E206. doi:10.1503/cmaj.191097
  16. Karila L, Roux P, Rolland B, et al. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014;20(25):4112-4118. doi:10.2174/13816128113199990620
  17. Venkatesan T, Levinthal DJ, Li BUK, et al. Role of chronic cannabis use: cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome. Neurogastroenterol Motil. 2019;31(suppl 2):e13606. doi:10.1111/nmo.13606
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Complementary and alternative therapies are gaining interest in the gastrointestinal (GI) community. Up to 27% of adults in the United States and Canada report using cannabis for medical reasons, and up to 39% of patients with inflammatory bowel disease (IBD) report past use for symptom management.1-3 Significant questions and challenges still remain surrounding the use of cannabis in GI disorders, including its varied legalization status globally.4,5

Cannabinoids can be broken down into endocannabinoids (naturally occurring substances within the body) such as 2-arachidonoylgylcerol (2-AG) and anandamide (AEA), which act within the body at the cannabinoid receptors (CB) CB1 and CB2.6 There are also plant-based cannabinoids (phytocannabinoids) that include the most commonly known cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). In addition, there are synthetic cannabinoids (manmade molecules that resemble THC or CBD), and synthetic receptor antagonists and agonists (manmade molecules that act directly at the cannabinoid receptors).

Studies have assessed cannabinoid use in many GI conditions—most notably IBD and irritable bowel syndrome (IBS)—however, medical marijuana use has only been approved in some states for Crohn’s disease or ulcerative colitis.4,7,8 In patients with IBS, there have been conflicting results, with a recent clinical trial of a synthetic CB2 agonist showing no significant change in abdominal pain scores.9 In patients with IBD, results are also varied, with some trials showing improvement in clinical measures but not endoscopic remission.10 These varied results could be due to differences in the formulation of cannabinoids studied and routes of administration.

While the endocannabinoid system is of high interest within the GI community due to its therapeutic potential, many challenges remain, such as legalization, widely varied compounds and doses of active ingredients, and a lack of large, high-quality randomized studies.5,11,12 More research is needed to delineate the exact mechanism to best interact with the endocannabinoid system, and what GI disease states might be most affected.

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