Gut Cannabinoid Receptors and the Treatment of IBD

Marc Moulin November 12, 2018 0 comments

Research shows that activating cannabinoid receptors in the gut may improve pain, diarrhea, and overall quality of life. 

Inflammatory Bowel Disease (IBD) is a broad term used to describe ulcerative colitis and Crohn’s disease. There are some differences between these two conditions. Generally, ulcerative colitis causes extended inflammation in the innermost lining of the large intestine, while Crohn’s disease causes inflammation of the lining of the entire digestive tract, with affected tissue between healthy digestive segments. Together, these two independent conditions affect approximately 1.6 million Americans, with 70,000 new cases diagnosed each year. With the goal of IBD treatment to reduce inflammation and ease painful symptoms, researchers have identified cannabis as a potential solution. Research shows that there are an abundance of cannabinoid receptors in the gut. Even better, when scientists activate them, they appear to provide IBD relief.[1]DiPatrizio, N. V. (2016). Endocannabinoids in the Gut. Cannabis and Cannabinoid Research1(1), 67-77.

Cannabinoids Receptors in the Gut Have Many Jobs

The endocannabinoid system (ECS) plays a role in controlling many gastrointestinal functions. Endocannabinoid signaling in the small intestine is stimulated by a few things, including:

  • Fasting
  • Tasting dietary fats

The system may also send out a general hunger signal on local CB1 receptors, to inhibit satiation. Other studies have provided evidence that CB1 receptors on enteric nerves control intestinal contractility. They do so by inhibiting the release of acetylcholine, an excitatory neurotransmitter.

Intestinal contractions are a normal part of digestion. However, unorganized or aggressive contractions, such as in a colon spasm, may require management because of the pain involved. In the medical research community, of greatest interest may be the interaction between the ECS and the epithelial barrier permeability of the large intestine. IBD associates with epithelial permeability. As a result, increasing evidence suggests that the ECS plays a part in these processes.

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Both THC and CBD May Improve Intestinal Permeability

A study, published in the British Journal of Pharmacology (2012) tackled the issue. The researchers treated human epithelial colon cancer cells with cytokines to induce an inflammatory response and increase permeability. They then applied various cannabinoids. These included THC and CBD, and the endocannabinoids anandamide and 2-AG. Based on the proposed relationship between cannabinoids and inflammatory markers in IBD, the results were both expected and surprising.[2]Alhamoruni, A., Wright, K. L., Larvin, M., & O’sullivan, S. E. (2012). Cannabinoids mediate opposing effects on inflammation‐induced intestinal permeability. British Journal of … Continue reading

THC and CBD enhanced recovery from the cytokine-induced increase in permeability. However, anandamide and 2-AG increased permeability, which would theoretically lead to more inflammation. Additionally, inhibiting the breakdown of anandamide and 2-AG worsened permeability, and inhibiting the synthesis of the endocannabinoids improved permeability. The authors concluded that their findings suggest that phytocannabinoids are a potential therapeutic for reversing intestinal permeability associated with inflammation.

Cannabis as an IBD Treatment in Humans?

Examples of successful preclinical evidence demonstrating the efficacy of cannabis for IBD treatment has translated into multiple human studies. For example, a group of Israeli researchers have been conducting research studies exploring the efficacy of cannabinoids for IBD treatment for almost a decade. Led by Dr. Timna Naftali, a 2011 retrospective study demonstrated subjective improvement in IBD symptoms, setting the stage for future prospective and randomized – controlled study designs.[3]Naftali, T., Lev, L. B., Yablecovitch, D., Half, E., & Konikoff, F. M. (2011). Treatment of Crohn’s disease with cannabis: an observational study. The Israel Medical Association Journal: … Continue reading

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In a study published in Clinical Gastroenterology and Hepatology (2013), the researchers found that inhaled THC produced a clinical response in Crohn’s Disease patients compared to a placebo. Specifically, this included improvements on the Crohn’s Disease Activity Score. But the patients also had improvements in their appetite, and slept better. Further, and perhaps most positive, cannabis did not cause serious side effects.[4]Naftali, T., Schleider, L. B. L., Dotan, I., Lansky, E. P., Benjaminov, F. S., & Konikoff, F. M. (2013). Cannabis induces a clinical response in patients with Crohn’s disease: a prospective … Continue reading

Recent Research On Cannabinoid Receptors in the Gut

Meanwhile, in a more recently published study in the European Journal of Gastroenterology and Hepatology (2019), the researchers identified the average dose of cannabis consumption among IBD patients and measured improvement in several IBD indicators. Among one-hundred and twenty-seven IBD patients, the average cannabis dose was thirty grams per month. This translates to twenty-one milligrams of THC, and one-hundred and seventy milligrams of CBD, per day. Significantly, this dosage led to a large improvement on the Harvey-Bradshaw Index, a subjective scale measuring general well-being, abdominal pain, and bowel movements.[5]Naftali, T., Schleider, L. B. L., Benjaminov, F. S., Lish, I., Konikoff, F. M., & Ringel, Y. (2019). Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption … Continue reading

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Improvement in Symptoms, but not in Disease Activity

Furthermore, patient employment increased from sixty-five to seventy-four percent. The patients found that their need for other medications also dropped. Nevertheless, as pointed out by Dr. Naftali herself, the research has yet to finally demonstrate that cannabis directly reduces IBD inflammation. In her fall for more research, Dr. Naftali says the following:

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“We have previously demonstrated that cannabis can produce measurable improvements in Crohn’s disease symptoms but, to our surprise, we saw no statistically significant improvements in endoscopic scores or in the inflammatory markers…” said Dr. Naftali. “We know that cannabinoids can have profound anti-inflammatory effects but this study indicates that the improvement in symptoms may not be related to these anti-inflammatory properties.”  Other researchers have subsequently expanded on this finding.

In a further review published in Inflammatory Bowel Diseases (2019), the authors comment that cannabis may provide some benefit to IBD sufferers. The benefits they cover include symptom control and quality of life. Unfortunately, however, undeniably small sample sizes and the failure to show improvements in biochemical markers or disease activity limit the data. For this reason, it might be important for physicians to monitor their IBD patients who have had success with cannabis and are thinking of stopping standard therapies.[6]Swaminath, A., Berlin, E. P., Cheifetz, A., Hoffenberg, E., Kinnucan, J., Wingate, L., … & Rubin, D. T. (2019). The role of cannabis in the management of inflammatory bowel disease: a … Continue reading

Cannabis as a Complementary Therapy

Presently, the lack of evidence demonstrating reduced inflammation suggests that for now, cannabis best serves as a complementary therapy to control IBD symptoms.

Moreover, physicians may not recommend forgoing traditional therapies for an independent cannabis treatment protocol. Regardless, researchers cannot yet make firm conclusions regarding the efficacy of cannabis in adults with IBD.[7]Kafil, T. S., Nguyen, T. M., MacDonald, J. K., & Chande, N. (2020). Cannabis for the Treatment of Crohn’s Disease and Ulcerative Colitis: Evidence From Cochrane Reviews. Inflammatory Bowel … Continue reading There is a need for larger studies with higher methodological quality to drive definitive conclusions about cannabis-basedIBD treatment. These will eventually take place.

However, the current evidence regarding cannabinoid receptors in the gut does suggest that supplementing traditional therapies with cannabis can improve quality of life. IBD patients currently consuming cannabis to manage their symptoms should continue to do so at the discretion of their primary care physician.