CRx MAGAZINE

Summer 2020

Inflammatory Bowel Disease — Indications for Cannabis Use

Inflammatory bowel disease (IBD) is an inflammatory condition affecting the gastrointestinal tract. This condition comprises both ulcerative colitis (UC) and Crohn’s disease (CD). In 2015, it was estimated that 1.3% of US adults—nearly 3 million people—reported having been diagnosed with IBD.1 Management of IBD can become frustrating for patients and practitioners alike when the few known conventional therapy options offer little relief or cause adverse side effects.

Compared with the cannabis consumption rates of the American population at large, a substantially greater percentage of IBD patients report using cannabis as a complementary alternative medicine to manage their symptoms.2 These patients report perceiving cannabis use to be effective for relief of abdominal pain, poor appetite, nausea, and frequency of bowel movements. Researchers, health care practitioners, and patients alike are encouraged by the anecdotal reports of improved symptom control, but many wonder whether cannabis use helps resolve the inflammatory response within the body or simply masks the symptoms of ongoing inflammation in active IBD.

Preliminary evidence supports the theory that cannabis may be effective in treating IBD and suggests that exogenous cannabinoids such as CBD and THC may help improve many of the symptoms associated with IBD. It’s for this reason that physicians and other health care practitioners must be familiar with the evidence surrounding cannabis therapy for IBD in order to advise their patients on safe use.

The Endocannabinoid System and IBD
One of the main barriers to finding an appropriate treatment for IBD is that the pathophysiology of the disease has yet to be fully established, although it’s clear that an inappropriate inflammatory response paired with a dysregulated immune system leads to relapsing episodes of inflammation in the gastrointestinal tract. To date, therapies for IBD include anti-inflammatory drugs, immune system suppressors, antibiotics, and other medications, followed by eventual surgery if needed.3

While these therapies are available, IBD patients often express frustration over their ineffectiveness or their associated adverse side effects, prompting them to seek complementary and alternative therapies such as cannabis consumption.4 Based on years of anecdotal reports of cannabis helping to alleviate symptoms in IBD patients, researchers have begun to explore the relationship between IBD, the endocannabinoid system (ECS), and gastrointestinal physiology, homeostasis, and inflammation.

The ECS—made up of receptors and endogenous cannabinoids found throughout the body—has been shown to play a role in the pathogenesis of IBD in animal studies.1 The ECS produces its own endogenous cannabinoids, anandamide and 2-arachidonoylglycerol, and also interacts with exogenous cannabinoids such as CBD and THC. Through the CB1 and CB2 receptors of the ECS, cannabinoids are able to exert their anti-inflammatory and immunosuppressive effects. The gastrointestinal system contains both CB1 and CB2 receptors in all layers of intestinal sections. The activation of CB1 receptors has been shown to “modulate several functions in the [gastrointestinal] tract, including gastric secretion, gastric emptying, and intestinal motility.”5 Several mouse studies have demonstrated the relationship between the ECS and the regulation of gut inflammation.1

While there’s still a need for more clinical studies in humans to reveal a possible role for cannabinoids in the management of IBD, in rodent studies, the ECS appears to protect the gastrointestinal tract by modulating the inflammatory response. This suggests that the ECS may serve as a “potentially promising therapeutic target against different [gastrointestinal] disorders” such as IBD.5

Medical Cannabis and CD: Review of the Literature
CD is a chronic IBD characterized by inflammation of the digestive tract. With CD, inflammation can occur at any point in the digestive system, from the mouth to the anus, most commonly manifesting in the small intestine.

While the symptomatic relief associated with cannabis use in CD patients remains largely anecdotal, a few studies point to the promise of cannabis being used as a potential therapeutic tool in the treatment of IBD.

In an animal study published in the Journal of Clinical Investigation, it was found that “the endogenous cannabinoid system is physiologically involved in the protection against excessive inflammation in the colon, both by dampening smooth muscular irritation caused by inflammation and by controlling cellular pathways leading to inflammatory responses.”6 These results strongly suggest that drugs targeting the ECS have the potential to be promising therapeutic agents in the treatment of Crohn’s disease and point to the need for further study.

Another study published in the Inflammatory Bowel Diseases Journal found that cannabis use provides
symptom relief in patients with IBD but was associated with worsening disease prognosis in Crohn’s patients. Results gathered in this study via anonymous questionnaire showed that of the 313 IBD patients surveyed, nearly 18% were using cannabis to relieve symptoms of IBD. Ninety-seven percent of those patients reported consuming cannabis via inhalation methods. Eighty-four percent reported that cannabis improved their perception of abdominal pain, 77% reported an improvement in abdominal cramping, 49% reported an improvement in joint pain, and 29% reported an improvement in diarrhea.7 While these self-reported statistics are encouraging, it was noted that the use of cannabis for more than six months “was a strong predictor of requiring surgery,” although the Crohn’s and Colitis Foundation reports that 75% of people with CD will eventually require surgery, regardless of cannabis use.8

In the first observational study of its kind to evaluate cannabis therapeutics for CD in humans, 21 of 30 subjects studied reported their symptoms improved “significantly after treatment with cannabis” as measured by the Harvey-Bradshaw index and a reduction in the need for other medications.9

In the first prospective, observational, single-arm pilot trial with human subjects, 13 long-standing IBD patients were prescribed cannabis inhalation treatment. After three months of cannabis treatment, patients reported an improvement in their perception of their general health, social function, ability to work, physical pain, and depression. The authors concluded that three months of cannabis treatment vastly improved “quality of life measurements, disease activity index, and caused weight gain and rise in BMI in longstanding IBD patients.”10

Finally, in the first prospective, randomized, double-blind, placebo-controlled trial to evaluate cannabis use in patients with CD, complete remission was achieved by 5 of 11 subjects in the cannabis group compared with 1 of 10 in the placebo group. A clinical response was observed in 10 of 11 subjects in the cannabis group compared with 4 of 10 in the placebo group. Three patients in the cannabis group were weaned from steroid dependency and the subjects receiving cannabis reported improved appetite and sleep with no significant side effects. The authors concluded that “a short course (eight weeks) of THC-rich cannabis produced significant clinical, steroid-free benefits to 10 of 11 patients with active Crohn’s disease, compared with placebo, without side effects.”11

Inherent flaws in human studies, small sample sizes, and a relatively limited number of preliminary studies point to the need for larger, standardized, placebo-controlled, and blinded trials of the use of cannabis in the management of CD.

Medical Cannabis and UC: Review of the Literature
UC is a chronic inflammatory disease of the large intestine in which the lining of the colon becomes inflamed; tiny, painful sores or ulcers develop and cause frequent bowel movements. There’s no known cure for UC, so the aim of treatment is to manage symptoms. Given the limited therapy options, patients are turning to alternative methods such as cannabis use to find relief, despite the lack of clinical evidence to support its efficacy. While there are studies that examine the relationship between IBD and cannabis, and studies that demonstrate the beneficial effect of cannabis for intestinal inflammation, there are few studies that have specifically looked at the relationship between UC and cannabis use.

A Cochrane review conducted in 2018 assessed the efficacy and safety of cannabis for the treatment of patients with UC. It examined only randomized controlled trials specific to cannabis use in UC and found that “the effects of cannabis and cannabidiol on UC are uncertain, thus no firm conclusions regarding the efficacy and safety of cannabis or cannabidiol in adults with active UC can be drawn.”11

Emerging evidence published in Medicine Journal in 2019 noted a promising correlation between cannabis use and outcomes in hospitalized ulcerative colitis patients. In this retrospective cohort study, it was found that “cannabis use may mitigate some of the well described complications of UC among hospitalized patients.” This study showed that hospitalized UC patients who self-reported cannabis use had less need for partial or total colectomy, a lower prevalence of a bowel obstruction, and an overall shorter hospital length of stay compared with cannabis nonusers.12

These findings point to the need for more studies and large clinical trials to explore the relationship between cannabis use and UC patient outcomes.

Does Cannabis Simply Mask the Inflammation?
Cannabinoids are known to play a critical role in gut pathology and appear to be a potential positive target for drug interventions aimed at the treatment of IBD. While preliminary evidence suggests that cannabis use and cannabinoid therapy many play a beneficial role in the management of IBD, the fact remains that cannabis is still classified as a Schedule I controlled substance, thus there have been no randomized controlled trials evaluating the effects of cannabis in IBD patients in the United States.

There’s a significant need to study the potential role of cannabinoids in the treatment of IBD. Most needed are human studies designed to determine whether cannabinoids have true therapeutic anti-inflammatory effects on the disease process or cannabis use is simply masking the debilitating symptoms caused by the disease. Understanding this is critically important in helping clinicians decide how to treat their patients. While cannabis use may cause a perceived improvement in symptoms, the concern is that cannabis could mask ongoing inflammation, leading patients to perceive that their disease is in remission when it isn’t. This could be harmful to patients if they stop seeing their physicians for routine care or choose to forego other treatment options.

Practical Recommendations for Clinicians
While there’s a lack of clinical evidence to recommend the use of cannabis in the management of CD or UC, the fact remains that there’s a large unmet need in the treatment of IBD with conventional medical therapy and cannabis use remains a popular alternative choice for many patients. Surveys on cannabis use in US and Canadian IBD patients published in the Journal of Gastroenterology & Hepatology in 2018 found that approximately 15% to 20% of patients use cannabis, and up to 40% have tried cannabis to relieve IBD symptoms.

In a January 2014 article published in the Inflammatory Bowel Disease Journal, of 313 respondents to a questionnaire, 47% reported trying cannabis because they thought it would help with their symptoms, 42% said they were frustrated by their disease, 38% said they wanted to try a different approach, and 27% said they tried cannabis because the medications prescribed by their doctors didn’t help.

Of these 313 respondents, only 39% reported discussing cannabis use with their doctors and 82% said their doctors were “indifferent or not supportive of the use of marijuana for IBD treatment.”7

With rapidly expanding medical and adult use cannabis programs, consumers are gaining access to cannabis products faster and more easily than ever before. This presents a significant opportunity for clinicians to step in and talk with their patients about their perceptions or current use of cannabis for the symptom management of their IBD and the benefits and the risk of using cannabis to treat IBD symptoms.

Anecdotal and some preliminary evidence suggest that cannabis use can help relieve abdominal pain, abdominal cramping, poor appetite, and nausea, and improve quality of life, increase body weight and BMI, and improve clinical disease activity as a result of the analgesic, anti-inflammatory, antimotility, and additional effects of cannabinoids.7

While long-term effects haven’t been well studied in an IBD population, the New England Journal of Medicine has identified several general long-term risks associated with cannabis use that are worth discussing with patients. These include a higher risk of motor vehicle accidents, chronic bronchitis symptoms, psychiatric disturbances, depression, and anxiety.13

Taking into account state laws and regulations, clinicians should be open to a discussion with their patients about their current or potential cannabis use for the management of IBD symptoms and should work with their patients to meet them where they are in order to maximize their treatment benefits and minimize harm.

Conclusion
Before cannabis can be recommended as an IBD treatment option, there’s a significant need for more research and clinical trials on the efficacy of cannabinoid therapeutics specifically as it relates to IBD. However, given the limited therapy options for IBD, cannabis use remains common among IBD patients for symptom relief. Physicians and other health care practitioners should be familiar with the potential benefits and the potential risks of using cannabis therapy for IBD in order to be able to advise their patients on safe use.

— Emily Kyle, MS, RDN, CDN, CLT, HCP, is a certified holistic cannabis practitioner.

References

1. Dahlhamer JM, Zammitti EP, Ward BW, Wheaton AG, Croft JB. Prevalence of inflammatory bowel disease among adults aged ≥18 years — United States, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(42):1166-1169.

2. Ahmed W, Katz S. Therapeutic use of cannabis in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12(11):668-679.

3. Inflammatory bowel disease (IBD): diagnosis and treatment. Mayo Clinic website. https://www.mayoclinic.org/diseases-conditions/inflammatory-bowel-disease/diagnosis-treatment/drc-20353320. Updated March 3, 2020.

4. Lal S, Prasad N, Ryan M, et al. Cannabis use amongst patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011;23(10):891-896.

5. Massa F, Storr M, Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med (Berl). 2005;83(12):944-954.

6. Massa F, Marsicano G, Hermann H, et al. The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest. 2004;113(8):1202-1209.

7. Storr M, Devlin S, Kaplan GG, Panaccione R, Andrews CN. Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn’s disease. Inflamm Bowel Dis. 2014;20(3):472-480.

8. Crohn’s & Colitis Foundation of America. Surgery for Crohn’s disease and ulcerative colitis. https://www.crohnscolitisfoundation.org/sites/default/files/legacy/assets/pdfs/surgery_brochure_final.pdf. Accessed March 1, 2020.

9. Naftali T, Lev LB, Yablecovitch D, Half E, Konikoff FM. Treatment of Crohn’s disease with cannabis: an observational study. Isr Med Assoc J. 2011;13(8):455-458.

10. Lahat A, Lang A, Ben-Horin S. Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective study. Digestion. 2012;85(1):1-8.

11. Kafil TS, Nguyen TM, MacDonald JK, Chande N. Cannabis for the treatment of ulcerative colitis. Cochrane Database Syst Rev. 2018;11(11):CD012954.

12. Kinnucan, J. Use of medical cannabis in patients with inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2018;14(10):598-601.

13. Volkow ND, Compton WM, Weiss SRB. Adverse health effects of marijuana use. N Engl J Med. 2014;371(9):879.

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