Cannabinoid-Based Therapy for the Treatment of Inflammatory Bowel Disease

Board-certified gastroenterologist and hepatologist discusses findings from a review by Kienzl et al.: Cannabinoids and opioids in the treatment of inflammatory bowel diseases. 

Clin Transl Gastroenterol. 2020;11(1):e00120.

In a review citing data from various surveys and clinical studies, Kienzl et al.³ examine the effectiveness of cannabis and opioids for treating inflammatory bowel disease (IBD). Among the authors’ crucial findings are the effects of cannabis on quality of life (QoL) and functional symptoms. Although cannabis is associated with improved subjective QoL, patients’ general satisfaction is from a symptom-benefit standpoint without any objective reduction in anti-inflammatory markers. Moreover, although cannabis seems to alleviate functional symptoms of IBD, there appears to be a significant amount of uncertainty regarding optimal doses and routes of administration. 

Regarding the role of opioids in IBD, the authors note several preclinical models demonstrated the beneficial effects of μ-opioid agonists on inflammation. However, they also point out the association between intestinal inflammation and antinociceptive tolerance. Therefore, as one would expect, prolonged opioid use increases the risk for misuse, adverse effects, all-cause mortality, and overall health care costs. The goal of treatment is to move patients to safer treatment options when possible. 

Need for Alternative Treatments

Ulcerative colitis and Crohn’s disease, collectively referred to as IBD, appear to be a product of inappropriate and misdirected immune responses, resulting in inflammation and damage to the intestinal mucosa in genetically predisposed individuals.¹ IBD has a high symptomatic and psychological burden and is associated with significant health care costs and complicated manifestations across multiple organ systems.² 

The clinical course of IBD often is complicated, and treatment varies based on disease severity and stage. Response to treatment is equally ascertained from an assessment of mucosal healing and the patient’s clinical response. With the rising prevalence of IBD,⁴ more effective treatment options are needed. Effective medical treatments are readily available but often have significant side-effect profiles, prompting many patients to seek alternative and complementary therapies for symptom management. The high incidence of pain, change in bowel habits, and extraintestinal manifestations in IBD increased interest in alternate treatment modalities such as cannabis. 

Cannabis has long been known for its myriad analgesic, anti-inflammatory, antiemetic, antidiarrheal, and other beneficial effects that could directly improve the management of IBD. There is a need for a multifaceted approach to determine how cannabis can positively alter the course of a patient’s IBD. This approach can be addressed by looking at the 3 primary applications for cannabis in IBD: as a symptom modifier and manager, anti-inflammatory drug, and mucosal healing agent.

• Symptom modifier and manager. Kienzl et al.’s review correlates cannabis use with significant improvement in a patient’s QoL, including pain control, better-controlled bowel habits, less nausea, and increased appetite. Cannabis also appears to have few known significant side effects—fewer than most other analgesics, particularly opioids.³ Physicians can more accurately determine the effectiveness of conventional therapy when a patient’s symptoms are more controlled and they can better cope with their underlying illness. At the same time, however, close monitoring is essential to ensure cannabis is not masking an underlying issue or inadequately controlled flare. 

• Anti-inflammatory agent. Cannabinoids have long been known to possess significant anti-inflammatory properties.⁵ The endocannabinoid system is densely wired throughout the gastrointestinal tract.⁶ These facts lead one to believe that cannabis should be a potent anti-inflammatory agent that could be helpful in IBD. However, improvement in objective markers of inflammation with cannabinoids has only been observed in mouse models, making this second application slightly more confounding.⁷ However, very few studies have followed these markers, and it is still unclear if cannabis is effective as an anti-inflammatory agent. If there is improvement in symptoms, the supposition is that improvement is partly due to the anti-inflammatory effects of cannabis. 

• Mucosal healing. Although some preliminary data suggest cannabis may promote mucosal healing, no conclusive evidence exists.⁸ Again, although there appears to be an association between potent anti-inflammatory agents and improved mucosal healing, further studies are needed to understand better the processes involved.

Limitations

Much of the review by Kienzl et al. focuses on subjective responses to questionnaires and surveys, likely due to the small number of retrospective controlled trials that objectively measure a patient’s true response to cannabis. Although cannabis can help ascertain actual disease severity, the question arises as to whether it is merely masking symptoms. Although the effects of cannabis still provide sufficient symptom relief, an opposing argument suggests that it conceals the accurate clinical picture.

Future Research

Very few clinical trials have assessed the risks and benefits of using medical cannabis to treat IBD. However, a prospective placebo-controlled study in Israel found a clear clinical response (ie, a decrease in Crohn’s Disease Activity Index score) without side effects.⁹ Although a significant percentage of patients achieved complete remission, the number was deemed statistically insignificant.

A clear improvement in QoL was observed in the cannabis group but without any noted change in inflammatory markers. Additionally, no differences in side effects or withdrawal symptoms were observed between the study groups. Patients in the cannabis group reported significantly less pain, improved appetite, improved daily functioning, and higher satisfaction with treatment.

The lack of research examining the possible effects of cannabis on IBD treatment and management is apparent. Higher volume randomized controlled studies looking at objective trends in inflammatory markers (eg, C-reactive protein, fecal calprotectin) are needed, preferably long-term data vs short-term dosing studies. Ideally, such studies would include endoscopic mucosal comparisons before and after cannabis administration.  

Finally, there is a need to broaden and extend studies to assess clinical response. Mucosal surveillance and objective monitoring are crucial to ensure the patient’s underlying disease has not worsened, but a more comprehensive monitoring of clinical response should also be considered. Medical care aimed at improving a patient’s symptoms and QoL should explore and consider the use of cannabis in treating IBD.