In recent years, a number of preclinical models have shown that cannabinoids may be highly effective at improving inflammation and, therefore, may be a potential treatment for inflammatory bowel diseases (IBDs). Like cannabinoids, opioids have also been shown effective at reducing inflammation in the gut, though opioids are generally associated with high rates of dependence and mortality. In a study published in Clinical and Translational Gastroenterology, researchers explored the underlying mechanisms of cannabinoids and opioids in IBD, the benefits of using these therapies for IBD, and related adverse effects.1

The Actions of Cannabinoids in IBD

The term “cannabinoids” refers to the more than 100 herbal ingredients in the cannabis plant and synthetic cannabinoids such as CP-55,940.1 Any IBD therapy involving cannabis is based on the way any of these cannabinoids activate various cannabinoid receptors in the body’s endocannabinoid system (ECS).1

Cannabinoid receptors are involved in a number of processes in the gastrointestinal tract, such as the alleviation of strong bowel contractions, regulation of mucosal permeability, and wound healing.1 The researchers of this study demonstrated that with prebiotic and antibody treatment, gut microbiota can modulate cannabinoid receptors in mice to improve diet-induced metabolic dysfunction associated with colitis. Cannabinoid receptors may also manipulate epithelial cells in the intestine to alter the composition of the gut microbiota and improve symptoms of IBDs.1

Evidence of Cannabis Benefits in IBD

Though a large amount of preclinical data has shown the efficacy of cannabinoids in mice with intestinal inflammation, there is limited clinical evidence surrounding the use of cannabis to improve IBD symptoms in humans. Existing clinical data are based on surveys and a small number of uncontrolled, underpowered clinical trials; however, the small clinical data that do exist show that cannabis may have therapeutic potential in IBD.

In patients with IBD, cannabis has been shown to relieve symptoms including abdominal pain, cramping, and diarrhea, with many patients reporting an improved overall well-being. Results from a retrospective, observational study that examined the effects of cannabis in 30 patients with Crohn disease showed there was a significant improvement of the Harvey Bradshaw index in 21 patients (14±6.7 to 7±4.7; P <.001) and that their need for medication and surgery was significantly reduced.2

Researchers of a separate prospective, placebo-controlled study that examined the effects of cannabis on 21 patients with Crohn disease showed that 45% of patients achieved complete remission with a Crohn Disease Activity Index score of 150 or less, and 90% experienced a decrease in Crohn Disease Activity Index score by 100 or greater (330±105 to 152±109).3 Compared with patients who received placebo, those who received cannabis reported improved sleep and appetite, and no significant side effects.

The Role of Opioids in IBD

Components of the endo-opioid system are shown to regulate functions in the gastrointestinal tract in a way similarly to that of the ECS, which suggests that opioids may also reduce intestinal inflammation and symptoms of IBD.1 Opioids are currently prescribed to reduce diarrhea, back pain, and abdominal pain associated with IBD.

The blocking of opioid receptors using medication has also shown clinical benefit for patients with IBD. Naltrexone, an antagonist of the mu-opioid receptor, has been shown to improve IBD symptoms and remission.1 The mu-opioid receptor is increased in patients with active ulcerative colitis and Crohn disease; therefore, naltrexone may help reduce intestinal inflammation in patients with these IBDs.

Adverse Effects of Cannabis and Opioids in IBD

Despite the potential efficacy and therapeutic benefits of cannabinoids in IBD, some patients who use cannabis have reported short-term side effects including dry mouth, dizziness, nausea, sleepiness, euphoria, anxiety, and hallucinations.1 Researchers hypothesize that these effects are triggered by the action of the psychotropic ingredient tetrahydrocannabinol on central cannabinoid receptors and likely only occur when using high doses of cannabis.

Researchers suggest that patients with IBD who use cannabis avoid vaping or using e-cigarette products that contain THC due to the risk for severe pneumonia and lung injury.1 Patients should also be aware of the risk for cannabis dependence and of the risks associated with long-term recreational use of cannabis such as lung and cardiovascular diseases, psychotic outcomes, reduced reproductive function in men, and deficits in cognitive function and neurological development in babies born to women who use cannabis during pregnancy and lactation.

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In regards to opioid use in IBD, IBD is currently identified as a risk factor for opioid misuse and dependence.1 Researchers point out that during a study in which nearly 45% of patients with IBD received an opioid prescription, more than one-third became persistent users. Use of opioids in IBD is also associated with constipation, nausea, fractures, bowel obstruction, cardiovascular events, and increased all-cause mortality.1

Conclusion

Strong preclinical evidence suggests that cannabis and many of its cannabinoids may improve intestinal inflammation and quality of life in patients with IBD; however, a lack of evidence remains surrounding the efficacy of cannabis in reducing independent anti-inflammatory markers of IBD. Additionally, the effects and safety of cannabis application methods (cannabis, cannabis oil, or cannabidiol) are still largely unexplored in clinical trials, as are optimal doses and routes of application. Researchers say that the future of cannabinoids in the treatment of IBD relies on more clinical trials that prove how cannabinoids can manipulate the ECS to improve IBD with minimal side effects.1

Opioids may be used in select acute settings to manage symptoms of IBD such as abdominal pain. However, the long-term use of opioids in IBD should be avoided due to the risk for misuse, serious adverse events, and premature mortality.

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References

1. Kienzl M, Storr M, Schicho R. Cannabinoids and opioids in the treatment of inflammatory bowel diseases. Clin Transl Gastroenterol. 2020;11(1):e00120.

2. 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.

3. Naftali T, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM. Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. Clin Gastroenterol Hepatol. 2013;11(10):1276-1280.

This article originally appeared on Gastroenterology Advisor