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Study: THC May Prevent Colon Cancer by Reducing Inflammation

October 8, 2020 in General News

A new paper based on research studies conducted by the Nagarkatti team at the University of South Carolina School of Medicine shows that the use of THC to treat inflammation may prevent the development of colon cancers in mice. In this article I will discuss the role that inflammation plays in so many diseases and conditions and will cite the Nagarkatti study.

As researchers gain more and more understanding of the causes of many diseases and disorders, the connection between unrestrained inflammation and disease has been made over and over again. This is abundantly clear for diseases of the gastrointestinal tract such as inflammatory bowel diseases (IBD), Chrohn’s disease and ulcerative colitis. The suppression of the inflammation in the colon seems to prevent the onset of cancers caused by carcinogens. THC has been shown to suppress inflammation in the gastrointestinal tract and may be an effective treatment option to prevent colorectal cancers in humans.

There is an alarming global increase in the incidence of IBD. It is now known that those with IBD have a greater risk of developing colorectal cancer. Clearly, if there are more cases of IBD, this will result in more cases of cancer. Researchers are noticing an unexplained and alarming increase in the rate of colon and rectal cancers in young and middle-aged adults in the US. In order to stop this increase, it is important to first understand what causes IBD and then to develop an effective treatment option.

For over 20 years, the Nagarkatti team has been studying the use of cannabinoids as a treatment option for inflammatory diseases. They just published a paper based on some of their findings.

The Nagarkatti Paper

The paper, Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer Through Myeloid Cell Deactivation Upstream of IL-22 Production, was published in IScience on August 27, 2020. It is based on research studies conducted at the University of South Carolina School of Medicine Columbia laboratories of the husband and wife team of cannabis researchers, Drs. Prakash and Mitzi Nagarkatti. It includes the Departments of Pathology, Microbiology and Immunology. Here is a link to a previous article I wrote about their cannabis researcher work.

Causes of IBD and Colitis

Researchers are not clear about the causes of IBD and colitis, but they are confident that there is a genetic component to its development. They also believe that environmental and microbial factors and each individual’s immune response to them play a role.

Major IBD Susceptibility Genes

NOD2, STAT3 and IL-23 are all known to be heavily involved in immune processes. In addition, (interleukin) IL-23, IL-17 and IL-22 are present in increased levels in the serum and intestines of those with IBD. While IL-17 and IL-23 have well-defined roles as pro-inflammatories in IBD, the role of IL-22 is not as clear cut. IL-22 is both anti-inflammatory and pathogenic.

Anti-Inflammatory

  • Regulates barrier surface
  • Increases epithelial and mucosal defenses
  • Releases anti-microbial peptides
  • Protects enterocyte stem cells
  • Clears Citrobacter rodentium infection

Pathogenic

  • Causes colorectal cancer by increasing epithelial cell STAT3 expression

Methodology
A well-established model of carcinogens, 10mg/kg of azoxymethane (AOM) injected intraperitoneally, followed by three cycles of the inflammatory agent dextran sodium sulphate (DSS), was used to induce colitis-associated colon cancer in mice. The mice were administered a single injection of AOM, followed 1 week later by the first of twice weekly 10mg/kg injections of THC or the control VEH given concurrently with the first cycle of 2 % DSS in their drinking water. Each weeklong cycle of DSS was followed by 2 weeks of unadulterated drinking water. This protocol was followed for three cycles which lasted nine weeks. All treatments were suspended after the third DSS cycle to assess the effects of THC on the initiation of cancer, but not on the possible direct effects of THC on tumors. The control mice were treated twice weekly, but received no disease carcinogens.

Results
1. Mice given DSS and AOM treated with THC lost less weight compared to the group that received VEH.
2. The THC group showed no tumor development while those in the VEH group developed tumors.
3. THC group exhibited a decrease in spleen size while the VEH group showed an increase in spleen size.
4. Colonoscopies with staining of the colon showed a reduction in the severity of inflammation and tumor stimulation in the THC group when compared to the VEH group.
5. The increase in the IL-22 seen in the colon of the VEH group was a result of cells in the intestinal epithelial cells (IEC). The THC group showed a decrease in IL-22-producing IECs.

Conclusion
The development of inflammatory colon diseases is the result of an imbalance of immune cells, bacteria and protective gut barriers. The way they interact can either promote or protect an individual from developing these disorders. Several studies suggest that cannabinoids have the potential to act as a protection.

Dr. Nagarkatti reiterated that these studies demonstrated the link between inflammation and colon cancer. THC prevents inflammation which inhibits the development of colon cancer. He believes that for patients who are high risk for colon cancer, THC or other anti-inflammatories may be beneficial. Furthermore, the results showed that THC acts through CB2 receptors which causes no psychoactive effects. However, the study author was careful to note that the results on mouse models does not necessarily translate to human models.

medicalxpress.com, Study Reveals How Cannabinoids May Be Useful To Prevent Colon Cancer, University of South Carolina, Sept. 15, 2020
IScience, Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer Through Myeloid Cell Deactivation Upstream of IL-22 Production, Sept. 25, 2020

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