Tetrahydrocannabinol (THC) may be able to prevent the development of colon cancers, say researchers from the University of South Carolina.
The researchers found that mice injected with both THC and carcinogens did not go on to develop any cancerous tumors in the colon, whereas a control group only given the carcinogens did.
The study, published in iScience, determined that THC was able to effectively suppress inflammation in the colon through activating the body’s CB2 endocannabinoid receptor, which in turn prevented the onset of cancers in this region.
The finding could have significant consequences for those with inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis.
THC suppresses tumor development in mice
In the study, mice were injected with either just a carcinogen designed to induce colon cancer or the carcinogen with an added 10 milligram per kilogram (mg/kg) dose of THC. By the end of the treatment period, the mice given the THC mixture had lost a significant amount of weight and experienced a significant decrease in spleen size.
However, none of the animals in the THC group went on to develop any colonic tumors. The overall severity of inflammation in the colon was also significantly lower in the animals given THC.
“The fact that we were able to show that treatment with THC prevents inflammation in the colon and at the same time inhibits the development of colon cancer supports the notion that inflammation and colon cancer are closely linked. Thus, in patients who are at a higher risk of developing colon cancer, THC or other anti-inflammatory agents may be beneficial,” Dr Prakash Nagarkatti, study author and the vice-president of research at USC, said in a statement.
After further investigation, the researchers determined that THC was able to alter the body’s inflammatory response through its agonism of the CB2 endocannabinoid receptor, a receptor that does not produce psychoactive effects. This particular interaction was able to prompt responses from the intestinal antigen-presenting cells (APCs) and T-regulatory cells (Tregs) which reduced inflammation in the colon.
“Our results showed that THC was acting through CB2 receptors, which is exciting and suggests that compounds that activate CB2 and cause no psychoactive effects may be beneficial to prevent IBD and colon cancer,” added Dr Mitzi Nagarkatti, fellow study author and chair of USC’s Department of Pathology, Microbiology and Immunology.
Crohn’s, ulcerative colitis, and cancer
With the rising incidence of inflammatory bowel disease (IBD) around the world, it would follow that there would be an equivalent increase in the numbers of people who are at risk of developing IBD-linked diseases, such as colon and rectal cancers.
As things stand, research has established a genetic component to the development of IBD, but the full mechanism behind the condition is still unknown.
This present study is not the first to investigate whether a cannabinoid might have a beneficial effect on IBD-related complications. A 2019 study published by researchers at the University of Nottingham, UK, found that another major cannabinoid, CBD, was effectively able to reduce the permeability of the human gastrointestinal tract and so reduce inflammation in the gut.
The randomized placebo-controlled, double-blind trial saw participants use aspirin to induce a state of temporary gut permeability. After examining the sugars present in the participants’ urine, the researchers found that a combination dose of CBD and the endocannabinoid-like molecule palmitoylethanolamide (PEA) was able to prevent inflammation-induced hyperpermeability in the subjects’ colons.
The gastrointestinal tract functions as a selectively permeable barrier, allowing water and nutrients from food to be absorbed into the body while rejecting harmful bacteria and lipopolysaccharides. Gut inflammation can disrupt this process and cause some of these harmful substances to cross the gastrointestinal barrier, which is thought to be another risk factor for developing IBD.
Reference: William Becker W, Alrafas HR, Wilson K, et al. Activation of cannabinoid receptor 2 prevents colitis-associated colon cancer through myeloid cell de-activation upstream of IL-22 production. iScience. 2020; doi:10.1016/j.isci.2020.101504