Endocannabinoids as a Treatment for Gut Infections?

For today, a SUPER interesting paper out of the University of Utah, about how endocannabinoids, signaling molecules of our bodies that “look like” chemicals found in marijuana, can help us fight gut infections.[i]  This would finally explain why cannabis (the plant from which marijuana is isolated) can lessen the symptoms of bowel diseases, including inflammatory bowel disease and irritable bowel syndrome.  Endocannabinoids are a fascinating area of research. They weren’t even discovered until 1992, and yet, they play a major role in functions from regulating immunity to mood to appetite.

Prior studies have shown that dysregulation of the natural endocannabinoid system of the body can lead to intestinal inflammation as well as affect the composition of the gut bacteria.  To study how endocannabinoids might affect pathogenic bacteria, the scientists used genetically altered mice that overproduce a particular cannabinoid (2-AG)  in various organs including the intestines.  They infected these animals, as well as normal controls, with Cibrobacter rodentium, which is a pathogenic bacteria that attacks the colon and causes inflammation and diarrhea.  The mutated rodents developed only mild symptoms, as opposed to the controls who became extremely sick.  The intestines of the mutated rodents also showed far less inflammation and infection, had lower fecal loads of C. rodentium, and cleared the infection way faster than the control animals.  To boot, when the control animals were given a drug that boosted levels of  2-AG, they had similar positive outcomes.

2-AG did not only work on alleviating infection with C. rodentium but also Salmonella typhimurium, and enterohemorrhagic E. coli, which is a particularly dangerous bacteria that also infects humans.

It gets even more interesting:  in vitro, when the researchers treated mammalian cells with tetrahydrolipstatin (which is an FDA approved drug that inhibits natural 2-AG production), the cells became more susceptible to infection.  It appears that 2-AG works by blocking a particular receptor on the pathogenic bacteria that is necessary to establish a virulent infection:  “Taken together, our findings establish that endocannabinoids are directly sensed by bacteria and can modulate bacterial function.”

We know that cannabinoids can lower inflammation but now,  it also appears that they work indirectly as well by affecting the microbiome as well as pathogens from establishing infection…which means, of course, that eventually we may end up using them as alternatives for antibiotics.  This would work not only in the intestines, but body wide.   Says the lead researcher, “By harnessing the power of natural compounds produced in the body and in plants…we may eventually treat infections in a whole new way.”[ii]

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[i] Melissa Ellermann et al. Endocannabinoids Inhibit the Induction of Virulence in Enteric Pathogens, Cell (2020). DOI: 10.1016/j.cell.2020.09.022

[ii] https://medicalxpress.com/news/2020-10-intestinal-infections-body-endocannabinoids.html

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