Manipulation of the Endocannabinoid System in Colitis

Abstract

Background Inflammatory bowel disease is a lifelong disease of the gastrointestinal tract whose annual incidence and prevalence is on the rise. Current immunosuppressive therapies available for treatment of inflammatory bowel disease offer limited benefits and lose effectiveness, exposing a significant need for the development of novel therapies. In the clinical setting, cannabis has been shown to provide patients with inflammatory bowel disease symptomatic relief, although the underlying mechanisms of their anti-inflammatory effects remains unclear. Methods This review reflects our current understanding of how targeting the endocannabinoid system, including cannabinoid receptors 1 and 2, endogenous cannabinoids anandamide and 2-arachidonoylglycerol, atypical cannabinoids, and degrading enzymes including fatty acid amide hydrolase and monoacylglycerol lipase, impacts murine colitis. In addition, the impact of cannabinoids on the human immune system is summarized. Results Cannabinoid receptors 1 and 2, endogenous cannabinoids, and atypical cannabinoids are upregulated in inflammation, and their presence and stimulation attenuates murine colitis, while cannabinoid receptor antagonism and cannabinoid receptor deficient models reverse these anti-inflammatory effects. In addition, inhibition of endocannabinoid degradation via monoacylglycerol lipase and fatty acid amide hydrolase blockade can also attenuate colitis development, and is closely linked to cannabinoid receptor expression. Conclusions While manipulation of the endocannabinoid system in murine colitis has proven to be largely beneficial in attenuating inflammation, there is a paucity of human study data. Further research is essential to clearly elucidate the specific mechanisms driving this anti-inflammatory effect for the development of therapeutics to target inflammatory disease such as inflammatory bowel disease.

The potential of metabolic and lipid profiling in inflammatory bowel diseases: a pilot study

“…Fatty acid amides seem to have a role in differentiating UC from colonic CD. These molecules play a role in inflammation, intracellular signaling, pain, immune function, reproduction, and appetite [27] and appear to attenuate colitis [28].…”

Cannabidiol: A budding industry!

“…), inflammatory bowel diseases (Leinwand et al . ), type 2 diabetes (Gruden et al . ) and cardiovascular diseases (Pacher et al .…”

“…While CB 1 receptors are most highly expressed in the central and peripheral nervous system and are primarily responsible for the psychoactive effects of THC, CB 2 receptors are mainly found on immune cells, although also in the brain, and their activation is associated with immunomodulatory effects (Cabral et al 2015). Since its initial discovery, the endocannabinoid system has been studied for its potential involvement in a wide range of pathophysiological processes linked to conditions such as cancer (Fraguas-S anchez et al 2018), inflammatory bowel diseases (Leinwand et al 2017), type 2 diabetes (Gruden et al 2016) and cardiovascular diseases (Pacher et al 2017).…”

Cannabis, a potential treatment option in pediatric IBD? Still a long way to go

“…Furthermore, inhibition of the metabolizing enzymes (FAAH, MAGL) ensures ongoing activity of the endocannabinoids ligands (AEA and 2-AG) and CB receptors [15]. Activation of CB2 receptors causes suppression of inflammation, resulting in improvement of mucosal healing in murine colitis models [15][16][17]. So, potentially the endocannabinoid system is a target for new therapies in IBD.…”