Autoimmune hepatitis is a rare but usually fatal disease in which the immune system mistakenly targets the liver and destroys it over time. The cannabinoid receptors CB1 and CB2 are both present in the liver, being activated when it is damaged. This has led scientists to investigate whether the endocannabinoid system, the system of receptors, ligands (the things that bind to receptors) and enzymes that involve cannabinoids, can be exploited to treat autoimmune hepatitis.
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Cannabinoids are important suppressors and modulators of the immune system, exerting anti-inflammatory effects and suppressing the immune response when activated. Although the abuse of cannabis via the CB1 receptor has been linked to liver damage in patients with hepatitis C, the CB2 receptor is thought to play a “protective role during liver diseases”.
This paper summarizes the extent of current knowledge of the endocannabinoid system and the ways that autoimmune hepatitis might be combated via this system.
When the body is infected or detects something in it that it does not want, it triggers an immune response. This is usually very effective but when it goes wrong and starts targeting healthy body tissue as in autoimmune hepatitis, the complications can be severe, even fatal.
The endocannabinoid system, and more specifically the CB2 receptor, is very important in immune responses. Through a complex series of interactions, activating the CB2 receptor on immune T-cells can cause them to apoptose (pop and die), migrate elsewhere, change their mode of attack, and/or reduce their effectiveness.
Other processes like inflammation are controlled in a similar way. Because of this regulatory role the endocannabinoid system plays, it is a good target for autoimmune conditions.
The endocannabinoid system responds to cannabinoids like THC and CBD. By ingesting cannabinoids, a patient can change how their immune system is functioning. Exogenous cannabinoids (from outside the body) from the cannabis plant usually reduce inflammation and the immune response. When the authors looked at the available data, they found that the endocannabinoid system is very much a part of autoimmune hepatitis.
Usually, CB1 and CB2 receptors are rarely expressed in adult livers. However, they are upregulated significantly in response to liver damage and a variety of liver diseases. It looks like CB1 and CB2 receptors are both very important in regulating the immune response and by targeting them with cannabinoids, the damage done to the liver by the dysfunctional immune system can potentially be limited or eliminated.
At this time, there is not enough known about the endocannabinoid system in hepatitis for it to be a viable target for cannabinoid therapy. There are serious concerns about CB1 receptor activation causing fibrosis of the liver. The animal models used in these studies are not very representative because rodent livers and human livers have different levels of cannabinoid receptors.
Better models need to be explored and exactly which cannabinoids would be most beneficial properly established. The endocannabinoid system is a promising avenue for treating autoimmune hepatitis, which is a usually fatal disease. However, the lack of solid data or good human models of the endocannabinoid system in hepatitis limits the current therapeutic applications of cannabinoids for hepatitis.