The endocannabinoid system’s crucial role in liver health

The liver’s intricate connection with the endocannabinoid system

The liver, a central organ in our metabolism, plays a pivotal role in converting nutrients into usable forms and detoxifying the body. Its resilience and robustness are unparalleled, given its primary function of detoxification. However, even this formidable organ has its limits and can succumb to diseases.

Recent revelations about the endocannabinoid system's role in the liver have shed light on its importance in maintaining liver health and potential therapeutic applications.

The liver's own endocannabinoid system

The significance of the endocannabinoid system in various liver processes is so profound that it's often referred to as a distinct cannabinoid system, termed the hepatic cannabinoid system. Both CB1 and CB2 receptors are present on all types of liver cells.

The intracellular processes steered by these cannabinoid receptors are primarily controlled by the endocannabinoids Anandamide and 2-AG (2-Arachinodylglycerol). Research on tissue samples has shown that during acute or chronic liver damage, there's a noticeable increase in the concentration of these cannabinoids in the liver tissue.

Endocannabinoids: The regulators of liver processes

Endocannabinoids, acting through cannabinoid receptors, seem to be vital for liver regeneration. These receptors can be visualised as regulators that control various metabolic processes in the liver.

The endocannabinoids Anandamide and 2-AG act as operators, fine-tuning these regulators. A well-coordinated regulation of these processes ensures smooth liver function and regeneration. Conversely, an imbalance in this system can lead to severe liver diseases.

Fatty liver and the overactive CB1 receptor

Fatty liver, often resulting from excessive alcohol consumption, can also manifest in individuals who consume alcohol in non-problematic quantities, termed non-alcoholic fatty liver. Research on human liver cell cultures and observations in mice have confirmed the central role of the CB1 receptor in the onset of this condition.

Elevated synthesis of Anandamide, a CB1 agonist, in affected liver cells leads to an overactive CB1 receptor, which seems to favour the development of a fatty liver. Experimental counter-tests using CB1 antagonists like Rimonabant and the synthetic cannabinoid AM251 have shown promising results in reversing this process.

CB2 receptor: The guardian against inflammation

As known from other bodily systems, inflammatory processes in the liver are also regulated by the CB2 receptor. Chronic inflammations can lead to liver cirrhosis, fibrosis, and even liver cancer. CB2 agonists, such as JWH-015, have shown potential in inhibiting the growth of liver cancer cells and slowing or halting the progression of fibrosis or cirrhosis.

Furthermore, the endocannabinoid 2-AG, acting as an agonist on the CB2 receptor, reduces oxidative and nitrosative stress in liver cells and stimulates the production of new liver cells through interaction with the cytokine Interleukin-6.

Cannabinoids: Pioneering new treatment approaches

The insights gained from understanding the endocannabinoid system's role in the liver suggest that cannabinoids could offer novel treatment options for severe liver diseases in the future.

A study conducted in 2008 on 315 patients with chronic Hepatitis C revealed a pronounced overactivity of the CB1 receptor. Although Hepatitis C is a viral infection, this research suggests that the severity and associated liver damage could be significantly reduced by administering a CB1 antagonist to the patient.

While a Phase 3 study using the CB1 antagonist Rimonabant had to be discontinued due to side effects, numerous other potential cannabinoids could be used for this purpose, which are largely non-toxic and act very selectively. It's anticipated that cannabinoids will play an increasingly significant role in treating liver diseases in the coming years.