CiiTECHLabs Most Recent Research
Why: According to the American Liver Foundation At least 25% of the US population has NAFLD (Non-Alcoholic Fatty Liver Disease). If left untreated, NAFLD can lead to liver damage, scarring, and cirrhosis. Patients with NAFLD are at a much higher risk of developing much more serious conditions including diabetes, high blood pressure and kidney disease.
Testing the Therapeutic Effect of Phytocannabinoids for Nonalcoholic Fatty Liver Disease (NAFLD)
Recent findings have revealed a significant role of the endocannabinoid (eCB) system in the pathogenesis of NAFLD via the regulation of both CB1 and CB2 receptors.
eCBs are endogenous lipid ligands that interact with the same cannabinoid receptors, which also recognize Δ9-tetrahydrocannabinol (THC), the psychoactive component of marijuana and mediate its biological effects. By activating CB1 receptors, eCBs increase appetite (the ‘munchies’) and lipogenesis in adipose tissue and liver and induce insulin resistance and dyslipidemia. These effects suggest that an overactive eCB/CB1 receptor system contributes to the development of visceral obesity, T2DM and their complications.
While CB1 receptors are present at very high levels in the brain, they are also present at much lower, yet functionally relevant, levels in many peripheral tissues, including the liver. In fact, obesity-induced hepatic steatosis depends on the activation of peripheral, including hepatic CB1 receptors. Briefly, the hepatic rate of de novo lipogenesis and related gene expression are increased by CB1 agonists and decreased by either globally acting or peripherally restricted CB1 antagonists in rodents.
The previous research project aimed to explore the therapeutic potential of CBD combined with our Proprietary Cannabinoid Formulation (PCF) in reversing the accumulation of fat in hepatocytes, and determine the downstream molecular pathway(s) involved in this phenomenon. Our working hypothesis was that phytocannabinoids (alone or in combination) could mitigate hepatic de novo lipogenesis or increase hepatic fatty acid β-oxidation to prevent the development of NAFLD. To that end, we carried out several experimental paradigms in which we tested whether PCF has the ability to reduce lipid accumulation in hepatocytes. We also tried to decipher the signaling pathway by which phytocannabinoids demonstrate their antisteatotic effect.
Our findings showed that CBD in a concentration of 20 µM was able to significantly reduce lipid accumulation in hepatocytes, whereas CBD combined with PCF was not as effective as CBD in any dose tested. Nevertheless, the combined effect of both CBD and PCF seemed to have a synergistic effect, as both compounds (in concentrations of 20 + 50 µM, respectively; and 20 + 20 µM, respectively) were able to significantly prevent the accumulation of lipids in hepatocytes.
Furthermore, our findings demonstrated that a mixture of CBD (20 µM) and PCF (50 µM) was able to change the expression profile of many genes and transcription factors involved in de novo fatty acid synthesis (lipogenesis); and mitochondrial fatty acid β‐oxidation.
Through our past and current clinical studies we have secured a provisional patent for the breakthrough technology of a unique cannabinoid formulation to potentially treat Obesity, Diabetes and their causes in NAFLD.
We have identified the cell genes that influence the uptake of fat. Our technology is able to direct that influence.