CBDHIGHBIO · Strategies to modulate the bioavailability of cannabinoids in edible products: in vitro tests, cytotoxicity, and pre-clinical assessment to generate reliable data for regulatory agencies

Strategies to modulate the bioavailability of cannabinoids in edible products: in vitro tests, cytotoxicity, and pre-clinical assessment to generate reliable data for regulatory agencies

The cannabidiol (CBD) - an active compound found in Cannabis plants -has been gaining a lot of attention due to its potential terapeutic effects. However, despite ease-of-administration, the oral ingestion of CBD has low bioavailability. In pharmaceutics, bioavailability represents the portion of a drug that is actually able to have an active effect after being introduced into the body. The low CBD bioavailability is mainly attributed to two factors: i) it has a poor capacity of being solubilized in water, and ii) it is highly degraded in liver as a consequence of the hepatic metabolism. These factors combined gives to CBD a bioavailability of aproximately 12-20%. Moreover, the CBD absorption is patient-dependent, which makes hard the prediction of the effects of CBD after oral ingestion. The improvement of CBD bioavailability may minimize the variability of CBD absorption by the body providing substantial advantages in provinding predictable effects for the consumers. A promising approach to enhance the oral bioavailability of CBD is its incorporation into lipid-based delivery systems. Lipids can enhance the oral bioavailability of poorly water-soluble compounds, such as CBD, via the improvement in solubilization in the intestinal milieu. Another interesting approach to enhance the oral bioavailability of CBD involves its incorporation into formulations that contain substances able to inhibit the cannabinoids-metabolizing enzymes, thereby preventing the CBD to be degraded by the hepatic metabolism. The substances that present this ability of inhibiting the metabolizing enzymes in the liver are called bioenhancers. Thus, a strategy that combines the use of lipid-based formulations to improve the water solubility of CBD with the inhibition of the activity of enzymes responsible for the degradation of CBD in the liver can substantially increase the CBD bioavailability. In this sense, the main objectives of the CBDHIGHBIO project are to modulate the CBD bioavailability using lipid-based formulations combined with the addition of bioenhancers to inhibit the hepatic metabolism of CBD. We hypothesize that the combination between CBD and bioenhancers can substantially improve the CBD bioavailability. The increased bioavailability can decrease the patient-dependency of CBD absorption enabling the establishment of more accurate and predictable effects on consumers, at lower doses.

Data: CORDIS, © European Union