Is the potential for bioaccumulation of cannabinoids underestimated? Insights from biomimetic chromatography in cannabinoid exposure evaluation

The use of cannabis-related products is currently experiencing extraordinary growth in popularity in the European and US markets. A wide variety of cannabis-related products have emerged, including oils, tinctures, edibles, topicals, cosmetics, and even beverages and sweets, offering the purported medical benefits without the psychoactive effects associated with Cannabis sativa. However, there is a significant gap in our understanding of bioaccumulation processes and their long-term effects, particularly as cannabinoids are highly lipophilic molecules. In this study, we used a biochromatographic approach to experimentally determine the lipophilicity, binding to phospholipids and affinity to plasma protein of selected cannabinoids to comprehensively assess their bioaccumulation potential. The results obtained clearly indicated that cannabinoids, including the particularly popular cannabidiol, promote bioaccumulation. Importantly, a higher affinity for phospholipids indicated non-specific binding, which can lead to phospholipidosis. Cannabinoids exhibit a stronger binding affinity to human serum albumin (HSA) compared to diclofenac, which might affect the pharmacokinetics of regularly taken medications when co-administered.