Cannabidiol Toxicity Driven by Hydroxyquinone Formation

Oxidative byproducts of cannabidiol (CBD) are known to be cytotoxic. However, CBD susceptibility to oxidation and resulting toxicity dissolved in two common solvents, ethanol (EtOH) and dimethyl sulfoxide (DMSO), is seldom discussed. Furthermore, CBD products contain a wide range of concentrations, making it challenging to link general health risks associated with CBD cytotoxicity. Here, we report on the effect of CBD and CBD analogues dissolved in EtOH or DMSO at various concentrations. The cells used in these studies were human umbilical vascular endothelial cells (HUVECs). Our findings show significant CBD oxidation to cannabidiol-quinone (CBD-Q) and subsequent cytotoxicity, occurring at 10 μM concentration, regardless of the solution delivery vehicle. Moreover, a new analogue of CBD, cannabidiol-diacetate (CBD-DA), exhibits significantly more stability and reduced toxicity compared with CBD or CBD-Q, respectively. This knowledge is important for determining concentration-dependent health risks of complex cannabinoid mixtures and establishing legal limits.