Effect of cannabidiol and hemp extract on viability and function of hepatocytes derived from human induced pluripotent stem cells

Since the passage of the 2018 Agriculture Improvement Act (2018 Farm Bill), the number of products containing cannabis-derived compounds available to consumers have rapidly increased. Potential effects on liver function as a result from consumption of products containing cannabidiol (CBD), including hemp extracts, have been observed but the mechanisms for the effects are not fully understood. In this study, hepatocytes derived from human induced pluripotent stem cells (iPSCs) were used to evaluate potential hepatic effects of CBD and hemp extract at exposure concentrations ranging from 0.1 to 30 μM. Despite that a significant reduction in cell viability occurred only in the 30 μM group for both CBD and hemp extract, significant changes to cytochrome P450 activity, mitochondrial membrane potential, and lipid accumulation occurred within the concentration range of 0.1-3 μM for both CBD and hemp extract. Albumin and urea production, caspase 3/7 activity, and intracellular glutathione were significantly affected within the concentration range of 3-30 μM by CBD or hemp extract. These findings indicate that CBD and hemp extract can alter hepatic function and metabolism. The current study contributes data to help inform the evaluation of potential hepatotoxic effects of products containing cannabis-derived compounds.