Human quad liver-on-chip system as a tool toward bridging the gap between animals and humans regarding toxicology and pharmacology of a cannabidiol-rich cannabis extract

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2024-08, p.1
• Main Authors: Ewing, Laura E, Skinner, Charles M, McGill, Mitchell R, Kennon-McGill, Stefanie, Clement, Kirsten, Quick, Charles M, Yee, Eric U, Williams, D Keith, Walker, Larry A, ElSohly, Mahmoud A, Gurley, Bill J, Koturbash, Igor
• Format: Article
• Language: English
• ISSN: 1525-6014; 1525-6014
• DOI: 10.1080/01480545.2024.2388292

Cannabidiol (CBD) is a major phytocannabinoid from . It is currently widely available and widely used in the USA, but despite its rapid progress to market, the pharmacology and toxicology of both CBD and cannabidiol-rich cannabis extracts (CRCE) remain largely unknown. The goals of this study were to investigate the potential of a novel human microphysiological system to emulate CRCE-induced hepatotoxicity and pharmacological properties demonstrated in animal models. For this purpose, C57BL6/J male mice were subjected to dosing with either 0, 61.5, 184.5, or 615 mg/kg of CRCE for 10 days. The liver-on-chip system, incorporating human primary hepatocytes, sinusoidal endothelial cells, as well as Kupffer and stellate cells was subjected to 0, 300, 1,200, or 4,400 ng/mL of CRCE (8 h exposure followed by 16 h washout) for 5 days. Administration of CRCE in mice resulted in nearly 4-fold elevations of plasma ALT at 615 mg/kg (