Vaping-induced Oxidation of CBD Causes Adduction of TOP2A and Interferes with Cellular Proliferation.

Abstract

Cannabidiol (CBD) vaping products pose a significant public health risk due to high cannabinoid concentrations, additives and contaminants, unsubstantiated claims of health benefits, and their implication in e-cigarette, or vaping, product use-associated lung injury (EVALI). However, research on the respiratory health effects of vaping CBD is limited. Here we show that the reactive electrophile CBD quinone (CBDQ) is present in significant quantities in commercial CBD vaping products. The effect of vaping on CBDQ concentration was variable across products, indicating that the additives and contaminants we detected in commercial products, including plasticizers, flavorings, and solvents, may play a role in catalyzing or inhibiting vaping-induced CBD oxidation. Using the UNC Vaping Product Exposure System (VaPES) and click chemistry methodologies, we demonstrate that, in human airway epithelial cells, CBDQ and commercial CBD liquids form covalent adducts with TOP2A, a key protein in DNA replication and cell division. CBDQ downregulated cell-cycle genes in an airway epithelial cell line, a finding that was replicated in differentiated human bronchial epithelial cells (HBECs) exposed to commercial CBD vaping products. In addition, CBDQ and vaped CBD products inhibited cell proliferation. We also show that CBDQ is ubiquitous in commercial CBD vaping products, may increase after vaping, and significantly alters the respiratory transcriptome, most notably inhibiting cell-cycle genes. Together these data suggest that CBD vaping products have significant effects on normal airway function and with chronic use could pose health risks including impaired wound healing and increased susceptibility to infections, diseases, and other environmental exposures.