Vaping products containing ?8-tetrahydrocannabinol (?8-THC), a largely unregulated isomer of the psychoactive component of marijuana ?9-THC, are sold throughout the U.S. and European Union. Despite the growing popularity of ?8-THC vaping products, very little is known about their respiratory health effects. We investigated whether vaping oxidizes ?8-THC to reactive electrophilic quinones, which can form covalent adducts with endogenous proteins and alter biological pathways in the respiratory epithelium. Vaped condensates were generated from ?8-THC commercial oil or juice and analyzed using liquid chromatography mass spectrometry (LC-MS). The potential for ?8-THC oxidation products to form adducts with proteins was assessed by trapping vaped ?8-THC oil with a model peptide followed by LC-MS analysis. Human bronchial epithelial cells (16HBEs) were exposed to ?8-THC or identified ?8-THC-derived oxidation products for 12 or 24 hours (n=3) and bulk RNA-sequencing was performed to identify altered pathways. Vaporization of the commercial ?8-THC oil generated high levels of both ?8-THC quinone (?8-THCQ) (5.9 nmol/mg) and CBD quinone (CBDQ) (13.2 nmol/mg). When vaped commercial ?8-THC oil was combined with the model peptide, we observed formation of ?8-THCQ and CBDQ cysteine adducts. RNA sequencing showed that at 12 hours 414 and 209 genes were altered and at 24 hours 2,360 and 108 genes were altered by ?8-THCQ and CBDQ respectively. Pathway analysis further revealed that ?8-THCQ and CBDQ may cause ciliary dysfunction, inflammation, and induce cellular stress pathways. Hence, vaping-induced oxidation of ?8-THC generates quinones that significantly alter the respiratory epithelium.