Nicotine clinical trials at University of California Health

Electronic nicotine delivery systems (ENDS) are a new rapidly growing global epidemic. More recently, electronic (e-) hookahs, have increased in popularity in the United States, with the greatest uptake by young female adults, who endorse marketing claims that these products are safer alternatives to traditional flavored hookah tobacco smoking. Unlike other ENDS such as e-cigarettes, e-hookah bowls are used through traditional water-pipes, allowing the vapor-containing nicotine, propylene glycol, glycerin, and flavorings-to pass through a water-filled basin, potentially altering the vapor, before it is inhaled through the user's mouth. Contributing to e-hookah bowls' popularity is the belief that the flavored smoke is detoxified as it passes through the water-filled basin, rendering e-hookah a safer tobacco alternative. However, an e-hookah bowl delivers flavored nicotine by creating a vapor of fine particles and volatile organic compounds that could induce vascular toxicity. The objective of this project is to investigate the effects of e-hookah bowl inhalation on endothelial function, vascular biomarkers and volatile compounds; and molecular mechanisms underlying e-hookah induced endothelial injury using freshly harvested human endothelial cells with a specific role of nicotine. In a cross-over study design, the investigators will first assess endothelial function measured by brachial artery flow-mediated dilation and markers of oxidative stress and inflammation in 18 young healthy hookah smokers 21-39 years old, before and after two separate 30-minute e-hookah bowl inhalation sessions using one brand of nicotine-containing and nicotine-free e-hookah liquid and, for control comparison, before and after sham hookah smoking. Then, in freshly harvested venous endothelial cells the investigators will assess nitric oxide bioavailability, and expression of markers of inflammation and oxidative stress before and after the sessions. To compare specific exposures across conditions, the research team will measure changes in plasma nicotine, and highly specific urinary mercapturic acid metabolites of acrolein and benzene. This proposed study will provide critical scientific data on the impact of e-hookah inhalation on vascular health and mechanisms of exposure on known cardiac risk factors. Results will provide critical data to the FDA to inform the development of regulations specific to hookah.