Nicotine Uptake as a Function of its Free-Base Dose

Principal Investigator: Cliff Watson / Elena Mishina

Funding Mechanism: Interagency Agreement

ID number: 224-10-9022

Award Date: 5/6/2011

Institution: Centers for Disease Control and Prevention

The public health community has long been concerned that smoking high free-base nicotine cigarettes results in higher amounts and rates of nicotine accumulation in the brain, which increases the addictive potential of cigarette smoking. However, this assertion is controversial, since a comparison of the amount of nicotine delivered to the human brain for high and low free-base nicotine cigarettes has never been conducted. The goal of this project is to determine whether the rates of nicotine absorption and nicotine distribution in the brain correlate with free-base nicotine concentrations in cigarettes. Investigators will examine nicotine uptake in 20 smokers by having them smoke high or low free-base nicotine cigarettes spiked with [11C]nicotine (a radiotraceable form of nicotine). Six smokers will have repeated positron emission tomography (PET) scans to image their brains under the same conditions to test for reproducibility; the remaining 14 will have two PET scans each after taking a puff from a high and a low free-base nicotine cigarette to compare the rate and amount of uptake of [11C]nicotine at high and low free-base nicotine levels. By elucidating the role of free-base nicotine in tobacco on nicotine delivery to the brain, this project may inform FDA regulatory activities related to product standards and application review.