Principal investigator: Dorothy Hatsukami, Ph.D.

Study 1: Comparisons of different rates of smoking reduction
This study will compare the effects of reducing cigarettes by 50%, 75% or 100% of baseline smoking using behavioral treatment. Subjects will reduce by the required amount for 6 weeks after which they will be asked to become or remain abstinent for 6 weeks. The primary outcome measures involve assessing changes in biomarker measures based on extent of reduction and the degree to which compensatory smoking occurs, which would contribute to toxin uptake.

Study 2: Comparisons of nicotine-free, extra low nicotine vs medicinal nicotine
In this study, smokers are randomly assigned to one of three conditions for six weeks: 1) nicotine-free cigarettes (0.05mg); 2) extra low nicotine cigarettes (0.3 mg); or 3) medicinal 4 mg nicotine lozenge. The tobacco toxin profiles across these various products will be compared. The effects of these products on biomarkers of exposure and risk factors for disease, compensatory smoking, components of tobacco addiction and short-term smoking cessation will be determined. Predictors of response to these products (e.g., compensatory smoking, compliance with product use, time to lapse) are examined.

Study 3: Nicotine antagonist treatment to reduce tobacco toxin exposure
The goal of this study is to compare the effects of nicotine vaccine vs. placebo vaccine on cigarette smoking. The primary outcome variables are the extent to which biomarker measures for tobacco toxin exposure change in each group. Other outcomes assessed will include determining the effects of the nicotine vaccine on compensatory smoking, measurements of different aspects of addiction, and time to lapse. Predictors of treatment response will be assessed. This study will further examine the role of nicotine in sustaining smoking behavior and examine predictors of individual differences in response to manipulations of nicotine dose.

Study 4: Nicotine antgonist treatment to reduce tobacco toxin exposure
The goal of this study is to further explore individual differences in smokers’ ability to reduce cigarette smoking when administered high dose nicotine and to determine if among non-responders, adding treatments that target other aspects of smoking may be effective in reducing cigarette smoking. Smokers will be assigned to 45 mg (3 16-hr 15 mg patch) of nicotine patch for a period of two weeks to identify smokers unable to reduce their smoking by at least 75% despite the use of high-dose nicotine replacement therapy. These individuals, who are considered to be unresponsive to nicotine replacement, will then be randomly assigned to 45 mg patch plus nicotine-free cigarettes or to 45 mg patch plus an inert oral substitute for a period of 4 weeks. Responders to high dose nicotine will be asked to continue with the high doses of nicotine for 4 more weeks. The goals of these treatments would be to reduce smoking by at least 75%. All subjects will then be required to undergo abstinence. During this abstinence phase, withdrawal symptoms and time to lapse will be examined. Predictors of successful reduction, compensatory smoking, and time to lapse will be analyzed. This study is important to determine which smokers are recalcitrant to high doses of nicotine and whether the addition of treatments mimicking the sensory aspects of smoking leads to successful reduction and ultimately cessation in this population.