Effects of high dose transdermal nicotine replacement in cigarette smokers

Rationale: Nicotine replacement therapies (NRT) have been evaluated to facilitate cigarette smoking reduction in smokers unwilling or unable to quit. In most of these studies, only conventional doses of NRT have been tested and higher doses may be required to result in significant reductions in smoking and in biomarkers of exposure. Objective: To determine if higher NRT doses in conjunction with smoking are safe and may promote significant reductions in cigarette smoking and biomarkers of exposure. Methods: A dose-ranging, within-subject design was implemented to evaluate the effects of 15, 30 and 45 mg nicotine-patch treatment on measures of safety and the extent of smoking reduction and biomarker exposure per cigarette in smokers (N = 20 completers) not immediately interested in quitting. Results: Concurrent smoking and NRT were generally tolerated and resulted in no changes in blood pressure or heart rate. Slightly less than 10% of the study sample was not given the highest dose of NRT due to side effects. Self-reported cigarette smoking decreased with increasing doses of nicotine replacement and significant reductions were observed for total NNAL (a carcinogen biomarker) and carbon monoxide. However, even at the 45 mg dose, increased carbon monoxide and total NNAL per cigarette occurred, even though cotinine levels increased on average, 69.3% from baseline. Conclusions: The present results suggest that the use of high dose NRT is safe, leads to significant reductions in smoking (- 49%), significant but less reductions in total NNAL (- 24%) and carbon monoxide (- 37%) due to compensatory smoking.