Abstract

Nicotine replacement therapy is believed to facilitate smoking cessation both by relieving withdrawal symptoms and by reducing the psychological reward from smoking. The latter might occur via down-regulation of nicotine receptors in the brain, which might require high levels of nicotine exposure. Our study examined the hypothesis that transdermal nicotine, dosed up to three times the doses currently recommended for smoking cessation, would suppress nicotine intake from ad libitum smoking in a dose-dependent manner. Eleven volunteers with no desire to quit smoking received placebo or 21, 42, and 63 mg/day transdermal nicotine, with and without cigarette smoking, in a blinded crossover study. Cigarette smoking was permitted as desired. Transdermal nicotine suppressed nicotine intake from cigarette smoking by 3%, 10% and 40% on average in the 21, 42 and 63 mg/day conditions. The number of cigarettes smoked per day declined from an average of 17.2 to 12.7 and the intake of nicotine per cigarette declined from 2.5 to 1.6 mg, comparing placebo and 63 mg nicotine conditions. Our study results suggest that high-dose transdermal nicotine has the potential to substantially suppress the intake of tobacco smoke and could be a useful strategy for smoking cessation therapy or for reducing the harm caused by smoking.