Nicotine is a neuro-stimulant with high addiction potential [1]. Similar to other drugs causing dependence, nicotine increases dopamine levels in the nucleus accumbens and activates the mesolimbic brain reward pathway [2]. Nicotine metabolism rate varies significantly between individuals and is strongly correlated to total nicotine clearance thus altering nicotine levels from a given intake [3]. Smokers are known to titrate their nicotine levels via cigarette consumption, number and volume of puffs, and depth of inhalation, to achieve and maintain desired levels; thus, nicotine clearance rate influences smoking behavior [4]. Individuals with fast metabolism typically smoke more, are less likely to succeed in quitting, and are more prone to nicotine dependence (ND) [5]. Consequently, those who smoke more have a greater risk for smoking-induced diseases [6]. Beyond the evident toxic effects of tobacco smoke, there is increasing evidence that, in addition to the known acute effects of nicotine [7], chronic nicotine exposure as such may also increase the risk of cancer by multiple mechanisms [8]. With the advent of other nicotine delivery devices than tobacco, such as e-cigarettes, the need to understand the long-term consequences and action mechanisms of nicotine and its metabolism are of high public health relevance.
