Background: Cigarette smoking is the main cause of preventable death in developed
countries. While the direct positive behavioral reinforcing effect of nicotine has historically been
considered the primary mechanism driving the development of TUD, accumulating contemporary
research suggests that the cognitive-enhancing effects of nicotine may also significantly contribute
to the initiation and maintenance of TUD, especially in individuals with pre-existing cognitive
Methods: We provide a selective overview of recent advances in understanding nicotine’s effects on
cognitive function, a discussion of the role of cognitive function in vulnerability to TUD, followed
by an overview of the neurobiological mechanisms underlying the cognitive effects of nicotine.
Results: Preclinical models and human studies have demonstrated that nicotine has cognitiveenhancing
effects. Attention, working memory, fine motor skills and episodic memory functions are
particularly sensitive to nicotine's effects. Recent studies have demonstrated that the α4, β2, and α7
subunits of the nicotinic acetylcholine receptor (nAChR) participate in the cognitive-enhancing
effects of nicotine. Imaging studies have been instrumental in identifying brain regions where nicotine
is active, and research on the dynamics of large-scale networks after activation by, or withdrawal
from, nicotine hold promise for improved understanding of the complex actions of nicotine
on human cognition.
Conclusion: Because poor cognitive performance at baseline predicts relapse among smokers who
are attempting to quit smoking, studies examining the potential efficacy of cognitive-enhancement
as strategy for the treatment of TUD may lead to the development of more efficacious interventions.