In summary, although nicotine is likely the principal bioactive agent that underlies the addictive properties of tobacco smoke [19,151–154], the reviewed literature suggests that the majority of adverse neurobiological and neurocognitive effects of chronic cigarette smoking are a function of the direct and indirect consequences of continual exposure of the cardiopulmonary system, cerebrovascular system and brain parenchyma to the combination of non-nicotine combustion products contained in cigarette smoke [13,14,155]. However, a significant amount of data regarding potential mechanisms contributing to the neurobiological and neurocognitive abnormalities observed in humans is derived from in vitro and animal studies. Consequently, it is unclear if all potential mechanisms are generalizable to humans.
