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General Background

Native Americans discovered the use of the tobacco plant, Nicotiana tabacum, during antiquity. By the time Columbus arrived in America, tobacco use was widespread throughout the Western Hemisphere and was well integrated into Native American cultures. Production of tobacco and its trade represented a major economic activity in the pre-Columbian Americas. Early European explorers learned of the tobacco plant from Native Americans, and by the mid-17th century tobacco was widely used in Europe.

The most important, but not the only, active psychopharmaceutical drug contained in the leaves of the tobacco plant is nicotine.1,2 Nicotine is a major metabolic product of the tobacco plant, and it is likely that it evolved as a protection against insect predators, as nicotine is a potent insect neurotoxin.3 Interestingly, nicotine has been exploited in this regard as a commercial insecticide. Nicotine, however, is the major addicting substance in tobacco, although the addiction to tobacco is more complex than addiction to nicotine alone. Other psychoactive compounds are also present in tobacco smoke, including monoamine oxidase inhibitors.4 These may have either direct effects or interact with other psychoactive drugs.1,2 In addition, conditioned behavior and social interactions are important drivers of smoking.58

Nicotine is a potent euphoriant. On a molar basis, nicotine is more active than such euphoria-inducing drugs as cocaine, amphetamine, or morphine.9 Nicotine elicits complex effects on the central nervous system (CNS), which are discussed in more detail below. Many of these effects, however, are perceived as desirable, accounting for the popularity of smoking. For example, nicotine ameliorates anxiety, reduces perception of pain,10 mitigates symptoms of depression,11 and induces a sense of well-being9 while causing a state of arousal.12 In contrast to many euphoriants that impair cognition, nicotine can improve task performance and attention time by measurable degrees in nonhabituated individuals and may have beneficial effects on cognition.12

Despite its perceived benefits, smoking of tobacco has long been controversial. King James of England wrote in 1604 “[Smoking is] a custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous to the lungs, and in the black stinking fume thereof, nearest resembling the horrible Stygian smoke of the pit that is bottomless.13” The Surgeon General's Report of 1964 outlined the convincing evidence for the health consequences of smoking.14 Since that time there has been a gradual increase in efforts to control tobacco use and the associated health consequences. Changes in social attitude, public health efforts, and both pharmacologic and nonpharmacologic approaches have been developed that have meaningful benefits. The current chapter will focus on treatment designed to help a smoker achieve abstinence.

Nicotine Addiction

Nicotine exerts its biologic effects on “nicotinic” receptors, a subset of cholinergic receptors, whose endogenous ligand is acetylcholine.15,16 Nicotinic receptors ...

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