Introduction

Nicotine administered by smoking and by transdermal patches has been shown to improve attention in dependent smokers, nondependent smokers, and nonsmokers significantly. Attentional improvements are also seen in patients with attention deficits including those with Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine delivered via means such as nicotine skin patches and novel nicotinic agonists holds promise for providing therapeutic treatment for attentional deficits.

Nicotine transdermal patches were originally developed by Rose and associates36-39 to help with smoking cessation. In fact, nicotine transdermal patches have proven to be useful in helping people to quit smoking1 14-16,21,2737,48 and they have become one of the standard treatments for smoking cessation in clinical practice. These patches may be useful for other types of therapeutic treatment as well. As reviewed in other chapters of this book, nicotine treatment shows promise for therapeutic treatment for Alzheimer's disease, schizophrenia, and Tourette's syndrome. The use of nicotine transdermal patches is clearly superior to nicotine from tobacco because the lack the variety of carcinogenic compounds and other toxins found in tobacco smoke. Also, the abuse liability of nicotine transdermal patches appears to be low because they deliver nicotine in a slow chronic fashion.32 Novel nicotinic ligands under development in a number of pharmaceutical companies and academic labs may further reduce the adverse effects of nicotinic therapy.

Nicotine has been reported by cigarette smokers to improve attentiveness;2947 however, since smoking withdrawal causes cognitive impairment,18 there is concern about the degree to which nicotine-induced attentional improvements may merely be an attenuation of a nicotine-withdrawal induced attentional impairment. Importantly, this issue has been resolved: nicotine has been found to improve attentiveness in nondeprived smokers.45 It has been shown that nicotine transdermal patches significantly improve choice accuracy and reduce response speed variability in normal nonsmoking subjects.23 This provides confirmation that nicotine has atten-tional improving effects apart from alleviation of nicotine withdrawal symptoms.

Nicotinic treatment may be useful for treatment of ADHD. As described later, acute and chronic studies to determine the effect of nicotine transdermal treatment in adults with ADHD have been concluded. In addition, Wilens and co-workers have determined the effect of the nicotinic agonist ABT-418 in the same population.49

The possibility of nicotinic treatment for ADHD arises from three lines of evidence: (1) attentional improving effects in smokers and nonsmokers administered nicotine; (2) the effect of nicotine stimulating the release of dopamine,50 — a primary mechanism of action of stimulants, such as methylphenidate and amphetamine, currently used to treat ADHD;20 and (3) the increased smoking in adults with ADHD — about twice the societal background rate.33 These adults with ADHD may be self-medicating with nicotine to attenuate their symptoms of ADHD. Nicotine or other nicotinic ligands may provide a promising new avenue for the treatment of ADHD, as suggested by acute and chronic studies of nicotine skin patch treatment in adults with this disorder.725 26

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