Recent advances in the treatment of tobacco dependence

Tobacco dependence is the leading preventable cause of adult morbidity and mortality in the world. Despite the magnitude of this global public health problem, relatively few medications (i.e. nicotine replacement therapy and sustained-release bupropion) are currently approved for the treatment of this pandemic. Nicotine and other components in tobacco smoke are more likely to produce a dependence state in cigarette smokers than alcohol and cocaine in regular users of those drugs of abuse. As our understanding of the neurobiology of tobacco dependence increases, so, too, grows the number of potential therapeutic targets by which we can intervene in this devastating addiction. The purpose of this manuscript is to review three novel mechanisms of action that may serve as therapeutic targets for the pharmacologic treatment of tobacco dependence. For each of these therapeutic targets, we discuss medications in development that affect these pathophysiologic mechanisms. First, we examine the role of the endocannabinoid system (ECS) in the development of nicotine dependence and highlight the development of rimonabant, the first selective antagonist of the cannabinoid type 1 (CB-1) receptor. Second, we explore how heterogeneity among various subtypes of nicotinic receptors might be exploited to develop more specific agents acting at these receptors such as varenicline-a partial agonist at the alpha 4 beta 2 nicotinic receptor. Finally, we examine how selective inhibitors of monoamine oxidase (MAO) such as selegiline might be used as adjunctive medications for the treatment of tobacco dependence. Published by Elsevier B.V. on behalf of Association for Research in Nervous and Mental Disease.