Treatment of nicotine addiction: present therapeutic options and pipeline developments

Abstract

Tobacco use is a global pandemic that poses a substantial and costly health burden. There are some treatment options are available, but currently marketed smoking-cessation drugs lack high levels of efficacy, particularly in real-life settings. Consequently, there is a compelling need for more effective pharmacotherapies to aid smokers in maintaining long-term abstinence. Advances in the understanding of the mechanisms involved in nicotine dependence have recently been translated into new medications and vaccines that interfere with nicotine signaling, many of which are currently at an advanced stage of development. In the present article we review current and emerging pharmacotherapies for tobacco dependence, focusing on the mechanistic rationale for their potential anti-addiction efficacy, major findings in preclinical and clinical studies, and future research directions.

Figure 1

Simplified model of the nicotine—acetylcholine—glutamate—GABA—dopamine neural circuitry promoting nicotine reward, dependence and withdrawal, and the related mechanism-based pharmacological rationale for the treatment of nicotine dependence. Nicotine from cigarette smoke reaches the midbrain and binds to α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) located on dopaminergic (blue), glutamatergic excitatory (red) and GABAergic inhibitory (green) neurons in the ventral tegmental area (VTA). This modulates the release of dopamine (DA) in the nucleus accumbens (NAc), which mediates the rewarding and addictive effects of nicotine. Based on this model, different pharmacological strategies have been proposed and studied for their potential use in the treatment of nicotine dependence.