Recent Cochrane reviews of controlled trials that studied nicotine replacement therapies, bupropion and nortriptyline, existing drug treatment of tobacco addiction, showed that their use increases the odds of quitting smoking approximately 1.5- to 2-fold regardless of the setting. However, this level of efficacy is substantially lower than that seen in other disease conditions. Optimization strategies are being studied to improve their efficacy.

Newer, emerging pharmacological therapies that show promise in the area of smoking cessation are the a4ß2 nicotinic acetylcholine (Ach) receptor (NAchR) agonists. Varenicline, the first drug of this new class, obtained the marketing authorization in summer 2006 in the USA. Varenicline is a partial agonist of the a4ß2 subtype of the NAchR. Varenicline has high affinity for the a4ß2 NAch and has low affinity for glutamatergic, histaminergic, adrenergic, muscarinic, or cholinergic receptors. The phase III studies of varenicline compared to bupropion and placebo has recently been published. Compared to bupropion (28 %) or placebo (18 %), abstinence rates with varenicline are between 40 to 45 %. A maintenance study showed that varenicline helps maintain abstinence if administered for one year. The adverse effect profile of varenicline includes nausea (25 to 30 % during the first weeks) and vivid dreams (a known adverse effect of nicotine replacement therapies). According to the FDA labeling varenicline has no contraindication. However, because the drug's elimination is almost exclusively renal, doses should be adjusted in severe renal failure. Other a4ß2 NAchR partial agonists are being developed and will probably be marketed in the next few years.

Nicotine vaccines are currently being researched as a smoking-cessation therapy. These are conjugated vaccines leading to the formation of a large nicotine-antibody complex that cannot cross the blood-brain barrier. Thus, nicotine from tobacco cannot enter the brain and exert its actions. Moreover, exogenous nicotine incorporated in the nicotine-antibody complex cannot be metabolized creating, theoretically, a lower need for nicotine intake. Vaccines are in phase I and II of their development. The development of nicotine vaccines raises several questions: what is their benefit/risk ratio on a population level? do they induce increased craving for cigarettes and increased frequency/intensity of withdrawal symptoms and consequent compensatory smoking? what is the number of injections needed to get a therapeutic antibody level?

Rimonabant, a selective cannabinoid 1 (CB1) receptor antagonist has also been developed in smoking cessation. The phase II and phase III studies of rimonabant in smoking cessation have not been published.

Keywords : smoking cessation, partial a4ß2 nicotinic receptor agonists, nicotine vaccines, CB1 antagonist