N-acetylcysteine for cessation of tobacco smoking

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The aim of this project is to investigate the efficacy of N-acetylcysteine (NAC) (1.8g/day) for smoking cessation in a randomised, placebo-controlled trial of current smokers who wish to quit smoking. The primary outcome measure will be 6 months of continuous abstinence from end of treatment (EoT) in tobacco smoking, confirmed by biological measures. Secondary outcome measures include point prevalence abstinence, time to relapse and cigarette consumption. Safety, tolerability and subgroup analyses will also be conducted. Hypotheses: Primary: Treatment with NAC will be superior to placebo for smoking cessation at follow-up (week 42), confirmed by assaying exhaled carbon monoxide and salivary cotinine. Secondary: Treatment with NAC will be superior to placebo for smoking cessation at treatment endpoint (week 16), confirmed by assaying exhaled carbon monoxide and salivary cotinine. NAC is an agent that replenishes the antioxidant glutathione, and also has intrinsic antioxidant actions, as well as modulating glutamatergic, neurotropic and inflammatory pathways.There is evidence that glutamate and in particular the cystine-glutamate exchange system, mediate drug intake, craving and behavioural sensitisation in preclinical models of addiction. Glutamate, which is increased by NAC via cysteine-glutamate exchange, is core to relapse in addiction. NAC can also improve some of the physical harms caused by tobacco smoke exposure, improving mucociliary transport and preventing oxidative damage to lung and other tissues. NAC has several advantages over other pharmacotherapies: a different mechanism of action for smoking cessation, an excellent tolerability profile, low cost and is readily available.