N-acetylcysteine for cessation of tobacco smoking: rationale and study protocol for a randomised controlled trial

Abstract

Background Tobacco smoking is a highly prevalent, addictive behaviour and a key public health priority. However available cessation therapies have low quit and high relapse rates, indicating an urgent need for more effective treatments. Predicated on promising preclinical and pilot clinical data, this paper presents a rationale and protocol for the trial of N-acetylcysteine (NAC) as a novel anti-craving smoking cessation aid. Methods Current smokers (n = 120) of at least 10 cigarettes a day are recruited through online advertisements, print publications and dissemination of flyers. Participants are randomised on a 1:1 ratio to receive either 16-week treatment of 1.8 g/day of NAC or placebo with all participants receiving quit support from the online QuitCoach tool. Participants are attending visits at baseline, 8 and 16 weeks with a 42-week post-discontinuation follow-up. The primary outcome measure is sustained abstinence at six months after treatment based on self-reported rating scales and confirmed by exhaled carbon monoxide and salivary cotinine levels. Secondary outcomes are timing of the first lapse and relapse, between-group cigarette consumption, withdrawal symptoms, general wellbeing and mood/anxiety symptoms. Between-group differences in adverse events and subgroup analyses for variables including gender and Diagnostic Statistics Manual 5 diagnostics will also be investigated. Discussion The planned trial addresses an issue of major importance to human health and, if an effect is shown, may result in substantial changes to the management of smoking and nicotine addiction with overt public health implications. Trial registration Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12617001478303. Registered on 19 October 2017.

The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders

“…Nicotine dependence results in glutamatergic adaptations in brain areas associated with reinforcement [ 173 ]. It is thought that NAC’s antioxidant properties, both increasing glutathione and modulating the glutamatergic system, could reverse the neuroplastic alterations associated with nicotine dependence and assist with smoking cessation [ 174 ]. NAC reduces nicotine-conditioned place preference and withdrawal signs in nicotine-dependent mice [ 175 ].…”

“…A similar 2-week RCT (48 participants) also found no significant difference between NAC (2,400 mg/day) and placebo on smoking levels, cravings scores, carbon monoxide levels, and anterior cingulate cortex glutamate, glutamine and glutathione on spectroscopy [ 180 ]. A large RCT is currently underway investigating the effects of NAC (1,800 mg/day) compared to placebo in ceasing tobacco use [ 174 ].…”

N-acetylcysteine in substance use disorder: a lesson from preclinical and clinical research

“…Adjunctive NAC at lower doses (1.8 g daily) significantly reduced abstinence score and inflammation state (soluble tumor necrosis factor receptor 2 levels) without the effect on anxiety and depression, as well as on the metabolism components [ 74 ]. Additionally, a larger study consisting of 8 and 16 weeks NAC treatment (1.8 g daily) with a 42-week post-discontinuation follow-up has been started [ 75 ]. In conclusion, a recommendation for NAC use for NUD cannot be made at this time, as further research is required.…”

N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial

“…A fixed-dose regimen of 1.8 g/day of NAC was prescribed. 19 Study design A total of 129 TUD patients from the CRATT program were invited to participate in this study, of whom only 76 agreed. However, 42 of these were found ineligible due to not meeting the inclusion criteria.…”