A placebo-controlled, randomised pilot trial of N-acetylcysteine or placebo for cessation of tobacco smoking.

Smoking represents a significant health threat to the population, however there remains a core group of consistent smokers that are largely unable to break the addiction. Novel therapies are required to assist this group with cessation. N-acetylcysteine (NAC) is a nutraceutical supplement that has shown efficacy compared to placebo in previous pilot studies for assisting smokers to quit or reduce their consumption of cigarettes. A double-blind, randomised trial with a treatment period of 16 weeks and a final follow-up at 42 weeks was conducted comparing 1.8g of effervescent NAC per day (n=47) with placebo (n=47) as an aide to smoking cessation. Both study arms received adjunctive online support through the QuitCoach program. Participants reported smoking at each timepoint (baseline and weeks 8, 16 & 42), which was confirmed through salivary cotinine and exhaled carbon monoxide testing. Primary and secondary analyses were undertaken using a modified intent-to-treat basis, including all participants with at least one valid post baseline outcome, regardless of treatment received or their withdrawal from the study. There was no significant difference in smoking outcomes between intervention groups among the 24 participants that competed follow-up. There were no significant differences in age, gender, or body mass index (BMI) between the groups lost to follow-up or recorded at follow-up. This study found no evidence to support NAC as a therapy for smoking cessation. The negative outcome could be the result of lack of treatment efficacy, or alternatively, small sample size, participant retention difficulties, dose, or duration of follow-up. Trial Registration: Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12617001478303. Registered on 19 October 2017.

Age as a predictor of quit attempts and quit success in smoking cessation: findings from the International Tobacco Control Four-Country survey (2002-14).

BACKGROUND AND AIMS: Past research has found that young smokers are more likely to make quit attempts; however, there are conflicting findings regarding age and quit success. This study examined the degree to which smoker age is related to making quit attempts and quit success. DESIGN: Ten waves of the International Tobacco Control Policy Cohort survey (ITC-4C) collected between 2002 and 2014, with nine wave-to-wave transitions with predictors at the first wave predicting quit attempts and success by the next wave. SETTING: Canada, the United States, the United Kingdom and Australia. PARTICIPANTS: Data from 15 874 smokers categorized into four age groups at baseline (18-24, 25-39, 40-54 and 55+ years). MEASUREMENTS: Age, quit attempts and success (defined as ≥ 30 days abstinence confirmed, if possible, on a third wave for recent attempts). FINDINGS: Older smokers were more likely to smoke daily (χ2  = 1557.86, r = 0.136, P < 0.001) than younger smokers. Daily smokers were less likely to report quit attempts (38.1 versus 58.2%) and to achieve 30 days of abstinence (22.9 versus 34.3%) than non-daily smokers. Older daily smokers were less likely to make quit attempts [0.61, confidence interval (CI) = 0.54-0.70, P < 0.001], even after controlling for indicators of nicotine dependence, country, sex, education, income, relationship status and household composition, than younger smokers. Younger smokers (< 25) were more likely to succeed for at least 30 days of abstinence, but only when compared with those aged 40-54 (OR = 0.83, 95% CI = 0.68-0.99). However, when controlling for heaviness of smoking the age effect disappeared. Significant interactions with age were found between age and intention when predicting quit attempts, and age and heaviness of smoking when predicting quit success. CONCLUSIONS: An international cohort study indicates that young smokers are more likely to attempt to quit and appear to have similar levels of success in abstaining from smoking compared with older smokers when controlling for dependence. Quit success in all ages is most predicted by lower levels of nicotine dependence.

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

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.

A review of the neurobiological underpinning of comorbid substance use and mood disorders.

BACKGROUND: There is evidence that substance use disorders and other mental disorders may have shared biological mechanisms. However, the neurobiological basis of this comorbidity remains only partially explained. This review describes the historical evolution of the dual disorders concept and approach, and reviews the existing literature on neurobiological findings specifically regarding comorbid substance use and mood disorders. METHODS: Searches were conducted using PubMed and Scopus in December 2017. A Boolean search was performed using combinations of "dual diagnosis" or "dual disorder" or "depression" or "bipolar" or "affective disorder" or "mood disorder" and "substance use" or "substance abuse" and "neurobiology" or "functional neuroimaging" or "genetics" or "neurotransmitters" or "neuroendocrinology" in the title or abstract, or as keywords, using no language restriction. RESULTS: 32 studies met the inclusion criteria. We found robust evidence for involvement of the neurotransmitters dopamine, GABA and glutamate and their receptors, as well as by the central corticotrophin-releasing hormone, hypothalamic-pituitary-adrenal axis activation, oxidative stress and inflammation. Recent studies focusing on neuroimaging and genetics have not shown consistent results. LIMITATIONS: Only two search tools were used; most identified studies excluded the population of interest (comorbid mood and substance abuse disorders). CONCLUSIONS: The neurobiological relevance for the occurrence of comorbid mood and substance abuse disorders has not been fully elucidated. Considering the high levels of individuals who experience comorbidity in these areas as well as the negative associated outcomes, this is clearly an area that requires further in-depth investigation. Furthermore, findings from this area can help to inform drug abuse prevention and intervention efforts, and especially how they relate to populations with psychiatric symptoms.