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Cigarette smoking is the single largest cause of preventable death and disease. Each year ~50% of smokers attempt to quit, but less than 5% are successful, despite using pharmacotherapy. Immunotherapy is being explored as a new approach to smoking cessation; several anti-nicotine vaccines are being developed, which reduce nicotine reinforcement. Anti-nicotine antibodies bind nicotine, preventing it from entering the brain and acting on nicotinic acetylcholine receptors (nAChRs). However, this approach also renders nicotine replacement therapy (NRT) ineffective. Cotinine, the major metabolite of nicotine, is a weak agonist at nAChRs, inducing striatal dopamine release; there is also evidence that it antagonises nicotine's actions. An anti-cotinine vaccine would reduce such antagonism by preventing cotinine from passing the blood-brain-barrier, and sequestering it in the bloodstream. This should enhance the efficacy of NRT and assist with a reduce-to-quit approach to smoking cessation. Here we characterise the immune response to anti-cotinine vaccination and study the impact of vaccination on measures of nicotine dependence. Anti-cotinine vaccination was found to be safe and immunogenic, with regular booster injections required to maintain antibody levels. Antibodies raised were specific for cotinine, retaining it in the blood. Upregulation of nAChRs by chronic nicotine administration was not increased after vaccination, and no effects on conditioned taste aversion were observed. However, increases in locomotor activity induced by repeated nicotine administration occurred earlier and were more pronounced in vaccinated rats. And in a model of nicotine withdrawal, abstinence scores were increased in vaccinated rats, due to the removal of cotinine-mediated antagonism of nicotine's actions. Antibody levels measured here were not as high as titres in studies of antinicotine vaccines; however, in view of the effects observed with comparatively low titres, vaccination against cotinine could offer a new approach to smoking cessation, provided higher titres of cotinine-specific antibodies can be achieved.

The UK government white paper on tobacco "Smoking Kills" set targets to reduce rates of smoking among adults from 28% to 24% by 2010. The success of behavioural smoking cessation programmes varies according to the type of intervention delivered (Viswesvaran & Schimidt, 1992). Group support programmes are the most commonly delivered smoking cessation interventions in the NHS, although in order to understand which methods are most effective, it is necessary to identify which psychosocial baseline factors predict successful outcomes. This study analysed the role of psychosocial predictors of decision to quit and 4-week abstinence in a community smoking cessation programme.

Background Women are less likely than men to successfully quit smoking when using NHS cessation services (The Information Centre, 2012, ICD, 2011). Methods The research used mixed methods and consisted of two studies. Study one was a secondary data analysis of service use data from cessation services in Glasgow, North Cumbria and Nottingham. The study examined whether women had lower cessation outcomes compared to men. Further analyses explored whether women using cessation support differed from men in terms of demographics, smoking behaviour, interpersonal characteristics or patterns of service use. The predictors of cessation success for women were identified. Study two consisted of 25 semi-structured interviews and 1 focus group (n=5) which explored women’s experiences of smoking, smoking cessation and NHS cessation support. Thematic analysis was used to analyse this data. Results Lower quit rates were observed for women in the English samples (4 weeks, 52.1% vs. 57.8%, 52 weeks, 12.7% vs. 17.2%) compared to men. Women experienced more markers of disadvantage compared to men. Disadvantage appeared to mediate smoking cessation outcomes in women by increasing nicotine addiction. Markers of nicotine dependence predicted smoking cessation outcomes in women. However, the qualitative investigation indicated that the emotional side of addiction also appeared to have an important role in the smoking behaviour for women. Variation existed in the preferred intensity of cessation support. However, knowledge of available cessation support options was low; suggesting that cessation services should ensure smokers make an informed choice about the format of cessation support they use. Conclusions The key finding of this thesis was that it highlighted that smoking and smoking cessation may be affected by the emotional role that smoking can have within women’s lives. Ways that NHS support could be altered to meet women’s needs are discussed within this thesis.