Smoking, cortisol and nicotine

Abstract

Cigarette smoking is associated acutely with elevated cortisol levels. However, the results of comparisons of cortisol levels in smokers and non-smokers have been inconsistent, and the significance of cortisol responses in smoking cessation is unclear. Here we describe one study comparing the cortisol profiles of smokers and nonsmokers over the day, and a second investigation in which cortisol was monitored during smoking cessation. In the first study, we collected saliva samples from 196 middle-aged men and women on working and weekend days repeatedly through the day. On both working and weekend days, cortisol levels were significantly higher in smokers after adjustment for age, gender and grade of employment. Cortisol responses to waking (the increase between waking and 30 min) were also greater in smokers.

The elevation in cortisol among smokers is generally attributed to nicotine exposure. Nicotine replacement therapy substantially improves abstinence rates, and has become a standard component of smoking cessation treatments, but the effects of nicotine replacement on cortisol are not known. In the second study, cortisol was monitored over 6 weeks of abstinence in 112 smokers treated with behavioural support and 15 mg nicotine patches. Smoking cessation was accompanied by an abrupt decrease in salivary cortisol, and this was sustained over the abstinence period. There was a marginal association between the decrease in cortisol and smoking relapse rates. These results suggest that the nicotine supplied through patches was not sufficient to block the cortisol reduction following smoking cessation. The contribution of these findings to understanding the role of neuroendocrine function in smoking is described.

Introduction

Tobacco smoking has a wide range of biological effects that contribute to its negative impact on health. Apart from carcinogenic processes, these include the stimulation of vasomotor dysfunction, impaired endothelial-dependent vasodilatation, and the modification of lipid profiles (Ambrose and Barua, 2004, Celermajer et al., 1993). Smoking has marked inflammatory effects, causes acute increases in leukocyte counts, and is associated with elevated levels of inflammatory markers such as C-reactive protein, interleukin (IL) 6, and tumour necrosis factor α. It also stimulates platelet hyperaggregability, increased blood viscosity and reduced fibrinolysis (Barua et al., 2002).

Tobacco smoking and nicotine have pronounced effects on endocrine function as well. Nicotinic acetylcholine receptors are found throughout the central nervous system and also in peripheral tissues. There are several binding sites for nicotine within the paraventricular nucleus of the hypothalamus (Kellar et al., 1999), and the endocrine effects of nicotine appear to be the result of a combination of action at postsynaptic cholinergic sites that acutely regulate corticotrophin releasing factor (CRF), and presynaptic action on monoaminergic neurones (Pickworth and Fant, 1998). Acutely, smoking increases adrenocorticotrophic hormone (ACTH) and cortisol levels. This response appears to require quite intense intake, involving more than one cigarette (Gilbert et al., 1992, Kirschbaum et al., 1992), and has been attributed to nicotine exposure (Newhouse et al., 1990, Seyler et al., 1984). Interestingly, it has recently been established that nitric oxide is an inhibitory mediator of nicotine-induced hypothalamic–pituitary–adrenocortical (HPA) activity, providing a direct link between inflammatory processes and the HPA activation stimulated by smoking (Gadek-Michalska and Bugajski, 2004).

The relationship between smoking, cortisol and nicotine is important for at least three reasons. First, the HPA axis is implicated in addictive processes, as discussed by other contributions to this special issue. Second, heightened levels of cortisol have a range of adverse effects on biological processes relevant to long-term health, including lipid profiles, immune function, central adiposity, bone mineral density and reproductive function (Steptoe and Ayers, 2004). Cortisol may therefore mediate some of the effects of smoking on health outcomes such as cardiovascular disease and the metabolic syndrome. Third, cortisol is highly sensitive to psychological stress. Smoking cessation is stressful for many smokers, and this may lead them to fail in quit attempts. It has been proposed that cortisol is directly involved in this process, and that changes in cortisol following smoking cessation may predict early relapse (al'Absi et al., 2004, Frederick et al., 1998).

Several aspects of the relationship between smoking and cortisol are discussed in other contributions. Here, we focus on two issues. The first is the relationship between habitual smoking and cortisol levels in everyday life; do smokers have higher, lower, or normal levels of cortisol? Second, we describe the pattern of cortisol change during a successful smoking cessation attempt supported by nicotine replacement, asking two questions: does cortisol concentration change with smoking cessation accompanied by nicotine replacement, and is it related to the likelihood of success in stopping smoking? Detailing these effects may help us to understand better the processes underlying smoking cessation.