Prospective examination of effects of smoking abstinence on cortisol and withdrawal symptoms as predictors of early smoking relapse
Introduction
This study evaluated the extent to which changes in cortisol concentrations and withdrawal symptoms during the first 24 h of abstinence are associated with early smoking relapse among smokers in the process of quitting. Our hypothesis was that exaggerated cortisol and mood changes during the first 24 h of smoking abstinence would predict early relapse. Although the last two decades have witnessed accelerated efforts to develop effective smoking cessation strategies, the long-term success rates have been disappointing (Fiore et al., 2000, Lee and D’Alonzo, 1993). Relapse after a cessation attempt is very common and rapid. Approximately 50% of smokers relapse within the first 3 days and 75% relapse within 2 weeks of abstinence (Garvey et al., 1992, Law and Tang, 1995, Rose, 1996). Little is known about the nature of early relapse. Efforts to better identify those at high risk for early relapse and understand factors associated with this relapse should help in targeting individuals most vulnerable to relapse during early abstinence.
Systematic investigation of effects of tobacco abstinence on biobehavioral systems involved in the stress response is lacking (Kreek and Koob, 1998). One particular stress biological system that has been recently implicated in relapse is the hypothalamic–pituitary–adrenocortical (HPA) system (Buczek et al., 1999, Koob and Le Moal, 1997, Kreek and Koob, 1998). Cortisol, the primary peripheral HPA hormone, is a central component of the stress response. Cortisol plays a significant role as a modulator of central nervous system activity during stress (Kosten and Ambrosio, 2002, Majewska, 2002, Piazza and Le Moal, 1998), and is produced in response to stressful events that are characterized by distress and negative emotion (al’Absi and Lovallo, 1993, Lovallo et al., 1990). Cortisol interacts with several neurotransmitters and neuropeptides that are modulated by nicotine or mediate nicotine’s effects, including acetylcholine, norepinephrine, dopamine, vasopressin, and β-endorphin (Koob and Le Moal, 1997, Pomerleau and Pomerleau, 1991, Roth et al., 1988).
Abstinence from smoking is associated with symptoms that include anxiety, depression, restlessness, irritability, and physical symptoms, and may be associated with detriment to cognitive performance (American Psychiatric Association, 1994, Hughes, 1992, Pritchard et al., 1992, Snyder et al., 1989, Stitzer and Gross, 1988). These symptoms begin within 4–24 h after smoking cessation and may contribute to risk for early relapse (Carey et al., 1993, Gritz et al., 1991, Shiffman, 1982, Shiffman et al., 1996a, Stitzer and Gross, 1988). These effects of abstinence resemble those that occur in response to acute stress (Hughes, 1992). It is therefore possible that abstinence from tobacco would result in a stress-like psychophysiological response profile. Withdrawal from other classes of drugs, such as opiates, cocaine, and alcohol, has been associated with various physiological changes that resemble those associated with stress (Cami et al., 1992, Mendelson et al., 1988, Wilkins and Gorelick, 1986).
The stimulating effects of acute doses of nicotine on cortisol have been documented in several laboratory studies (Kirschbaum et al., 1992, Pomerleau et al., 1983, Wilkins et al., 1982), although the significance of this cortisol increase in mediating the reinforcing properties of smoking is not clear. If cortisol enhances the benefits smokers draw from cigarettes, then a decline in cortisol levels following abstinence may be another marker associated with intensity of withdrawal symptoms and increased risk for relapse. Such a marker may reflect an effect of abstinence that is part of a withdrawal syndrome or an independent marker of abstinence. The impact of this decline may be particularly strong in light of the observation that smokers show heightened adrenocortical activity compared with non-smokers (al’Absi et al., 2003), possibly rendering smokers less able to mount an adaptive response during stressful events. One study assessed cortisol changes from pre to post-treatment, and found a positive association between cortisol drops and distress after quitting, regardless of participants’ success in maintaining abstinence (Frederick et al., 1998).
Previous studies have demonstrated gender differences in smoking patterns (King et al., 1990, Waldron, 1991), and have shown that women have more difficulties quitting (Ward et al., 1997, Wetter et al., 1999) and are more likely to use smoking to cope with negative affect than men (Dicken, 1978, Waldron, 1991). These response patterns may predispose women to readily develop conditioned responses to smoking-related stimuli (Perkins et al., 2001), and may therefore exacerbate withdrawal symptoms and predispose female smokers to relapse more often than men. It is possible that gender differences in psychobiological factors contribute to this nicotine-related mood modulation, and therefore lead to different effects of smoking abstinence.
This study addressed the extent to which mood deteriorations and cortisol changes during the first 24 h of abstinence predict early relapse in men and women. The design included a baseline measurement of diurnal salivary cortisol levels and mood states during a 24-h period while participants were still smoking at their normal rates. A second assessment was conducted during the first 24-h period of abstinence (quit date) and also included salivary cortisol levels, mood states, and withdrawal symptoms. Individuals who relapsed within the first week (early relapsers) were compared with those who maintained abstinence beyond the first week. We also assessed depression, anxiety, and perceived stress to assess the extent to which they differ between early relapsers and those who maintained abstinence. We predicted that: (1) smoking abstinence would increase withdrawal symptoms and reduce cortisol concentrations and (2) participants who relapse during the first week of abstinence would exhibit exaggerated mood and cortisol changes during abstinence relative to measures obtained during ad libitum.
Section snippets
Participants
Seventy-two smokers, ages 18–68 (means±S.E.M.=37.2±1.68), primarily Caucasian (94%), were recruited by newspaper advertisements and by posters placed in the university community. A preliminary telephone screening interview was conducted. This interview included questions concerning any current or recent history of medical or psychiatric disorders, medication intake, and whether potential participants met smoking criteria (having smoked an average of 15 cigarettes or more per day for a minimum
Participant characteristics
Table 1 shows demographic and smoking variables of participants who relapsed and those who maintained abstinence. Both groups (relapsers and abstinents) were of comparable age, body mass index (BMI), years of education, and physical activity (Fs(1,68)<3.0, Ps>0.09). Both groups did not differ in age of first cigarette, daily smoking rate, duration of smoking at the current rate, ratings of their motivation to quit, and number of previous quit attempts (F(1,67)<2.4, P>0.12). Relapsers had higher
Discussion
The primary finding of this study is that smokers who relapsed during the first week after quitting exhibited an exaggerated drop in morning cortisol concentrations and experienced intense withdrawal symptoms and distress during the first day of abstinence. To our knowledge, this is the first study to assess and demonstrate that diurnal changes in cortisol concentrations after smoking cessation predict early relapse. This study extends an earlier study that found a positive association between
Acknowledgements
We thank Deanna Ellestad, Angie Harju, Laurie Franks, Huong Timp, Jonathan Erickson, and Andrew Cumings for assistance with data collection and management. We thank Clemens Kirschbaum of the University of Düsseldorf, Germany, for assistance with the cortisol and cotinine assays. This research was supported in part by grants to Dr. al’Absi from the National Cancer Institute (CA 88272). Dr. al’Absi was also supported by grants from the National Institute on Drug Abuse (DA013435). Dr. Hatsukami
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2022, Pharmacology Biochemistry and BehaviorCitation Excerpt :Ghrelin can stimulate the HPA axis, dependent on dose and route of administration (Wellman et al., 2013). A reduced HPA stress response following 24–48 h of withdrawal predicts early relapse at one month (al'Absi et al., 2003, 2004a,b, 2005, 2014, 2015), while high levels of basal total ghrelin was predictive of early relapse (al'Absi et al., 2014). Despite the current increased interest in ghrelin, many findings remain inconsistent; necessitating further study.