Prospective examination of effects of smoking abstinence on cortisol and withdrawal symptoms as predictors of early smoking relapse

This study addressed the hypothesis that exaggerated mood and cortisol changes during the first 24h of smoking abstinence are associated with early relapse. Salivary cortisol levels and mood reports were measured during 24-h ad libitum smoking and the first 24-h abstinence period of a quit attempt. Seventy-two habitual smokers (34 women and 38 men) who were interested in smoking cessation participated. Cotinine concentrations in saliva and expired carbon monoxide were measured before and after abstinence and 1 week after the quit date to verify smoking status. Abstinence produced significant withdrawal symptoms in all participants and reduced cotinine and carbon monoxide levels. While participants showed the expected diurnal changes in cortisol levels, those who relapsed within the first week post quitting exhibited a greater drop in morning cortisol concentrations during abstinence relative to their ad libitum smoking levels. Participants who relapsed reported greater withdrawal symptoms, craving for cigarettes, and distress, and they also reported greater reduction in positive affect during the first 24-h period of abstinence than those who maintained abstinence. These results support the hypothesis that early relapse is associated with exaggerated mood and adrenocortical perturbations observed during the first day of abstinence.     

Pre-quit depression level and smoking expectancies for mood management predict the nature of smoking withdrawal symptoms in college women smokers

We assessed smoking withdrawal symptoms over a six-day period of abstinence among 21 female college students who were daily cigarette smokers [M = 20.3 (4.4); cigarettes per day] and were in the preparation stage of change for quitting smoking. We predicted that reported withdrawal symptoms would covary with baseline depression scores and baseline outcome expectancies for cigarette smoking as a mood management tool. Depression scores at baseline significantly predicted mood-related smoking withdrawal symptoms of Depression–Dejection and Vigor from the Profile of Mood States (POMS). Smoking outcome expectancies for relief of negative affect measured at baseline significantly predicted symptoms of Confusion–Bewilderment and Anger–Hostility. Neither baseline depression nor baseline smoking expectancies for mood management predicted smoking withdrawal symptoms measured by the Smoking Withdrawal Questionnaire (SWQ; [Shiffman, S. M., & Jarvik, M. E. (1976). Smoking withdrawal symptoms in two weeks of abstinence. Psychopharmacology, 50, 35–39]). Results imply that women smokers with baseline depressive symptomatology and expectancies for smoking to relieve negative mood endure greater abstinence-induced mood disturbance, but similar levels of other smoking withdrawal symptoms during initial abstinence. These results may inform smoking cessation efforts.     

Attenuated adrenocorticotropic responses to psychological stress are associated with early smoking relapse

Rationale Research has demonstrated that psychosocial stressors increase smoking and risk for smoking relapse. Alterations in biological systems involved in the stress response caused by chronic smoking may contribute to early relapse. Objectives We examined the extent to which pituitary–adrenocortical and cardiovascular responses to stress following the first 24 h of a quit attempt predict early relapse. Methods Seventy-two smokers interested in cessation attended a laboratory stress session 24 h after the beginning of their cessation attempt. Adrenocorticotropin (ACTH), plasma and salivary cortisol concentrations, systolic and diastolic blood pressure (BP), and heart rate (HR) responses to acute psychological stressors (public speaking and cognitive challenges) were used to predict relapse over a 4-week follow-up period. Results Those who relapsed within 4 weeks showed attenuated hormonal and cardiovascular responses to stress and exaggerated withdrawal symptoms. Cox proportional hazards survival analysis showed that attenuated ACTH, plasma cortisol, systolic and diastolic BP, positive affect, and exaggerated withdrawal symptoms and smoking urges during acute stress predicted early relapse. Stepwise model showed that ACTH, diastolic BP, and exaggerated withdrawal symptoms remain as significant predictors. When baseline smoking and psychological measures were included in the model, changes in ACTH, diastolic BP, and both factors of smoking urges remained significant predictors of relapse. Conclusions These results demonstrate that altered stress response predicts increased vulnerability for smoking relapse.     

Dehydroepiandrosterone sulfate, cortisol, mood state and smoking cessation: relationship to relapse status at 4-week follow-up

It has been hypothesized that increased baseline dehydroepiandrosterone sulfate (DHEAS) levels may act as a natural antidepressant to attenuate negative affect during cocaine withdrawal and abstinence, decreasing the probability of relapse. The current study extends this model to assess factors related to risk of relapse in a sample of 68 nicotine dependent participants. Repeated measures ANOVAs were used to examine mood state, salivary DHEAS and cortisol levels across three assessment periods in participants who had relapsed over a 4-week follow-up period (n=51, 23 women) compared to those who maintained abstinence (n=17, 8 women). Total scores on the Profile of Mood States differed between those who had relapsed and those who maintained abstinence (p=0.008). However, DHEAS and cortisol levels, as well as the ratio of cortisol to DHEAS, did not differ significantly between groups. These findings suggest that, although DHEAS-related enhancement of resiliency to withdrawal may occur, the extent of this protective effect may be modulated by additional factors that warrant further research.     

Circulating leptin levels are associated with increased craving to smoke in abstinent smokers

The adipocyte hormone leptin regulates satiety and energy expenditure. Recent evidence suggests that leptin is associated with increased craving for alcohol and with shorter length of abstinence during alcohol treatment. This study examined leptin's associations with craving for cigarettes and smoking relapse among smokers interested in cessation. Participants (32 smokers; 14 women) attended a laboratory session 24 h following their designated quit day where circulating leptin levels and craving for smoking were assessed. Other measures of withdrawal symptoms, affect, physical symptoms, as well as neuroendocrine and cardiovascular measures were collected before and after performing two stress tasks (public speaking and cognitive tasks). High circulating leptin levels were associated with increased craving, withdrawal symptoms, negative affect, physical symptoms, and reduced positive affect. Circulating leptin levels were not related to cardiovascular and neuroendocrine measures, responses to acute stressors, or to smoking relapse. These results indicate that circulating leptin is a promising biological marker of craving for smoking and warrant further investigation of the links between appetite regulation and nicotine dependence.     

Effects of selegiline (l-deprenyl) during smoking and short-term abstinence

RATIONALE: Changes in dopamine level are thought to play an important role in both smoking reward and withdrawal symptoms during abstinence. Medications that modulate dopamine levels may have beneficial effects on both withdrawal symptom levels and on response to smoking lapses during abstinence. OBJECTIVES: To examine the effects of the selective MAO-B inhibitor selegiline on withdrawal symptoms, smoking behavior and smoking satisfaction ratings. METHODS: Fifteen smokers received selegiline (10 mg/day) and placebo (in counterbalanced order) on Monday through Thursday of 2 study weeks, separated by a 2-week washout. During each study week, ad lib smoking sessions were scheduled to assess smoking behavior both before and after a brief period of abstinence. Subjective withdrawal symptoms and mood were measured daily, and a modified Stroop test sensitive to withdrawal was scheduled during the period of abstinence. RESULTS: Selegiline decreased craving, especially during abstinence, and impaired performance on the modified Stroop test during subjects' attempts to abstain. Medication also reduced number of cigarettes smoked and smoking satisfaction ratings during the smoking sessions both before and after the brief abstinence attempt. CONCLUSION: These results are consistent with an important role of dopamine in smoking behavior and abstinence. They suggest that pharmacological reduction of MAO-B levels during the early part of a quit attempt may aid in smoking cessation.     

Reduction of abstinence-induced withdrawal and craving using high-dose nicotine replacement therapy

Rationale Decreasing withdrawal and craving during smoking cessation is a major aim of cessation medications. Prior studies have shown that Nicotine Replacement Therapy (NRT) decreases withdrawal symptom severity but have relied on retrospective reports and lacked robust measures of baseline symptoms or symptoms during unmedicated abstinence. Objectives and methods We tested the effect of high-dose (35 mg) nicotine patch on withdrawal and craving during abstinence using real-time assessment with electronic diaries during ad libitum smoking, a brief period of experimentally directed trial abstinence, and the first 3 days of cessation. Subjects were 324 smokers randomized to high-dose nicotine patches or placebo. Results Treatment with active patches reduced withdrawal and craving during cessation and completely eliminated deprivation-related changes in affect or concentration. Conclusion High-dose NRT reduces withdrawal symptoms and craving and can eliminate some symptoms entirely. Saul Shiffman and Stuart Ferguson consult exclusively for GlaxoSmithKline Consumer Healthcare on matters relating to existing smoking cessation products. Dr. Shiffman also has an interest in a new smoking cessation product, and is a founder of invivodata, inc., which provides electronic diaries for clinical trials.     

Relationship of perceived risks of smoking cessation to symptoms of withdrawal, craving, and depression during short-term smoking abstinence

The current study examined the relationship between perceived risks of quitting smoking and the self-reported experience of risks (e.g., cravings) during short-term abstinence. Participants (n=55) were daily smokers enrolled in a study of contingency management for smoking cessation with biochemically confirmed abstinence for 1 week. Participants were divided into groups of higher and lower perceived risk of quitting. There were no differences by risk group in demographics or baseline smoking, nicotine dependence, cravings, withdrawal, and depression. Although participants with higher levels of perceived risks reported a similar pattern of cravings and withdrawal symptoms during abstinence, they experienced higher levels of cravings, withdrawal symptoms, and depression than participants with lower risk beliefs. There were no differences in the relationship of risk to withdrawal symptoms by gender. Smokers with higher levels of perceived risk may find it more difficult to quit and remain abstinent due to higher levels of anticipated or experienced withdrawal symptoms and may benefit from targeted behavioral interventions with regard to risk perception and enhanced coping with withdrawal and other effects of smoking cessation.     

Anxiety sensitivity: Relationship to negative affect smoking and smoking cessation in smokers with past major depressive disorder

The present study evaluated whether anxiety sensitivity (AS) was related to negative reinforcement smoking motives and increased risk of relapse during the early stages of a quit attempt. Specifically, the role of AS was evaluated in 60 smokers with past major depressive disorder (MDD) during smoking cessation. Consistent with expectations, AS scores, as indexed by the 16-item Anxiety Sensitivity Index (ASI) [Behaviour Research and Therapy 24 (1986) 1], were positively correlated with smoking to reduce negative affect but were not significantly correlated with smoking for other reasons. Higher ASI scores also were associated with increased risk of lapsing during the first 7 days after quit day. Results suggest that smokers with heightened levels of AS may smoke more often to manage negative moods and may be less able to tolerate early withdrawal symptoms, specifically during early stages of a quit attempt.     

Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers

Rationale Clinical studies have shown that topiramate, an anticonvulsant medication, may be effective as a treatment for smoking cessation. However, less is known about topiramate effects on nicotine withdrawal and craving and its interactions with a smoked cigarette. Objectives The objective of this study was to investigate the effects of topiramate treatment on abstinence-related nicotine withdrawal, cue-induced cigarette craving, and the acute effects of a smoked cigarette. Materials and methods Fifteen female and 25 male cigarette smokers were randomly assigned to 9-day treatment with topiramate (final titration dose, 75 mg/day) or placebo. On the last day of treatment, after a 3-h smoke-free abstinence period, participants were evaluated for symptoms of nicotine withdrawal and then underwent cigarette and neutral cue reactivity testing. Thirty minutes after completing cue exposure testing, participants were then evaluated for the acute effects of a smoked cigarette. Cue reactivity and acute smoking measures included subjective ratings of cigarette craving and withdrawal and physiological measures of skin conductance and temperature, heart rate, and blood pressure. In addition, smoking topography was measured using a puff volume apparatus. Results Topiramate treatment enhanced subjective ratings of withdrawal after the 3-h abstinence period and reduced pre-cue skin conductance levels. Cigarette cue exposure resulted in a moderate increase in craving, which was unaffected by treatment. Topiramate treatment enhanced the rewarding effects of a smoked cigarette, even while participants smoked less per puff and achieved lower plasma nicotine levels. Conclusion Results suggest that topiramate enhances both nicotine withdrawal and reward. These findings question the utility of topiramate treatment for smoking cessation.     

Attempts to quit smoking and relapse: Factors associated with success or failure from the ATTEMPT cohort study

Objective

To identify predictors of attempts to stop smoking and predictors of relapse.

Methods

This study included 2431 smokers from pre-existing Internet panels in the United States, United Kingdom, Canada, France, and Spain. These panel members are Internet users who have registered voluntarily and agreed to participate in various online research studies. Respondents were aged 35–65 years, smoked ≥ five cigarettes per day and intended to stop smoking in the next 3 months. They were followed every 3 months for up to 18 months via Internet contact on measures relating to quit attempts, smoking status, motivation to quit, nicotine cue, weight and weight concern, health-related factors, withdrawal symptoms, and smoking cessation aids.

Results

In this study, recent quit attempts strongly predicted future attempts, but also predicted subsequent relapse. Motivation to quit was predictive of future attempts but not of relapse/abstinence following the attempts. Relapse to smoking was associated with nicotine dependence, exposure to smoking cues, craving, withdrawal symptoms, and lack of smoking cessation aids.

Conclusions

The findings lend support to a model of cessation in which level of motivation to stop generates quit attempts but plays little role in relapse. Dependence, social smoking cues, and a recently failed quit attempt are important factors in relapse.     

Attenuated beta endorphin response to acute stress is associated with smoking relapse

Stress has been cited as an important precipitator of smoking relapse. Dysregulation of neurobiological pathways related to stress might mediate effects of stress on smoking relapse. This study assessed the extent to which beta endorphin response to stress is associated with early smoking relapse. Forty-five smokers interested in smoking cessation were recruited and attended a laboratory session 24 h following the beginning of their abstinence period. During this session beta endorphin samples were collected before and after performing two acute stressors (public speaking and cognitive tasks). Participants also attended four weekly follow-up sessions to assess their smoking status. Results were compared between smokers who relapsed within the 4-week follow-up period and those who maintained abstinence over the same period. The acute stressors were associated with significant increases in measures of craving and withdrawal symptoms (ps<0.01). While baseline measures of beta endorphin did not differ between relapsers and successful abstainers (F<1), results demonstrated that smokers who relapsed exhibited attenuated beta endorphin response to the two stressors relative to those who maintained abstinence over the same period (ps<05). These results support recent evidence indicating that a dysregulated stress response is a key component in predicting smoking relapse.     

Smokers deprived of cigarettes for 72 h: effect of nicotine patches on craving and withdrawal

Abstract Rationale. Research on the effects of nicotine abstinence and nicotine replacement has not provided consistent information about the impact of replacement therapies on tobacco withdrawal and craving. Objective. This study investigated craving and withdrawal symptoms over a 72-h period of abstinence from cigarettes. Methods. Twenty-four healthy volunteers, not intending to quit smoking, were housed in an experimental unit during three 72-h conditions, consisting of either free smoking, enforced smoking cessation with nicotine replacement therapy (NRT) patches, or enforced smoking cessation with placebo patches. The conditions were adhered to using a randomized crossover design, each separated by at least 10 days of washout. Patches, administered in a double-blind fashion, were given as nicotine (21 mg/24 h) and placebo every 24 h. Self-reported cigarette craving and withdrawal were assessed using multi-item scales at fixed intervals over each condition period. Urinary and plasma cortisol levels were also assayed at fixed intervals over each period. Results. Craving intensity was significantly lower with free smoke than with placebo and with NRT patches than with placebo. No difference in craving levels was found between those who smoked or those who had NRT patches. Withdrawal symptoms were significantly lower with free smoke than with either placebo or NRT patches, but there was no difference in levels of withdrawal between those on NRT patches and those on placebo. During the placebo and NRT patch periods, craving intensity displayed a circadian rhythm, with craving levels lowest in the morning and peaking in the evening. Nicotine delivered via the patch had no impact on these circadian variations in craving. There was no evidence of systematic temporal variations in craving levels during the free smoking period. Conclusions. The data suggested that craving and withdrawal symptoms may be sustained by different physiological pathways, and that only selected components of cigarette craving are influenced by NRT. Electronic Publication     

A randomised placebo-controlled trial of oral hydrocortisone for treating tobacco withdrawal symptoms

Rationale  

Many smokers experience a decline in cortisol to sub-normal levels during the first days of smoking cessation. A greater decline in cortisol is associated with more intense cigarette withdrawal symptoms, urge to smoke and relapse to smoking. Findings from an uncontrolled study suggest that glucocorticoids could ameliorate cigarette withdrawal.     

Psychophysiological effects of nicotine abstinence and behavioral challenges in habitual smokers

We tested the hypothesis that psychophysiological responses to behavioral challenges are enhanced by short-term abstinence from smoking. Blood pressure (BP), salivary cortisol levels, and withdrawal symptoms were measured after a period of smoking abstinence (18 h) or ad libitum smoking, during rest, and in response to acute behavioral challenges. Thirty habitual smokers (15 women and 15 men) participated in two laboratory sessions conducted on two separate days (after abstinence or ad libitum smoking). Cotinine concentrations in saliva and expired carbon monoxide were measured in both conditions. Abstinence produced significant withdrawal symptoms in all participants, with women reporting greater desire to smoke than men. Participants showed greater systolic BP responses to the behavioral challenges in the abstinence condition than the control condition. They also showed worse cognitive performance on the challenges in the abstinence than in the ad libitum condition. Men had greater salivary cortisol levels than women, and both men and women showed the expected decline in cortisol levels across time, but showed no difference between the abstinence and ad libitum smoking conditions in the laboratory or during ambulatory measurements. These results indicate that abstinence alters mood, performance, and BP responses to acute challenges but not adrenocortical responses. It is possible that these changes mediate stress-related vulnerability to smoking relapse.     

Smoking cessation treatment in community-based substance abuse rehabilitation programs

Nicotine dependence is highly prevalent among drug- and alcohol-dependent patients. A multisite clinical trial of smoking cessation (SC) treatment was performed at outpatient community-based substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment, Clinical Trials Network. Cigarette smokers (N=225) from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned in a 2:1 ratio to receive either (1) SC treatment as an adjunct to substance abuse treatment-as-usual (TAU) or (2) substance abuse TAU. Smoking cessation treatment consisted of 1 week of group counseling before the target quit date and 8 weeks of group counseling plus transdermal nicotine patch treatment (21 mg/day for Weeks 1-6 and 14 mg/day for Weeks 7 and 8) after the target quit date. Smoking abstinence rates in SC, 10%-11% during treatment and 5%-6% at the 13- and 26-week follow-up visits, were significantly better than those in TAU during treatment (p< .01). In addition, SC was associated with significantly greater reductions as compared with TAU in cigarettes smoked per day (75% reduction, p< .001), exhaled carbon monoxide levels (p< .001), cigarette craving (p< .05), and nicotine withdrawal (p< .05). Smoking cessation did not differ from TAU on rates of retention in substance abuse treatment, abstinence from primary substance of abuse, and craving for primary substance of abuse. Compliance with SC treatment, moderate at best, was positively associated with smoking abstinence rates. Smoking cessation treatment resulted in significant reductions in daily smoking and modest smoking abstinence rates without having an adverse impact on substance abuse rehabilitation when given concurrently with outpatient substance abuse treatment. Substance abuse treatment programs should not hesitate to implement SC for established patients.     

Attention-deficit/hyperactivity disorder (ADHD) symptoms, craving to smoke, and tobacco withdrawal symptoms in adult smokers with ADHD

Background

Tobacco withdrawal symptoms may be confounded with attention-deficit/hyperactivity disorder (ADHD) symptoms among smokers with ADHD.

Objective

(1) To assess overlap between ADHD symptoms and tobacco/nicotine withdrawal symptoms and craving; (2) to assess the relationship between craving or withdrawal symptoms and the effect of osmotic-release oral system methylphenidate (OROS-MPH) on ADHD symptoms; (3) to assess the association of ADHD symptoms, craving, and withdrawal symptoms with abstinence.

Methods

Secondary analysis of a randomized, placebo controlled smoking cessation trial assessing the efficacy of OROS-MPH taken in addition to nicotine patch among individuals with ADHD. ADHD symptoms, withdrawal symptoms, and craving were assessed at baseline and 2, 4 and 6 weeks after a target quit day.

Results

Withdrawal symptoms and craving showed limited and modest overlap with ADHD symptoms prior to abstinence but more extensive and stronger correlation after quit day. Compared to placebo, OROS-MPH reduced ADHD symptoms; this effect was attenuated by controlling for withdrawal symptoms, but not by craving. Craving, but not ADHD symptoms and withdrawal symptoms, was associated with abstinence during the trial.

Conclusion

When treating smokers with ADHD (1) craving, rather than tobacco withdrawal symptoms or ADHD symptoms may be the more effective therapeutic smoking cessation targets; (2) careful distinction of craving, withdrawal symptoms, and ADHD symptoms when assessing withdrawal phenomena is needed.     

Symptoms of Depression and Smoking Behaviors Following Treatment with Transdermal Nicotine Patch

Subscales from the Center for Epidemiologic Studies Depression Scale (CESD), assessed prior to treatment, were examined as predictors of withdrawal, craving, and affect during the first week of abstinence, as well as smoking abstinence during the first week of abstinence and at the end of treatment. The negative affect and somatic features CESD subscales were related to higher levels of nicotine withdrawal. The relationship between the interpersonal disturbance CESD subscale and nicotine withdrawal approached significance. This study suggests the need to examine novel psychological mechanisms that may account for the relationship between depression symptoms and smoking cessation.     

Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers

Rationale Nicotine administration alters neuroactive steroids in rodent models, and serum levels of the neuroactive steroid DHEAS (dehydroepiandrosterone sulfate) appear to be higher in smokers. These molecules may be relevant to tobacco addiction and affective symptoms.Objectives This study aims to investigate DHEAS, allopregnanolone, pregnenolone, and other steroids in male smokers to determine potential associations with nicotine dependence severity and negative affect.Materials and methods Allopregnanolone and pregnenolone serum levels were determined by gas chromatography/mass spectrometry, while DHEAS and other steroid levels were determined by radioimmunoassay in 28 male smokers. Correlational analyses were performed to determine potential associations with rating measures, including the Fagerstrom Test for Nicotine Dependence (FTND), the addiction subscale of the Ikard Smoking Motivation Questionnaire (ISMQ), the craving item on the Reasons to Smoke (RTS) Questionnaire, and the negative affect and craving subscales of the Shiffman–Jarvik Withdrawal Questionnaire.Results DHEAS levels were inversely correlated with the negative affect subscale of the Shiffman–Jarvik Withdrawal Questionnaire (r=−0.60, p=0.002) and the RTS craving item (r=−0.43, p=0.03), and tended to be inversely correlated with the FTND scores (r=−0.38, p=0.067) and the ISMQ addiction subscale (r=−0.38, p=0.059), adjusting for age. Allopregnanolone levels were positively correlated with cotinine levels (r=0.57, p=0.006); pregnenolone levels tended to be positively correlated with cotinine levels (r=0.40, p=0.066).Conclusions DHEAS levels were inversely correlated with negative affect and craving measures, and may predict nicotine dependence severity. Allopregnanolone levels were positively correlated with cotinine levels, suggesting that this neuroactive steroid may be upregulated in smokers. Neuroactive steroids may represent novel smoking cessation agents.     

Severity of withdrawal symptomatology in follicular versus luteal quitters: The combined effects of menstrual phase and withdrawal on smoking cessation outcome

Women are at an increased risk of relapse after a smoking cessation attempt. While the reasons for this phenomenon are not fully understood, recent research indicates that both the menstrual cycle and negative symptomatology may play a role. The goal of this study was to describe the association between withdrawal symptoms during attempted smoking cessation, and to investigate the impact of these symptoms on smoking cessation outcomes as defined by 7-day point prevalence at 14 and 30 days. Negative symptoms associated with the premenstrual period were also assessed. Participants (n = 202) were 29.8 (SD ± 6.6) years old and smoked 16.6 (SD ± 5.6) cigarettes per day. They were randomly assigned to quit smoking in the follicular (n = 106) or luteal (n = 96) menstrual phase. We observed several significantly more severe premenstrual and withdrawal symptoms in the luteal phase. Regardless of quit phase, most withdrawal symptoms were associated with an increased risk of relapse at 14 and 30 days post quit date. Participants attempting to quit smoking in the follicular phase who had higher levels of Anger and Craving were more likely to relapse to smoking at 14-days (OR = 2.00, p-value = 0.026; OR = 2.63, p-value = 0.006; respectively). These data suggest that the menstrual cycle may play a role in smoking cessation outcome, as well as in the symptomatology experienced during a cessation attempt.