Andrea H. Weinberger

Stress decreases the ability to resist smoking and potentiates smoking intensity and reward

We have developed a novel human laboratory model to examine two primary aspects of stress-precipitated tobacco relapse: (1) Does stress reduce the ability to resist the first cigarette? (2) Once the first cigarette is initiated, does stress facilitate subsequent smoking? Using a within-subject design, daily smokers (n = 37) who were nicotine deprived overnight received a personalized imagery induction (stress or neutral) on two separate days, and then had the option of initiating a tobacco self-administration session or delaying initiation for up to 50 min in exchange for three levels of monetary reinforcement. Subsequently, the tobacco self-administration session entailed a 1-hour period in which subjects could choose to smoke using a smoking topography system. Following the stress induction, subjects were less able to resist smoking, smoked more intensely (increased puffs, shorter inter-puff interval, and greater peak puff velocity), and perceived greater satisfaction and reward from smoking. Stress significantly increased hypothalamus–pituitary–adrenal (HPA) axis reactivity, tobacco craving, negative emotion, and physiologic reactivity relative to the neutral condition. In addition, increased cortisol, ACTH, and tobacco craving were associated with reduced ability to resist smoking following stress. These findings have implications for understanding the impact of stress on smoking relapse and model development to assess smoking lapse behavior.

A Placebo-Controlled Trial of Bupropion Combined with Nicotine Patch for Smoking Cessation in Schizophrenia

BACKGROUND Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (approximately 22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizophrenia. METHODS A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary outcome measures were continuous smoking abstinence in the last 4 weeks of the trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target quit date (TQD) (week 26). RESULTS Smokers assigned to the BUP+TNP group (n = 29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than the PLO+TNP group (n = 29, 1/29, 3.4%) [Fishers Exact Test, p < .05]; at 6-months post-TQD, 4/29 (13.8%) versus 0/29 (0.0%) achieved 7-day point prevalence smoking abstinence (p = .11). Neither bupropion SR nor smoking abstinence significantly altered the positive or negative symptoms of schizophrenia. The combination was well-tolerated in smokers with schizophrenia. CONCLUSIONS Combination therapy with bupropion SR+TNP versus placebo+TNP is well-tolerated and significantly improved short-term smoking abstinence in smokers with schizophrenia.

Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study.

Background: There is evidence for nicotinic hypercholinergic mechanisms in depression. Clinical relationships between tobacco use and depression suggest important effects of nicotine in major depressive disorder (MDD). It has been hypothesized that cigarette smoking may exert antidepressant effects, presumably mediated through stimulation of nicotinic acetylcholine receptor systems. We compared the nicotinic antagonist, mecamylamine hydrochloride (MEC), with placebo as an augmentation strategy for patients with MDD who were refractory to selective serotonin reuptake inhibitor (SSRI) treatment. Methods: Twenty-one SSRI-treated subjects with MDD were randomized to MEC (up to 10 mg/d; n = 11) or placebo (PLO group; n = 10) during an 8-week trial. The primary outcome measure was the change in depressive symptoms assessed using the 17-item Hamilton Depression Rating Scale during the 8-week trial. Results: There was a significant reduction in 17-item Hamilton Depression Rating Scale scores in the MEC versus PLO groups, as evidenced by a significant medication × time interaction (F1,19 = 6.47, P < 0.05). Five (45.5%) of 11 subjects in the active study medication group demonstrated a 50% or more decrease in depressive symptoms from baseline as compared with 1 (10%) of 10 subjects assigned to placebo medication, but this difference was not significant (P = 0.15; Fisher exact test). The primary side effects of MEC were constipation and orthostatic hypotension. Conclusions: These preliminary findings suggest that the nicotinic acetylcholine receptor antagonist, MEC, may have utility as an augmentation strategy for patients with SSRI-refractory MDD.

Nicotine withdrawal in U.S. smokers with current mood, anxiety, alcohol use, and substance use disorders

BACKGROUND The current study examined tobacco withdrawal symptoms and withdrawal-related discomfort and relapse in smokers with and without current mood disorders, anxiety disorders, alcohol use disorders (AUD), and substance use disorders (SUD). METHODS The subsample of current daily smokers (n=8213) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, Wave 1, 2001-2002, full sample n=43,093) were included in these analyses. Cross-sectional data compared smokers with and without current psychiatric disorders on withdrawal symptoms using logistic regression models. The effects of having a co-morbid psychiatric disorder and AUD/SUD compared to a psychiatric disorder alone on nicotine withdrawal were also examined. RESULTS Participants with a current mood disorder, anxiety disorder, AUD, or SUD were more likely to report withdrawal symptoms and reported more withdrawal symptoms than those without current disorders. Having a current mood disorder, anxiety disorder, or SUD was also associated with increased likelihood of withdrawal-related discomfort and relapse. There were no significant interactions between psychiatric disorders and AUDs/SUDs on withdrawal symptoms or behavior. CONCLUSIONS Participants with a current Axis I disorder were more likely to experience tobacco withdrawal symptoms and withdrawal-related discomfort and relapse. Having a co-morbid psychiatric disorder and AUD/SUD did not synergistically increase the experience of withdrawal-related symptoms or relapse. It is important to identify Axis I disorders in smokers and provide these smokers with more intensive and/or longer treatments to help them cope with withdrawal symptoms and prevent relapse.

The impact of cigarette smoking on stimulant addiction.

Objectives: Stimulant users smoke cigarettes at high rates; however, little is known about the relationship between tobacco and stimulants. Methods: Our goal in this article is to synthesize a growing literature on the role of cigarette smoking in stimulant addiction. Results: Early nicotine exposure may influence the development of stimulant addiction. Preclinical and clinical studies suggest a facilitatory role of nicotinic agonists for stimulant addiction. Smoking appears to be associated with more severe stimulant use and poorer treatment outcomes. Conclusions: It is important to assess smoking and smoking-related variables within stimulant research studies to more fully understand the comorbidity. Integrating smoking cessation into stimulant treatment may improve nicotine and stimulant treatment outcomes.

How can we use our knowledge of alcohol-tobacco interactions to reduce alcohol use?

Currently, 8.5% of the US population meets criteria for alcohol use disorders, with a total cost to the US economy estimated at

The relationship of major depressive disorder and gender to changes in smoking for current and former smokers: longitudinal evaluation in the US population.

234 billion per year. Alcohol and tobacco use share a high degree of comorbidity and interact across many levels of analysis. This review begins by highlighting alcohol and tobacco comorbidity and presenting evidence that tobacco increases the risk for alcohol misuse and likely has a causal role in this relationship. We then discuss how knowledge of alcohol and tobacco interactions can be used to reduce alcohol use, focusing on whether (a) smoking status can be used as a clinical indicator for alcohol misuse, (b) tobacco policies reduce alcohol use, and (c) nicotinic-based medications can be used to treat alcohol use disorders.

Gender Differences in Associations between Lifetime Alcohol, Depression, Panic Disorder, and Posttraumatic Stress Disorder and Tobacco Withdrawal

AIMS Although depression and smoking are correlated highly, the relationship of major depressive disorder (MDD) to smoking cessation and relapse remains unclear. This study compared changes in smoking for current and former smokers with and without current and life-time MDD over a 3-year period. DESIGN Analysis of two waves of longitudinal data from the National Institute on Alcohol Abuse and Alcoholisms National Epidemiologic Survey on Alcohol and Related Conditions (wave 1, 2001-02; wave 2, 2004-05). SETTING Data were collected through face-to-face interviews from non-institutionalized United States civilians, aged 18 years and older, in 50 states and the District of Columbia. PARTICIPANTS A total of 11 973 adults (54% male) classified as current or former daily smokers at wave 1 and completed wave 2. MEASUREMENTS Classification as current or former smokers at wave 1 and wave 2. FINDINGS Smoking status remained stable for most participants. Wave 1 current daily smokers with current MDD [odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.03, 1.85] and life-time MDD (OR = 1.52, 95% CI: 1.15, 2.01) were more likely than those without the respective diagnosis to report continued smoking at wave 2. Wave 1 former daily smokers with current MDD (OR = 0.44, 95% CI: 0.26, 0.76) were less likely to report continued abstinence at wave 2. None of the gender × MDD diagnosis interactions were significant. Patterns of results remained similar when analyses were limited to smokers with nicotine dependence. CONCLUSIONS Current and life-time major depressive disorders are associated with a lower likelihood of quitting smoking and current major depressive disorder is associated with greater likelihood of smoking relapse.

Developing and Validating a Human Laboratory Model to Screen Medications for Smoking Cessation

This study examined the interaction of gender and lifetime psychiatric status on the experience of nicotine withdrawal using retrospective data from the National Comorbidity Survey (NCS; N = 816). Multiple regression analyses were performed to examine the main and interactive effects of gender and major depression, alcohol abuse/dependence, panic disorder, and PTSD on indices of withdrawal. Major depression and alcohol abuse/dependence were associated with longer duration of withdrawal symptoms in women. Women also showed stronger associations between major depression and recurrent withdrawal symptoms and PTSD and smoking relapse to alleviate withdrawal. Men showed a stronger association between alcohol abuse/dependence and smoking relapse to alleviate withdrawal. When developing and providing smoking cessation interventions, it is important to consider the gender-specific effects of lifetime psychiatric status on withdrawal.

Prefrontal cognitive dysfunction is associated with tobacco dependence treatment failure in smokers with schizophrenia

INTRODUCTION To facilitate translational work in medications development for smoking cessation, we have developed a human laboratory analogue of smoking lapse behavior. Our paradigm models 2 critical features of smoking lapse: the ability to resist the first cigarette and subsequent ad libitum smoking. In this paper we present the results of 2 studies designed to develop and validate the effect of nicotine deprivation on smoking lapse behavior. METHODS Study 1 (n = 30) was designed to develop the model parameters by examining varying levels of nicotine deprivation (1, 6, and 18 hr; within-subject) and identifying optimum levels of monetary reinforcement to provide while modeling the ability to resist smoking. Study 2 was designed to validate the model by screening smoking cessation medications with known clinical efficacy. Subjects (n = 62) were randomized to either varenicline 2 mg/day, bupropion 300 mg/day, or placebo, and we then modeled their ability to resist smoking and subsequent ad libitum smoking. RESULTS In Study 1, increasing levels of nicotine deprivation and decreasing levels of monetary reinforcement decreased the ability to resist smoking. In Study 2, the lapse model was found to be sensitive to medication effects among smokers who demonstrated a pattern of heavy, uninterrupted, and automated smoking (i.e., smoked within 5 min of waking). Ratings of craving, mood, withdrawal, and subjective cigarette effects are presented as secondary outcomes with results mirroring clinical findings. CONCLUSIONS Our smoking lapse model demonstrates promise as a translational tool to screen novel smoking cessation medications. Next steps in this line of research will focus on evaluating predictive validity.