Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: A randomized trial

Background

Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.

Methods

Smokers (N = 172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.

Results

The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).

Conclusions

For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.     

Cigarette smoking status in pathological gamblers: association with impulsivity and cognitive flexibility

Background

While the majority of pathological gamblers are current cigarette smokers (CS), some have quit smoking (former smokers, FS) while others never smoked (never smokers, NS). The reasons for elevated smoking rates in pathological gambling are not known, but gamblers may use nicotine as a putative cognitive enhancer. This study evaluated impulsivity and cognitive flexibility in a sample of pathological gamblers with differing smoking status.

Methods

Fifty-five subjects with pathological gambling (CS, n = 34; FS, n = 10; NS, n = 11) underwent cognitive assessments using the Stop-Signal (SST) and Intradimensional/Extra-dimensional (ID/ED) set-shift tasks.

Results

CS reported less severe gambling problems than either FS or NS on the Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling, and CS was associated with significantly fewer directional errors on the SST task, compared to NS. In addition, in CS, higher daily cigarette consumption was associated with fewer total errors on the ID/ED task.

Conclusions

The potential role of nicotine as a cognitive enhancer was supported by objective tests of impulsivity and cognitive flexibility. Human laboratory studies using nicotine challenges in pathological gambling will shed further light on this relationship.     

The effects of dopaminergic drugs in the dorsal hippocampus of mice in the nicotine-induced anxiogenic-like response

Rationale

Nicotine, an active alkaloid of tobacco has an acetylcholine property that alters anxiety-like behaviors in rodents. Moreover, several investigations suggest that the mesolimbic/cortical dopamine systems to be involved in the drugs affecting anxiety. The dopaminergic modulation of acetylcholine synaptic transmission has also been also suggested by different studies. Furthermore, modulation of such behaviors in rodents may be mediated through the dorsal hippocampus.

Objectives

In the present study, a possible role of the dorsal hippocampal acetylcholine receptor mechanism in nicotine's influence on anxiogenic-like responses has been investigated.

Methods

During test sessions, the hole-board was used to investigate the effects of SCH23390, sulpiride, SKF38393 and quipirole on nicotine response in mice.

Results

Intraperitoneal (i.p.) administration of nicotine (0.5 mg/kg) decreased the number of head dips but had no effect on other behaviors. Intra-dorsal hippocampal injections of ineffective doses of SCH23390 (SCH; 0.125 and 0.25 μg/mouse) or sulpiride (SUL; 0.5 and 0.75 μg/mouse) reversed head dips induced by nicotine but did not impact other exploratory behaviors. Furthermore, co-administration of ineffective doses of SKF38393 (SKF; 4 μg/mouse, dorsal hippocampus) or quipirole (QUI; 0.5 μg/mouse) in conjunction with an ineffective dose of nicotine (0.25 mg/kg, i.p.) decreased head dips induced by nicotine, but were otherwise ineffective.

Conclusion

These results may indicate a modulatory effect for the dorsal hippocampus dopamine receptors (D₁ and D₂) on an anxiogenic-like response induced by nicotine.     

Association between nicotine replacement therapy use in pregnancy and smoking cessation

Background

There is an urgent need to find better ways of helping pregnant smokers to stop. Randomized controlled trials (RCTs) have not detected an effect of nicotine replacement therapy (NRT) for smoking cessation in pregnancy. This may be because of inadequate dosing because of faster nicotine metabolism in this group. In England, many pregnant smokers use single form and combination NRT (patch plus a faster acting form). This correlational study examined whether the latter is associated with higher quit rates.

Methods

Routinely collected data from 3880 pregnant smokers attempting to stop in one of 44 Stop Smoking Services in England. The outcome measure was 4-week quit rates, verified by expired-air carbon monoxide level < 10 ppm. Outcome was compared between those not using medication versus using single form NRT (patch or one of the faster acting forms), or combination NRT. Potential confounders were intervention setting (specialist clinic, home visit, primary care, other), intervention type (one-to-one, group, drop-in, other), months pregnant, age, ethnicity and occupational group in multi-level logistic regressions.

Results

After adjustment, combination NRT was associated with higher odds of quitting compared with no medication (OR = 1.93, 95% CI = 1.13–3.29, p = 0.016), whereas single NRT showed no benefit (OR = 1.06, 95% CI = 0.60–1.86, p = 0.84).

Conclusions

Use of a combination of nicotine patch and a faster acting form may confer a benefit in terms of promoting smoking cessation during pregnancy. While this conclusion is based on correlational data, it lends support to continuing this treatment option pending confirmation by an RCT.     

The association between smoking bans and nicotine dependence: A longitudinal analysis of current smokers in Canada

Background

While a substantial body of research has examined the effects of smoking bans on smoking behavior, little is known about the relationship between smoking bans and nicotine dependence. The objective of this study was to examine whether home and workplace smoking bans are associated with reduced nicotine dependence among continuing smokers.

Methods

We used longitudinal data of 1073 adult daily smokers from the Canadian National Population Health Survey (2004–2010). Generalized estimating equations were used to examine the association between smoking bans and nicotine dependence.

Results

Smokers living in homes where smoking is restricted were less likely to be nicotine dependent (OR = 0.40, 95% CI = 0.32–0.50) than smokers living in homes with no such smoking restriction. Workplace smoking policies had no significant association with nicotine dependence (complete ban: OR = 0.79, 95% CI = 0.56–1.11; partial ban: OR = 0.82, 95% CI = 0.57–1.16). There was some evidence that workplace smoking bans were significantly associated with nicotine dependence when single items of the Fagerstrom test were considered.

Conclusions

This paper demonstrates that the presence of a home smoking ban was associated with lower nicotine dependence among continuing smokers. The relationship of workplace bans with nicotine dependence was less clear and was contingent on the measure of nicotine dependence employed. These findings further confirm the importance of bans on smoking in the home, workplace, and other public places on reducing tobacco-related harms.     

Estimating tar and nicotine exposure: Human smoking versus machine generated smoke yields

Objective

Determine human smoked (HS) cigarette yields of tar and nicotine for smokers using their own brand in their everyday environment.

Method

A robust, filter analysis method was used to estimate the tar and nicotine yields for 784 subjects. Seventeen brands were chosen to represent a wide range of styles: 85 and 100 mm lengths; menthol and non-menthol; 17, 23, and 25 mm circumference; with tar yields [Federal Trade Commission (FTC) method] ranging from 1 to 18 mg. Tar bands chosen corresponded to yields of 1–3 mg, 4–6 mg, 7–12 mg, and 13+ mg.

Results

A significant difference (p < 0.0001) in HS yields of tar and nicotine between tar bands was found. Machine-smoked yields were reasonable predictors of the HS yields for groups of subjects, but the relationship was neither exact nor linear. Neither the FTC, the Massachusetts (MA) nor the Canadian Intensive (CI) machine-smoking methods accurately reflect the HS yields across all brands. The FTC method was closest for the 7–12 mg and 13+ mg products and the MA method was closest for the 1–3 mg products. The HS yields for the 4–6 mg products were approximately midway between the FTC and the MA yields. HS nicotine yields corresponded well with published urinary and plasma nicotine biomarker studies.     

Implicit alcohol cognitions in risky drinking nicotine users with and without co-morbid major depressive disorder

Objective

Alcohol consumption, nicotine use, and major depressive disorder (MDD) are highly co-morbid. The negative reinforcement model of addiction would suggest that smokers may consume alcohol to relieve negative affective symptoms, such as those associated with MDD and withdrawal from nicotine. Over time, these behaviors may become so strongly paired together that they automatically activate a desire to use alcohol, even in the absence of conscious or deliberate intention. This study examined implicit alcohol cognitions in 146 risky drinking nicotine users (n = 83) and non-users (n = 63), to help uncover cognitive mechanisms that link drinking, nicotine use, and depression together. We proposed that nicotine users with a history of MDD would have stronger implicit motivations to drink than non-nicotine users without MDD.

Method

Participants were assessed on lifetime MDD (n = 84) or no MDD (n = 62), and then completed an Implicit Association Task designed to test the strength of associations between alcohol pictures and “approach” words.

Results

Regression analyses showed that implicit alcohol–approach attitudes were stronger among risky drinking nicotine users than non-users. Alcohol–approach motivations were also stronger among risky drinking nicotine users compared to non-users with a history of MDD; nicotine use was unrelated to implicit alcohol cognitions for risky drinkers without MDD.

Conclusions

Implicit cognitive processes may be targeted in behavioral and pharmacological treatments in risky drinking nicotine users, particularly those with depression comorbidity.     

Alcohol problems as a signal for sensitivity to nicotine dependence and future smoking

Background

Alcohol use is a well-documented risk factor for the emergence of chronic smoking behavior. Very little is known, however, about the mediating pathways through which alcohol and/or alcohol-related problems influence future smoking.

Methods

Data were drawn from the longitudinal Social and Emotional Contexts of Adolescent Smoking Patterns Study (SECASPS). Adolescents who had smoked under 100 cigarettes in their lifetime (n = 898; experimenters) and adolescents who had smoked over 100 cigarettes, but fewer than 5 cigarettes per day (n = 152: current smokers) were examined separately (grouping variable). Path analysis was performed to investigate the association between alcohol related problems at baseline (primary predictor) and smoking regularity at the 48 month follow-up (primary outcome), both directly and through mediating variables of smoking quantity and frequency, and nicotine dependence (averaged across these measures at 6-, 15-, and 24-month assessment waves).

Results

Among experimenters, after controlling for smoking and alcohol use, the association between alcohol-related problems at baseline and smoking frequency 48 months later was fully mediated by nicotine dependence symptoms. Among current smokers, only past smoking behavior was associated with 48-month smoking frequency.

Conclusions

Alcohol-related problems are a risk factor for future smoking among novice adolescent smokers above and beyond drinking or smoking per se. By signaling sensitivity to nicotine dependence symptoms, alcohol related problems represent an easily measureable risk factor that can be used to identify and intervene with adolescents before more chronic smoking behaviors emerge.     

Relation between cigarette smoking and cognitive function in euthymic individuals with bipolar disorder

Background

Individuals with bipolar disorder have higher rates of cigarette smoking and cognitive deficits when compared to the general population. Emerging evidence indicates that both smoking and cognitive deficits are associated with more severe illness presentation and course.

Methods

The data were derived from a study evaluating a novel treatment for cognitive function in bipolar disorder. Smoking status was determined by self-report; cognitive function was evaluated with a comprehensive cognitive battery, which included measures of psychomotor speed, attention, memory, learning and executive function. The relations between smoking status and cognitive measures were evaluated with two independent-samples t-test and multiple regression.

Results

The sample comprised forty-three subjects with bipolar disorder (Type I/II). There were no consistent differences in neuropsychological performance between current smokers (N = 16) and non-smokers (N = 27) on most tasks. The occurrence of subjective cognitive failures, as measured with the Cognitive Functioning Questionnaire, was non-significantly lower for smokers compared to non-smokers. Lifetime “smoking load” was negatively associated with premorbid intelligence as estimated by the National Adult Reading Test.

Conclusion

This pilot study provides preliminary evidence that cigarette smoking may exert a salutary effect on subjective, but not objective, measures of cognitive function in euthymic bipolar patients. A larger sample size evaluating this hypothesis would be less vulnerable to type II error.     

Young adult waterpipe smokers: Smoking behaviors and associated subjective and physiological effects

Introduction

The purpose of this pilot study was to investigate smoking behaviors and subjective and physiological effects of nicotine on young adult occasional waterpipe smokers.

Methods

This study utilized a repeated-measures design that included one repeated factor for condition (nicotine and non-nicotine). For each participant, the sequencing of the repeated factor was assigned using random allocation. The two nicotine conditions were nicotine (0.75 g) and non-nicotine (0 g placebo) tobacco. Over the course of two weeks, twenty-two participants completed subjective (Acute Subjective Effects of Nicotine) and physiological (blood pressure, heart rate, and CO level) measures. Additional measures (QSU and MNWS-R) were used to assess for withdrawal symptoms.

Sample

The participants (n = 22) were young adults (23 ± 3.1 years); 71% smoked waterpipe once a month in the past year and 29% smoked waterpipe 1–2 times per week. In addition, 60% reported sharing their waterpipe with friends while smoking. None of the participants reported using any other forms of tobacco products.

Results

Under the nicotine condition, participants tended to smoke longer (i.e. smoking duration, p = 0.004), take more puffs (p = 0.03), take shorter puffs (p = 0.03), and inhale less volume with each puff (p = 0.02). The repeated measures analysis of the factor headrush revealed an effect of the nicotine condition (F = 9.69, p < 0.001, partial η² = 0.31) and time (F = 8.17, p = 0.02, partial η² = 0.30). Heart rate increased significantly across the nicotine condition (F = 7.92, p = 0.01, partial η² = 0.31) and over time (F = 12.64, p = 0.01, partial η² = 0.41).

Conclusions

This study demonstrates how differences between nicotine and non-nicotine waterpipe smoking are associated with changes in smoking behaviors, experiencing a headrush and an increase in heart rate.     

Reevaluating the nicotine delivery kinetics hypothesis

Rationale

The view of smoking as an addiction to nicotine implies that nicotine is an addictive drug and a primary reinforcer. However, nicotine other than in tobacco does not appear to be very rewarding for smokers. This potential anomaly to the nicotine addiction thesis is resolved by the proposition that the reward associated with smoking depends on “high-nicotine boli.” According to the nicotine delivery kinetics hypothesis, smoked nicotine reaches the brain in 5–10 s in high concentrations, which provide reinforcing “hits” of nicotine to the brain.

Objectives

Because of its essential role in the nicotine addiction thesis, this review set out to examine the current empirical basis of the nicotine delivery kinetics hypothesis.

Materials and methods

We reviewed studies that bear on two questions: First, does nicotine from cigarettes reach the brain significantly faster than from other nicotine delivery devices? Second, is there a relationship between delivery kinetics and any rewarding effects of nicotine?

Results

There is little empirical support for the nicotine delivery kinetics hypothesis. Several studies found that arterial nicotine levels associated with smoking are much lower than predicted by the nicotine delivery kinetics thesis and not higher than with other nicotine delivery devices. More importantly, comparisons of nicotine delivery devices with varying speeds of delivery do not suggest any correlation between nicotine delivery profile and subjective reward.

Conclusions

This review indicates that the wide endorsement of the nicotine delivery kinetics hypothesis is unjustified. Critical research is required to resolve the anomalies within the nicotine addiction theory of smoking.

     

Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake

Background

Quit attempts may have different outcomes based on menstrual cycle phase on quit day. This is the first preliminary study examining whether smoking cessation outcomes vary by menstrual cycle phase of quit date in women receiving a 6-week open trial of sustained release (SR) bupropion.

Methods

Thirty-three treatment-seeking premenopausal women were studied. Abstinence outcomes were compared for women quitting during the luteal versus follicular phase.

Results

Women receiving bupropion SR whose self-selected quit date occurred in the luteal phase had significantly higher rates of point prevalence abstinence during the final week of a 6-week post-quit treatment period than women quitting in the follicular phase (62.5% versus 29.4%; p < 0.05). A similar, but non-significant, pattern of findings was demonstrated for continuous abstinence during the treatment phase and for point prevalence abstinence at 3-month follow-up.

Conclusions

Women receiving bupropion SR were significantly more likely to be abstinent at treatment completion if quitting occurred during the luteal phase. This is consistent with recent findings of outcome related to cycle phase at quit date in the absence of pharmacotherapy, and differs from findings utilizing nicotine replacement. Results add to emerging data suggesting that smoking cessation interventions with varying mechanisms of action may result in different outcomes for premenopausal women based on gonadal hormones at quit date.     

The needle and the damage done: clinical and behavioural markers of severe femoral vein damage among groin injectors

Aim

To identify factors associated with severe femoral vein (FV) damage among groin injectors (GIs) on oral opioid substitution treatment.

Design

A cohort study.

Setting

Drug treatment centres in South East England.

Participants

GIs attending an ultrasound ‘health-check’ clinic.

Measures

Femoral ultrasonography and clinical grading of venous disease in each leg.

Method

Comparison of 67 GIs with severely damaged FV and 86 GIs with minimal/moderate damage.

Findings

The majority were men (69.3%) and the mean age was 36.2 years with mean duration of injecting drug use (IDU) of 13.3 years. There were no significant between-group differences in age, gender or duration of IDU. Severe FV damage was associated with longer duration of groin injecting (GI; P < 0.005), use of thick needles (blue-hub, 23G; or green-hub, 21G; P < 0.001), benzodiazepine injection (P < 0.005), history of deep vein thrombosis (DVT, P < 0.001) and recurrent DVT (P < 0.001), presence of depressed groin scar (P < 0.001) and chronic venous disease (CVD, P < 0.001). Logistic regression analysis revealed needle size (β 1.2, Wald 4.9, P < 0.05) and DVT (β 3.3, Wald 38.5, P < 0.001) as the main predictors of severe FV damage.

Conclusion

Needle and syringe exchange services should consider only supplying appropriate lengths of orange-hub needle (25G) on request from GIs. Early cessation of GI, avoidance of benzodiazepine injection and prompt diagnosis and treatment of DVT might also reduce the prevalence of severe FV damage among GIs and the associated healthcare burden. Routine examination of injecting sites among these patients should include an assessment of severity of venous disease in each leg.     

A new look at quantifying tobacco exposure during pregnancy using fuzzy clustering

Background

Prenatal tobacco exposure is a risk factor for the development of externalizing behaviors and is associated with several adverse health outcomes. Because pregnancy smoking is a complex behavior with both daily fluctuations and changes over the course of pregnancy, quantifying tobacco exposure is a significant challenge. To better measure the degree of tobacco exposure, costly biological specimens and repeated self-report measures of smoking typically are collected throughout pregnancy. With such designs, there are multiple, and substantially correlated, indices that can be integrated via new statistical methods to identify patterns of prenatal exposure.

Method

A multiple-imputation-based fuzzy clustering technique was designed to characterize topography of prenatal exposure. This method leveraged all repeatedly measured maternal smoking variables in our sample data, including (a) cigarette brand; (b) Fagerstrom nicotine dependence item scores; (c) self-reported smoking; and (d) cotinine level in maternal urine and infant meconium samples. Identified exposure groups then were confirmed using a suite of clustering validation indices based on multiple imputed datasets. The classifications were validated against irritable reactivity in the first month of life and birth weight of 361 neonates (Male_{_n} = 185; Female_{_n} = 176; Gestational Age__Mean = 39 weeks).

Results

This proposed approach identified three exposure groups, non-exposed, lighter-tobacco-exposed, and heavier-tobacco-exposed based on high-dimensional attributes. Unlike cut-off score derived groups, these groupings reflect complex smoking behavior and individual variation of nicotine metabolism across pregnancy. The identified groups predicted differences in birth weight and in the pattern of change in neonatal irritable reactivity, as well as resulted in increased predictive power. Multiple-imputation-based fuzzy clustering appears to be a useful method to categorize patterns of exposure and their impact on outcomes.     

Dependence on the nicotine gum in former smokers

We conducted an Internet survey in 2004–2007 in 526 daily users of the nicotine gum, to assess use of, and dependence on the nicotine gum in former smokers. We used modified versions of the Nicotine Dependence Syndrome Scale (NDSS-G), the Cigarette Dependence Scale (CDS-G) and the Fagerström Test (FTND-G). After 30 days, 155 participants (29%) indicated their gum use. Higher dependence on the gum predicted a lower chance of stopping using it at follow-up (odds ratio = 0.36 for each standard deviation unit on CDS-G, p = 0.001). More long-term (> 3 months) than short-term (< = 3 months) users of the gum agreed with: “I use the nicotine gum because I am addicted to it” (83% vs. 7%, p < .001), and fewer long-term users reported that they used the gum to avoid relapsing to smoking (42% vs. 92%, p < .001). Long-term users had higher ratings of dependence on the gum than short-term users, as assessed with NDSS-Gum, CDS-Gum and FTND-Gum (all p < .001). Most long-term users reported symptoms of dependence on the nicotine gum. Lower levels of dependence on the gum predicted cessation of gum use. However, long term use of the nicotine gum has no known serious adverse consequence, and may be beneficial if it prevents late relapse.     

Sensitivity and tolerance to nicotine in smokers and nonsmokers

We studied the responses of smokers and life-long non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n=8), non-smokers on a 30 mg patch (n=8) and smokers on a 30 mg patch (n=8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD=3.7), 10.9 (SD=4.2) and 4.1 (SD=2.7) ng/ml in the three groups, respectively (P<0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch ( C_max 13.9 ng/ml, SD=4.9; T_max 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P<0.01) within the first hour, and seven dropped out (P<0.01) at 3–8 h due mainly to severe nausea, vomiting or headache ( C_max 18.4 ng/ml, SD=4.9; T_max 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour ( C_max 7.9 ng/ml, SD=3.0; T_max 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication.     

Correlates of use of electronic cigarettes versus nicotine replacement therapy for help with smoking cessation

Introduction

Electronic- or e-cigarettes are nicotine-delivery devices commonly used by smokers to quit or reduce smoking. At present, not much is known about the characteristics of smokers who specifically try e-cigarettes to quit smoking compared to the nicotine replacement therapy (NRT) products approved by the U.S. Food and Drug Administration (FDA). Determining the characteristics of smokers who are likely to choose e-cigarettes as cessation aids would help develop strategies to impart valid information about e-cigarettes to such smokers as facts regarding the safety and utility of e-cigarettes emerge.

Methods

This study is based on 834 daily smokers [mean age = 45.8 (standard deviation = 13)] from Hawaii. Demographic, smoking- and cessation-related variables were examined as correlates of ever use of e-cigarette only or any FDA-approved NRT product only or both as cessation aids.

Results

Results indicated that younger smokers, non-White smokers, and smokers reporting higher income, lower nicotine dependence, shorter smoking history, and higher lifetime quit attempts were more likely to have tried e-cigarettes but not NRT products for help with smoking cessation.

Conclusion

Smokers who are attracted to use e-cigarettes but not FDA-approved NRT products may differ from smokers who are likely to have used NRT products but not e-cigarettes in terms of demographic (e.g., age, ethnicity) and smoking- or cessation-related characteristics (e.g., nicotine dependence, quit attempts). Given the lack of knowledge regarding the health effects of e-cigarettes and their efficacy as cessation aids, future research needs to continue characterizing smokers who are likely to use e-cigarettes for smoking cessation.     

Deficits in default mode network activity preceding error in cocaine dependent individuals

Background

Cocaine dependence is associated with cognitive deficits and altered task-related cerebral activation in cognitive performance (see Li and Sinha, 2008, for a review). Relatively little is known whether these individuals are also impaired in regional brain activation of the default mode network (DMN). We demonstrated previously that greater activation of the default brain regions precedes errors in a stop signal task performed by healthy controls (SST, Li et al., 2007). We seek to determine whether individuals with cocaine dependence are impaired in DMN activity, specifically activity preceding error, as compared to the healthy people. We also examine the relation to years of cocaine use.

Methods

Individuals with cocaine dependence (CD, n = 23) and demographics-matched healthy controls (HC, n = 27) performed a SST that employed a tracking procedure to adjust the difficulty of stop trials and elicit errors approximately half of the time. Blood oxygenation level dependent (BOLD) signals of go trials preceding stop error as compared to those preceding stop success trials were extracted with generalized linear models using statistical parametric mapping.

Results

HC showed activation of bilateral precuneus and posterior cingulate cortices and ventromedial prefrontal cortex (vmPFC) preceding errors during the SST. In contrast, despite indistinguishable stop signal performance, CD did not show these error predicting activations. Furthermore, the effect size of error-preceding vmPFC activation was inversely correlated with years of cocaine use.

Conclusions

These findings indicate DMN deficits and could potentially add to our understanding of the effects of chronic cocaine use on cerebral functions in cocaine dependence. Work to further clarify potential changes in functional connectivity and gray matter volume is warranted to understand the relevance of DMN to the pathology of cocaine misuse.     

Slower nicotine metabolism among postmenopausal Polish smokers

Background

A non-invasive phenotypic indicator of the rate of nicotine metabolism is nicotine metabolite ratio (NMR) defined as a ratio of two major metabolites of nicotine – trans-3′-hydroxycotinine/cotinine. The rate of nicotine metabolism has important clinical implications for the likelihood of successful quitting with nicotine replacement therapy (NRT). We conducted a study to measure NMR among Polish smokers.

The effect of chewing gum on self-reported nicotine withdrawal: Is it the flavor,the act of chewing,or both?

A healthy alternative that has been shown to lessen the severity of nicotine withdrawal symptoms during brief periods of nicotine abstinence (e.g., 3–4 h) is confectionary chewing gum (Cohen and colleagues, 1997, 1999, & 2001). The current study sought to build upon this line of research by examining the impact of chewing gum on nicotine withdrawal severity over an extended period of nicotine abstinence (e.g., 24 h) while also identifying the specific attributes of chewing gum that may be responsible for the reported decreases in withdrawal. Specifically, the acts of chewing, flavor, as well as the combination of the two, were independently examined. Twenty-four dependent cigarette smokers participated in three experimental conditions (e.g., a flavorless gum base, flavor strips, and flavored chewing gum) as well as a no product control across four weeks while abstaining from smoking for 24 h each week. Using repeated measures ANOVAs, a significant difference in withdrawal severity was reported by participants across conditions, F(3, 69) = 2.89, p < .05. Follow-up analyses revealed that the flavored gum condition yielded significantly lower withdrawal scores than the flavorless gum base and no product control conditions. These findings indicate that chewing gum appears useful in lessening the severity of nicotine withdrawal symptoms over a 24-hour period of nicotine abstinence and that it is a combination of flavor and chewing that appears to lead to this effect.