Galantamine (GAL), a reversible and competitive inhibitor of acetylcholinesterase, is used clinically in the treatment of Alzheimer’s dementia. Some preclinical and clinical studies support the potential efficacy of cholinesterase inhibitors for smoking cessation, although their effects on the behavioral and physiological responses to nicotine have not been examined. The goal of this study was to characterize GAL’s actions on multiple outcomes including withdrawal severity and cognitive performance, as well as subjective and physiological responses to nicotine administered intravenously.
A total of 12 smokers participated in a double-blind, placebo-controlled, crossover study. Smokers had two 4-day treatment periods, assigned in random sequence, to GAL (8 mg/day) or placebo treatment. On day 4 of each treatment phase, smokers had an experimental session in which they received an intravenous (IV) dose of saline or 1 mg/70 kg nicotine, one hour apart, in a random order.
GAL attenuated the self-reported rating of “craving for cigarettes” and prevented decrements in performance in a Go/No-Go task. In response to IV nicotine, GAL treatment attenuated the self-report ratings of “like the drug effects,” “good drug effects,” “bad drug effects,” and “stimulated.”
These findings support the potential utility of GAL as a treatment for smoking cessation.
galantamine; nicotine dependence; intravenous nicotine; nicotine abstinence
In preclinical and clinical studies, medications enhancing the GABA neurotransmission attenuate nicotine reward. Pregabalin, a GABA analogue, presumably interacts with brain glutamate and GABA neurotransmission. The goal of this study was to determine pregabalin's effects on smoking behavior, nicotine withdrawal, craving for cigarettes, and cognitive performance.
Twenty-four smokers participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects had a 4-day treatment period with either pregabalin (300 mg/day) or placebo and following a washout period were then crossed over for 4 days to the other treatment. In each treatment period, starting at midnight of Day 1, participants were asked to stop smoking until the experimental session on Day 4. During the experimental session measures of ad lib smoking behavior, tobacco withdrawal, craving for cigarettes, and cognitive performance were obtained.
Pregabalin treatment, compared to placebo, did not reduce the smoking behavior during the first 3 days of treatment or during ad lib smoking period. Pregabalin treatment attenuated some tobacco withdrawal symptoms including ratings of anxious, irritable, and frustrated in abstinent smokers. Pregabalin treatment also attenuated the subjective ratings of “liking” in response to smoking. Under pregabalin treatment, smokers made more errors in a sustained attention task.
These findings provide limited support for pregabalin as a treatment for nicotine addiction.
GABA; pregabalin; nicotine; cigarette smoking; attentional bias
The Implicit Association Test (IAT) has been used to assess automatic affective responses to drug cues. Smokers (N = 57) completed the IAT at four experimental sessions. They abstained from smoking before two of the sessions (AB), and smoked normally before the other two sessions (NON). At one AB (and NON) session, they smoked a cigarette about 40 minutes before completing the IAT (S), and at the other they did not smoke (NS). Overall, participants exhibited a negative IAT effect, indicating that they found the classification task easier when smoking was paired with bad than when smoking was paired with good. Using repeated measures ANOVA, the IAT effect was made less negative by pre-session Abstinence, and made more negative by Smoking. It was most negative in the NON-S condition. Using Generalized Estimating Equations analyses, the IAT effect was positively associated with pre-task craving ratings assessed on the Questionnaire of Smoking Urges-Brief, but was not associated with a physiological measure of automatic affective responses (startles while viewing smoking vs. neutral pictures). The IAT effect was associated with scores on the Fagerstrom Test for Nicotine Dependence. In sum, automatic affective responses assessed with the smoking IAT are associated with measures of smoking motivation and dependence.
Implicit Association Test; Startle; Craving; Dependence
Appearance changes resulting from breast cancer treatment impact the quality of life of breast cancer survivors, but current approaches to evaluating breast characteristics are very limited. It is challenging, even for experienced plastic surgeons, to describe how different aspects of breast morphology impact overall assessment of esthetics. Moreover, it is difficult to describe what they are looking for in a manner that facilitates quantification. The goal of this study is to assess the potential of using eye-tracking technology to understand how plastic surgeons assess breast morphology by recording their gaze path while they rate physical characteristics of the breasts, e.g., symmetry, based on clinical photographs. In this study, dwell time, transition frequency, dwell sequence conditional probabilities, and dwell sequence joint probabilities were analyzed across photographic poses and three observers. Dwell-time analysis showed that all three surgeons spent the majority of their time on the anterior–posterior (AP) views. Similarly, transition frequency analysis between regions showed that there were substantially more transitions between the breast regions in the AP view, relative to the number of transitions between other views. The results of both the conditional and joint probability analyses between the breast regions showed that the highest probabilities of transitions were observed between the breast regions in the AP view (APRB, APLB) followed by the oblique views and the lateral views to complete evaluation of breast surgical outcomes.
Breast neoplasm; Eye movements; Biomedical image analysis; Decision support; Evaluation research
A growing literature suggests that anhedonia—an affective dimension related to the inability to experience pleasure—is associated with poor smoking cessation outcomes. Despite these findings, research of the motivational mechanisms linking anhedonia and smoking has been limited. Accordingly, the present study examined (a) relationships between anhedonia and motivationally relevant smoking characteristics and (b) whether anhedonia moderated the effects of tobacco deprivation on appetitive and aversive aspects of smoking urges.
Smokers (N = 212; ≥5 cigarettes/day) first attended a baseline session during which measures of anhedonia and smoking characteristics were completed. Prior to a subsequent experimental session, a portion of participants were randomized to one of two groups: (a) 12-hr tobacco deprivation before the session (n = 51) and (b) ad libitum smoking (n = 69).
Smokers with higher levels of anhedonia reported a greater number of past failed quit attempts and a higher proportion of quit attempts that ended in rapid relapse within 24 hr, rs > .20, ps < .05. Anhedonia did not consistently correlate with smoking heaviness, chronicity, and dependence motives. Anhedonia significantly moderated the influence of tobacco deprivation on appetitive smoking urges, such that deprivation effects on appetitive urges were stronger in high anhedonia smokers (β = .64) than in low anhedonia smokers (β = .23). Anhedonia did not moderate deprivation effects on aversive smoking urges. This pattern of results remained robust when controlling for baseline negative affect.
These findings elucidate anhedonia’s link with smoking relapse and could be useful for developing cessation interventions for anhedonic smokers.
Chronic cocaine users are known to have cognitive deficits that are predictive of poor treatment response. Whether these deficits improve with medications targeting specific cognitive functions has not been examined in previous studies. The goal of this study was to evaluate galantamine’s efficacy on selected cognitive outcomes, including measures of sustained attention, response inhibition, and attentional bias in recently abstinent cocaine users. Galantamine, a reversible and competitive inhibitor of acetylcholinesterase, is used clinically in the treatment of Alzheimer’s dementia. In a randomized, double-blind, parallel-group study, 34 participants were randomized to galantamine (8 mg/day) or placebo treatment for 10 days. Cognitive and self-report mood measures were obtained at baseline and on days 5 and 10 after the initiation of treatment. Galantamine treatment, compared to placebo, improved the reaction time, F(2,50)=8.6, p <0.01, detection sensitivity (A′), F(2,50)=4.9, p <0.03, number of hits, F(2,50)=4.2, p <0.04, and number of correct rejections, F(2,50)=5.6, p <0.02, on the Rapid Visual Information Processing (RVIP) task. With the exception of speeding the reaction time on the Stroop, galantamine did not affect performance on other tasks, (p>0.05). These results demonstrate that medications can enhance cognitive function (e.g. sustained attention) in abstinent cocaine users. The potential efficacy of galantamine as a treatment for cocaine abuse needs to be further evaluated in clinical trials.
Galantamine; cholinesterase inhibitor; cocaine; cognitive function
Most attempts to quit smoking end in failure, with many quitters relapsing in the first few days. Responses to smoking-related cues may precipitate relapse. A modified emotional Stroop task—which measures the extent to which smoking-related words disrupt performance on a reaction time (RT) task—was used to index the distracting effects of smoking-related cues. Smokers (N = 158) randomized to a high-dose nicotine patch (35 mg) or placebo patch completed the Stroop task on the 1st day of a quit attempt. Smokers using an active patch exhibited less attentional bias, making fewer errors on smoking-related words. Smokers who showed greater attentional bias (slowed RT on the first block of smoking words) were significantly more likely to lapse in the short-term, even when controlling for self-reported urges at the test session. Attentional bias measures may tap an important component of dependence.
attentional bias; emotional Stroop; relapse; smoking cessation
The attentional blink (AB) occurs when ongoing processing of one target (T1) in a series of rapidly presented stimuli impairs processing of a subsequently presented second target (T2), such that T2 cannot be consciously perceived or reported. There is evidence that the AB can be influenced by the emotional or motivational salience of T2. We examined whether the AB could be attenuated by smoking-related stimuli in smokers. Heavy smokers (N = 55) performed an AB task on two occasions, once following 12-hr of abstinence and once following ad libitum smoking. T2s were either smoking-related or neutral (household-related) words, and lagged T1 by 0 to 7 distracter words. T1s were all neutral words. Each word was presented for 130 ms. Subjects were required to recall T1 and T2 immediately after each trial. There was a significant word type by lag interaction, whereby smoking-related T2s were recalled better than neutral T2s at early, but not late, lags. The word type effect at early lags was significantly associated with attentional bias assessed on the smoking Stroop task, but was not significantly moderated by abstinence. These data indicate that, in heavy smokers, smoking-related stimuli are more likely to engage conscious awareness than neutral words under conditions of limited attentional resources.
Attentional Blink; Attentional Bias; Smoking Cues
Previous studies have documented the existence of signs and symptoms of the acute tobacco abstinence syndrome; however, less attention has been paid to quantifying the magnitude of these effects.
The present study quantified the relative magnitude of subjective, cognitive, and physiological manifestations of acute tobacco abstinence.
Smokers (N = 203, ≥15 cig/day) attended two counterbalanced laboratory sessions, one following 12-hr of abstinence and the other following ad-lib smoking. At both sessions, they completed an extensive battery of self-report measures (withdrawal, affect, hunger, craving, subjective attentional bias towards smoking cues), physiological assessments (heart rate, blood pressure, brain EEG), and cognitive performance tasks (psychomotor processing, sustained attention, objective attentional bias).
Abstinence effects were largest for craving, subjective attentional bias, negative affect, overall withdrawal severity, concentration difficulty, hunger, and heart rate. Effects were moderate for positive affect and EEG power. Effects were small, but reliable, for psychomotor speed, sustained attention, and somatic symptoms. Effects on performance-based indices of attentional bias towards smoking-related cues were small and reliable for some indices but not others. Effects were small and inconsistent for blood pressure and EEG frequency. Variation in internal consistency accounted for 33% of the variation in abstinence effect sizes across measures.
There was a wide range of effect sizes both across and within domains, indicating that the acute tobacco abstinence syndrome is not a monotonic phenomenon. These findings may be indicative of the relative magnitudes of signs and symptoms that the average smoker may exhibit during acute abstinence.
Tobacco Abstinence; Smoking Deprivation; Nicotine Withdrawal; Smoking; Tobacco Dependence
Varenicline, a partial nicotinic acetylcholine receptor (nAChR) agonist, is approved for smoking cessation. A few preclinical studies examined the pharmacological effects of varenicline, alone or in combination with nicotine. How varenicline affects the pharmacological effects of pure nicotine has not been examined in humans. The goal of this study was to characterize varenicline’s actions on nicotine’s dose-dependent effects in abstinent smokers.
Six male and 6 female smokers participated in a double-blind, placebo-controlled, crossover study. Smokers had two, 4-day treatment periods, assigned in random sequence, to varenicline (1 mg/day) or placebo treatment. On day 4 of each treatment phase, smokers had an experimental session, where they received 3 escalating doses of intravenous (IV) nicotine (0.1, 0.4, and 0.7 mg/70 kg), in 30 minute intervals. Varenicline’s effects were assessed through subjective, physiological and cognitive performance outcomes to nicotine administered via IV route.
In response to IV nicotine, varenicline treatment attenuated the rating of drug strength, high, head rush, and stimulated. Varenicline also attenuated nicotine-induced increases in heart rate. Varenicline had mixed effects on cognitive performance. Smokers under varenicline treatment, compared with placebo, reported enhanced positive mood measured with the Positive and Negative Affect Schedule (PANAS).
These findings provide new insights into the mechanisms of action of varenicline in smoking cessation.
varenicline; nicotine dependence; intravenous nicotine; nicotine abstinence
Numerous studies report smokers’ increased craving and physiological arousal when exposed to cigarette stimuli. These responses are attributed to learning processes (e.g., classical conditioning) and are associated with motivational factors that maintain nicotine dependence. However, much less is known about the degree to which these responses are maintained or diminished during quitting.
Treatment-seeking smokers (N = 104) were randomly assigned to continue smoking or to enter a 2-week treatment program. Abstainers (n = 25) were continuously abstinent for 14–17 days at the time of testing. Control subjects (n = 38) continued to smoke at their usual rate. Participants who were assigned to treatment but resumed smoking during the study (n = 41) were considered to be relapsers. Approximately 2 weeks after baseline measurements, abstainers and controls viewed a series of neutral (n = 12) and cigarette (n = 12) pictures, rating them for craving and arousal (feelings of calm vs. excitement).
Non-cued craving (measured during exposure to neutral cues) was diminished in abstaining smokers. However, cigarette cues produced craving increases of the same magnitude in both abstainers and controls, showing that these cues still had evocative power for both groups. Abstaining smokers, who were not physiologically monitored, had lower self-reports of arousal to cigarette pictures than did controls, but the groups did not differ in arousal to neutral pictures.
These findings suggest that the foundations of cue-induced craving, generalized craving, and physiological arousal associated with craving may arise from separate processes.
In recent preclinical studies, the role of nitric oxide (NO) in nicotine dependence has become increasingly evident. Inhibition of NO synthesis blocks acquisition of conditioned place preference, and attenuates the nicotine abstinence syndrome in rodents. These findings have not been followed up in human studies. In order to obtain preliminary data on NO inhibition in human smokers, we conducted a randomized, double-blind, crossover study (N = 12) of minocycline, a tetracycline derivative antibiotic, that inhibits the neuronal nitric oxide (NO) synthase enzyme with resultant inhibition of NO production. Medication effects were assessed through a smoking choice procedure as well as subjective and physiological responses to nicotine administered via the intravenous route (IV). Minocycline treatment did not affect smoking self-administration in our choice procedure and did not affect most of the subjective responses to IV nicotine or sample smoking. Following IV nicotine administration, there was a greater reduction in craving for cigarettes under minocycline, compared to placebo. Similarly, smokers had greater reduction in their craving for cigarettes following sample smoking under minocycline treatment. These findings provide limited support for the potential use of minocycline as a treatment of nicotine dependence.
nitric oxide; nitric oxide synthase; minocycline; nicotine dependence; intravenous nicotine
Cognitive processing biases toward smoking-related and affective cues may play a role in tobacco dependence. Because processing biases may occur outside conscious awareness, the current study examined processing of smoking-related and affective stimuli presented at subliminal conditions. A pictorial subliminal repetition priming task was administered to three groups: (1) Nonsmokers (n = 56); (2) Smokers (≥10 cigarettes/day) who had been deprived from smoking for 12 h (n = 47); and (3) Nondeprived smokers (n = 66). Prime stimuli were presented briefly (17 ms) and were followed by a mask (to render them unavailable to conscious awareness) and then a target. Participants were required to make a speeded classification to the target. A posttask awareness check was administered to ensure that participants could not consciously perceive the briefly presented primes (i.e., smoking paraphernalia, neutral office supplies, and happy, angry, and neutral facial expressions). The groups differed in the degree to which they exhibited a processing bias for smoking-related stimuli, F(2, 166) = 4.99, p = .008. Deprived smokers exhibited a bias toward processing smoking (vs. neutral office supply) stimuli, F(1, 46) = 5.67, p = .02, whereas nondeprived smokers and nonsmokers did not (ps > .22). The three groups did not differ in the degree to which they exhibited a subliminal processing bias for affective stimuli. Tobacco deprivation appears to increase smokers’ subliminal processing of smoking-related (vs. neutral) stimuli but does not influence subliminal processing of affective stimuli. Future research should investigate whether subliminal biases toward smoking-related stimuli influence relapse.
tobacco addiction; subliminal processing; smoking-related stimuli; affective stimuli; incentive salience
Gender differences in tobacco withdrawal are of considerable clinical importance, but research findings on this topic have been mixed. Methodological variation in samples sizes, experimental design, and measures across studies may explain the inconsistent results. The current study examined whether male (n = 101) and female (n = 102) smokers (≥15 cigarettes/day) differed in abstinence-induced changes on a battery of self-report measures (withdrawal, affect, craving), cognitive performance tasks (attention, psychomotor performance), and physiological responses (heart rate, blood pressure, brain electroencephalogram). Participants attended 2 counterbalanced laboratory sessions, 1 following 12 hr of abstinence and the other following ad libitum smoking. Results showed that women reported greater abstinence-induced increases in negative affect, withdrawal-related distress, and urge to smoke to relieve withdrawal distress. In contrast, both genders reported similar abstinence-induced changes in positive affect and urge to smoke for pleasure. Men and women exhibited generally similar abstinence-induced changes in physiological and cognitive performance measures. In addition, gender did not moderate the association between withdrawal symptoms and baseline measures of smoking behavior and dependence. Abstinence-induced changes in withdrawal distress mediated the effect of gender on latency until the 1st cigarette of the day at trend levels (p < .10). These findings suggest that there are qualitative gender differences in the acute tobacco withdrawal syndrome that may underlie gender-specific smoking patterns.
gender differences; nicotine withdrawal; affect; craving; smoking
In preclinical studies, medications which decrease glutamate release have been shown to block some of the effects of psychostimulants. One such medication is riluzole, marketed for the treatment of Amyotrophic Lateral Sclerosis (ALS). The goal of this study was to determine riluzole’s effects on acute physiological and subjective responses to d-amphetamine in healthy volunteers. Seven male and 5 female subjects participated in an outpatient double-blind, placebo-controlled, crossover study. Across 4 sessions, subjects were randomly assigned to a sequence of 4 oral treatments: placebo, 20 mg d-amphetamine alone, 100 mg riluzole alone, or d-amphetamine plus riluzole. Outcome measures included heart rate, blood pressure, plasma cortisol, performance on the Sustained Attention to Response Test (SART), and subjective measures. D-amphetamine increased heart rate, blood pressure and plasma cortisol levels while inducing psychostimulant-type subjective effects. On the SART, d-amphetamine enhanced the speed of correct responses but also significantly increased the number of errors of commission. Riluzole at 100 mg did not block, the typical subjective and physiological responses to 20 mg d-amphetamine. Riluzole alone induced amphetamine-like subjective responses. On the SART test, riluzole increased the number errors of commission, but unlike d-amphetamine, did not speed reaction time. The mechanism accounting for these findings is unclear, but may involve processes other than decreased glutamate release by riluzole. The effects of glutamate medications on psychostimulant responses need to be further examined.
AMPA; d-amphetamine; dopamine; glutamate psychostimulant; riluzole
Survey data suggest that in Texas Latino youth exhibit higher rates of susceptibility to smoking than youth from other ethnic groups. In this analysis we examined the relationship between susceptibility to smoking and well-known risk factors associated with smoking initiation among a cohort of 11 to 13 year old Mexican origin youth residing in Houston, Texas.
We analyzed cross-sectional survey data from 1,187 participants who reported they had never smoked, even a puff of a cigarette. The survey assessed peer and family social influence, school and neighborhood characteristics, level of family acculturation and socioeconomic status, and attitudes toward smoking. Bivariate associations, Student's t-tests, and logistic regression analysis were used to examine predictors of susceptibility.
Overall, 22.1% of the never-smokers were susceptible to smoking. Boys were more likely to be susceptible than girls (25.6% vs. 18.9%), and susceptible children were slightly older than non-susceptible children (12.1 vs. 11.8 years). In addition, multivariate analyses revealed that positive expectations about smoking exerted the strongest influence on susceptibility status (odds ratio = 4.85). Multivariate analyses further revealed that compared to non-susceptible participants, susceptibles were more likely to report peer influences supportive of smoking, lower subjective social status and more detentions at school, more temptations to try smoking and to have a mother and a brother who smokes.
Our findings suggest that interventions that target positive expectations about smoking may be useful in this population. Furthermore, because youth encounter smoking-initiation risk factors in different social environments, our results underscore the continued need for both family- and school-based primary prevention programs to adequately combat their influence. The results also can be used to inform the development of culturally sensitive programs for Mexican origin youth.
This study examined associations between three temperament dimensions measured by the Temperament and Character Inventory-125 (Cloninger, 1992) and tobacco abstinence effects. Smokers (N = 203, ≥15 cig/day) attended two laboratory sessions, one following 12hr of abstinence and the other following ad libitum smoking (order counterbalanced). Participants completed measures of withdrawal symptoms, cigarette urges, and affect. Smokers high in Novelty Seeking reported greater abstinence-induced increases in several nicotine withdrawal symptoms, negative affect, and cigarette craving. Smokers high in Harm Avoidance reported greater abstinence-induced increases in negative affect and urges to smoke to relieve distress. Reward Dependence was not associated with abstinence effects. Novelty Seeking and Harm Avoidance showed independent predictive associations with negative affect and urges, and their associations with abstinence effects persisted when controlling for FTND scores. Smokers with different temperaments display different patterns of acute tobacco withdrawal, and may benefit from treatments matched to their particular abstinence profile.
Temperament; Temperament and Character Inventory; Nicotine Withdrawal; Novelty Seeking; Harm Avoidance; Reward Dependence
Population studies conducted in Sweden have revealed an association between attendance at cultural activities and health. Using data from US residents, we examined whether the association could be observed in the US.
Participants in the current study included 1,244 individuals who participated in the 1998 General Social Survey.
A significant association between cultural activities and self-reported health (SRH) was observed, even after controlling for age, gender, marital status, race, number of children, subjective social class, employment status, household income, and educational attainment. Specifically, the more cultural activities people reported attending, the better was their SRH.
The data confirm that an association between cultural activity and health is present in a US sample. The data do not mean that the association is causal, but they suggest that further longitudinal research is warranted.