Impact of varenicline on cue-specific craving assessed in the natural environment among treatment-seeking smokers

Rationale

Varenicline is believed to work, in part, by reducing craving responses to smoking cues and by reducing general levels of craving; however, these hypotheses have never been evaluated with craving assessed in the natural environments of treatment-seeking smokers.

Objectives

Ecological momentary assessment procedures were used to assess the impact of varenicline on cue-specific and general craving in treatment-seeking smokers prior to quitting.

Methods

For 5 weeks prior to quitting, 60 smokers carried personal digital assistants that assessed their response to smoking or neutral cues. During week 1 (baseline), participants did not receive medication; during weeks 2–4 (drug manipulation), participants were randomized to receive varenicline or placebo; during week 5 (standard therapy), all participants received varenicline. Craving was assessed before each cue; cue-specific craving and attention to cue were assessed after each cue.

Results

During all phases, smoking cues elicited greater craving than neutral cues; the magnitude of this effect declined after the first week. General craving declined across each phase of the study. Relative to the placebo condition, varenicline was associated with a greater decline in general craving over the drug manipulation phase. Varenicline did not significantly attenuate cue-specific craving during any phase of the study.

Conclusions

Smoking cues delivered in the natural environment elicited strong craving responses in treatment-seeking smokers, but cue-specific craving was not affected by varenicline administered prior to the quit attempt. These findings suggest that the clinical efficacy of varenicline is not mediated by changes in cue-specific craving during the pre-quit period of treatment-seeking smokers.     

Alcohol craving in outpatients with alcohol dependence: rate and clinical correlates

OBJECTIVE: The present study was undertaken to assess the rate and severity of alcohol craving symptoms among registered alcohol-dependent patients at a Veterans Affairs outpatient clinic. We also examined the relationship between alcohol craving and the clinical characteristics of alcohol-dependent patients. METHOD: Participants included 101 alcohol-dependent veterans enrolled in an outpatient addiction clinic. Alcohol craving was measured by the Penn Alcohol Craving Scale. Alcoholism severity and clinical characteristics were assessed with the Addiction Severity Index, Timeline Followback method, and other instruments. Three alcohol-craving groups (low, moderate, and high) were identified and compared using their demographic and clinical characteristics. Multiple regression analysis was performed to evaluate the relationship between the potential predictors and alcohol craving. RESULTS: The rate of alcohol craving was as follows: low craving (46%), moderate craving (29%), and high craving (25%). When these three craving groups were compared using univariate analyses, patients with higher alcohol craving had significantly higher alcohol composite scores (last 30 days) and severe alcohol dependence (last 1 year). In multiple regression analysis, the model explained 50% of the variance in alcohol craving, with alcoholism severity (42%), withdrawal symptoms (5%), and depression (3%) as significant predictors. CONCLUSIONS: Patients in an outpatient treatment setting had a wide range of alcohol cravings. Level of alcohol craving was directly associated with several increased indices of alcohol- and non-alcohol-related morbidity.     

Effects of exercise on craving and cigarette smoking in the human laboratory

Exercise is increasingly being pursued as a treatment to reduce cigarette smoking. The efficacy of clinical, exercise-based cessation interventions may be enhanced by conducting laboratory studies to determine maximally effective conditions for reducing smoking, and the mechanisms through which the effects on smoking are achieved. The main purpose of this study was to assess whether the effects of exercise on two components of craving (anticipated reward from smoking, anticipated relief from withdrawal) mediated the relationship between exercise and delay (in min) to ad libitum smoking. Experiment 1 (N = 21) assessed the effects of exercise intensity (inactivity, low, moderate) on craving components up to 60 min post-exercise. Because moderate-intensity exercise most effectively reduced craving on the reward component, all participants exercised at a moderate intensity in Experiment 2. Using an ABAB within-subjects design, Experiment 2 (N = 20) evaluated whether the effects of moderate-intensity exercise on reward and relief components of craving mediated the relationship between exercise and participants' delays (in min) to ad libitum smoking. Delays were significantly longer after exercise (M = 21 min) versus inactivity (M = 4 min), and the effects of exercise on delay were mediated through the reward component of craving. Future research should continue to explore the mechanisms through which exercise influences behavioral indices of smoking in the human laboratory. Additionally, given the benefits uniquely afforded by exercise-based cessation interventions (e.g., improving mood and other health outcomes), implementing these interventions in clinical settings may contribute substantially to improving public health.     

The relationship between chronic ethanol exposure and cigarette smoking in the laboratory and the natural environment

Few studies have examined the association between ethanol use and cigarette smoking topography. In particular, no study has objectively investigated the relationship between chronic ethanol exposure and cigarette smoking. The aim of this study was to quantify the relationship between cigarette smoking and past and current ethanol use. Male and female cigarette smokers (n=77) between the ages of 30 and 65 years were recruited and grouped as a function of their past and current ethanol use. Group 1 (n=18) included subjects who were ethanol abstinent for the 3 months prior to the study and had no history of alcohol abuse (as defined by DSM-III criteria). Group 2 (n=19) included subjects who were current regular ethanol users and had no history of alcohol abuse. Group 3 (n=20) included subjects who were ethanol abstinent and had a history of alcohol abuse. Group 4 (n=20) included current regular ethanol users with a history of alcohol abuse. A history of alcohol abuse was associated with an intensified pattern of cigarette smoking. Significant differences were observed for total daily smoke exposure, cigarette number, puff number, total puff and inhalation volume, and the nicotine, tar and carbon monoxide yields of the cigarettes smoked. Increased expired-air carbon monoxide and serum cotinine levels were also observed. Current ethanol use was not associated with an increased cigarette smoking pattern. These data suggest that alcohol abusers are at greater risk of contracting cigarette-related pathology.Supported by National Institute on Drug Abuse Research Grant No. DA 05013 and DA 02988     

Nicotine withdrawal and craving in adolescents: Effects of sex and hormonal contraceptive use

While sex differences in the nicotine withdrawal (NW) symptoms and craving (NC) have been extensively described in adult cigarette smokers, few studies have investigated these phenomena in adolescents. We investigated the effect of gender and hormonal contraception (HC) on NW and NC during the first 14 days of cessation in adolescent smokers using data from a randomized, placebo-controlled, double-blind trial of the transdermal nicotine replacement therapy for smoking cessation.Analyses showed similar levels of NW severity in males and females, regardless of HC use. However, significantly higher NC was observed in females compared to males, (2.22 ± 0.12 vs. 1.65 ± 1.14; p = 0.003). Further, females not using HC reported the highest level of NC (2.38 ± 0.16) followed by females using HC (2.08 ± 0.25) and males (1.71 ± 0.16; p = 0.007).The current findings suggest that adolescent females experience similar NW severity to males, but have stronger NC. Further, the use of hormonal contraceptives may impact the severity of craving. Addressing these different symptoms in adolescents may be useful in increasing smoking cessation rates in this special population of smokers.     

Methamphetamine craving induced in an online virtual reality environment

The main aim of this study was to assess self-reported craving and physiological reactivity in a methamphetamine virtual reality (METH-VR) cue model created using Second Life, a freely available online gaming platform. Seventeen, non-treatment seeking, individuals that abuse methamphetamine (METH) completed this 1-day, outpatient, within-subjects study. Participants completed four test sessions: 1) METH-VR, 2) neutral-VR, 3) METH-video, and 4) neutral-video in a counterbalanced (Latin square) fashion. The participants provided subjective ratings of urges to use METH, mood, and physical state throughout each cue presentation. Measures of physiological reactivity (heart rate variability) were also collected during each cue presentation and at rest. The METH-VR condition elicited the greatest change in subjective reports of “crave METH”, “desire METH”, and “want METH” at all time points. The “high craving” participants displayed more high frequency cardiovascular activity while the “low craving” participants displayed more low frequency cardiovascular activity during the cue conditions, with the greatest difference seen during the METH-VR and METH-video cues. These findings reveal a physiological divergence between high and low craving METH abusers using heart rate variability, and demonstrate the usefulness of VR cues for eliciting subjective craving in METH abusers, as well as the effectiveness of a novel VR drug cue model created within an online virtual world.     

Smoking produces a smaller increase in heart rate in the natural smoking environment than in the laboratory

We tested whether the physiological effects of smoking a cigarette under standard conditions in a laboratory are similar to those seen in a room at home. On two separate test days ten healthy smokers were prepared with a small physiological recorder and were then requested to carry out a protocol requiring them to smoke one of their cigarettes in their usual way either (1) in the laboratory where they had never smoked previously, or (2) at home, alone in a quiet room where they regularly smoke. The experiment which counterbalanced the order of testing showed that in both test situations smoking produced a clear increase in heart rate (HR) and in skin conductance (SC); however, when testing was carried out in the home environment the increase in the HR was significantly less than in the laboratory. No significant differences were found for the baseline HR values in the two environments and there were no significant situational effects in the SC data. It was concluded that under conditions of normal smoking, data on the physiological effects of a cigarette in the laboratory may not be fully generalizable to those seen in the natural smoking situation. Several possible mechanisms of this situationally-specific effect of smoking were discussed.     

Effects of alternative reinforcer and craving on the choice to smoke cigarettes in the laboratory

We examined to what extent craving for cigarettes and the magnitude of an alternative monetary reinforcer were predictors of the choice to smoke in the human laboratory. Twelve non-treatment-seeking nicotine-dependent volunteers participated in a series of outpatient sessions during which they had repeated opportunities to select between three puffs of a cigarette and a variety of monetary alternatives ($0.50-3), responding under a progressive-ratio schedule. Level of cigarette craving was measured at baseline and between each choice opportunity. The probability of choosing a cigarette decreased significantly with the increase in the magnitude of the alternative reinforcer. Baseline level of craving did not significantly alter the probability of choosing a cigarette, but a craving component related to the anticipation of positive effects from smoking, assessed repeatedly between choice opportunities, was predictive of the choice to smoke. These results demonstrate that the cigarette puff self-administration procedure is sensitive to environmental manipulations and cigarette puff choice can be modified by the availability of an alternative reinforcer. This paradigm models the motivational component associated with choice to smoke and could be used to evaluate the effects of pharmacological and behavioral interventions to decrease cigarette smoking.     

Alcohol craving predicts drinking during treatment: an analysis of three assessment instruments

OBJECTIVE: The purpose of this investigation was to examine the utility of thee craving instruments to predict drinking during treatment. The three assessments used were the Penn Alcohol Craving Scale (PACS), the Alcohol Urge Questionnaire (AUQ) and Items 1-6 of the Obsessive subscale (OBS) of the Obsessive Compulsive Drinking Scale (OCDS). METHOD: The three instruments were administered during the course of a 9-month, double-blind, placebo-controlled trial of 100 mg/day of naltrexone, and a manual-based psychosocial intervention using the BRENDA manual conducted at the University of Pennsylvania's Treatment Research Center. Participants (133 men and 50 women at the initiation of the study) used these instruments to self-report craving on a weekly or biweekly basis. The weekly number of drinks was reported using the Timeline Followback interview. The data were analyzed with generalized estimating equations using craving scores at 1 week as the independent variable and number of drinks in the subsequent treatment week as the dependent variable. RESULTS: Each of the three scales predicted drinking during the subsequent treatment week. The PACS was the strongest predictor followed closely by the OBS and then the AUQ. Most important, craving as measured by the three scales was a stronger predictor of subsequent drinking than was drinking during the prior treatment week. CONCLUSIONS: Craving assessment provides a useful means of predicting drinking during treatment. Such information would be helpful in designing clinical trials and for many treatment modalities.     

Alcohol cue reactivity in alcohol-dependent adolescents

OBJECTIVE: There is substantial evidence that adults with alcohol dependence show different responses (increased craving, increased salivation, changes in heart rate) to alcohol-related stimuli (i.e., alcohol cue reactivity) than nonalcoholics. Alcohol cue reactivity appears to be related to dependence severity and has been used to predict treatment outcomes, where more reactive alcoholics have poorer outcomes than less reactive alcoholics. Adolescents may also develop alcohol dependence, though it is uncertain whether they experience craving and cue reactivity in the presence of alcohol-associated stimuli. METHOD: To examine whether adolescents with alcohol dependence show alcohol cue reactivity, 28 alcoholic adolescents and 25 nonalcoholic adolescents (ages 14-19 years) were compared using a standard cue reactivity procedure, where participants view, hold and sniff different beverages, one of which is their preferred alcoholic beverage. Cue reactivity was assessed with subjective craving ratings, salivation (grams), and heart rate (beats per minute). Analyses were conducted by covarying response to control beverages. RESULTS: Alcoholics responded with both greater craving and greater salivation to the alcohol cue (controlling for response to control cues) than did nonalcoholics, supporting the hypothesis that adolescent alcoholics show alcohol cue reactivity. Heart rate showed no differential cue effect between alcoholics and controls. CONCLUSIONS: Findings support that adolescent alcoholics experience alcohol cue reactivity, as evidenced by increased salivation and subjective craving in the presence of alcohol-related stimuli. Investigation of treatments that may reduce alcohol craving and cue reactivity in adolescents with alcohol dependence is warranted.     

Alcohol increases cigarette smoking: a laboratory demonstration

Most people would agree that a relationship exists between drinking alcohol and smoking cigarettes, but there is very little empirical evidence demonstrating a direct causal association. Study of the relationship has been hampered by the lack of a simple laboratory methodology. This article describes an efficient experimental paradigm. Fourteen male narcotic addicts in methadone maintenance treatment volunteered to come to the laboratory for two smoking sessions, during which each subject was given either an alcoholic drink or orange juice, followed by three cigarettes at 20-minute intervals. Drinking alcohol significantly increased the amount and rate of smoking. However, not all subjects reacted to alcohol with increased smoking, and we were unable to account for those individual differences. Our finding supports the theory that a direct causal mechanism linking smoking and drinking exists. That link probably has clinical significance, because there is evidence that ex-smokers are at particularly high risk when they drink alcohol.     

Alcohol prevention among adolescents: a French experiment

Under the guidance of experts, 120 secondary school students from three wine-producing and three other areas of France discussed their experience with alcohol; assessed the value of materials used in primary prevention programmes; produced themselves such materials and evaluated the impact of the different approaches. From the affective and cognitive interactions resulted a noticeable change of the participants' attitude.     

Coordination compounds in the natural environment

The paper gives a brief overview from the complexation of metals by different ligands in the natural environment and it shows by several examples how transport, biological availability and environmental influences of the metals are attached by these processes.     

A human laboratory study of the effects of quetiapine on subjective intoxication and alcohol craving

Rationale  

The available treatments for alcoholism are only modestly effective, and patients vary widely in their treatment response. Quetiapine, an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT_1A and 5-HT_2A, H₁, and α1 and α2 receptors was shown to promote abstinence, reduce drinking days, and reduce heavy drinking days in a 12-week double-blind placebo-controlled trial.     

Dimensions of impulsive behavior in adolescents: laboratory behavioral assessments

Impulsivity is a multifaceted construct that defines a range of maladaptive behavioral styles. The present research aimed to identify different dimensions of impulsive behavior in adolescents from a battery of laboratory behavioral assessments. In one analysis, correlations were examined between two self report and seven laboratory behavioral measures of impulsivity. The correlation between the two self report measures was high compared to correlations between the self report and laboratory behavioral measures. In a second analysis, a principal components analysis was performed with just the laboratory behavioral measures. Three behavioral dimensions were identified -- "impulsive decision-making", "impulsive inattention", and "impulsive disinhibition". These dimensions were further evaluated using the same sample with a confirmatory factor analysis, which did support the hypothesis that these are significant and independent dimensions of impulsivity. This research indicates there are at least three separate subtypes of impulsive behavior when using laboratory behavioral assessments with adolescent participants.     

Cue-induced cigarette craving and mixed emotions: A role for positive affect in the craving process

Craving is an important component of nicotine addiction, and extant research has demonstrated a clear link between cue-induced craving and negative affect, with mixed results in the positive affect domain. The current study was designed to test the idea that cue-reactive craving might be associated with a mixed emotional process, or the simultaneous experience of positive and negative affect. Participants were 86 non-deprived regular smokers and tobacco chippers who provided simultaneous ratings of positive and negative affect during cue exposure to pleasant, unpleasant, neutral and cigarette cues. Results indicated that self-reported craving was elevated in response to cigarette cues compared to other valenced cue types and craving was higher to pleasant cues than either neutral or unpleasant cues. Mixed emotional responses were higher to cigarette cues than other cue types. In addition, mixed emotional responses to cigarette cues predicted craving even after controlling for smoker type, difficulties regulating negative emotion, baseline craving level and mixed emotional responses to neutral cues. As the first study to investigate mixed emotions and cigarette craving, our results highlight the importance of examining the relationship between cue-reactive craving and emotional response using models of emotion that allow for measurement of nuanced emotional experience. In addition, our findings suggest that positive affect processes may indeed play a role in craving among non-deprived smokers.     

Alcohol use and tobacco abstinence among adolescents in cessation treatment: preliminary findings

Although adult alcohol use is negatively associated with tobacco cessation, this relationship has not been reported for adolescents. We assessed the relationship between alcohol use and point prevalence abstinence from smoking in a sample of tobacco-dependent adolescents undergoing cessation treatment. Alcohol use both at baseline and) during tobacco cessation treatment was examined as predicting smoking abstinence in 101 adolescents (age=15.1years, S.D.=1.31years; age at first cigarette=11.3years, S.D.=1.93years; age at first drink=12.01years, S.D.=2.87years) attending a total of 642 treatment visits. Mixed regression analysis showed that participants who reported alcohol use during tobacco cessation treatment were significantly less likely to abstain from tobacco smoking (OR=0.42, 95% CI=0.23-0.78, t=-2.78, df=540, p=0.0057). However, pre-enrollment alcohol use was not significantly associated with either short- or long-term tobacco abstinence. If confirmed in a larger group of adolescents, our findings suggest that youths attempting to quit smoking should abstain from alcohol.