Nicotine absorption during electronic cigarette use among regular users.

BACKGROUND: The capability of electronic cigarette devices (e-cigs) to deliver nicotine is key to their potential to replace combustible cigarettes. We compared nicotine delivery and subjective effects associated with the use of two classes of e-cigarettes and cigarettes. METHODS: 14 e-cigarette users were instructed to vape their own e-cigarette device every 20 seconds for 10 minutes while blood was drawn at 1, 2, 4, 6, 8, 10,12, and 15 minutes after initiating vaping. Users rated withdrawal symptoms and side effects before and after vaping. E-cigarette devices were classified as first-generation (same size as cigarette, no activation button) or advanced (larger than cigarette with an activation button). Separately, 10 cigarette smokers completed a similar protocol. Fisher's Exact Test and two-sided t-tests were used as appropriate to determine differences in outcomes between first-generation e-cigarette users, advanced e-cigarette users, and smokers. RESULTS: Compared to first-generation devices, advanced devices were associated with greater serum nicotine Cmax (ng/ml) (11.5 v. 2.8, p = 0.0231) and greater nicotine boost (ng/ml) (10.8 v. 1.8, p = 0.0177). Overall, e-cigarettes users experienced a significant reduction in withdrawal and craving, although there were no significant differences between users of first-generation and advanced devices. Comparing e-cigarettes overall to cigarettes, cigarettes were associated with greater Cmax (25.9 v. 9.0, p = 0.0043) and greater nicotine boost (21.0 v. 8.2, p = 0.0128). CONCLUSIONS: Advanced e-cigarettes delivered significantly more nicotine than first-generation devices but less than combustible cigarettes. Overall, e-cigarette use was associated with a reduction in withdrawal and craving with no reported side effects. The wide variation in nicotine absorption from different e-cigarette devices should be considered in studies of e-cigarettes for smoking cessation.

Changes in resting state functional brain connectivity and withdrawal symptoms are associated with acute electronic cigarette use.

Resting state functional brain connectivity (rsFC) may be an important neuromarker of smoking behavior. Prior research has shown, among cigarette smokers, that nicotine administration alters rsFC within frontal and parietal cortices involved in executive control, as well as striatal regions that drive reward processing. These changes in rsFC have been associated with reductions in withdrawal symptom severity. We currently have a limited understanding of how rsFC is affected by the use of electronic cigarettes (ecigs), an increasingly popular class of products, the members of which deliver nicotine with varying effectiveness. The current study used fMRI to determine the effects of ecig use on rsFC and withdrawal symptoms. Independent component, dual regression, and permutation analyses were conducted on rsFC collected from ecig users before and after an ecig use episode (n=9) that occurred after 14h of nicotine abstinence. Similar to the known effects of nicotine administration, ecig use decreased rsFC of two clusters in the right frontal pole and frontal medial cortex with an attentional control salience network, and decreased rsFC of five clusters in the left thalamus, insula, and brain stem with a reward network encompassing the striatum. Ecig use increased inverse coupling between the prefrontal reward network and the right frontoparietal executive control network. Reductions in craving and difficulty with concentration were correlated with decreases in coupling strength between reward and executive control networks. These preliminary results suggest that the effects of ecig use on rsFC are similar to those seen with nicotine administration in other forms. In order to gain insight into the addictive potential of ecigs, further research is needed to understand the neural influence of ecigs across the range of nicotine delivery within this class of products.

Effects of cognitive load on neural and behavioral responses to smoking-cue distractors.

Smoking cessation failures are frequently thought to reflect poor top-down regulatory control over behavior. Previous studies have suggested that smoking cues occupy limited working memory resources, an effect that may contribute to difficulty achieving abstinence. Few studies have evaluated the effects of cognitive load on the ability to actively maintain information in the face of distracting smoking cues. For the present study, we adapted an fMRI probed recall task under low and high cognitive load with three distractor conditions: control, neutral images, or smoking-related images. Consistent with a limited-resource model of cue reactivity, we predicted that the performance of daily smokers (n = 17) would be most impaired when high load was paired with smoking distractors. The results demonstrated a main effect of load, with decreased accuracy under high, as compared to low, cognitive load. Surprisingly, an interaction revealed that the effect of load was weakest in the smoking cue distractor condition. Along with this behavioral effect, we observed significantly greater activation of the right inferior frontal gyrus (rIFG) in the low-load condition than in the high-load condition for trials containing smoking cue distractors. Furthermore, load-related changes in rIFG activation partially mediated the effects of load on task accuracy in the smoking-cue distractor condition. These findings are discussed in the context of prevailing cognitive and cue reactivity theories. These results suggest that high cognitive load does not necessarily make smokers more susceptible to interference from smoking-related stimuli, and that elevated load may even have a buffering effect in the presence of smoking cues under certain conditions.

Cue-reactivity in experienced electronic cigarette users: Novel stimulus videos and a pilot fMRI study.

Some individuals who try electronic cigarettes (e-cigarettes) continue to use long-term. Previous research has investigated the safety of e-cigarettes and their potential for use in smoking cessation, but comparatively little research has explored chronic or habitual e-cigarette use. In particular, the relationship between e-cigarette cues and craving is unknown. We sought to bridge this gap by developing a novel set of e-cigarette (salient) and electronic toothbrush (neutral) videos for use in cue-reactivity paradigms. Additionally, we demonstrate the utility of this approach in a pilot fMRI study of 7 experienced e-cigarette users. Participants were scanned while viewing the cue videos before and after 10min use of their own e-cigarettes (producing an 11.7ng/ml increase in plasma nicotine concentration). A significant session (pre- and post-use) by video type (salient and neutral) interaction was exhibited in many sensorimotor areas commonly activated in other cue-reactivity paradigms. We did not detect significant cue-related activity in other brain regions notable in the craving literature. Possible reasons for this discrepancy are discussed, including the importance of matching cue stimuli to participants' experiences.

Views of Experienced Electronic Cigarette Users.

BACKGROUND: Awareness and use of electronic cigarettes (e-cigs) has increased significantly in the last five years, but little is known about the experiences, satisfaction, opinions and preferences of e-cigs users. METHOD: 1177 participants completed an online survey about their electronic cigarette preferences, of which 200 were randomly selected for analysis. The data was analyzed using both qualitative and quantitative methods. RESULTS: Participants found the design, the ability to customize, and the quality of vapor to be the most important characteristics of the device. Participants thought the most positive aspects of e-cig use were help to quit smoking, improved overall health, and reduced cost. The negative aspects associated with use were mainly related to side effects, such as dry mouth. When asked to explain how e-cigs were used differently than cigarettes, participants reported puffing more regularly, but taking fewer puffs per session. CONCLUSIONS: Experienced e-cig users stated that initiating e-cig use helped them to quit or reduce their conventional smoking, which they believe reduced their health risks. In comparison to cigarette smoking, e-cig users reported using their e-cig more times per day, but with fewer puffs at each use time. Users acknowledged that more research is needed to understand the safety and long-term effects of use. They mentioned dry mouth as a common side effect and common problems with reliability of e-cigs. Understanding these views may help health professionals to assess and assist e-cig users, and in the future, may help regulators to improve quality and reduce risks.

Factors Associated With Electronic Cigarette Users' Device Preferences and Transition From First Generation to Advanced Generation Devices.

INTRODUCTION: Electronic cigarettes (e-cigs) are becoming increasingly popular but little is known about how e-cig users' transition between the different device types and what device characteristics and preferences may influence the transition. METHODS: Four thousand four hundred twenty-one experienced e-cig users completed an online survey about their e-cig use, devices, and preferences. Participants included in analysis were ever cigarette smokers who used an e-cig at least 30 days in their lifetime and who reported the type of their first and current e-cig device and the nicotine concentration of their liquid. Analyses focused on transitions between "first generation" devices (same size as a cigarette with no button) and "advanced generation" devices (larger than a cigarette with a manual button) and differences between current users of each device type. RESULTS: Most e-cig users (n = 2603, 58.9%) began use with a first generation device, and of these users, 63.7% subsequently transitioned to current use of an advanced generation device. Among users who began use with an advanced generation device (n = 1818, 41.1%), only 5.7% transitioned to a first generation device. Seventy-seven percent of current advanced generation e-cig users switched to their current device in order to obtain a "more satisfying hit." Battery capabilities and liquid flavor choices also influenced device choice. CONCLUSION: E-cig users commonly begin use with a device shaped like a cigarette and transition to a larger device with a more powerful battery, a button for manual activation and a wider choice of liquid flavors.

Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users.

INTRODUCTION: Electronic cigarettes (e-cigs) are becoming increasingly popular, but little is known about their dependence potential. This study aimed to assess ratings of dependence on electronic cigarettes and retrospectively compare them with rated dependence on tobacco cigarettes among a large sample of ex-smokers who switched to e-cigs. METHODS: A total of 3,609 current users of e-cigs who were ex-cigarette smokers completed a 158-item online survey about their e-cig use, including 10 items designed to assess their previous dependence on cigarettes and 10 almost identical items, worded to assess their current dependence on e-cigs (range 0-20). RESULTS: Scores on the 10-item Penn State (PS) Cigarette Dependence Index were significantly higher than on the comparable PS Electronic Cigarette Dependence Index (14.5 vs. 8.1, p < .0001). In multivariate analysis, those who had used e-cigs longer had higher e-cig dependence scores, as did those using more advanced e-cigs that were larger than a cigarette and had a manual button. Those using zero nicotine liquid had significantly lower e-cig dependence scores than those using 1-12 mg/ml, who scored significantly lower than those using 13 or greater mg/ml nicotine liquid (p < .003). CONCLUSIONS: Current e-cigarette users reported being less dependent on e-cigarettes than they retrospectively reported having been dependent on cigarettes prior to switching. E-cig dependence appears to vary by product characteristics and liquid nicotine concentration, and it may increase over time.

Weak ventral striatal responses to monetary outcomes predict an unwillingness to resist cigarette smoking.

As a group, cigarette smokers exhibit blunted subjective, behavioral, and neurobiological responses to nondrug incentives and rewards, relative to nonsmokers. Findings from recent studies suggest, however, that there are large individual differences in the devaluation of nondrug rewards among smokers. Moreover, this variability appears to have significant clinical implications, since reduced sensitivity to nondrug rewards is associated with poorer smoking cessation outcomes. Currently, little is known about the neurobiological mechanisms that underlie these individual differences in the responsiveness to nondrug rewards. Here, we tested the hypothesis that individual variability in reward devaluation among smokers is linked to the functioning of the striatum. Specifically, functional magnetic resonance imaging was used to examine variability in the neural response to monetary outcomes in nicotine-deprived smokers anticipating an opportunity to smoke-circumstances found to heighten the devaluation of nondrug rewards by smokers in prior work. We also investigated whether individual differences in reward-related brain activity in those expecting to have access to cigarettes were associated with the degree to which the same individuals subsequently were willing to resist smoking in order to earn additional money. Our key finding was that deprived smokers who exhibited the weakest response to rewards (i.e., monetary gains) in the ventral striatum were least willing to refrain from smoking for monetary reinforcement. These results provide evidence that outcome-related signals in the ventral striatum serve as a marker for clinically meaningful individual differences in reward-motivated behavior among nicotine-deprived smokers.

Greater BOLD activity but more efficient connectivity is associated with better cognitive performance within a sample of nicotine-deprived smokers.

The first few days of an attempt to quit smoking are marked by impairments in cognitive domains, such as working memory and attention. These cognitive impairments have been linked to increased risk for relapse. Little is known about individual differences in the cognitive impairments that accompany deprivation or the neural processing reflected in those differences. In order to address this knowledge gap, we collected functional magnetic resonance imaging (fMRI) data from 118 nicotine-deprived smokers while they performed a verbal n-back task. We predicted better performance would be associated with more efficient patterns of brain activation and effective connectivity. Results indicated that performance was positively related to load-related activation in the left dorsolateral prefrontal cortex and the left lateral premotor cortex. Additionally, effective connectivity patterns differed as a function of performance, with more accurate participants having simpler, more parsimonious network models than did worse participants. Cognitive efficiency is typically thought of as less neural activation for equal or superior behavioral performance. Taken together, findings suggest cognitive efficiency should not be viewed solely in terms of amount of activation but that both the magnitude of activation within and degree of covariation between task-critical structures must be considered. This research highlights the benefit of combining traditional fMRI analysis with newer methods for modeling brain connectivity. These results suggest a possible role for indices of network functioning in assessing relapse risk in quitting smokers as well as offer potentially useful targets for novel intervention strategies.