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Introduction: Sexual and gender minority (SGM) youth have higher rates of nicotine vaping than other youth in the United States. While social media can be effective in reaching youth and discouraging vaping, informed cultural tailoring is necessary to ensure effective messaging to SGM youth. This study aimed to understand SGM youth perspectives on anti-vaping social media messages and tailoring approaches., Methods: In-depth, qualitative videoconference interviews were conducted from February to July 2022 with 34 SGM youth recruited in the United States via social media ads. The interview guide addressed participants' beliefs about vaping, the context of vaping, perspectives on tailoring messages, and responses to examples of social media anti-vaping messages. Coding and thematic analysis followed a team-based approach., Results: SGM youth perspectives fell into four categories - representation and diversity, facts and evidence, empowering messages, and source credibility. Participants stressed the importance of accurate, genuine representation of SGM youth in messages, but also noted that more overt representation may be seen as tokenizing. Participants recommended partnering with known LGBTQ+ influencers who can promote or share anti-vaping messages on social media platforms. They also recommended using culturally tailored language, including statistics specific to SGM youth, and invoking themes of empowerment to improve the relevance, reach, and effectiveness of anti-vaping campaigns., Conclusions: Findings can inform future efforts to develop anti-vaping messages for SGM youth with effective reach through social media. Nuanced perspectives on SGM representation in messages suggest a careful approach to tailoring. Concerns around inauthenticity may be minimized by ensuring SGM youth are included in message development and dissemination., Implications: This study describes the importance of being attentive to the tailoring preferences among the current generation of sexual and gender minority youth. Findings will inform social media-based messaging strategies that discourage nicotine vaping tailored for SGM youth in health campaign material design and evaluation, ensuring that tailored messages are designed in ways that avoid unintended consequences. The study also describes methods for effectively engaging SGM youth in research to improve the relevance of health education materials for this population and increase reach, which in turn can lead to reduction in vaping practices among SGM youth., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Non-combusted tobacco products, particularly those authorized as modified risk tobacco products (MRTPs), may appeal to young adults. This cross-sectional study explored young adults' attention to reduced exposure claims in IQOS advertising and its associations with product perceptions and use intentions., Methods: Fifty-one young adults aged 21-29 (mean age = 24.5 years old, 54.9% who smoked cigarettes, 47.1% male, 66.7% White) viewed an IQOS advertisement containing two reduced exposure claims (one large, one detailed) for 20 seconds during eye-tracking, then completed post-exposure questionnaires (risk beliefs, harm perceptions, attitudes, use intentions). We compared attention and questionnaire measures by smoking status and examined associations between attention to reduced exposure claims and questionnaire measures., Results: Overall, the large (vs. detailed) reduced exposure claim attracted young adults' attention more quickly, but the detailed claim held attention longer than all other advertisement features (p's < .001). There were no differences by smoking status in how quickly either claim attracted or held initial attention, but young adults who smoked (vs. did not smoke) spent more cumulative time looking at the large claim and less time looking at the detailed claim (p's < .05). Among those who smoked, greater dwell time on the detailed reduced exposure claim was associated with more beliefs about reduced harm, lower perceived risk of addiction, and greater intentions to try IQOS (p's <.05)., Conclusions: Detailed information on reduced exposure in IQOS advertising may convey reduced risk and potentially promote uptake of IQOS among young adults who smoke and attend to this content., Implications: Findings from this exploratory, single-exposure study demonstrate differences in young adults' attention to reduced exposure claims in an IQOS advertisement based on their smoking status. Among those who smoke, greater attention to detailed reduced exposure information was associated with reduced perceptions of harm compared to cigarettes, and greater intentions to try IQOS. Findings suggest that among young adults who smoke cigarettes and visually engage with this content, detailed text containing IQOS' authorized reduced exposure claims is interpreted as reduced risk information and may promote uptake of this product., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: In the United States, e-cigarettes have entered a new regulatory era, needing authorizations from FDA to remain on or enter the marketplace. This study explored the impact of e-cigarette authorization messages on product perceptions and interest., Methods: We conducted an online experiment in June 2022 with nationally-representative samples of adults (21+) who smoke cigarettes (n=866) and youth ages 15-20 (n=859). They were randomized to one of five conditions: viewing an ad for a fictional e-cigarette brand with no reference to FDA (control), an ad with an "authorized for sale by FDA" claim in varying presentation styles (plain text, FDA "approved" stamp, FDA logo), or reading a fictional news excerpt about the product's authorization plus control ad. We compared group differences on product interest, susceptibility, harm perceptions and message perceptions., Results: Among adults who smoke, there were no effects on product interest nor susceptibility, but ratings of the product's harmfulness compared to cigarettes were lower among those in the news versus control condition (β=-0.25, p=.04). Among youth, odds of susceptibility were higher among ever e-cigarette users who viewed the ad with the FDA logo authorization message relative to the control ad (OR=6.3, 95% CI:1.67-23.9, p<0.01). About 40% of all participants agreed the authorization claim makes them think the product is safe to use, but fewer (14-19%) agreed it makes them more interested in trying it., Conclusions: FDA e-cigarette authorization messages may impact some beliefs about product harm. More research is needed to track potential impacts on product use., Implications: This study provides new data about the potential impact of messages about FDA authorization of e-cigarette products (presented as ad claims or a news story) on authorized product perceptions, interest and susceptibility among adults who smoke cigarettes and youth. Our results suggest that FDA e-cigarette authorization messages may impact harm-related beliefs among adults who smoke and product susceptibility among youth who have ever used e-cigarettes before, though real-world effects are likely to be impacted by message type and format, and perceived message source and credibility. Authorization messages are likely to be misinterpreted as "FDA approval" by some; therefore, providing clarifications about authorization meaning and standards are relevant where possible., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Although exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence., Aims and Methods: Thirty-three male and 33 female non-treatment-seeking smokers participated in a double-blind, randomized, placebo-controlled crossover study of 200 mg of progesterone or placebo daily over a four-day abstinence period. Smoking behavior and subjective effects of nicotine were assessed at baseline and after final drug administration. Nicotine withdrawal, smoking urges, mood states, and neural response to smoking cues were measured at baseline, after the first drug administration, and after the final drug administration., Results: No main effect of drug (progesterone vs. placebo) emerged for any outcome. Significant sex by drug interactions emerged for nicotine withdrawal (p = .020), perceived strength of nicotine (p = .040), and perceived bad effects of nicotine (p = .029). Males receiving progesterone reported worse nicotine withdrawal (p = .046) and a trend towards decreased bad effects of nicotine (p = .070). Males on progesterone also reported greater tension and anxiety relative to placebo (p = .021). Females on progesterone perceived nicotine's effects as being stronger relative to placebo (p = .046)., Conclusions: Progesterone causes sex-dependent effects on smoking-related outcomes during brief abstinence. Specifically, progesterone in males may increase rather than decrease nicotine withdrawal and negative affect during abstinence, potentially hindering efforts to quit smoking., Implications: In male and female smokers undergoing a brief period of abstinence, we examined the effects of progesterone on smoking outcomes. While progesterone had limited effects in female smokers, in males, it worsened nicotine withdrawal and negative affect. Our findings emphasize the importance of analyzing sex differences in future studies examining progesterone as a potential treatment and suggest that progesterone in males could potentially exacerbate aspects of nicotine dependence., Clinicaltrials.gov Registration: NCT01954966. https://clinicaltrials.gov/ct2/show/NCT01954966., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: US FDA issued an advance notice of proposed rulemaking to reduce nicotine in cigarettes. To maximize the benefits of this potential standard, very low nicotine content (VLNC) cigarettes must be communicated in a way that does not result in misperceptions., Aims and Methods: Adults (n = 567 who smoke; n = 610 non-smokers) from an online platform were randomized to a control message previously associated with accurate addictiveness perceptions of VLNC cigarettes but health misperceptions or to one of five messages that also included messaging on nicotine morbidity effects or VLNC cigarettes morbidity or mortality effects. p value <.01 was significant., Results: In participants who smoke, perceived lung cancer risk (responses: 1, very little risk to 10, very high risk) if smoked VLNC cigarettes regularly was higher in conditions that communicated mortality effects of VLNC cigarettes compared to the control (7.12-7.18 vs. 5.97, p values < .01). In non-smokers, perceived lung cancer risk was higher in all five message conditions when compared with the control (7.58-8.22 vs. 6.35, p values < .01). Proportion who responded accurately (ie, False) to the statement Cigarettes with 95% less nicotine are safer than cigarettes with normal nicotine levels was higher in conditions describing VLNC morbidity or mortality effects when compared with the control in both participants who smoke (52.04-67.37% vs. 30.85%, p values < .01) and do not smoke (62.50-72.38% vs. 32.00%, p values < .01)., Conclusions: Messaging on mortality effects of VLNC cigarettes (ie, cigarettes with 95% less nicotine are as deadly as current cigarettes) was associated with more accurate perceptions of the health risks of VLNC cigarettes than the control; however, misperceptions remained in one-third of participants., Implications: One approach to communicating a VLNC cigarette standard to the public is to include messaging on the mortality effects of VLNC cigarettes. However, further study and possible refinement of this message condition are recommended since approximately one-third of participants exposed to this message still perceived VLNC cigarettes to be safer than normal nicotine content cigarettes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The Food and Drug Administration announced intent to reduce the nicotine content in cigarettes. There is limited evidence on how reduced nicotine content cigarette (RNC) marketing affects product beliefs and use, and research on this is needed to inform regulations., Methods: In an online experiment, 426 young adult cigarette smokers (aged 18-30 years) were randomized in a 2 (implicit: red package vs. blue package) × 2 (explicit: corrective message vs. no corrective message) design to view an advertisement for previously commercially available RNCs. Outcomes were advertisement content recall, product beliefs, and use intentions. Participants' responses to open-ended assessment of their beliefs about the stimuli were coded to identify prevailing themes., Results: Red packaging and corrective messaging were independently associated with greater advertisement content recall (p = .01 and p = .04, respectively). There were no significant main or interaction effects on product beliefs or use intentions. Controlling for condition, advertisement content recall was significantly associated with less favorable product beliefs (p < .001) and favorable product beliefs were associated with intent to use the product (p < .001). Open-ended responses converged on the finding that respondents were interested in RNCs, but expressed skepticism about effectiveness and value., Conclusions: Brief exposure to an RNC advertisement with red packaging and corrective messaging were each independently associated with greater advertisement content recall. The results indicate: (1) interest and confusion among young adult smokers regarding RNCs, (2) beliefs about RNCs are influenced by marketing, and (3) beliefs are associated with intention to use RNCs., Implications: Findings from this study demonstrate the importance of advertising effects on beliefs about RNC products and support the need to regulate advertising and labeling alongside product regulation. More detailed study of advertisement features that affect consumers' beliefs about RNCs and how they impact their processing of explicit messaging about product risks will be important to guide regulatory decision-making., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: The World Health Organization's Framework Convention on Tobacco Control recommends prominent pictorial health warnings on tobacco products. To advance research methods, theory and understanding of how tobacco product warning labels (TPWLs) work, the US National Cancer Institute convened a grantee meeting. Our article describes the key insights that emerged from the meeting, situated within the context of the scientific literature., Results & Recommendations: First, presentations confirmed that large, pictorial TPWLs motivate people to try to quit and encourage smoking cessation. Second, pictorial TPWLs increase attention, knowledge, negative affect, and thinking about the warning. Third, TPWL studies have primarily used brief-exposure laboratory studies and observational studies of sustained exposure through national policy implementation, with a few randomized trials involving several weeks of exposure-with generally consistent results found across study designs. Fourth, novel assessment methods include brain imaging, eye tracking and "best-worst" discrete choice experiments. To make TPWL even more effective, research is needed to confirm the mechanisms of their influence, their impact across vulnerable populations, and their effect on social media posts about tobacco products. Research is also needed on the effect of trial design choices, the predictive validity of new measurement approaches, and warning labels for non-cigarette tobacco products., Implications: To improve scientific understanding of TPWL effects, this grantee meeting summary describes emerging research methods, theory and study results. Directions for future research include examination of the mechanisms of how warning labels work across diverse tobacco products and across different populations and contexts., (Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2018.)

Introduction: The U.S. Food and Drug Administration (FDA) has stated its interest in reducing the addictiveness of combustible cigarettes by lowering their nicotine content. Delineating risk perceptions of reduced nicotine content (RNC) cigarettes prior to federal regulation may inform the content of future educational campaigns accompanying this policy., Methods: Five hundred non-treatment-seeking, daily smokers naïve to RNC cigarettes (63.0% male, 51.6% nonWhite, mean [SD] cigarettes per day = 15.69 [7.58], age = 43.44 [11.46]) completed a 10-item RNC cigarette risk perception questionnaire at baseline in two, unrelated experimental studies. We used multinomial logistic regression models to identify demographic (eg, gender) and smoking-related (eg, nicotine dependence) correlates of RNC cigarette risk perceptions., Results: Although the majority of participants did not misperceive RNC cigarettes as less harmful than regular or high nicotine cigarettes, a large portion of the sample held misperceptions about RNC cigarettes' addictiveness (56.4%) and cessation aid potential (63.4%). More than 20% of the sample reported being unsure about RNC-related risks, especially tar content (51.8%). NonWhite smokers were 2.5 to 3 times more likely to be incorrect about multiple RNC cigarette risks (p = .002-.006)., Conclusions: If the FDA mandates a reduced nicotine content standard for cigarettes, educational campaigns will be needed to correct misperceptions about RNC cigarettes' addictiveness and potential to aid cessation as well as inform consumers about their safety risks. Campaigns tailored toward nonWhite smokers may also be needed to correct misperceptions of RNC cigarette risks held by this subgroup., Implications: The FDA has stated its interest in reducing cigarettes' addictiveness by lowering their nicotine content, enabling smokers to quit. Our findings suggest that most smokers who have not used RNC cigarettes do not perceive these products as less addictive or as cessation tools, stressing a need for future educational campaigns to correct these misperceptions. Campaigns are also needed to educate uninformed smokers about RNC cigarettes and should consider targeting messages toward subgroups likely to hold misperceptions about the risks and benefits of using these products (eg, nonWhite smokers)., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Recent research has shown that message congruency is beneficial to recall of pictorial health warning label (PWL) content after initial exposure. Despite less attention to the text warning, smokers exposed to congruent PWLs were more likely to recall the text and the message. This study aimed to replicate these findings and to examine whether congruency also affects recall after multiple exposures over time., Methods: A total of 320 daily smokers (39.7% female; cigarettes/day: M = 15.31, SD = 7.15) were randomized to one congruent or incongruent PWL and attended 4 laboratory sessions over 10 days. During each session, eye movements were recorded while viewing the PWL and open-ended recall of label content was assessed after exposure., Results: Smokers who were exposed to a congruent PWL were more likely to recall the text (p = .01) and the message (p = .02) and less likely to recall the image (p = .003) of the PWL after initial exposure. By day 4, incongruent PWLs were recalled equally well as congruent PWLs. Independent of condition, image recall was initially high and remained high whereas text and message recall was relatively low initially but increased over time. It was not until day 7 that about 80% of text and message recall was observed., Conclusions: Even when exposed to the same PWL over time, smokers require multiple exposures to recall the text and the message of a PWL. More research on the effects of congruency in the natural environment, where smokers are exposed to multiple PWLs, is needed., Implications: The findings of this study, and of previous work showing that message congruency in PWLs is beneficial to initial recall of PWL content, could potentially help to address legal challenges regarding the implementation of PWLs in the United States. Factually correct text warnings have been uncontested on US cigarettes packages since 1966. Congruent PWLs simply provide a means to visually support the same information as the existing text using a medium that better garners attention to the health information. Investigating and understanding longer-term effects of congruency are important and can empirically inform future warning label development, both in the United States via the Family Smoking Prevention and Tobacco Control Act, and via other governing bodies., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Understanding how smokers perceive reduced nicotine content cigarettes will be important if the FDA and global regulatory agencies implement reduced nicotine product standards for cigarettes. Prior research has shown that some smokers incorrectly believe "light" cigarettes are less harmful than regular cigarettes. Similar misunderstandings of health risk could also apply to reduced nicotine cigarettes. To date, most studies of reduced nicotine cigarettes have blinded subjects to the nicotine content. Therefore, little is known about how smokers experience reduced nicotine content cigarettes when they are aware of the reduced content, and how use may be impacted., Methods: The present study was a within-subjects experiment with 68 adult daily smokers who smoked two identical very low nicotine content Quest 3 (0.05 mg nicotine yield) cigarettes. Subjects were told that one cigarette contained "average" nicotine content, and the other contained "very low" nicotine content. After smoking each cigarette, subjects completed subjective measures about their smoking experience., Results: Subjects rated the "very low" nicotine cigarette as less harmful to their health overall compared to the "average" nicotine cigarette; this effect held true for specific smoking-related diseases. Additionally, they rated the "very low" nicotine cigarette as having less desirable subjective effects than the "average" nicotine cigarette and predicted having greater interest in quitting smoking in the future if only the "very low" nicotine cigarette was available., Conclusions: Explicit knowledge of very low nicotine content changes smokers' perceptions of very low nicotine content cigarettes, resulting in reduced predicted harm, subjective ratings and predicted future use., Implications: Before a reduced nicotine product standard for cigarettes can be implemented, it is important to understand how product information impacts how smokers think about and experience very low nicotine content cigarettes. Prior research has shown that smokers incorrectly believed light cigarettes were less harmful products. As such, smokers may also misunderstand the health risks associated with smoking very low nicotine content cigarettes. This study highlights the importance of smokers' perceptions of nicotine content in cigarettes on the perceived health risks and the subjective effects of smoking very low nicotine content cigarettes., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Despite a worldwide increase in the use of Make Your Own (MYO) cigarettes, there is little research characterizing MYO smokers in the United States and the cigarettes they make., Methods: In a single laboratory visit, exclusive MYO smokers brought 5 MYO cigarettes they prepared at home, completed demographic and smoking history questionnaires, and prepared 25 cigarettes using their own tobacco and materials., Results: Participants were mostly male (86.7%), average age of 41.3 years, and smoked an average of 19.5 (SD = 7.9) MYO cigarettes per day. They produced two types of cigarettes-by rolling tobacco in a paper leaf (Roll Your Own [RYO, n = 56]) and by injecting tobacco into a tube (Personal Machine Made [PMM, n = 42]). The PMM cigarettes were significantly larger than RYO cigarettes (p < .001). Home- (0.97 g) and laboratory-produced (0.95 g) PMM cigarettes did not differ by weight; however, the RYO cigarettes made at home (0.45 g) were slightly, but significantly, larger than those produced in the laboratory [0.43 g (p < .05)]. There was significant internal consistency in the weight of RYO and PMM cigarettes (intraclass correlation coefficient = 0.82, 0.84, respectively). Time to produce RYO cigarettes (53 s/cigarette) was significantly longer than that of PMM cigarettes (42 s/cigarette) (p < .01)., Conclusions: By using commercially available tobacco, tubes, and paper, experienced MYO smokers can quickly and consistently prepare cigarettes that may be useful in laboratory smoking topography and exposure experiments. Increasing the regulation of Factory Made (FM) cigarettes may lead to increased use of MYO cigarettes with unknown toxicant exposure and health risks to their consumers.

Introduction: This study examines the impact of smoking cues employed in antismoking advertisements on former smokers. Previous findings indicate that visual smoking cues in antismoking advertisements with weak antismoking arguments can elicit smoking urges in smokers and undermine message effectiveness. This study extends these observations to former smokers asking whether smoking cues in antismoking advertisements influence former smokers' self-efficacy, attitudes, and intention to refrain from smoking, along with smoking urges and perceived message effectiveness., Methods: The study was a mixed 2 (smoking cues; present vs. absent) × 2 (argument strength [AS]; high vs. low) design where smoking cue was a between-subject factor and AS was a within-subject factor. Potential participants recruited via online ads were screened in a phone interview for their eligibility. A total of 105 former smokers (aged 21-65) participated in the study, which was conducted in a laboratory setting. Repeated measure ANOVA and MANOVA were used for the analyses., Results: The results showed that the presence of smoking cues in antismoking ads undermines former smokers' behavioral self-efficacy, attitude, and intention about smoking abstinence, which increased as AS for the ads increased. Former smokers' reports of smoking urge were not affected by smoking cues or AS. However, consistent with previous findings for smokers, the presence of cues weakened perceived message effectiveness of antismoking ads rated by former smokers., Conclusions: The effect of smoking cues on former smokers' self-efficacy, attitude, and intention to refrain from smoking is problematic. Inclusion of smoking cues in antismoking ads should be undertaken only when accompanied by strong arguments.

Introduction: The study examines the effectiveness of antismoking public service announcements (PSAs) among adult smokers as a function of smoking cues and the argument strength of the PSAs. Consistent with the previous cue-reactivity studies, smoking cues are defined as one of the following visual scenes: (a) objects associated with smoking, (b) holding or handling cigarettes, and (c) actual smoking behaviors. Argument strength indicates smoker's judgments of perceived strength and persuasiveness of the arguments extracted from the PSAs., Methods: Data were collected through a web-based experiment of a random sample of general population of smokers (n = 566 adults aged 19 years or older). Each participant was shown 4 PSAs randomly selected from a set of 60. Data were analyzed using multilevel modeling to assess the effects of smoking cues and argument strength. Effectiveness measures include perceived persuasiveness, transportation, valenced thought, negative emotion, and smoking-related thoughts., Results: Argument strength is a significant predictor of outcome variables. Although there were no significant main effects of smoking cues on any outcome variables, smoking cues were found to interact with argument strength such that the association between argument strength and outcome variables became weaker for PSAs in the smoking cue condition compared with those in the no-cue condition., Conclusions: The interaction between smoking cues and argument strength suggests that smoking cues in antismoking PSAs undermine a significant part of what makes PSAs effective-their arguments against smoking. In designing antismoking messages, the inclusion of smoking cues should be weighed carefully.

Background: Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of the partial nicotine agonist varenicline on ERPs., Methods: We measured the effects of varenicline and nicotine on the mouse P20 and varenicline and smoking on the human P50 in a paired-click task. Eighteen mice were tested following nicotine, varenicline, and their combination. One hundred and fourteen current smokers enrolled in a placebo-controlled within-subject crossover study to test the effects of varenicline during smoking and abstinence. Thirty-two subjects participated in the ERP study, with half receiving placebo first and half varenicline first (VP)., Results: Nicotine and varenicline enhanced mouse P20 amplitude, while nicotine improved P20 habituation by selectively increasing the first-click response. Similar to mice, abstinence reduced P50 habituation relative to smoking by reducing the first-click response. There was no effect of varenicline on P50 amplitude during abstinence across subjects. However, there was a significant effect of medication order on P50 amplitude during abstinence. Subjects in the PV group displayed reduced P50 during abstinence, which was blocked by varenicline. However, subjects in the VP group did not display abstinence-induced P50 reduction., Conclusions: Data suggest that smoking improves sensory processing. Varenicline mimics amplitude changes associated with nicotine and smoking but fails to alter habituation. The effect of medication order suggests a possible carryover effect from the previous arm. This study supports the predictive validity of ERPs in mice as a marker of drug effects in human studies.

Introduction: Antitobacco media campaigns using public service announcements (PSAs) have shown promise in reducing smoking initiation and increasing intentions to quit. Research on what makes an effective PSA has had mixed outcomes. The present study tested the effects of specific message features in antitobacco PSAs, using theory-based physiological and self-report outcomes., Methods: PSAs were categorized as high or low in message sensation value (MSV) and strength of argument and presented to 200 current smokers in a 2 x 2 factorial design. Physiological responses-specifically, heart rate, skin conductance, zygomaticus major, and corrugator supercilii-were assessed while participants viewed the PSAs. Beliefs, attitudes, efficacy, norms, and intentions to quit were assessed immediately following viewing., Results: Corrugator activity was significantly greater in the high MSV condition. Among those low in sensation seeking, low MSV PSAs elicited higher self-efficacy, whereas the reverse was true for high sensation seekers. High MSV PSAs elicited higher negative beliefs in low sensation seekers. Adding physiological measures to a model predicting intention to quit did not improve the explained variance., Discussion: The present study represents the first comprehensive theory-based experimental investigation of the effects of different features of antitobacco PSAs and provides a framework for future research in identifying effective features of such PSAs. Results illustrate the importance of considering individual differences, characterizing both PSA content and format, and outcome and response measures when evaluating antitobacco PSAs.

Introduction: Studies have found that smoking-related cues elicit smoking urges in addicted smokers. This work presents the first cue-reactivity study in the context of antismoking advertisements., Methods: Using a two (no cue vs. smoking cue) by two (high vs. low argument strength) mixed design, we tested the hypothesis that smoking cues presented in antismoking advertisements elicit smoking urges. The study tested 96 adult smokers using both self-reported and psychophysiological measures of smoking urge. It also explored gender differences during the urge elicitation., Results: Smoking cues in antismoking advertisements elicited smoking urges in the weak argument condition., Discussion: Antismoking advertisements with smoking cues and weak antismoking arguments could produce boomerang effects on smokers through urge elicitation.

Introduction: Nitrosation of nicotine or its metabolites in the human body could lead to formation of the 2 carcinogenic tobacco-specific nitrosamines-N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)., Methods: We investigated the possibility of endogenous formation of NNN in people who had stopped smoking and used the 21-mg nicotine patch for 6 months. We quantified urinary biomarkers of exposure to NNN-the sum of NNN and its pyridine-N-glucuronide, referred to as total NNN. Also measured were NNK metabolites-the sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides, referred to as total NNAL., Results: The average decline of urinary total NNN was less drastic than that of total NNAL: 22% of baseline total NNN and 7.3% of baseline total NNAL were detected in urine 24 weeks after smoking cessation and patch use (p = .02). The average ratio of total NNN to total NNAL in the same urine samples increased from 0.14 in baseline urine to 0.38 after 24 weeks of nicotine patch use., Discussion: Overall, these results demonstrate that endogenous formation of NNN may occur in nicotine patch users. However, the levels of urinary total NNN during patch use were generally extremely low. Moreover, in 10 of 20 subjects analyzed here, the rate of decline in total NNN was similar to that in total NNAL, indicating that endogenous formation of NNN is virtually nonexistent in these subjects. Supplementation with ascorbic acid could be a simple approach to block possible NNN formation in nicotine patch users.

Nicotine dependence has a complex multifactorial etiology, underscoring the value of applying a transdisciplinary research model. The important goal of treating nicotine dependence can be realized by transdisciplinary research that translates discoveries in basic neuroscience, pharmacology, genetics, and behavioral science to develop new treatment models that can be translated readily into the clinic and community. As part of this special issue highlighting work at the Transdisciplinary Tobacco Use Research Centers (TTURCs), we describe transdisciplinary research at the University of Pennsylvania TTURC aimed at elucidating the neurobiological and genetic basis of nicotine dependence, the development of novel medications, and the translation of this research to practice.

Nicotine is metabolized into biologically inactive cotinine primarily by the cytochrome P450 enzyme CYP2A6. CYP2A6 genetic variations have been phenotypically grouped as slow, intermediate, and normal metabolizers. Slow metabolizers smoke fewer cigarettes daily and weekly, and have lower carbon monoxide (CO) and plasma nicotine levels, suggesting a reduced smoking rate compared with normal metabolizers. CYP2A6 also is involved in the metabolic activation of tobacco-specific procarcinogenic nitrosamines, such as 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). NNK is one of the most abundant and potent procarcinogens in cigarette smoke. The present study investigated the association of CYP2A6 genotype with smoking topography, a quantifiable measure of smoking behavior, in a sample of treatment-seeking smokers prior to treatment. Smoking topography measures indicative of quantity of smoke exposure--number of puffs, mean puff volume, and total puff volume--were the outcome variables. Covariates associated with smoking topography were included in the analyses. Results indicated that CYP2A6 genotype group had a significant effect on mean puff volume and total puff volume, but not number of puffs, such that slow metabolizers exhibited reduced puffing compared with others. Smokers having CYP2A6 variants resulting in low activity metabolize nicotine more slowly, and convert procarcinogen nitrosamines to carcinogens more slowly, than do normal metabolizers. The results from this study also suggest a behavioral mechanism that may account for reduced cancer risk in slow metabolizers.

Cigarette smoking, like many addictive behaviors, has been shown to have a genetic component. The dopamine transporter (DAT) gene (SLC6A3) encodes a protein that regulates synaptic levels of dopamine in the brain and is a candidate gene for addictive behaviors. We have collected smoking information from a national probability sample of 3383 adult volunteers contacted via a random-digit dialing telephone interview. A subset of individuals provided DNA from cheek swabs returned via the mail for subsequent genetic analysis of self-reported smoking behavior. DNA samples were genotyped at a variable number of tandem repeats (VNTR) polymorphism in the 3'-untranslated region of the DAT gene. If we classify smokers as non- (<100 cigarettes), former and current, we fail to replicate both Lerman et al. (Health Psychology 18:14-20, 1999) and Sabol et al. (Health Psychology 18:7-13, 1999) and support the absence of effects found by Jorm et al. (American Journal of Medical Genetics (Neuropsychiatric Genetics) 96:331-334, 2000). When we distinguish between never-smokers (no cigarettes ever) and non-smokers (1-99 in lifetime), we find a reliable trend essentially in the opposite direction from Lerman et al. (1999), with the 10-copy allele being more frequent in never-smokers. Biobehavioral research on cigarette smoking should distinguish between never- and non-smokers. We have also developed an improved set of polymerase chain reaction conditions to increase the frequency of successful amplification of DAT'sw VNTR, which is a long, G+C-rich repeat.