Mobile, Remote, and Individual Focused: Comparing Breath Carbon Monoxide Readings and Abstinence Between Smartphone-Enabled and Stand-Alone Monitors.

INTRODUCTION: Newly available, smartphone-enabled carbon monoxide (CO) monitors are lower in cost than traditional stand-alone monitors and represent a marked advancement for smoking research. New products are promising, but data are needed to compare breath CO readings between smartphone-enabled and stand-alone monitors. The purpose of this study was to (1) determine the agreement between the mobile iCO (Bedfont Scientific Ltd) with two other monitors from the same manufacturer (Micro+ pro and Micro+ basic) and (2) determine optimal, monitor-specific, cotinine-confirmed abstinence cutoff values. METHODS: Adult (≥18) smokers (n = 26) and nonsmokers (n = 21) provided three breath CO samples (using three different monitors) in each of 10 sessions, and urine cotinine was measured for gold standard determination of abstinence. CO comparisons (N = 437) were analyzed using regression-based Bland-Altman Analysis of Agreement; receiver operating characteristics curves were used to determine optimal abstinence cutoffs. RESULTS: Bland-Altman analyses indicated that the iCO monitor provided higher CO results than both Micro+ monitors. Sensitivity and specificity analyses showed that the optimal CO cutoff for determining abstinence was <3 ppm for the Micro+ pro (88% sensitivity, 93% specificity) and Micro+ basic (83% sensitivity, 98% specificity), but was higher for the iCO (<6 ppm; 73% sensitivity, 100% specificity). CONCLUSIONS: Relative to both Micro+ monitors, the smartphone-enabled iCO provided systematically higher CO values and required a higher cutoff to reliably determine smoking abstinence. This does not indicate that CO values obtained using the iCO are not valid; instead, these results suggest that monitor-specific abstinence cutoffs are needed to ensure accurate bioverification of smoking status. IMPLICATIONS: Results from this study indicate that CO values from the smartphone-enabled iCO should not be used interchangeably with the stand-alone Micro+ pro and Micro+ basic, particularly when lower CO values (<10 ppm) are critical (ie, determination of abstinence vs confirming smoking status for study inclusion). Optimal CO cutoffs recommended for determining abstinence on Micro+ and iCO monitors are at <3 and <6 ppm, respectively.

Differences in Magnitude of Cue Reactivity Across Durations of Smoking History: A Meta-analysis.

BACKGROUND: Cue-elicited craving may vary due to duration of smoking history, increasing as more years of smoking strengthen associations between nicotine intake and cues. However, research on this relationship is virtually absent. This project assessed the relationship between cue reactivity and years of smoking. METHODS: Data from 53 studies (68 effect sizes) were analyzed. Eligible studies were those measuring self-reported craving following cue exposure in nontreatment seeking smokers and reporting mean years smoking. Preliminary subgroup analyses identified methodological factors influencing cue-reactivity effect sizes; primary meta-regression analysis assessed differences across years smoking; exploratory analyses assessed potential for ceiling effects. RESULTS: Effect sizes varied due to abstinence requirement and cue presentation modality, but not dependence severity. Unexpectedly, meta-regression analysis revealed a decline in effect sizes across years smoking. Exploratory analyses suggested declines may have been due to a ceiling effect in craving measurement for those with longer smoking histories-more experienced smokers reported higher levels of craving at baseline or following neutral cue exposure, but all reported similar levels of craving after smoking cue exposure. CONCLUSIONS: Methodological factors and duration of smoking history influenced measurement of cue reactivity. Highlighted were important relationships between years smoking and magnitude of cue reactivity, depending on use of baseline or neutral cue comparisons. Further research is needed to assess differences in cue reactivity due to duration of smoking history using participant-level data, directly testing for ceiling effects. In addition, cue-reactivity studies are needed across young adults to assess onset of associations between nicotine intake and cues. IMPLICATIONS: This meta-analysis project contributes to the cue-reactivity literature by reporting on the previously ignored relationship between duration of smoking history and magnitude of cue-elicited craving. Results suggest that declines in cue-reactivity effect sizes across years of smoking may have been due to study-level methodological factors, but not due to differences in sample-level dependence severity. Cue-reactivity effect sizes were stable across years of smoking in studies using a neutral cue comparison but declined sharply in studies when baseline assessment (typically coupled with an abstinence requirement) was used.

A Procedure to Standardize Puff Topography During Evaluations of Acute Tobacco or Electronic Cigarette Exposure.

INTRODUCTION: Documenting factors that influence differential sensitivity to acutely inhaled nicotine products requires carefully controlling the amount of exposure (dose), and thus a procedure by which to control such exposure. METHODS: We evaluated consistency of puff volume from intermittent acute exposures to smoked tobacco cigarettes (study 1, n = 45, plus a comparison study of uninstructed use with n = 59) and to vaped electronic cigarettes (e-cigarettes; study 2, n = 27 naive to e-cigarettes) in adult-dependent smokers. All in primary studies 1 and 2 participated in research administering different nicotine levels in each product under blind conditions, one per session using within-subject designs. In both studies, participants followed an automated instructional procedure on a computer monitor standardizing the timing and amount of exposure to each product during a given trial, with four trials per session, each separated by 20 minutes. Puff volume per trial via Clinical Research Support System (CReSS) was the primary dependent measure to determine consistency across trials via intraclass correlation coefficients (ICCs). RESULTS: Control over topography with both inhaled products was demonstrated by highly significant ICCs for puff volume across trials. Instructed control with own brand was generally better in study 1 than with uninstructed smoking in the comparison sample, as expected. As intended, reliability of puff volume generally did not differ by menthol preference or sex in either study, but ICCs in study 2 tended to be lower for some men using the placebo e-cigarette. CONCLUSIONS: This instructional procedure may substantially improve control over amounts of acute exposure to tobacco or e-cigarette use. IMPLICATIONS: Control over topography in studies of acute exposure to these inhaled products can potentially aid validity of research into differential sensitivity to use, so findings can be attributed to factors of interest and not to variable exposure. Our procedure minimized variability in exposure to the same product and between moderate nicotine products, but remaining differences suggest that compensation for very low or no nicotine commercial products may be difficult to totally eliminate with these instructions alone. Further study is needed to determine this procedure's utility with other inhaled products among experienced users and when comparing different products in between-groups analyses.

A Forced-Choice Procedure to Assess the Acute Relative Reinforcing Effects of Nicotine Dose per se in Humans.

INTRODUCTION: A method to assess acute reinforcement due to nicotine may aid identification of doses needed to maintain dependence. After describing development of a forced-choice procedure, results are presented from two studies using it to determine the relative reinforcing effects of nicotine dose per se. AIMS AND METHODS: Choice between a higher versus a very low or no nicotine option, via smoking (Study 1, n = 59) and via nasal spray (Study 2, n = 42), was assessed in nontreatment-seeking dependent smokers abstinent overnight. Using a within-subject design, different nicotine levels for each product were administered under blind conditions, initially to assess their discriminability (Study 1: 1.3-17 mg/g each vs. 0.4 mg/g nicotine Spectrum cigarettes; Study 2: 2.5 µg/kg vs. 0 µg/kg nicotine per spray). At the end of sessions for each study, participants engaged in forced-choice trials to assess preference, requiring a fixed number of puffs/sprays for one and/or the other. RESULTS: Confirming the procedure's validity, the choice of the higher nicotine option was significantly greater than that for the very low or no nicotine option in both studies. In Study 1, choice relative to 0.4 mg/g was greater for cigarettes 5.3 mg/g or more but not 2.3 mg/g or less (p = .003 for the interaction of higher content vs. 0.4 mg/g comparison). In Study 2, choice was greater for the nicotine versus placebo spray (p < .005), as nicotine was preferred nearly twice as much as the placebo. CONCLUSION: This forced-choice procedure may efficiently determine the relative reinforcing value of a nicotine dose per se. IMPLICATIONS: The forced-choice procedure described here may identify nicotine doses that are acutely reinforcing in dependent smokers. A priori research of choice comparisons between small versus zero nicotine doses could inform clinical research in larger and more diverse samples to determine nicotine contents in cigarettes, and perhaps in other commercial products, that are not reinforcing and, thus, likely to reduce the risk of their addictiveness. This procedure may also be applicable to assessing changes in acute nicotine reinforcement due to different product formulations, novel drugs, or other manipulations, perhaps helping inform development of new interventions for cessation or harm reduction.

Reinforcement Enhancing Effects of Nicotine Via Patch and Nasal Spray.

INTRODUCTION: Confirming preclinical findings, nicotine in humans (via smoking) enhances reinforcement from nondrug rewards. Recent demonstration of similar effects with nicotine via e-cigarettes suggests they may also occur when using nicotine replacement therapies (NRT). METHODS: Effects of nicotine via NRT patch or nasal spray were assessed on responding reinforced by music, video, or monetary rewards, or for no reward (control). Nontreatment seeking smokers (N = 31) participated in three virtually identical experimental sessions, each following overnight abstinence (CO ≤ 10 ppm). In a fully within-subjects design using a double-dummy procedure, these sessions involved: (1) nicotine patch (Nicoderm 14 mg) plus placebo spray, (2) placebo patch plus nicotine spray (Nicotrol, 2 × 1 mg/trial), or (3) placebo patch plus placebo spray. Session order was counter-balanced. RESULTS: Relative to placebo, reinforced responding due to nicotine via spray or patch was greater for video reward (both p < .01) but not for music reward (both p > .10). Similar results for NRT spray and patch confirms preclinical findings indicating no difference between fast and slow nicotine delivery, respectively, on reinforcement enhancing effects. Withdrawal relief was unrelated to these effects of nicotine via NRT on nondrug reinforcement. CONCLUSIONS: Nicotine from NRT has some reinforcement enhancing effects in humans, possibly in a manner consistent with nicotine via e-cigarettes but not tobacco smoking. Our findings could suggest differential dose-dependency of available rewards to enhanced reinforcement by nicotine. Such effects may help contribute to the efficacy of NRT for aiding smoking cessation, but more research focusing on dose-dependency of these nicotine actions is needed. IMPLICATIONS: Acute nicotine from smoking enhances reinforced responding for nondrug sensory rewards. Yet, nonsmoked nicotine, including from NRT medications of patch and nasal spray, may act more selectively across rewards, perhaps due to lower dosing exposure. Our results suggest that nicotine via NRT enhances responding for visual (video) reward, but not from auditory (music) reward, just as in prior results using e-cigarettes. Withdrawal relief from NRT was unrelated to reinforced responding, consistent with positive (and not negative) reinforcement from this nicotine. Further research evaluating the dose-response effects of nicotine may clarify differences in enhanced reinforcement depending on the type of available reward.

Acute perceptions of preferred cigarettes when blinded to brand.

BACKGROUND: Marketing claims often have promoted specific perceptions that users should expect from acutely smoking that cigarette brand. Yet, little controlled study has determined the degree to which actual perceptions are based on the cigarette's tobacco constituents in the absence of knowledge about the brand's identity. METHODS: 194 adult dependent smokers rated their perceptions on 'liking', 'satisfying', 'strong' and perceived amount of 'nicotine' after smoking ad lib one of their preferred brands of cigarettes. All did so either when blinded (n=118) or unblinded (n=76) to the brand they were given, with the blinding conditions from separate studies. These between-groups secondary analyses determined differences in perceptions based on blinding to brand, controlling for age and cigarettes/day. RESULTS: All perceptions were lower for those smoking own brand under blinded versus unblinded conditions, as hypothesised. Consistent with lowered perceptions for smoking one's own brand obtained from the 118 blinded to brand, their 'somewhat' ratings for a 'how similar to own brand' item indicated uncertainty, just mid-way between 'not at all' and 'very much' on the 0-100 visual analogue scale. (The 76 unblinded were already informed it was their own brand.) CONCLUSIONS: Acute perceptions of one's own cigarette are substantially lower when smokers are simply unaware of brand, relative to those aware it is their preferred brand. Results support the notion that perceptions of smoking own brand are enhanced by marketing efforts to associate brands with expectations of pleasurable subjective effects, beyond the impact due solely to the cigarette's manufactured product constituents.

Sex Differences in Subjective Responses To Moderate Versus Very Low Nicotine Content Cigarettes.

Introduction: Men and women may be differentially sensitive to the acute perceptual responses to smoking cigarettes that vary in nicotine content ("dose") but are matched on non-nicotine constituents. Methods: Dependent adult smokers (43 M, 31 F) took four controlled puffs from Spectrum research cigarettes that were moderate (16-17 mg/g) or very low (0.4 mg/g) in nicotine content, and matched on "tar." To ensure reliable responses, each cigarette was administered singly five times in random order under blind conditions, with one or the other provided every 15 minutes over a 2.5-hour session following overnight abstinence. Subjective perceptions (eg, "satisfying", "how much nicotine") were rated after each cigarette. Results: Subjective ratings differed due to cigarette nicotine content, as expected, and did so differentially between men and women. The interaction of nicotine content by sex was significant for most rated subjective perceptions of the cigarette, as multivariate analyses showed that differences due to nicotine content were highly significant for men (p < .001) but only marginal for women (p = .08). Conclusions: Relative to men, women's subjective responses to acute smoking are less sensitive to differences in cigarette nicotine content. To our knowledge, this is the first comparison of sex differences in response to very carefully controlled doses of smoked nicotine per se. Further research should examine possible sex differences in nicotine dosing administered by other smoked and nonsmoked methods, as well as the developmental pattern of these differences during onset and during cessation of dependent smoking. Implications: Subjective perceptions of smoking cigarettes varying in nicotine contents differ between men and women. These results with research cigarettes are similar to other studies with carefully dosed nicotine administration by other means, supporting the notion that women, relative to men, are less sensitive to pharmacological factors and more sensitive to nonpharmacological factors in acute cigarette smoking. Future studies are warranted to examine sex differences in other responses to controlled nicotine intake via smoking, and via other smoked and nonsmoked methods of administering nicotine doses.

Validating Use of Internet-Submitted Carbon Monoxide Values by Video to Determine Quit Status.

INTRODUCTION: Daily visits to biochemically verify continuous smoking abstinence via expired-air carbon monoxide (CO) may deter participation in cessation trials. One way to reduce need for daily visits while continuing to monitor abstinence success may be use of a recent procedure to verify abstinence from daily CO values via the Internet. This method requires participants submit to study staff video recordings of themselves correctly using a CO monitor. However, it has not been clearly demonstrated that those classified quit via Internet-submitted videos of CO would be reliably classified quit when assessed in lab. METHODS: Our study examined agreement in quit status from Internet-submitted CO values with quit status via CO collected in later same-day lab visits. Participants (n = 23) were from a short-term cessation study who agreed to record and submit videos of offsite CO testing, in addition to attending daily lab visits. All CO values were obtained via Bedfont pico+ Smokerlyzer monitors, with CO < 8 ppm indicating quit. During two 4-day practice quit attempts, a video was submitted before daily lab visits, up to eight videos each. RESULTS: Of the total of 150 videos submitted, 97 videos indicated "not quit" and 53 "quit." Cohen's Kappa indicated substantial agreement in quit status between assessments, 0.70, p < .001, as 85% of the videos indicating "quit" CO were also "quit" CO in lab. CONCLUSIONS: To our knowledge, these results are the first validation of daily Internet-submitted CO values to confirm daily quit status, supporting the utility of this approach for close monitoring of continuous abstinence. IMPLICATIONS: This study compared consistency between quit status from CO values submitted over the Internet and quit status via CO collected in later same-day lab visits. Findings indicate substantial agreement in quit status between these two methods of CO assessment. Our results validate the use of Internet-submitted CO values to verify daily quit status. This method can be used in future cessation trials as a means to biochemically validate continuous abstinence without the burden of daily lab visits or relying on self-report of recent smoking lapses.

Assessing Discrimination of Nicotine in Humans Via Cigarette Smoking.

INTRODUCTION: Nicotine's interoceptive stimulus effects likely help explain smoking's reinforcing efficacy, but human studies have been limited by difficulties controlling dosing via tobacco inhalation. Our objective was to describe a procedure to study nicotine discrimination via smoking. METHODS: Dependent smokers abstinent overnight (>12 hours) were first "trained" to discriminate between two cigarettes differing in nicotine content, based on four puffs of exposure, and then tested on whether they successfully acquired that discrimination. After piloting with Quest brand commercial cigarettes, 29 subjects engaged in the main study with cigarettes available through NIDA (Spectrum; 16mg vs. 0.4mg nicotine content). Discrimination training first involved two trials, one with each cigarette, prior to six testing trials. Due to results with the first 20 subjects, the remaining nine received two training trials with each cigarette (four total). Subjective perceptions were also assessed during each testing trial, and puff choice between the two cigarettes available concurrently was assessed after testing, on the last two trials. RESULTS: All five pilot subjects successfully discriminated Quest 1 versus Quest 3 (defined by at least five out of six trials correct, ie, >80%). Yet, only 10 of 20 subjects (50%) were able to discriminate the two Spectrum cigarettes based on two training trials. After changing to four training trials, eight of nine subjects were able to discriminate (89%). Subjective perceptions and puff choice differed between cigarettes more in those able versus unable to discriminate them. CONCLUSIONS: With sufficient training exposures, smokers can discriminate nicotine between cigarettes differing in nicotine contents. IMPLICATIONS: The interoceptive stimulus effects of nicotine are critical to understanding reinforcement from cigarette smoking behavior. Because of the very recent availability of Spectrum research cigarettes from NIDA, with specific known amounts of nicotine content, the study of nicotine discrimination in humans via cigarette smoking may now be feasible. Our results demonstrate that, with sufficient training, smokers can behaviorally discriminate nicotine from four puffs' exposure between cigarettes differing in nicotine contents. Future research should evaluate human discrimination of nicotine from greater amounts of cigarette smoke exposure, as well as in response to other procedural variations.

Initial Evaluation of Fenofibrate for Efficacy in Aiding Smoking Abstinence.

INTRODUCTION: Primate and rodent models show that peroxisome proliferator-activated receptor-alpha (PPAR-α) ligands, including fibrate medications, reduce nicotine reinforcement, reward, and related effects. We tested fenofibrate, the most common U.S. Food and Drug Administration-approved fibrate for lipid control versus placebo for initial evidence of efficacy in smoking cessation using a validated cross-over procedure for early Phase 2 evaluations. METHODS: Adult dependent smokers (N = 38) in this 4-week within-subjects study were those already intending to try to quit in the next 2 months. All smoked ad libitum during weeks 1 (baseline) and 3 (washout) and began fenofibrate (160 mg/d; dosing approved for lipid control) or placebo near the end of weeks 1 and 3. Following each 4-day dose run-up, they were then instructed to try to quit for 4 days (Tuesday-Friday) during weeks 2 and 4, with the order of medication conditions counter-balanced and administered double-blind. Abstinence was verified daily in each 4-day quit period by self-report of no smoking in the prior 24 hours and carbon monoxide < 5 ppm. Secondary measures of acute smoking reinforcement and cue reactivity prior to quitting, and smoking reduction when trying to quit, were also assessed. RESULTS: No differences between fenofibrate versus placebo were found on days quit (means ± SEM of 1.8±0.3 vs. 1.9±0.3, respectively). Similarly, there were no differences in any of the secondary measures (all P > .20). CONCLUSIONS: Although higher dosing or other proliferator-activated receptor-alpha agonists may show efficacy, this study indicates that fenofibrate does not aid ability to stop smoking during a brief practice quit period in dependent smokers high in current quit interest.

Sex differences in acute relief of abstinence-induced withdrawal and negative affect due to nicotine content in cigarettes.

INTRODUCTION: Acute cigarette smoking may relieve withdrawal and negative affect due to tobacco abstinence to a greater extent in women versus men. Yet, the relative contribution of the cigarette's nicotine content to this sex difference is not clear. METHODS: Non-quitting dependent adult smokers (N = 44; 21 males, 23 females) participated in 2 virtually identical sessions, each after abstaining overnight (CO < 10 ppm) and differing only in the nicotine content of the designated cigarette. While blind to brand markings, they consumed a total of 24 puffs in controlled fashion for 2 hr in each session, either from a nicotine (Quest 1, 0.6 mg) or denicotinized (Quest 3, 0.05 mg) cigarette. Withdrawal symptoms were obtained before and after smoking, and negative affect was assessed after each period of cigarette exposure consisting of 6 puffs every 25 min. RESULTS: Men and women did not differ in baseline withdrawal and negative affect due to overnight abstinence, but reductions in each symptom were significantly influenced by the interaction of sex × nicotine/denicotinized cigarette (both p < .05). In men, but not in women, each symptom was generally decreased more by the nicotine versus denicotinized cigarette, and the nicotine cigarette reduced each to a greater degree in men versus women. CONCLUSIONS: Sex differences in relief of abstinence-induced withdrawal and negative affect due to the nicotine content in cigarettes are consistent with prior research indicating that nicotine per se, compared to non-nicotine smoke stimuli, is less rewarding in women versus men.

Effect of Flavored on! Nicotine Pouch Products on Smoking Behaviors: Protocol for a Sequential, Multiple Assignment, Randomized Controlled Trial.

BACKGROUND: Cigarette smoking is a leading cause of morbidity and mortality. For adults who smoke cigarettes and cannot or will not quit smoking, smoke-free products, such as nicotine pouches, have been recognized as a potential alternative to smoking combusted cigarettes to reduce harm due to cigarette smoking. The role of flavors in these smoke-free products in tobacco harm reduction has not been fully understood. OBJECTIVE: This study evaluates the effect of flavors in on! nicotine pouch products (research products) in the reduction of cigarette smoking among adults who smoke cigarettes in their natural environment. METHODS: This study uses a sequential, multiple assignment, randomized trial design. Approximately 400 eligible adults who smoke cigarettes will be enrolled and randomized to have access to either the Original (unflavored) on! nicotine pouch product only or a complete flavor profile (ie, Berry, Cinnamon, Citrus, Coffee, Mint, Original, and Wintergreen) of on! nicotine pouch products. After 3 weeks, participants in the Original-only arm will be randomized again, with half remaining in the Original-only arm and half having access to the complete flavor profile for another 3 weeks. Primary outcomes are expired-air carbon monoxide (CO) levels. Secondary outcomes are self-reported cigarette consumption and CO-verified cigarette abstinence. RESULTS: Recruitment and data collection started in September 2023 and is projected to last until March 2025. We anticipate completing the data analysis in 2025. As of May 2024, we have enrolled 314 participants. CONCLUSIONS: This study will provide empirical evidence about the effect that flavor availability in smoke-free products may have in reducing cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT06072547; https://clinicaltrials.gov/study/NCT06072547. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56565.

Optimal carbon monoxide criteria to confirm 24-hr smoking abstinence.

INTRODUCTION: Smoking cessation is typically verified biochemically by expired-air carbon monoxide (CO) levels below 9 ppm (i.e., ≤8 ppm), but this CO criterion may lead many who have smoked within 24hr to be misclassified as abstinent. METHODS: Adult dependent smokers (N = 261; 124 men, 137 women) prospectively recorded each cigarette smoked and provided CO on five consecutive days during each of two short-term attempts to quit smoking. Participants were those recruited for crossover tests of the effects of placebo versus medication (nicotine patch or varenicline) on the ability to initiate 24-hr abstinence. All had either a high or low interest in permanently quitting smoking soon (within 3 months) and were randomized to the presence or absence of daily ($12) monetary reinforcement of abstinence. RESULTS: Total accuracy of sensitivity to detect smoking (83%) plus specificity to verify abstinence (87%) was optimal at a CO criterion for abstinence below 5 ppm (≤4 ppm), compared with below 9 ppm (sensitivity of 60%, specificity of 97%). Overall CO detection of sensitivity and specificity was higher in those with high versus low quit interest, but reinforcement of abstinence made no difference. CONCLUSIONS: Results indicate a CO criterion half that used in most clinical research may optimally validate 24-hr cessation and reduce misclassification of smokers as "abstinent."

Possible reinforcement enhancing effects of bupropion during initial smoking abstinence.

INTRODUCTION: Due to a drop in nicotine, smoking cessation may attenuate reinforcement from sensory stimuli unrelated to nicotine intake. Recent rodent research suggests that bupropion may reverse this attenuation, perhaps helping explain its efficacy in aiding cessation. METHODS: In a within-subjects, crossover study, smokers responded on a simple computer task for brief music reward available on a progressive ratio 50% schedule. Testing was done on three separate occasions: after ad lib smoking during prequit baseline and on the first day of two brief quit attempts while taking bupropion or placebo, in counter-balanced order. Number of operant responses was the measure of reinforcement. To more clearly assess abstinence and medication effects, those meeting 24-hr abstinence criteria (CO < 5 ppm; n = 5) or clearly failing to abstain (CO > 10 ppm; n = 5) during both medication conditions were compared. RESULTS: Among abstainers, repeated measures ANOVA showed that reinforced responding decreased by nearly 50% from baseline after quitting on placebo (p = .03), while responding after quitting on bupropion was similar to that during baseline (-17%; p = .20). In contrast, those unable to abstain showed virtually identical reinforced responding due to either medication or baseline. CONCLUSIONS: These exploratory findings confirm that responding for a reward unrelated to smoking decreases after abstinence and are consistent with animal research showing bupropion effects on enhancing reinforced responding.

Smoking in response to negative mood in men versus women as a function of distress tolerance.

INTRODUCTION: Negative mood situations often increase smoking behavior and reward, effects that may be greater among women and smokers low in tolerance for distress. METHODS: Adult dependent smokers (N = 164; 86 men, 78 women) first completed measures of distress tolerance via self-report and by mirror-tracing and breath-holding tasks. They then participated in 2 virtually identical laboratory sessions, involving induction of negative versus neutral mood (control) via pictorial slides and music. They rated negative affect (NA) before and during mood induction and smoked their preferred brand ad libitum during the last 14 min of mood induction. Our aim was to examine mood effects on NA, smoking reward ("liking"), and smoking intake (puff volume and number) as a function of sex and distress tolerance. RESULTS: Negative mood induction increased NA, as planned, and smoking reward and intake compared with neutral mood. Increases in NA and puff volume due to negative mood were greater in women compared with men, as hypothesized, but no main effects of the self-report or behavioral distress tolerance measures were seen in responses to mood induction. However, unexpectedly, lower self-reported distress tolerance was associated with greater smoking intake due to negative (but not neutral) mood in men and generally due to neutral (but not negative) mood in women. CONCLUSIONS: Negative mood may increase smoking intake more in women compared with men. Yet, low distress tolerance may enhance smoking intake due to negative versus neutral mood differentially between women and men, suggesting that sex and distress tolerance may interact to influence smoking responses to negative mood.

The reliability of puff topography and subjective responses during ad lib smoking of a single cigarette.

INTRODUCTION: Acute smoking behavior (i.e., puff topography) and subjective responses during the ad lib smoking of a single cigarette in the laboratory may provide useful measures of smoking reinforcement and reward, respectively. However, the reliability of such measures is not clear, leaving uncertain the utility of a single assessment of smoking behavior as an individual difference measure. METHODS: Dependent smokers (N = 94) smoked normally prior to each of 4 laboratory sessions during which they were instructed to smoke 1 cigarette of their preferred brand in ad libitum and unblinded fashion and then rate it for subjective effects. Puff topography (puff number, total volume, and maximum volume) was assessed via portable Clinical Research Support System device. Subjective reward and perception were assessed by visual analog scales of "liking" and "how strong," respectively. The reliability of puff topography and subjective measures was determined across days by intra-class correlations (ICCs). Differences due to sex and nicotine dependence (high and low Fagerström Test for Nicotine Dependence score) were also examined. RESULTS: Reliability was highly significant for each measure. ICCs were .70 for total puff volume, .60 for maximum puff volume, .73 for puff number, .64 for liking, and .78 for how strong. Reliability generally did not differ by sex or dependence, but absolute values for total volume and maximum puff volume were greater in men and in high dependent smokers. Liking was also greater in high dependent smokers. CONCLUSIONS: Puff topography and subjective measures during the ad lib smoking of a single cigarette are highly reliable. Smoking responses during a single ad lib smoking session may be useful in identifying stable individual differences in smoking reinforcement and reward.

Acute subjective sensory perceptions predict relative reinforcing effects of smoked nicotine.

INTRODUCTION: Smoking is believed partially reinforcing via immediate sensory perceptions. Yet, unknown is whether a cigarette's relative reinforcing efficacy can be predicted by these perceptions and whether this relationship may vary due to constituents known to alter those perceptions. METHODS: Sensory perceptions of acute smoking were examined as predictors of subsequent cigarette choice behavior. Also tested was whether nicotine content or menthol affected this relationship. Adult dependent smokers (N = 37) participated in five sessions comparing cigarettes varying in nicotine contents (NIC; 1.3, 2.3, 5.5, 11.2, and 17.4 mg/g), relative to the very lowest nicotine content, 0.4 mg/g (VLNC). Non-menthol (n = 17) and menthol (n = 20) cigarettes-matched on nicotine-were provided based on participant preference. One NIC was compared versus VLNC per session (single-blinded); NIC content order was randomized across sessions on separate days. Perceptions (e.g., "liking", "satisfying") were measured immediately after initial sampling of NIC or VLNC, followed by a validated puff-by-puff choice procedure to determine preference for each NIC versus VLNC. RESULTS: NIC perceptions (difference from VLNC) and puff choices increased with nicotine. Menthol moderated associations between perceptions and nicotine; and between puff choices and nicotine. Perceptions were predictive of puff choice-greater magnitude of difference in perceptions between VLNC and NIC led to more NIC puff choices. When testing perceptions' prediction of puff choices, neither the main effect of menthol or interaction of Perceptions X Nicotine Condition were significant. CONCLUSIONS: Consistent with assumed-but rarely tested-causes of smoking reinforcement, sensory perceptions from a cigarette predict its relative reinforcing efficacy.

Comparing video observation to electronic topography device as a method for measuring cigarette puffing behavior.

BACKGROUND: Smoking topography, or puffing behavior, is an important measure of how consumers may use tobacco products. However, numerous issues may prevent collection of this data via in-person, electronic topography device (e.g., CReSS). This study compared cigarette topography measures collected by video observation and electronic device. METHODS: Laboratory smoking sessions were video recorded and scored for 96 cigarettes collected from 34 daily, adult non-treatment-seeking smokers (73.5 % male, 82.4 % White). Participants smoked three of their preferred brand cigarettes using an electronic topography device, providing carbon monoxide (CO) samples before and after each cigarette. Analyses compared measures from both assessment methods and examined associations with device-obtained total puff volume and CO boost. RESULTS: Agreement analyses indicated robust similarity between methods for measures of puff count and total interpuff interval (Intraclass Correlation Coefficient [ICC]'s > 0.96,p's < 0.001; Bland-Altman [B-A] plotted differences within a priori limit of clinical significance) but diverged on total duration (ICC's > .93, p's < .001, yet B-A plots outside a priori limits). Regardless of assessment method, total duration and puff count (but not total interpuff interval) predicted total puff volume (p's < .001). None predicted CO boost (p's = .07-.90)." CONCLUSIONS: Although some topography outcomes (e.g., total puff volume) cannot be assessed via video observation, video-observed measures of puff count, total duration, and total interpuff interval are generally interchangeable with their topography device-obtained counterparts. Thus, video observation is likely a sufficient substitute method for assessing cigarette topography when using an electronic device is not possible.

Cessation classification likelihood increases with higher expired-air carbon monoxide cutoffs: a meta-analysis.

BACKGROUND: Expired-air carbon monoxide (CO) is commonly used to biochemically verify smoking status. The CO cutoff and CO monitor brand may affect the probability of classifying smokers as abstinent, thus influencing conclusions about the efficacy of cessation trials. No systematic reviews have tested this hypothesis. Therefore, we performed a meta-analysis examining whether the likelihood of smoking cessation classification varied due to CO cutoff and monitor brand. METHODS: Eligible studies (k = 122) longitudinally assessed CO-verified cessation in adult smokers in randomized trials. Primary meta-regressions separately assessed differences in quit classification likelihood due to continuous and categorical CO cutoffs (Low, 3-4 parts per million [ppm]; [SRNT] Recommended, 5-6 ppm; Moderate, 7-8 ppm; and High, 9-10 ppm); exploratory analyses compared likelihood outcomes between monitor brands: Bedfont and Vitalograph. RESULTS: The likelihood of quit classification increased 18% with each 1 ppm increase above the lowest cutoff (3 ppm). Odds of classification as quit significantly increased between each cutoff category and High: 261% increase from Low; 162% increase from Recommended; and 150% increase from Moderate. There were no differences in cessation classification between monitor brands. CONCLUSIONS: As expected, higher CO cutoffs were associated with greater likelihood of cessation classification. The lack of CO monitor brand differences may have been due to model-level variance not able to be followed up in the present dataset. Researchers are advised to report outcomes using a range of cutoffs-including the recommended range (5-6 ppm)-and the CO monitor brand/model used. Using higher CO cutoffs significantly increases likelihood of quit classification, possibly artificially elevating treatment strategies.

Differences in acute reinforcement across reduced nicotine content cigarettes.

RATIONALE: The smallest difference in nicotine that can change a smoker's cigarette preference is not clearly known. OBJECTIVE: A procedure to efficiently identify the difference in nicotine needed to change cigarette preference could help inform research to gauge effects of a nicotine reduction policy. METHODS: Using a within-subject design, we assessed preference for research cigarettes varying in nicotine contents (NIC; 18.7, 10.8, 5.3, 2.3, and 1.3 mg/g of tobacco), relative to a very low nicotine cigarette (VLNC; 0.4 mg/g), in 17 adult-dependent non-menthol smokers abstinent overnight. Only one NIC was compared vs. the VLNC per session, with order of the five NIC contents randomized across sessions on five separate days. Preference for each NIC vs. VLNC was determined by validated forced choice procedure, with those NIC chosen more than VLNC indicating greater reinforcement due to greater nicotine per se. Secondarily, less preference for lower NIC (vs. VLNC), relative to choice for the highest NIC, 18.7 mg/g (vs. VLNC), indexed reduced reinforcement. RESULTS: Overall, NIC choices increased as their nicotine increased, as anticipated. Relative to the 0.4 mg/g VLNC, choice was greater for NIC ≥ 5.3 mg/g but not ≤ 2.3 mg/g. Correspondingly, relative to choice for 18.7 mg/g, choice was less for NIC ≤ 2.3 mg/g but not ≥ 5.3 mg/g. CONCLUSIONS: Although replication with larger samples and longer access is needed, results indicate that nicotine reduction to ≤ 2.3 mg/g in cigarettes would attenuate reinforcement. This choice procedure may efficiently inform future clinical trials to assess relative reinforcing effects of smoking reduced nicotine cigarettes.