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.

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.

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 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.

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.

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 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.

An electronic, smart lighter to measure cigarette smoking: A pilot study to assess feasibility and initial validity.

Understanding variability in smoking patterns may inform smoking cessation interventions. Retrospective reports of cigarettes smoked per day may be biased and typically do not provide temporal precision regarding when cigarettes are smoked. However, real-time, user-initiated tracking, such as logging each time a cigarette is smoked, can be burdensome over long time frames. In this study, adult, non-treatment seeking daily smokers (N = 22) used an electronic, smart lighter to light and timestamp cigarettes for 14 days. Participants reported number of cigarettes smoked per day (CPD) via a mobile device (daily diary) and retrospectively reported CPD at the end of the study using the Timeline Followback (TLFB). Self-reported lighter satisfaction and adherence varied with 68% of participants reporting that they liked using the lighter and participants reporting using the lighter for 92% of cigarettes smoked, on average. Lighter-estimated CPD did not differ from daily diary-estimated CPD, but was significantly lower than TLFB estimates. The lighter resulted in greater day-to-day variability relative to other methods and fewer rounded cigarette counts (digit bias) relative to the TLFB. The lighter appears to be feasible for capturing data on smoking patterns in daily smokers. Though false positive cigarettes are likely low, additional technologies that augment data captured from the lighter may be necessary to reduce false negatives (missed cigarettes) and alternative lighter designs may appeal more to certain smokers.

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.

Discrimination of nicotine content in electronic cigarettes.

INTRODUCTION: Behavioral discrimination of nicotine has only recently been assessed in humans, administered mostly by nasal spray before the newly available Spectrum research cigarettes differing in nicotine content. Here we wanted to explore applicability of these procedures to assess discrimination of nicotine administered by e-cigarettes. METHODS: In this feasibility study, 16 adult smokers were tested on ability to discriminate e-cigarettes with nicotine concentrations of 36, 24, and 12 mg/ml, one per session (in that order), from a placebo (0 mg/ml), each identified only by letter code. Reliable discrimination was defined by accurately identifying which was which (i.e. nicotine vs placebo) on >85% of trials (i.e. ≥7 of 8; p < .05). Subjective perceptions were also assessed. RESULTS: Discrimination from placebo was shown with 36 mg/ml and with 24 mg/ml nicotine in 15 of 16 subjects, but only 10 discriminated placebo from 12 mg/ml nicotine. Subjective items previously related to acute nicotine exposure ("how much nicotine", "head rush/buzzed" on 0-100 VAS) generally showed nicotine concentration-dependent effects, as expected, but so did "throat irritation". CONCLUSIONS: Preliminary results confirm feasibility of using our behavioral procedure to assess ability to discriminate nicotine administered via these e-cigarettes, broadening generalizability of this procedure beyond nicotine via nasal spray and smoked tobacco cigarettes. Findings also suggest its applicability with testing discrimination of nicotine via other methods of rapid dosing (e.g., hookah, novel products), including the newer e-cigarette products. Further study with larger samples may identify individual difference and other factors influencing nicotine discrimination administered via e-cigarettes and other products.

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.

Tobacco smoking may delay habituation of reinforcer effectiveness in humans.

BACKGROUND: The effectiveness of nonconsummatory reinforcers habituate, as their ability to maintain reinforced responding declines over repeated presentations. Preclinical research has shown that nicotine can delay habituation of reinforcer effectiveness, but this effect has not been directly demonstrated in humans. OBJECTIVE: In preliminary translational research, we assessed effects of nicotine from tobacco smoking (vs. a no smoking control) on within-session patterns of responding for a brief visual reinforcer. METHODS: Using a within-subjects design, 32 adult dependent smokers participated in two experimental sessions, varying by smoking condition: no smoking following overnight abstinence (verified by CO ≤ 10 ppm), or smoking of own cigarette without overnight abstinence. Adapted from preclinical studies, habituation of reinforcer effectiveness was assessed by determining the rate of decline in responding on a simple operant computer task for a visual reinforcer, available on a fixed ratio schedule. RESULTS: Reinforced responding and duration of responding were each significantly higher in the smoking vs. no smoking condition. The within-session rate of responding declined significantly more slowly during the smoking vs. no smoking condition, consistent with delayed habituation of reinforcer effectiveness. Follow-up analyses indicated that withdrawal relief did not influence the difference in responding between conditions, suggesting the patterns of responding reflected positive, but not negative, reinforcement. CONCLUSIONS: These results are a preliminary demonstration in humans that smoked nicotine may attenuate habituation, thereby maintaining the effectiveness of a reinforcer over a longer period of access. Further research is needed to confirm habituation and rule out alternative causes of declines in within-session responding.

Evaluation of menthol per se on acute perceptions and behavioral choice of cigarettes differing in nicotine content.

Subjective perceptions and self-administration of cigarettes are each influenced by nicotine. Yet, differences specifically due to menthol in perceptions and choice of cigarettes varying in nicotine, and the association between these responses, have not been directly tested. Using a mixed between- and within-subjects design, acute responses to each of two menthol or non-menthol Spectrum research cigarettes, moderate (16-17 mg/g) versus very low (0.4 mg/g) in nicotine contents, were compared following brief abstinence in adult smokers preferring menthol ( n=44) or non-menthol ( n=29) brands. To ensure reliable perceptions, they experienced five exposures to each cigarette, then chose between them. All perceptions and choices were greater for moderate vs very low nicotine, as expected, and the magnitude of difference in four of six perceptions was associated with subsequently greater choice of the moderate nicotine cigarette. Importantly, virtually no differences were found between menthol and non-menthol, as nearly all perceptions, cigarette choices, and the association between perceptions and choice were not moderated by menthol or the interaction of nicotine by menthol. Our results indicate perceptions and reinforcement from cigarettes do not differ due to menthol when nicotine content and smoking topography are carefully controlled. Thus, regardless of menthol, smoking perceptions directly predict self-administration behavior.

Initial Cross-Over Test of A Positive Allosteric Modulator of Alpha-7 Nicotinic Receptors to Aid Cessation in Smokers With Or Without Schizophrenia.

Preclinical research shows that compounds acting at α7 nicotinic receptors (nAChRs) can reduce nicotine self-administration, suggesting that a positive allosteric modulator (PAM) of α7 receptors, JNJ-39393406, may aid smoking cessation. Moreover, individuals with schizophrenia, who have very high rates of smoking, have reduced expression of α7 nAChRs and may particularly benefit from this compound. In two parallel studies using a within-subject cross-over design, 36 healthy smokers (Study 1) and 62 smokers with schizophrenia (Study 2), both groups high in quit interest, attempted to initiate quitting temporarily during each of two 3-week phases. Treatments were the α7 nicotinic receptor PAM JNJ-39393406 (100 mg b.i.d.) or placebo (double-blind, counter-balanced). In each phase, all smoked ad lib with no drug on week 1 or during dose run-up on week 2, and then tried to quit every day during week 3. Abstinence (confirmed by CO <5 p.p.m.) and smoking reduction (CO <8), as well as cigarettes/day (in Study 1), were assessed daily (Monday-Friday) each quit week and compared between conditions. Secondary outcomes included abstinence symptoms (withdrawal and craving) and cognitive test responding (N-back; continuous performance task). In both studies, compared with placebo, active JNJ-39393406 did not increase the number of abstinent days nor reduce total smoking exposure. We also found no significant improvements in craving, withdrawal, or cognitive function. With this dose and study duration, our findings do not support further testing of this α7 nAChR PAM compound for possible efficacy in smoking cessation, in smokers with or without schizophrenia.

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.

ANALYSIS OF AGREEMENT BETWEEN EXPIRED-AIR CARBON MONOXIDE MONITORS.

INTRODUCTION: The current study examined the level of agreement in expired-air carbon monoxide (CO) values, focusing especially on those confirming abstinence, between the two most commonly used CO monitors, the Vitalograph BreathCO and the Bedfont piCO+ Smokerlyzer. METHODS: Expired-air samples were collected via both monitors from adult dependent smokers (44 M, 34 F) participating in studies using CO values to confirm abstinence durations of: 24 hours, 12 hours, or no abstinence. All met DSM-IV nicotine dependence criteria and had a mean (SD) Fagerström Test of Cigarette Dependence score of 5.1 (1.8). Paired data collected across multiple visits were analyzed by regression-based Bland-Altman method of Limits of Agreement. FINDINGS: Analysis indicated a lack of agreement in CO measurement between monitors. Overall, the Bedfont monitor gave mean (±SEM) readings 3.83 (±.23) ppm higher than the Vitalograph monitor. Mean differences between monitors were larger for those ad lib smoking (5.65±.38 ppm) than those abstaining 12-24 hours (1.71±.13 ppm). Yet, there also was not consistent agreement in classification of 24 hour abstinence between monitors. CONCLUSIONS: Systematic differences in CO readings demonstrate these two very common monitors may not result in interchangeable values, and reported outcomes in smoking research based on CO values may depend on the monitor used.

Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence.

Because electronic cigarettes (e-cigs) containing nicotine may relieve smoking abstinence symptoms similar to nicotine replacement therapy medication, we used within-subjects designs to test these effects with a first-generation e-cig in nonquitting and quitting smokers. In Study 1, 28 nontreatment-seeking smokers abstained overnight prior to each of 3 sessions. Minnesota Nicotine Withdrawal Scale (MNWS) withdrawal (and craving item) relief was assessed following 4 exposures (each 10 puffs) over 2 hr to e-cigs that either did (36 mg/ml) or did not (i.e., placebo, 0 mg/ml) contain nicotine or after no e-cig. Relief was greater after nicotine versus placebo e-cig (p < .05) but not after placebo versus no e-cig, showing relief was due to nicotine per se and not simple e-cig use behavior. Using a crossover design in Study 2, smokers preparing to quit soon engaged in 2 experimental 4-day quit periods on separate weeks. In weeks 1 and 3, all received a nicotine or placebo e-cig on Monday to use ad libitum while trying to abstain from smoking on Tuesday through Friday. (Week 2 involved resumption of ad libitum smoking.) MNWS and Questionnaire of Smoking Urges (QSU) craving were assessed at daily visits following 24-hr abstinence. Of 17 enrolled, 12 quit for ≥24 hr at least once, allowing test of relief because of e-cig use on quit days. Withdrawal and craving were reduced because of nicotine versus placebo e-cig use (both p < .05). In sum, compared with placebo e-cigs, nicotine e-cigs can relieve smoking abstinence symptoms, perhaps in a manner similar to Food and Drug Administration-approved nicotine replacement therapy products, although much more research with larger samples is needed. (PsycINFO Database Record

Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans.

Preclinical research documents that, aside from the primary and secondary reinforcing effects of nicotine intake itself, nicotine also acutely enhances the reinforcing efficacy of non-drug reinforcers ("rewards"). Study of these effects in humans has largely been overlooked, but very recent findings suggest they may have clinical implications for more fully understanding the persistence of tobacco dependence. This overview first outlines the topic and notes some recent human studies indirectly addressing nicotine effects on related responses (e.g., subjective ratings), explaining why those findings do not directly confirm enhancement of behavioral reinforcement per se due to nicotine. Then, the methodology used in the subsequently presented studies is described, demonstrating how those studies specifically did demonstrate enhancement of reinforced responding for non-drug rewards. The main section focuses on the limited controlled research to date directly assessing nicotine's acute reinforcement-enhancing effects in humans, particularly as it relates to reinforced behavioral responding for non-drug rewards in non-human animal models. After detailing those few existing human studies, we address potential consequences of these effects for dependence and tobacco cessation efforts and then suggest directions for future research. This research indicates that nicotine per se increases responding in humans that is reinforced by some rewards (auditory stimuli via music, visual stimuli via video), but perhaps not by others (e.g., money). These reinforcement-enhancing effects in smokers are not due to dependence or withdrawal relief and can be restored by a small amount of nicotine (similar to a smoking lapse), including from e-cigarettes, a non-tobacco nicotine product. Future clinical research should examine factors determining which types of rewards are (or are not) enhanced by nicotine, consequences of the loss of these nicotine effects after quitting smoking, potential individual differences in these effects, and the possibility that nicotine via nicotine replacement therapy and non-nicotine quit medications may attenuate loss of these effects upon quitting. Further study with humans of nicotine's reinforcement-enhancing effects may provide a more complete understanding of smoking persistence and added mechanisms of cessation medication efficacy.

Preliminary test of cigarette nicotine discrimination threshold in non-dependent versus dependent smokers.

BACKGROUND: Despite its potential for understanding tobacco dependence, behavioral discrimination of nicotine via smoking has not been formally examined as a function of nicotine dependence level. METHODS: Spectrum research cigarettes were used to compare non-dependent with dependent smokers on the lowest content of nicotine they could discriminate (i.e., "threshold"). Dependent (n=21; 16M, 5F) or non-dependent (n=7; 4M, 3F) smokers were tested on ability to discriminate between cigarettes with nicotine contents of 17, 11, 5, 2, and 1mg/g, one per session, from an "ultra-low" cigarette with 0.4mg/g (all had 9-10mg "tar"). All abstained from smoking overnight prior to sessions, and number of sessions was determined by the lowest nicotine content they could reliably discriminate from the ultra-low on >80% of trials (i.e., ≥5 of 6). Subjective perceptions and cigarette choice behavior were also assessed and related to discrimination behavior. RESULTS: Discrimination thresholds (and most perceptions) did not differ between dependent and non-dependent smokers, with median thresholds of 11mg/g for both subgroups. Yet, "liking" and puff choice for threshold cigarettes were greater in dependent but not non-dependent smokers, while cigarettes with nicotine contents below threshold did not support "liking" or choice in both groups. CONCLUSIONS: In sum, this preliminary study suggests threshold for discriminating nicotine via smoking may not vary by dependence level, and further study is needed to confirm that cigarettes unable to be discriminated are also not reinforcing.