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

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.

Threshold dose for discrimination of nicotine via cigarette smoking.

RATIONALE: The lowest nicotine threshold "dose" in cigarettes discriminated from a cigarette containing virtually no nicotine may help inform the minimum dose maintaining dependence. OBJECTIVES: Spectrum research cigarettes (from NIDA) differing in nicotine content were used to evaluate a procedure to determine discrimination thresholds. METHODS: Dependent smokers (n = 18; 13 M, 5 F) were tested on ability to discriminate cigarettes with nicotine contents of 11, 5, 2.4, and 1.3 mg/g, one per session, from the "ultralow" cigarette with 0.4 mg/g, after having discriminated 16 mg/g from 0.4 mg/g (all had 9-10 mg "tar"). Exposure to each was limited to 4 puffs/trial. All subjects were abstinent from smoking overnight prior to each session, and the number of sessions was determined by the participant's success in discrimination behavior on >80 % of trials. Subjective perceptions and behavioral choice between cigarettes were also assessed and related to discrimination behavior. RESULTS: The median threshold was 11 mg/g, but the range was 2.4 to 16 mg/g, suggesting wide variability in discrimination threshold. Compared to the ultralow, puff choice was greater for the subject's threshold dose but only marginal for the subthreshold (next lowest nicotine) cigarette. Threshold and subthreshold also differed on subjective perceptions but not withdrawal relief. CONCLUSIONS: Under these testing conditions, threshold content for discriminating nicotine via cigarettes may be 11 mg/g or greater for most smokers, but some can discriminate nicotine contents one-half or one-quarter this amount. Further study with other procedures and cigarette exposure amounts may identify systematic differences in nicotine discrimination thresholds.

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.

Reinforcement enhancing effects of acute nicotine via electronic cigarettes.

BACKGROUND: Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. METHODS: We assessed acute effects of nicotine via electronic cigarettes ("e-cigarettes") on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled "36mg/ml") or placebo ("0″) e-cigarette, or no e-cigarette use. A fourth session involved smoking one's own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. RESULTS: Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). CONCLUSIONS: Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use.