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.

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.

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.

Threshold dose for behavioral discrimination of cigarette nicotine content in menthol vs. non-menthol smokers.

RATIONALE: The lowest threshold content (or "dose") of nicotine discriminated in cigarettes may differ due to menthol preference. OBJECTIVES: Menthol and non-menthol Spectrum research cigarettes differing in nicotine content were used to determine discrimination thresholds. METHODS: Dependent smokers preferring menthol (n = 40) or non-menthol (n = 21) brands were tested on ability to discriminate cigarettes (matched for their menthol preference) with nicotine contents of 16-17, 11-12, 5, 2, and 1 mg/g, one per session, from an "ultra-low" cigarette with 0.4 mg/g. Controlled exposure to each cigarette was four puffs/trial, and the number of sessions was determined by the lowest nicotine content they could discriminate on >80% of trials (i.e., ≥5 of 6). We also assessed subjective perceptions and behavioral choice between cigarettes to relate them to discrimination responses. RESULTS: Controlling for Fagerstrom Test of Nicotine Dependence score, discrimination thresholds were more likely to be at higher nicotine content cigarettes for menthol vs. non-menthol smokers (p < .005), with medians of 16 vs. 11 mg/g, respectively. Compared to the ultra-low, threshold and subthreshold (next lowest) cigarettes differed on most perceptions and puff choice, but menthol preference did not alter these associations. Notably, threshold cigarettes did, but subthreshold did not, increase choice over the ultra-low. CONCLUSIONS: Threshold for discriminating nicotine via smoking may be generally higher for menthol vs. non-menthol smokers. More research is needed to identify why menthol smoking is related to higher nicotine thresholds and to verify that cigarettes unable to be discriminated do not support reinforcement.

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.