Society for Research on Nicotine and Tobacco as an Outgrowth of the 1988 Surgeon General's Report on Nicotine Addiction: Reflections of the Early Presidents.

INTRODUCTION: The Society for Research on Nicotine and Tobacco began in the United States as a scientific organization "to stimulate the generation and dissemination of new knowledge concerning nicotine and tobacco in all its manifestations." Now in its 30th year, the Society is taking on new challenges in tobacco control, nicotine vaping, product regulation, and public policy. AIMS AND METHODS: This Review describes the formative years of the Society from the perspective of researchers who were in leadership positions during that time, documenting how biobehavioral and clinical research in the first 10 years was a continuation of the scientific mission of the 1988 United States Surgeon General's Report on Nicotine Addiction and summarizing organizational innovations during each president's term of office. CONCLUSIONS: The Society's promotion of scientific research served as a catalyst for funding, policy, and regulation, setting the stage for its influence and credibility. IMPLICATIONS: This Commentary provides context and an overview of the scientific research and the organizational innovations that occurred during the early years of the Society for Research on Nicotine and Tobacco using publications and available documentation. The Society was able to thrive because biobehavioral research on nicotine addiction provided the scientific underpinnings for the tobacco control enterprise as a whole. The objective of this Commentary is to describe formative events in the Society's history based on the accomplishments of its early leaders.

Behavioral activation for smoking cessation and the prevention of smoking cessation-related weight gain: A randomized trial.

BACKGROUND: Post-cessation weight gain (PCWG) is an obstacle to smoking cessation. This trial evaluated a behavioral intervention targeting alternative rewards to smoking and high calorie snacking to promote smoking cessation while mitigating PCWG. METHODS: Adult smokers (n = 288; 119 females, 169 males) received eight weeks of transdermal nicotine and were randomized to eight sessions of behavioral activation for smoking cessation and the mitigation of PCWG (BAS+) or standard smoking cessation counseling (SC). Primary outcomes were 7-day point prevalence abstinence and PCWG 26 weeks after the target quit date. Change in caloric intake from pre-treatment through the 26-week follow-up was a secondary outcome. Data were collected from September 2016 to February 2021, and analyses were completed in July 2022. RESULTS: BAS+ and SC did not differ in smoking abstinence rates at the 26-week follow-up (OR=0.80, 95%CI 0.50-1.27, p = 0.34; 18% versus 23%). There were no significant differences in PCWG between BAS+ and SC who were 7-day point prevalence abstinent (ß = -0.29, 95%CI -2.13 to 1.65, p = 0.77; 2.60 versus 2.20 pounds, respectively) or among those continuously abstinent (5.78 versus 5.34 pounds, respectively). There were no significant differences in caloric intake between BAS+ and SC from baseline to the 26-week follow-up (ß = 110.65, 95%CI -96.72 to 318.02, p = 0.30; -19.1 versus -116.9 kcals/day, respectively). CONCLUSIONS: The results do not support the efficacy of BAS+ for smoking cessation and the prevention of PCWG. These findings join a growing body of research highlighting the challenge of minimizing PCWG and promoting smoking abstinence.

The 2022 Ferno Award Address: CrEATE, an Efficient Crossover Evaluation of Addiction Treatment Efficacy.

Dozens of drugs have been evaluated in recent decades for initial evidence of efficacy to aid smoking cessation (i.e. "early Phase 2" testing, according to U.S. FDA terminology), with the vast majority failing to show efficacy. Even small randomized clinical trials (RCTs), the most common early Phase 2 tests, are costly undertakings, made more unappealing by their high likelihood of failure. At the same time, another early Phase 2 approach, acute tests of drug effects on surrogate endpoints such as withdrawal or craving severity, are more practical but have little predictive clinical validity. Described here is an innovative procedure that optimally combines the validity of clinical trials with the practical advantages of surrogate endpoint studies to more efficiently determine whether or not a novel drug warrants continued clinical development. This CrEATE procedure, or Crossover Evaluation of Addiction Treatment Efficacy, does so by assessing short-term quit success in smokers highly motivated to quit when briefly treated with active drug versus placebo in a crossover design, so that quit efficacy from both conditions is compared within participants. The program to develop and evaluate CrEATE demonstrates its sensitivity to efficacy from all three FDA-approved first-line cessation medications (NRT, varenicline, bupropion), tested here as model drugs, as well as specificity in identifying lack of efficacy with a drug known to be ineffective for cessation (modafinil). CrEATE has subsequently been used to evaluate a few novel interventions, concluding they lack efficacy in increasing quit success. Future directions for the potential utility of CrEATE are provided. Implications: The ability of CrEATE to reach a Go/No Go decision more quickly and with far less cost lowers the risk of failure, meaning widespread use of the procedure should encourage the evaluation of more novel candidate drugs. With its greater efficiency, failed tests, unfortunately the most likely outcome in early Phase 2 studies, will cause less waste of resources. At the same time, CrEATE tests that indicate a novel treatment has efficacy will justify the substantial time and expense of moving forward to evaluate the drug in late Phase 2 RCTs.

Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

This review of research on behavioral discrimination of nicotine and how it informs public health policy for reducing risk of tobacco dependence is adapted from Kenneth A. Perkins's American Psychological Association Division 28 (Psychopharmacology and Substance Abuse) 2020 Med Associates Brady/Schuster Award Lecture. The author's initial programmatic clinical research on nicotine is introduced, especially efforts to develop and validate a novel method of acute nicotine dosing. After the public health rationale for characterizing the discriminative stimulus effects of nicotine in humans are described, details from two separate programs of research on nicotine discrimination in humans are presented. The first, conducted with nicotine dosing by nasal spray, documented that humans could discriminate nicotine administered rapidly, examined nicotine's neuropharmacological specificity, identified discrimination threshold dose in smokers and nonsmokers, and explored other conditions that might alter ability to discriminate its effects. The second, more recent program focused on threshold doses for discrimination of nicotine by cigarette smoking, a program that was very difficult to do until the past decade, and how nicotine's self-reported "reward" and preference via choice behavior relate to its discriminability. Differences due to menthol and degree of tobacco dependence were also examined. For each of these two programs, the main findings of selected studies are noted, followed by very recent work on nicotine discrimination and choice that informs Food and Drug Administration's efforts to formulate public policy to improve health and reduce the nearly half million American deaths per year due to persistent tobacco use. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Balancing Consideration of the Risks and Benefits of E-Cigarettes.

The topic of e-cigarettes is controversial. Opponents focus on e-cigarettes' risks for young people, while supporters emphasize the potential for e-cigarettes to assist smokers in quitting smoking. Most US health organizations, media coverage, and policymakers have focused primarily on risks to youths. Because of their messaging, much of the public-including most smokers-now consider e-cigarette use as dangerous as or more dangerous than smoking. By contrast, the National Academies of Science, Engineering, and Medicine concluded that e-cigarette use is likely far less hazardous than smoking. Policies intended to reduce adolescent vaping may also reduce adult smokers' use of e-cigarettes in quit attempts. Because evidence indicates that e-cigarette use can increase the odds of quitting smoking, many scientists, including this essay's authors, encourage the health community, media, and policymakers to more carefully weigh vaping's potential to reduce adult smoking-attributable mortality. We review the health risks of e-cigarette use, the likelihood that vaping increases smoking cessation, concerns about youth vaping, and the need to balance valid concerns about risks to youths with the potential benefits of increasing adult smoking cessation.

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.

Preclinical and clinical research on the discriminative stimulus effects of nicotine.

Across species, nicotine can produce robust discriminative stimulus (DS) effects, as with other drugs of abuse, a feature that has been harnessed to advance our understanding on the neuropharmacological mechanisms of nicotine's actions. With the crucial role played by nicotine in supporting tobacco dependence, nicotine DS effects have presented an ideal platform to develop novel generation of smoking cessation compounds. Findings from preclinical strands of research have invigorated the field of human discrimination research to objectively assess nicotine's interoceptive stimulus effects. As such, translation studies provide proof of concept for nicotine DS research as a method to assess the subjective effects of nicotine per se, separate from non-nicotine stimuli involved in smoking. Recent clinical studies with low doses have demonstrated that perceiving nicotine's DS effects is necessary, yet not sufficient, for that dose to be reinforcing. These measures have been instrumental in developing novel strategies with regards to establishing threshold doses of nicotine contained in tobacco products, to then determine subthreshold doses that cannot be discriminated and, therefore, fail to maintain reinforcement. Findings from preclinical and clinical nicotine DS research could substantially inform public health policies aimed at regulating nicotine content of consumer products so that they minimize risks of dependency. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.

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.

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.

Increased subjective and reinforcing effects of initial nicotine exposure in young adults with attention deficit hyperactivity disorder (ADHD) compared to matched peers: results from an experimental model of first-time tobacco use.

Individuals with attention deficit hyperactivity disorder (ADHD) are at increased risk for adverse cigarette smoking outcomes, and little is known about factors underlying this risk. This study sought to evaluate the effects of initial nicotine exposure in young adults with and without ADHD using a novel paradigm of exposure to model initial smoking experiences. Participants were young adult nonsmokers (n = 61 ADHD, n = 75 Control) between the ages of 18-25 years (inclusive) who reported never having smoked a full cigarette, and no tobacco use in the prior 3 years. Participants were exposed to three different blinded doses of intranasally administered nicotine (0, 0.5, 1.0 mg) across three separate fixed dose experimental sessions. In subsequent sessions, participants were given the opportunity to self-administer nicotine under two different conditions-high and low cognitive demand. Physiological, subjective, and reinforcing effects of nicotine were the main outcomes. Nicotine plasma levels, and no group differences in effects of nicotine on heart rate or blood pressure, confirmed comparable dosing exposure across groups. ADHD participants reported significantly greater dizziness following nicotine, and greater pleasant subjective effects across all conditions, compared to non-ADHD non-smokers. There were no group differences on subjective reports of bad or unpleasant effects. Subsequent nicotine self-administration was significantly higher among non-smokers with ADHD, and their choices of nicotine were not influenced by cognitive condition. There are meaningful differences between young adults with and without ADHD with respect to the initial subjective and reinforcing effects of nicotine; and interventions to prevent use should start prior to typical age of experimentation among ADHD patients.

Research on Behavioral Discrimination of Nicotine May Inform FDA Policy on Setting a Maximum Nicotine Content in Cigarettes.

INTRODUCTION: The Food and Drug Administration may set a maximum nicotine content in cigarettes to minimize smoking's addictiveness. Our recent research may indirectly support setting levels applicable to the population of dependent smokers below 1 mg/g (mg nicotine/g of tobacco filler). METHODS: Using a within-subjects design in laboratory-based studies totaling 61 nontreatment seeking adult dependent smokers, Spectrum research cigarettes with nicotine contents ranging from 1.3 to 17 mg/g (just one per session) were compared with the lowest content available, 0.4 mg/g. Identified for each participant was the smallest difference in nicotine content, or "threshold," between cigarettes that still supported behavioral discrimination (ie, ability to objectively distinguish their difference). The next lower nicotine content cigarette, not discriminated (by definition), was labeled their "subthreshold." Subjective perceptions and choice behavior were also assessed. RESULTS: Thresholds varied widely among all 61 smokers but, importantly, fewer than 7% of smokers could discriminate the two lowest, 1.3 versus 0.4 mg/g nicotine, meaning more than 90% could not do so. Moreover, we found a consistent association between their nicotine discrimination threshold and their subjective perceptions and subsequent reinforcement behavior later in the session. Specifically, a participant's discrimination threshold cigarette was also more highly rated and preferred (ie, self-administered), whereas their subthreshold cigarette was rated similarly to the 0.4 mg/g and not preferred. CONCLUSIONS: Cigarette nicotine content below the threshold for perceiving nicotine's effects (ie, its discriminability) in nearly all smokers from a no nicotine comparison is likely below 1.0 mg/g, or less than or equal to 10% of that in typical commercial cigarettes. IMPLICATIONS: Cigarettes with nicotine contents able to be discriminated (threshold) are also reinforcing, and those unable to be discriminated are not reinforcing, as anticipated. Yet, research explicitly comparing cigarettes with contents below 1.0 mg/g versus no nicotine (ie, a "placebo") is needed with larger samples. Results may confirm what nicotine content lower than 1.0 mg/g is below the threshold for discrimination (and self-administration) in the vast majority (>95%) of adult dependent smokers as well as teens beginning to smoke. Identifying that content would strongly support the Food and Drug Administration policy to establish a maximum nicotine content in cigarettes that will not maintain dependence.

Predictive utility of subtyping women smokers on depression, eating, and weight-related symptoms.

OBJECTIVE: Smoking and overweight or obesity are preventable causes of disease and death. Women are reluctant to quit smoking because of concerns about postcessation weight gain, underscoring the need to elucidate patterns of weight concerns and associated psychosocial factors that may affect smoking cessation outcomes. The present study aimed to subtype women smokers based on psychosocial and behavioral factors associated with smoking and weight, and examine the utility of these subtypes to predict abstinence and postcessation weight gain. METHOD: Weight-concerned women (N = 343) were randomized to 1 of 2 smoking cessation counseling adjuncts and 1 of 2 cessation medication conditions. At baseline, women were weighed and completed measures of depression, weight or appearance concerns, and eating behaviors. At 3-, 6-, and 12-months after the target quit date, women were weighed and completed self-report and biochemical smoking assessments. RESULTS: Latent profile (LP) analyses supported a 3-profile model. The groups had typical (53%, LP1), minimal (33%, LP2), and high (14%, LP3) levels of depressive symptoms and weight concerns. At 12-months posttarget quit date, women in LP3 were more likely to relapse than women in LP1 (odds ratio, OR = 2.93). Among abstinent women, those in LP2 and LP3 gained more postcessation weight than those in LP1. CONCLUSIONS: Heterogeneity in symptoms of depression, weight or appearance concerns, and eating behaviors was captured by three groups of women smokers, with unique risks for relapse and postcessation weight gain. The distinct profiles identified may help personalize the delivery of care for smoking cessation and, ultimately, reduce disease risk. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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.