Assessment of Drug Delivery Kinetics to Epidermal Targets In Vivo.

It has proven challenging to quantify 'drug input' from a formulation to the viable skin because the epidermal and dermal targets of topically applied drugs are difficult, if not impossible, to access in vivo. Defining the drug input function to the viable skin with a straightforward and practical experimental approach would enable a key component of dermal pharmacokinetics to be characterised. It has been hypothesised that measuring drug uptake into and clearance from the stratum corneum (SC) by tape-stripping allows estimation of a topical drug's input function into the viable tissue. This study aimed to test this idea by determining the input of nicotine and lidocaine into the viable skin, following the application of commercialised transdermal patches to healthy human volunteers. The known input rates of these delivery systems were used to validate and assess the results from the tape-stripping protocol. The drug input rates from in vivo tape-stripping agreed well with the claimed delivery rates of the patches. The experimental approach was then used to determine the input of lidocaine from a marketed cream, a typical topical product for which the amount of drug absorbed has not been well-characterised. A significantly higher delivery of lidocaine from the cream than from the patch was found. The different input rates between drugs and formulations in vivo were confirmed qualitatively and quantitatively in vitro in conventional diffusion cells using dermatomed abdominal pig skin.

Racial disparities in intensity of smoke exposure and nicotine intake among low-dependence smokers.

BACKGROUND: Compared to white smokers, Black smokers are at disproportionately higher risk for smoking-related disease, despite consuming fewer cigarettes per day (CPD). To examine racial disparities in biobehavioral influences on smoking and disease risk, we analyzed the relationship between self-reported tobacco dependence and intensity of tobacco smoke exposure per cigarette, on the one hand, and intensity of nicotine intake per cigarette, on the other. METHODS: In 270 Black and 516 white smokers, smoke exposure was measured by expired carbon monoxide (CO), and nicotine intake was measured by plasma cotinine (COT) and cotinine+3'-hydroxycotinine ([COT + 3HC]). Using linear regression analyses, we analyzed how the Fagerström Test for Cigarette Dependence (FTCD) predicted intensity of smoke exposure per cigarette (CO/CPD) and intensity of nicotine intake per cigarette (COT/CPD; [COT + 3HC]/CPD), and how race moderated these relations. RESULTS: Overall, Black smokers consumed fewer CPD than white smokers and had higher levels of CO/CPD, COT/CPD, and [COT + 3HC]/CPD. These elevations were most pronounced at lower levels of dependence: amongst Black smokers, FTCD negatively predicted intensity of smoke exposure as measured by CO/CPD (B = -0.12, 95% CI = -0.18, -0.05, p = 0.0003) and intensity of nicotine intake as measured by [COT + 3HC]/CPD (B = -1.31, 95% CI = -2.15, -0.46, p = 0.002). CONCLUSIONS: Low-dependence Black smokers had higher intensities of both smoke exposure and nicotine intake per cigarette compared to similarly dependent white smokers, suggesting that measures of dependence, exposure, and intake underestimate incremental risk of each cigarette to Black smokers.

An adapted smoking-cessation intervention for Turkish-speaking migrants in Switzerland: Predictors of smoking outcomes at one-year follow-up.

BACKGROUND: Migrant populations usually report higher smoking rates. Among those migrant populations, Turkish- and Kurdish-speaking migrants are often overrepresented. Providing equal access to health services is one of the major challenges of our time. The need for adapted smoking-cessation treatments for Turkish-speaking populations to achieve equity in health led, in 2006, to the development and implementation of the Tiryaki-Kukla smoking-cessation program. The aims of the current study were to evaluate one-year quit rates for smoking-cessation courses held from 2006-2018 and investigate whether certain characteristics predict long-term smoking cessation or reduction. METHODS: Program evaluation included a pre/post questionnaire (session 1/ 3 months after the quit day) and a follow-up telephone call twelve months after the quit day. To elucidate factors associated with long-term smoking cessation and reduction, Cox regression analysis and Weighted Generalized Equation Models were used. RESULTS: Of the 478 who participated in smoking-cessation courses, 45.4% declared themselves non-smokers at one-year follow-up. This quit rate is higher than that achieved during the preliminary evaluation of the program involving 61 participants (37.7%). Predictors of long-term smoking cessation were course length (eight vs. six sessions) (95% CI = 1.04-1.36, p = .01), adherence to the course (95% CI = 0.98-0.99, p<0.01), use of pharmacotherapy or nicotine replacement therapy products (95% CI = 0.74-0.98, p = .02), and time passed in the morning until the first cigarette is smoked (95% CI5min = 1.17-1.77, p<0.001; 95% CI30min = 1.09-1.65, p<0.01). Predictors of change in cigarettes smoked per day among smokers were-the time passed until the first cigarette in the morning (5min p < .001; 30min p < .001; 60min p < .01)-, gender (p < .001), and level of motivation to quit at baseline (p = .04). CONCLUSIONS: Our findings are consistent with existing evidence supporting adapted smoking cessation interventions to reduce health inequity in migrant populations. However, achieving harm reduction in smokers with higher dependence scores remains challenging.

Varenicline rescues nicotine-induced decrease in motivation for sucrose reinforcement.

Varenicline is one of the top medications used for smoking cessation and is often prescribed before termination of nicotine use. The effect of this combined nicotine and varenicline use on the reward system and motivation for primary reinforcement is underexplored. The goal of this study was to assess the effects of nicotine and varenicline on motivation for a food reinforcer. In Experiment 1, we first assessed the responding for sucrose after pretreatment with nicotine (0, 0.1, or 0.4 mg/kg) and varenicline (0.0, 0.1, 1.0 mg/kg) using a behavioral economics approach. The responding for sucrose was then assessed using a progressive ratio schedule of reinforcement after pretreatment with all possible combinations of nicotine and varenicline doses. In Experiment 2, rats were assessed for the consumption of sucrose in home cages after pretreatment with nicotine and varenicline. We found that (a) nicotine decreased economic demand for sucrose, (b) varenicline rescued nicotine-induced reduction in economic demand for sucrose, and (c) history of varenicline treatment predicted responding for sucrose on a progressive ratio schedule of reinforcement where rats with a history of varenicline treatment responded significantly lower for sucrose across nicotine doses than rats that had not been exposed to varenicline. The results of Experiment 2 largely confirmed that nicotine decreases motivation for sucrose using a passive consumption protocol and that varenicline rescues this effect. Overall, these findings suggest that varenicline interacts with the effects of nicotine by restoring nicotine-induced reduction in motivation for appetitive rewards.

Assessment of nicotine release from nicotine-loaded chitosan nanoparticles dry powder inhaler formulations via locomotor activity of C57BL/6 mice.

PURPOSE: This study aimed to assess the activity of controlled release nicotine from dry powder inhaler formulation via locomotor activity of C57BL/6 mice. METHODS: To achieve this we built a nose-only inhalation device for pulmonary administration of nicotine to mice and determined the optimal operational parameters. We used the locomotor activity test to compare the effects of the inhaled nicotine hydrogen tartrate-loaded chitosan nanoparticles (NHT-CS) with NHT in C57BL/6 mice. The minimum inhaled dose of NHT-CS required to alter locomotor activity was compared with inhaled and subcutaneously (s.c) injected NHT. Finally, histological examination of lung tissues was performed to ensure inhalation of NHT-CS did not cause lung damage. RESULTS: We found a flow rate of 0.9 L/min and an exposure time of 5 min achieved optimal delivery of nicotine. A minimum of 0.88 mg inhaled of NHT-CS or 0.59 mg inhaled of NHT was required to alter locomotor activity similarly to injection of 0.5 mg/kg nicotine, suggesting the reformulation process did not alter the activity of NHT-CS. No differences between untreated and NHT-CS treated lung tissue upon histological examination were observed. CONCLUSIONS: The results indicated the inhaled NHT-CS is a viable preclinical option for developing novel inhalation formulations as a potential anti-smoking therapeutic.

Assessment of individual differences in response to acute bupropion or varenicline treatment using a long-access nicotine self-administration model and behavioral economics in female rats.

Bupropion and varenicline are widely prescribed pharmacological treatments for smoking cessation. These treatments are only marginally effective in clinical populations but most preclinical studies show that they are effective in decreasing self-administration in rats on a group level. The present study investigated individual differences in responding to bupropion or varenicline in a preclinical model of long-access to nicotine (0.03 mg/kg/inf; 12 h/day) in female rats. Rats were first assessed for their individual economic demand for nicotine and for their individual performance in open field and elevated plus maze prior to nicotine access and during withdrawal. Rats were then tested for the acute effects of bupropion, varenicline, and yohimbine. We found that neither bupropion nor varenicline decreased responding for nicotine on test days. On the contrary, a moderate dose of bupropion (30 mg/kg) significantly increased responding for nicotine. We also found that rats with higher demand for nicotine were more sensitive to pretreatment with yohimbine which resulted in increased responding for nicotine during the dose-effect tests. Finally, we show that rats that had a higher demand for nicotine also were more persistent in seeking nicotine during extinction and reinstatement tests with nicotine or yohimbine as triggers. Our findings suggest that the length of access to daily nicotine may be an important factor underlying the response to pharmacological treatments like bupropion or varenicline. Future studies modeling chronic treatment approaches that include both sexes will be needed to further extend our findings.

Comparison of the Relative Abuse Liability of Electronic Cigarette Aerosol Extracts and Nicotine Alone in Adolescent Rats: A Behavioral Economic Analysis.

Background: Characterizing the determinants of the abuse liability of electronic cigarettes (ECs) in adolescents is needed to inform product regulation by the United States Food and Drug Administration (FDA). We recently reported that Vuse Menthol EC aerosol extract containing nicotine and a range of non-nicotine constituents (e.g., menthol, propylene glycol) had reduced aversive effects compared to nicotine alone in adolescent rats, whereas Aroma E-Juice EC aerosol extract did not. The current study used a behavioral economic approach to compare the relative abuse liability of these EC extracts and nicotine alone in an i.v. self-administration (SA) model in adolescents. Methods: Adolescents were tested for the SA of EC extracts prepared using an ethanol (ETOH) solvent or nicotine and saline, with and without 4% ETOH (i.e., the same concentration in the EC extracts) in 23 h/day sessions. Results. Although acquisition of SA was faster for nicotine + ETOH compared to all other formulations, the elasticity of demand for all nicotine-containing formulations was similar. Conclusions: EC aerosol extracts did not have greater abuse liability than nicotine alone in adolescents. These data suggest that nicotine may be the primary determinant of the abuse liability of these ECs in youth, at least in terms of the primary reinforcing effects of ECs mediated within the central nervous system.

Clinical trial recruitment of adult African American smokers from economically disadvantaged urban communities.

This investigation evaluated the effectiveness and challenges of multiple recruitment methods, described as proactive, reactive, and combination methods, among adult African American smokers (N = 527) from economically disadvantaged urban communities enrolled to test progressively reduced nicotine content investigational cigarettes. The study evaluated success using descriptive statistics to measure the volume of phone calls and percentage of eligible participants per method. Reactive and combination strategies effectively prompted participants to call about the study. Combination methods yielded the highest eligibility rates. Findings demonstrate the unique recruitment successes within this population across a range of recruitment methods and may inform improved methods to recruit and engage African Americans in clinical trials.

Insurance coverage and utilization of nicotine patches after receipt of a prescription.

Introduction: Changes in reimbursement policy have made nicotine replacement therapy (NRT) much more available, but little is known about what happens to patients after they receive their prescription. This study describes rates of successfully filling prescriptions for NRT and its association with type of insurance. Methods: We identified 224 patients who received a prescription for NRT during an outpatient visit to an academic medical center between January 1st 2016 and February 10th 2017. We conducted telephone surveys to assess whether they tried to fill their prescriptions and if so, determine the effects of insurance type on the ability to successfully fill the prescription. Results: Of 117 patients completing the survey, 23 (19.6%) did not attempt to fill and 6 (5.1%) had no insurance. Of the 90 patients with insurance who attempted to fill their prescription, 67 (74.4%) were successful and 23 (25.6%) were unsuccessful in obtaining medications. Success varied by insurance with successful fills ranging from 34 (87.2%) of those with commercial insurance, 24 (70.6%) with Medicaid, to 9 (52.9%) with Medicare. Of 37 participants living with another smoker, 31 (83.7%) wanted an NRT prescription specifically for their partner; several volunteered that they had shared patches with their partner. Conclusions: Despite widespread coverage for NRT, many patients may still encounter difficulties in getting their prescriptions filled. Some tobacco users might also benefit from getting NRT prescriptions for their partners that smoke.

Evaluation of Sex Differences in the Elasticity of Demand for Nicotine and Food in Rats.

INTRODUCTION: Animal studies can inform policy regarding nicotine levels in tobacco products and e-cigarette solutions. Increasing the price of nicotine-containing products decreases their use, but it is unknown how the relationship between price and consumption is affected by both sex and nicotine dose. METHODS: A behavioral economics procedure was used to determine the demand elasticity for nicotine in male and female rats. Demand elasticity describes the relationship between price and consumption. A high level of elasticity indicates that consumption is relatively sensitive to increases in price. The rats self-administered a low dose (0.01 mg/kg/inf) or a standard dose (0.03 mg/kg/inf) of nicotine for 9 days under a fixed-ratio (FR) 1 schedule. Then the price (FR schedule) of nicotine was increased, and a demand analysis was conducted. A similar study was conducted with palatable food pellets. RESULTS: There were no sex differences in nicotine or food intake under the FR1 schedule. However, demand for 0.03 mg/kg/inf of nicotine was more elastic in females than males. Demand for 0.01 mg/kg/inf of nicotine and food was more elastic in males than females. CONCLUSIONS: These findings indicate that there are no differences in nicotine and food intake between males and females when the price is low. When the price of nicotine or food is increased, males maintain their old level of intake longer than females when they have access to a standard dose of nicotine, and females maintain their intake longer when they have access to a low dose of nicotine or food. IMPLICATIONS: This behavioral economics analysis indicates that there is no sex difference in nicotine intake when the price of nicotine is low. Increasing the price of nicotine decreases nicotine intake in a dose- and sex-specific manner. Males maintain their old level of intake longer when they have access to a standard dose of nicotine and females when they have access to a low dose. This has implications for tobacco regulatory policy. In a regulatory environment where only low nicotine-containing products are allowed, increasing the price of nicotine products may lead to a greater decrease in nicotine use in males than females.

A custom-built low-cost chamber for exposing rodents to e-cigarette aerosol: practical considerations.

Objectives: To (1) design and build a low-cost exposure chamber system for whole-body exposure of rodents to electronic cigarette aerosol, (2) provide detailed instructions with particular focus on automated e-cigarette activation, and (3) develop a simple mathematical model for aerosol levels in the exposure chamber.Methods: We built the system with standard laboratory equipment and an open-source electronics platform (Arduino) for e-cigarette activation. Arduino is used to control a solenoid, which pushes the activation button of so-called "Mod" e-cigarettes, and a pump to move the aerosol from the mouthpiece of the e-cigarette into the chamber. For "Pods" and "Cigalikes," the solenoid is not used as they are activated by the vacuum created by the pump. Aerosol concentrations were measured with a light-scattering laser photometer.Results: The system allows varying the air exchange rate, monitoring aerosol levels, and programing arbitrary puff topography. Aerosol concentrations observed for different chamber operating conditions (puff time and period, e-cigarette power output, air exchange rate) were consistent with the mathematical model.Conclusions: Our low-cost exposure chamber can be used in animal experimental studies of the health effects of e-cigarettes. Our model allows estimating design parameters such as chamber volume, air exchange rate, and puff period.

Economic demand analysis of within-session dose-reduction during nicotine self-administration.

BACKGROUND: This study determined if a within-session dose-reduction design sufficiently captures elasticity of demand for nicotine in male and female rats using environmental enrichment to manipulate demand elasticity. METHODS: Male and female Sprague-Dawley rats were trained to self-administer nicotine (60 µg/kg/infusion). In Experiment 1, rats began daily dose-reduction for nine sessions following acquisition. Rats then underwent a minimum of five within-session dose-reduction sessions where each dose was available for 10 min. In Experiment 2, rats were reared in isolated, social, or enriched housing followed by acquisition of nicotine self-administration. Rats then underwent within-session dose-reduction. Housing environments were then switched, followed by additional testing sessions. Consumption was calculated for each dose and exponential demand curves were fit. RESULTS: No sex differences in acquisition of nicotine self-administration were detected for either experiment. In experiment 1, demand intensity (Q0; estimated intake if nicotine were freely available), was higher with between- compared to within-session dose-reduction, although elasticity of demand (α; rate of decline in nicotine intake as a function of increasing unit price), was lower. In Experiment 2, animals reared in enrichment had fewer infusions during acquisition compared to animals in isolation. Enriched males had reduced demand intensity compared to both isolated and social males, whereas isolated females had reduced intensity compared to enriched females. CONCLUSIONS: The within-session dose-reduction procedure for nicotine self-administration replicated effects of environmental enrichment on consumption behaviors. Additionally, this procedure captured differences in nicotine demand due to sex, laying important groundwork for future translational research on mechanisms of nicotine dependence.

Reduced adolescent risk-assessment and lower nicotinic beta-2 expression in rats exposed to nicotine through lactation by forcedly drinking dams.

Few animal studies focus on consequences of nicotine postnatal exposure, particularly through lactation. We have recently shown that forced nicotine drinking elevates maternal care, paradoxically provoking arousal and stress in pups. Present work aimed to evaluate the specific contribution of altered maternal cares, compared to the sequelae merely due to nicotine effects. Two groups were compared to water-drinking control dams: (i) free-choice dams (H2O+NIC group) drinking from two bottles, containing either nicotine or water; (ii) forced dams (NIC+NIC group) drinking from two bottles, both containing nicotine. We previously demonstrated that nicotine was indeed transferred to the lactating offspring. Regarding behavioural consequences at adolescence, both H2O+NIC and NIC+NIC rats were slower than controls in discovering a novel over a familiar compartment, whilst only NIC+NIC rats exhibited reduced risk-related avoidance and assessment behaviour. Brain analyses at adulthood suggest that, in prefrontal cortex, nicotine per se reduced serotonin, while the maternal overcare reduced CHRN-B2 gene-expression. As a whole, unescapable nicotine-enhanced maternal care could have an impact on the offspring arousal by acting on prefrontal CHRN-B2 gene-expression. When present results are translated to consequences of non-voluntary exposure in humans, we propose that children receiving altered attentions by a smoking caregiver might undergo a neuro-behavioural development biased towards emotional shyness.

Chronic Nicotine Exposure Alters Metabotropic Glutamate Receptor 5: Longitudinal PET Study and Behavioural Assessment in Rats.

Using positron emission tomography (PET), a profound alteration of the metabotropic glutamate receptor 5 (mGluR5) was found in human smoking addiction and abstinence. As human PET data either reflect the impact of chronic nicotine exposure or a pre-existing vulnerability to nicotine addiction, we designed a preclinical, longitudinal study to investigate the effect of chronic nicotine exposure on mGluR5 with the novel radiotracer [18F]PSS232 using PET. Twelve male dark Agouti rats at the age of 6 weeks were assigned randomly to three groups. From day 0 to day 250 the groups received 0 mg/L, 4 mg/L, or 8 mg/L nicotine solution in the drinking water. From day 250 to 320 all groups received nicotine-free drinking water. PET scans with [18F]PSS232 were performed in all animals on days 0, 250, and 320. To assess locomotion, seven tests in square open field arenas were carried out 72 days after the last PET scan. During the first four tests, rats received 0 mg/L nicotine and for the last three tests 4 mg/L nicotine in the drinking water. After 250 days of nicotine consumption [18F]PSS232 binding was reduced in the striatum, hippocampus, thalamus, and midbrain. At day 320, after nicotine withdrawal, [18F]PSS232 binding increased. These effects were more pronounced in the 4 mg/L nicotine group. Chronic administration of nicotine through the drinking water reduced exploratory behaviour. This preliminary longitudinal PET study demonstrates that chronic nicotine administration alters behaviour and mGluR5 availability. Chronic nicotine administration leads to decreased [18F]PSS232 binding which normalizes after prolonged nicotine withdrawal.

Dual use of electronic cigarettes and tobacco in New Zealand from a nationally representative sample.

OBJECTIVE: There is strong interest in the use of electronic cigarettes (e-cigarettes) globally. Not much is known about the dual use of e-cigarettes and combustible tobacco cigarettes, or if there are demographic differences among dual users and e-cigarette only users. This paper reports on the demographics of dual users and e-cigarette only users in New Zealand in a nationally representative sample. METHODS: The Health and Lifestyles Survey (HLS) is a biennial face-to-face in-house survey of New Zealand adults aged 15 years or over. The HLS was completed by 3,854 participants in 2016. RESULTS: There is clear evidence of significant dual use in the current sample: most current e-cigarette users (63.9%) were dual users. Respondents 45 years and older were twice as likely to be dual users as those aged 15 to 34 years. CONCLUSION: The current study found evidence for substantial dual use of e-cigarettes and combustible tobacco cigarettes among adult e-cigarette users, particularly among users aged 45 years and over. Implications for public health: Public health initiatives should provide clear advice that e-cigarettes should be used as a smoking cessation tool and not as a way to allow the consumption of combustible tobacco to continue.

"They're thinking, well it's not as bad, I probably won't get addicted to that. But it's still got the nicotine in it, so ": Maturity, Control, and Socializing: Negotiating Identities in Relation to Smoking and Vaping-A Qualitative Study of Young Adults in Scotland.

Objective: To explore the understandings of and engagement with e-cigarettes, of young adults from disadvantaged backgrounds, and how these may have an impact on existing smoking identities. Methods: Twenty-two small group and 11 individual qualitative interviews were conducted in Central Scotland with 72 16-24 year olds between September 2015 and April 2016. Participants were mostly smokers and ex-smokers from socioeconomically disadvantaged backgrounds. Results: Although most participants had tried e-cigarettes, they generally held ambivalent views about e-cigarettes and vaping. Two overarching themes were identified which helped in understanding this. Firstly, e-cigarettes were understood by the participants in relation to their existing smoking identities. Vaping was viewed as less controllable and more addictive than smoking, which did not fit with their self-identity as controlled smokers. Secondly, they felt that vaping could not replace the social and cultural importance that smoking had in their lives. Conclusion: This study suggests that though young adults from disadvantaged areas are trying e-cigarettes for various reasons, vaping is rarely sustained. Through their own experiences of vaping and their observations of others vaping, the participants perceive the behavior as endangering an existing acceptable and controlled smoking identity. Additionally, e-cigarettes were considered to be a jarring presence in existing social situations where smoking was valued. This study, therefore, provides insights into how young adults may be rationalizing their continued smoking in the face of potentially less harmful alternatives. Implications: As new and novel nicotine delivery devices, and due to their similarity to smoking, e-cigarettes have the potential to help smokers in their quit attempts. However, the findings from this study raise questions about whether e-cigarettes are regarded as having this potential by young adult smokers from disadvantaged socioeconomic environments where smoking is more commonplace and acceptable.

Rats choose high doses of nicotine in order to compensate for changes in its price and availability.

Restricting when and where smoking can occur is a major focus of public health policies in Western countries. In conjunction with increased taxation, these approaches have contributed to a reduction in smoking uptake among adolescents, yet the consequences for established smokers are less clear. In order to further explore this relationship, we developed a novel animal model of restricted nicotine self-administration. Rats were trained to choose between three doses of nicotine (15, 30 and 60 µg/kg/infusion) under conditions where nicotine was (1) freely available at a low cost (20-second post-infusion time-out, fixed-ratio 1 [FR1]), (2) available under restricted access at a low cost (300-second post-infusion time-out, FR1), or (3) freely available at a high cost (20-second post-infusion time-out, FR5). We demonstrate that as access to nicotine is restricted or when cost increases, rats compensate for these changes by increasing their intake of the highest dose of nicotine available. This preference was impervious to treatment with the smoking cessation medication varenicline, but was reduced when the cost of the highest dose only was increased, or when nicotine was again made freely available at a low cost. These results provide the first evidence in rats that nicotine availability and cost influence nicotine choice independently of variations in nicotine and context exposure. They imply that established smokers may compensate for changes in the availability and cost of tobacco by increasing their rate of smoking when they are free to do so.

Tobacco company strategies to identify and promote the benefits of nicotine.

BACKGROUND: In response to a changing regulatory and consumer landscape, tobacco companies developed new strategies to promote cigarettes and smoking. We examined one of these strategies: to fund and conduct scientific research related to potential benefits of nicotine, and to use their findings to promote nicotine. METHODS: Qualitative analysis of previously secret tobacco industry documents from the Truth (formerly Legacy) Tobacco Documents Library (industrydocuments.library.ucsf.edu/tobacco), triangulated with data from other sources, including the online search engine Google, from the 1970s to December 2017. RESULTS: After publication of the 1988 Surgeon General's report on nicotine addiction, tobacco companies (particularly RJ Reynolds) intensified efforts to promote the benefits of nicotine while downplaying its addictiveness and health risks. Activities included building relationships with academic institutions and funding scientific studies of the benefits of nicotine on cognition and other performance areas through intramural and extramural programmes. Companies then promoted their research findings through public relations campaigns, often minimising nicotine's health risks by comparing it to caffeine or coffee. These comparisons appeared in highly publicised scientific meetings and interviews with the press. Nicotine-positive messages reappeared in the popular press and on some company websites in the 2010s. CONCLUSIONS: Tobacco companies implemented strategies to promote benefits of nicotine to scientific and general audiences while minimising its health risks. These strategies reappeared at the time novel tobacco products like electronic cigarettes were introduced. A greater awareness of the source of claims related to purported benefits of nicotine could inform discussions about emerging tobacco products.

Behavioral Economic Purchase Tasks to Estimate Demand for Novel Nicotine/tobacco Products and Prospectively Predict Future Use: Evidence From The Netherlands.

INTRODUCTION: The demand for alternative nicotine/tobacco products is not well established. This paper uses a behavioral economic approach to test whether smokers have differential demand for conventional factory-made, electronic, and very low nicotine content cigarettes (FMCs/ECs/VLNCs) and uses the prospective cohort design to test the predictive validity of demand indices on subsequent use of commercially available FMCs and ECs. METHODS: Daily smokers (≥16 years) from the Netherlands completed an online survey in April 2014 (N = 1215). Purchase tasks were completed for FMCs, ECs, and VLNCs. Participants indicated the number of cigarettes they would consume in 24 h, across a range of prices (0-30 euro). The relationship between consumption and price was quantified into four indices of demand (intensity, Pmax, breakpoint, and essential value). A follow-up survey in July 2015 measured FMC and EC use. RESULTS: At baseline, greater demand was observed for FMCs relative to ECs and VLNCs across all demand indices, with no difference between ECs and VLNCs. At follow-up, greater baseline FMC demand (intensity, essential value) was associated with lower quit rates and higher relapse. EC demand (Pmax, breakpoint, essential value) was positively associated with any EC use between survey waves, past 30 day EC use, and EC purchase between waves. CONCLUSIONS: Smokers valued FMCs more than ECs or VLNCs, and FMCs were less sensitive to price increases. Demand indices predicted use of commercially available products over a 15 month period. To serve as viable substitutes for FMCs, ECs and VLNCs will need to be priced lower than FMCs. IMPLICATIONS: Purchase tasks can be adapted for novel nicotine/tobacco products as a means to efficiently quantify demand and predict use. Among current daily smokers, the demand for ECs and VLNCs is lower than FMCs.

The Effect of Price on the Consumption of Reduced Nicotine Cigarettes.

BACKGROUND: Price affects the demand for cigarettes, indicating that smokers, perhaps especially lower income smokers, may choose low nicotine cigarettes (LNC) if they were commercially available and cost less than fully nicotinized conventional cigarettes. The present study tests the hypothesis that smokers will prefer purchasing LNCs at a lower price point than conventional cigarettes given a fixed budget. METHOD: A laboratory-based, within-subject, 3 (nicotine level) × 3 (price) factorial design provided smokers opportunities to purchase standard (0.7 per mg tobacco), moderately reduced (0.3 mg), and very low-nicotine (0.03 mg). Spectrum research cigarettes according to an escalating price structure (low-nicotine costing the least, high-nicotine costing the most) given a fixed, laboratory-provided "income." Participants were 20 overnight-abstinent smokers who previously smoked and rated each of the three cigarettes. RESULTS: Overall, smokers rated LNCs as less satisfying compared with standard nicotine cigarettes (SNC), t(18) = -5.40, p < .001. In the free-choice session, subjects were more likely to choose LNC that cost less compared with SNC that cost more, even after an 8-hour abstinence period, F(2, 19) = 4.32, p = .03. Those selecting LNC or moderate nicotine cigarettes after abstinence smoked more cigarettes per day, t(17) = 2.40, p = .03 and had higher dependence scores on the HONC, t(18) = 2.21, p = .04 that those selecting SNC. CONCLUSION: The results indicate that smokers' response to price points when purchasing cigarettes may extend to LNC if these were commercially available. Differential cigarette prices based on nicotine content may result in voluntary selection of less addicting products. IMPLICATIONS: The Food and Drug Administration has proposed a rule that would reduce nicotine content in commercially available cigarettes. However, it is not known how smokers may respond in an environment where products of differing nicotine content and of differing prices are available. This study demonstrates that price may be an important factor that could lead smokers to select reduced nicotine products voluntarily, even if those products are rated as inferior or less satisfying.