A reduced exposure heated tobacco product was introduced then abruptly taken off United States shelves: results from a tobacco harm reduction natural experiment.

BACKGROUND: A heated tobacco product (HTP) authorized for purchase in the United States by the Food and Drug Administration as a reduced harm product was removed from the market after about 2 years of sales. Adults who used the HTP were surveyed to determine the impact of the introduction and removal of the HTP on past and current tobacco behaviors. METHODS: Adults who were using the HTP before its United States market removal (n = 502) completed a cross-sectional online survey to determine their tobacco use behaviors at three timepoints: prior to HTP initiation, just before HTP market removal, and at the time of the survey which was administered approximately 10 months post-removal. Descriptive statistics summarized outcome variables and paired bivariate testing was used to compare percent change between timepoints. Multivariable logistic regression and general linear models estimated associations of tobacco use behaviors and cigarette consumption. RESULTS: Overall, significantly fewer adults consumed cigarettes while using HTP than before they tried the product (63.0% vs. 89.9%, p value < 0.0001) and the number of cigarettes consumed per week (CPW) decreased (106.3-39.0, p value < 0.0001). After HTP removal, the percent of adults who consumed cigarettes increased non-significantly (63.0-67.5%, p value = 0.0544) while CPW increased significantly (39.0-76.6 CPW, p value < 0.0001). At the time of the survey, over 25% of the sample continued to use the HTP and 7.2% reported use of no tobacco products. Electronic nicotine delivery system use had increased significantly from the prior period (27.4% increase, p value < 0.0001). CONCLUSION: This study demonstrates reduction or elimination of combustible cigarette smoking while adults were using HTPs and some increased smoking after market removal, albeit at lower levels. If unable to find satisfying alternatives, adults who smoke and transition to reduced harm products may return to smoking or purchase products illicitly if their preferred products are removed from the regulated market.

Characterization of Ad Libitum Use Behavior of On! Nicotine Pouches.

Objectives: Actual use of nicotine pouch products is not well studied. The objectives of this study were to characterize on ® nicotine pouch (Test Products (TP)) use behavior, including association with cigarette and smokeless tobacco (ST) product use. Methods: Adults who smoke cigarettes (AS) and/or adults who use ST (ASTU) (N=1147) that were not planning to quit and had expressed interest in trying and using TP after a 5-day trial were offered ad libitum use of TPs (7 flavors at 5 nicotine levels) for 6 weeks. Results: Participants used a median of ~5-6 pouches/day of a variety of flavors and nicotine levels. In the final week of the study, 27% of AS and 71% of ASTU reported no use of cigarettes or ST respectively, while reporting continued use of TPs. Additionally, 39% of AS and 14% of ASTU reduced consumption of cigarettes or ST products respectively by 50%-99%, compared to reported use at screening. We found a statistically significant inverse relationship between TP flavor varieties and number of cigarettes/ST. Conclusions: These data suggest that TPs can be potential substitutes for cigarettes/ST products, and complete switching may offer harm reduction potential for AS and ASTU not interested in quitting.

Awareness and use of tobacco products among underage individuals: findings from the altria client services underage tobacco use survey 2020-2022.

BACKGROUND: Tobacco use among underage individuals is a public health concern. Timely data about tobacco products, especially emerging products such as novel oral nicotine products (NPs), can provide critical information for the prevention of underage tobacco use. With a recent federal law raising the legal age of purchase of tobacco products from 18 to 21, it is of interest to benchmark awareness and use of tobacco products in the new underage population, young adults 18-20 years old. This study provides estimates on awareness and use of tobacco products among underage individuals 13-20 years old during May 2020 to August 2022 in the United States. METHODS: Altria Client Services Underage Tobacco Use Survey (UTUS) is a repeated cross-sectional survey conducted every quarter-year. A stratified random sampling approach was used to draw nationally representative samples of household dwelling individuals 13-20 years old. Information about the awareness and use of tobacco products was obtained via online self-administration or phone interviews after a consent/assent process. RESULTS: A sizable portion of underage individuals were aware of NPs (~ 40% among youth and ~ 50% among underage young adults), although past 30-day use was low (< 2%). The lowest levels of awareness and use were observed for heated tobacco products and snus. E-cigarettes were the most used tobacco products among underage individuals. Underage young adults (i.e., 18-20 year olds) were more likely to use tobacco products than youth (i.e., 13-17 year olds). There was no substantial change over time in the awareness and use of tobacco products during the study period despite a slight increase in past 30-day prevalence of e-cigarette use among youth between quarter 1 of 2021 and quarter 2 of 2022. CONCLUSIONS: The awareness and use of tobacco products remained relatively stable between May 2020 and August 2022. There is a notable level of awareness of novel NPs among underage individuals.

Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users.

RATIONALE: Oral tobacco-derived nicotine products include on!® nicotine pouches (NPs) which are tobacco-leaf free and available in multiple flavors and nicotine levels. Switching completely to NPs from cigarettes and moist smokeless tobacco (MST) has the potential to reduce harm for adult tobacco consumers. However, the dependence potential of NPs is not established. Therefore, we characterized the abuse potential of NPs with different nicotine levels compared to cigarettes and MST. OBJECTIVES: To evaluate nicotine pharmacokinetics (PK) and subjective effects of NPs (ranging from 1.5 to 8 mg nicotine) compared to own brand cigarettes (OBCs) and MST (OBMST). METHODS: We used a randomized, in-clinic, partial single-blind, 7-way crossover design to assess nicotine PK and subjective effects in dual users of cigarettes and MST. RESULTS: The mean nicotine Cmax for NPs increased with nicotine level, ranging from 3.5 ng/mL (1.5 mg NP) to 15.4 ng/mL (8 mg NP), compared with 12.2 ng/mL for OBCs and 9.8 ng/mL for OBMST. Nicotine tmax was much longer for all NPs and OBMST (32.5-34.4 min) compared to OBCs (8.5 min). Reductions in urges to smoke after use of the 2 mg, 3.5 mg, and 8 mg NPs were not statistically different (p > 0.05) relative to OBC. Also, NPs resulted in lower ratings of positive subjective effects relative to OBCs and OBMST. CONCLUSIONS: Overall, based on the study results and literature reported nicotine PK values for cigarettes and MST, the abuse potential of NPs is not likely to be higher than OBCs and OBMST. NPs may be potentially acceptable switching products for users of cigarettes and MST products.

Human Abuse Liability Assessment of Tobacco and Nicotine Products: Approaches for Meeting Current Regulatory Recommendations.

Many regulatory bodies now recommend that tobacco product manufacturers provide information regarding new tobacco products' abuse liability to inform regulatory authorization of currently marketed tobacco products or new product applications (including premarket tobacco product applications in the United States). In addition, the US Food and Drug Administration (FDA) recommends including this information as part of modified risk tobacco product applications. Regulators, including FDA, and many public health officials and researchers consider abuse liability assessment a model which predicts the likelihood that the use of the tobacco product would result in addiction and be used repeatedly or even sporadically resulting in undesirable effects. Abuse liability of a new, potentially reduced harm product can also inform its ability to substitute completely for more harmful tobacco products. While many methods exist, no standard tobacco product abuse liability assessment has been established. The purpose of this review is to provide background information and practical recommendations for human abuse liability testing methods to meet tobacco regulatory needs. A combination of nicotine test product pharmacokinetic, subjective effect and/or behavioral response, and physiological response data relative to comparator products with known abuse liability satisfies some regulatory requirements. Implications: This review provides a practical inspection of the current, international regulatory recommendations for abuse liability assessment of tobacco and regulatory review of such information within the United States and also recommends study designs and methods for abuse liability testing of tobacco products based on scientific and regulatory knowledge. Given that tobacco product abuse liability testing is of increasing interest to regulatory bodies globally, especially with the emergence of novel tobacco products, this timely work provides background and functional recommendations for tobacco product abuse liability testing.

Youth susceptibility to tobacco use: is it general or specific?

BACKGROUND: Susceptibility to tobacco use predicts tobacco use onset among youth. The current study aimed to estimate the extent of overlap in susceptibilities across various tobacco products, investigate sociopsychological correlates with susceptibilities, and examine whether the relationship linking susceptibility with the onset of use is product-specific or is accounted for by a general susceptibility-onset relationship. METHODS: The study population consisted of US youth 12-17 years old who had never used a tobacco product, sampled in the longitudinal Population Assessment of Tobacco and Health study wave 4 (Dec. 2016-Jan. 2018; n = 10,977). Tobacco product-specific susceptibility at wave 4 was assessed via questions about curiosity, likelihood to try, and likelihood of use if a best friend offered. The onset of use of various tobacco products was defined as first use occurring between the wave 4 and wave 4.5 (Dec. 2017-Dec. 2018) assessments (n = 8841). Generalized linear regression and structural equation models were used for data analysis. RESULTS: There is a large degree of overlap in susceptibilities across tobacco products (65% of tobacco-susceptible youth were susceptible to more than one tobacco product). Tobacco-susceptible youths were more likely to have recently used cannabis, consumed alcohol, or to have been associated with tobacco-using peers. Structural equation models suggest that the susceptibility-onset relationship largely operates in a non-product-specific manner after accounting for the general susceptibility-to-tobacco-onset relationship. CONCLUSIONS: Youth susceptibility to tobacco use overlaps widely across different tobacco products and other risky behaviors. Findings from this study support a holistic approach towards the prevention of risk behaviors, supplemented by product-specific strategies when needed.

Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes.

RATIONALE: on!® nicotine pouches (NPs) are oral tobacco-derived nicotine products that are tobacco-leaf free and are available in a variety of flavors and nicotine strengths. Switching completely to NPs from cigarettes may present the potential to reduce harm in adult smokers (AS) unable or unwilling to quit smoking. We characterized the abuse potential of six different flavor variants of NPs compared to cigarettes. OBJECTIVES: The objective of this study was to evaluate the nicotine pharmacokinetics (PK) and subjective effects of different flavor variants of NPs compared to participants' own brand cigarettes (OBCs) in AS. METHODS: In this single-blind, randomized, 7-way crossover study, we assessed nicotine PK, subjective measures (using well-established questionnaires), and product use behavior associated with six flavors of 4 mg NPs and OBCs in AS that remained in clinic for the duration of the test period. RESULTS: Nicotine Cmax values ranged from 9.0 to 11.5 ng/mL for the NPs and 16.3 ng/mL for OBCs. The tmax ranged from 30.1 to 34.9 min for ONPs and 7.5 min for OBCs. Use of NPs resulted in lower ratings of urge to smoke or craving a cigarette. All the NPs were considered pleasant, but not as much as OBCs. Flavor did not appear to influence the nicotine PK or subjective responses. CONCLUSIONS: Based on the nicotine PK parameters and subjective responses, we conclude that NPs, regardless of flavor, likely have lower abuse potential than cigarettes. Overall, this study suggests that the NPs may be potentially acceptable switching products for adult smokers.

Characterization of the Abuse Potential in Adult Smokers of a Novel Oral Tobacco Product Relative to Combustible Cigarettes and Nicotine Polacrilex Gum.

Novel noncombustible tobacco products offer adult smokers (ASs) alternatives to combustible cigarettes lower on the continuum of risk; however, the abuse potential of such products has not been well studied. The objective of this study was to evaluate the abuse potential of 2 chewable tobacco-derived nicotine containing products, VERVE Chews Blue Mint (test 1) and Green Mint (test 2), in ASs compared with own-brand cigarettes (CIGS) and nicotine polacrilex gum (GUM) using subjective measures and nicotine pharmacokinetics. ASs used the test products during a 5-day at-home trial prior to completing an in-clinic 4-period randomized crossover study. During the study ASs used test products, CIGS, and GUM once on separate days. Responses to Tobacco/Nicotine Withdrawal and Direct Effects of Product questionnaires were documented, and blood samples were collected to assess nicotine pharmacokinetics during each product use. Nicotine pharmacokinetic parameters (Cmax and AUC) were statistically significantly lower with use of test products compared with CIGS and statistically significantly higher compared with GUM. No appreciable differences were noted between the 2 flavors for any of the end points measured. Reductions in maximum urge to smoke and maximum responses to the question "Is the Product 'Pleasant' Right Now?" for the test products were statistically significantly lower than CIGS but comparable to GUM. Similar results were observed for responses to other items in the 2 questionnaires. The test products, under the conditions of this study, carry lower abuse potential than own-brand cigarettes and similar to nicotine polacrilex gum.

Characterization of puff topography of a prototype electronic cigarette in adult exclusive cigarette smokers and adult exclusive electronic cigarette users.

Puff topography is an important measure of how consumers use e-vapor products. The purpose of this study was to evaluate the feasibility of using SODIM Smoking Puff Analyzer Mobile Device (SPA/M) to measure puff topography during use of a prototype e-cigarette (e-cig) in exclusive cigarette smokers (CS) and e-cig users (EC) under ad lib conditions in a clinic. Adult CS (n = 13) and EC (EC; n = 10) completed a 7-hr use session with the e-cig (2% tobacco-derived nicotine by weight, cartridge based system approximately the size of a king size cigarette). E-liquid usage was determined from cartridge weight. CS also smoked a single cigarette with the SPA/M. The SPA/M reliably recorded puff parameters throughout the study period, with CS puffs averaging 47.9 ±â€¯18.2 ml volume, 2.3 ±â€¯0.8 s duration, and 21.5 ±â€¯4.6 ml/s flow rate. EC puffs averaged 53.4 ±â€¯19.2 ml volume, 3.0 ±â€¯1.3 s duration, and 19.6 ±â€¯5.0 flow rate. CS average e-liquid use was 292 ±â€¯214 mg and EC averaged 415 ±â€¯305 mg over 7 h. When compared to a single use of their own brand cigarettes, CS took longer (2.3 ±â€¯0.8 vs.1.7 ±â€¯0.4 s) puffs with similar puff volume (47.9 ±â€¯18.2 vs. 44.1 ±â€¯10.5 ml) from the e-cig prototype. The puff duration, flow rate and peak flow were significantly lower (p < 0.05) with the e-cigs compared to cigarettes. Experienced EC and CS appeared to use the e-cig prototype differently, which is consistent with the literature. The SPA/M could be a useful tool in assessing e-cig use behavior for regulatory purposes.

Electronic cigarettes: effective nicotine delivery after acute administration.

INTRODUCTION: Electronic cigarettes (ECs) are marketed as nicotine delivery devices. Two studies with EC-naïve participants suggest that ECs deliver little or no nicotine. In those studies, standard-sized ECs were used, though experienced EC users often use larger devices that house higher voltage and/or longer lasting batteries. Whether user experience and device characteristics influence EC nicotine delivery is uncertain. The purpose of the present study was to examine the effects of ECs in experienced users who were using their preferred devices. METHODS: Eight EC users (3 women) who had been using ECs for at least 3 months, completed one 5-hr session using devices they provided and the flavor/strength nicotine cartridges they selected. Sessions consisted of 4 phases: baseline, 10 puffs (30-s interpuff interval) from the device, 1-hr ad lib puffing period, and a 2-hr rest period (no puffing). Outcome measures in each phase included plasma nicotine concentration, heart rate, and subjective ratings of nicotine/product effects and abstinence symptoms. RESULTS: Relative to baseline, plasma nicotine and heart rate increased significantly within 5 min of the first puff and remained elevated throughout the ad lib puffing period. Increases in ratings of direct effects of nicotine and product were observed as well as decreases in abstinence symptoms. CONCLUSIONS: User experience and/or device characteristics likely influence EC nicotine delivery and other effects. Systematic manipulation of these and other variables could elucidate conditions that produce intended effects.

Indoor air quality in Virginia waterpipe cafes.

INTRODUCTION: A revised indoor air quality law has been implemented in Virginia to protect the public from the harmful effects of secondhand smoke exposure. This legislation contains exemptions that include allowances for smoking in a room that is structurally separated and separately ventilated. The objective of the current study was to examine the impact of this law on air quality in waterpipe cafés, as well as to compare the air quality in these cafés to restaurants that allow cigarette smoking and those where no smoking is permitted. METHODS: Indoor air quality in 28 venues (17 waterpipe cafés, five cigarette smoking-permitted restaurants and six smoke-free restaurants (five with valid data)) in Virginia was assessed during 4 March to 27 May 2011. Real-time measurements of particulate matter (PM) with 2.5 µm aerodynamic diameter or smaller (PM2.5) were obtained and occupant behaviour/venue characteristics were assessed. RESULTS: The highest mean PM2.5 concentration was observed for waterpipe café smoking rooms (374 µg/m(3), n=17) followed by waterpipe café non-smoking rooms (123 µg/m(3), n=11), cigarette smoking-permitted restaurant smoking rooms (119 µg/m(3), n=5), cigarette smoking-permitted restaurant non-smoking rooms (26 µg/m(3), n=5) and smoke-free restaurants (9 µg/m(3), n=5). Smoking density was positively correlated with PM2.5 across smoking rooms and the smoke-free restaurants. In addition, PM2.5 was positively correlated between smoking and non-smoking rooms of venues. CONCLUSIONS: The PM2.5 concentrations observed among the waterpipe cafés sampled here indicated air quality in the waterpipe café smoking rooms was worse than restaurant rooms in which cigarette smoking was permitted, and state-required non-smoking rooms in waterpipe cafés may expose patrons and employees to PM2.5 concentrations above national and international air quality standards. Reducing the health risks of secondhand smoke may require smoke-free establishments in which tobacco smoking sources such as water pipes are, like cigarettes, prohibited.

Clinical laboratory assessment of the abuse liability of an electronic cigarette.

AIMS: To provide an initial abuse liability assessment of an electronic cigarette (EC) in current tobacco cigarette smokers. DESIGN: The first of four within-subject sessions was an EC sampling session that involved six, 10-puff bouts (30 seconds inter-puff interval), each bout separated by 30 minutes. In the remaining three sessions participants made choices between 10 EC puffs and varying amounts of money, 10 EC puffs and a varying number of own brand cigarette (OB) puffs, or 10 OB puffs and varying amounts of money using the multiple-choice procedure (MCP). The MCP was completed six times at 30-minute intervals, and one choice was reinforced randomly at each trial. SETTING: Clinical laboratory. PARTICIPANTS: Twenty current tobacco cigarette smokers. MEASUREMENTS: Sampling session outcome measures included plasma nicotine, cardiovascular response and subjective effects. Choice session outcome was the cross-over value on the MCP. FINDINGS: EC use resulted in significant nicotine delivery, tobacco abstinence symptom suppression and increased product acceptability ratings. On the MCP, participants chose to receive 10 EC puffs over an average of $1.06 or three OB puffs and chose 10 OB puffs over an average of $1.50 (P < 0.003). CONCLUSIONS: Electronic cigarettes can deliver clinically significant amounts of nicotine and reduce cigarette abstinence symptoms and appear to have lower potential for abuse relative to traditional tobacco cigarettes, at least under certain laboratory conditions.

Waterpipe tobacco products: nicotine labelling versus nicotine delivery.

BACKGROUND: Waterpipe tobacco package labelling typically indicates "0.0% tar" and "0.05% or 0.5% nicotine". OBJECTIVE: To determine the extent to which nicotine labeling is related to nicotine delivery. METHODS: 110 waterpipe smokers engaged in a 45-minute waterpipe smoking session. Puff topography and plasma nicotine were measured. Three waterpipe tobacco brands were used: Nakhla (0.5% nicotine), Starbuzz (0.05% nicotine), and Al Fakher (0.05% nicotine). Data were analyzed by one-way ANOVA. RESULTS: Topography did not differ across brands. Peak plasma nicotine varied significantly across brands. Al Fakher had the highest nicotine delivery (11.4 ng/ml) followed by Nakhla (9.8 ng/ml) and Starbuzz (5.8 ng/ml). CONCLUSIONS: Nicotine labelling on waterpipe tobacco products does not reflect delivery; smoking a brand with a "0.05% nicotine" label led to greater plasma nicotine levels than smoking a brand with a "0.5% nicotine" label. Waterpipe tobacco products should be labelled in a manner that does not mislead consumers.

Influence of escalating alternative reinforcer values on cigarette choice.

The availability of alternative reinforcers reduces drug taking. Escalating alternative reinforcer values have been used to initiate and maintain abstinence from drug use. A reset in reinforcer value has been added to the schedule of alternative reinforcer presentation to discourage relapse. The purpose of this preliminary study was to test the influence of escalating and escalating and resetting alternative reinforcer value on cigarette choice in the human laboratory. Fourteen daily cigarette smokers completed this experiment, which required one practice and three experimental sessions. During each experimental session, subjects made six choices between smoking a cigarette and receiving money, available under Constant, Escalating or Escalating and Resetting conditions. The total number of cigarettes chosen and puffs taken, but not the maximum consecutive number of cigarettes choices, was decreased in the Escalating condition relative to the Constant condition. The maximum number of consecutive cigarettes chosen was decreased in the Escalating and Resetting condition relative to the Constant condition. The proportion of money earned was increased in the Escalating condition relative to the Constant and Escalating and Resetting conditions. These initial findings indicate that whereas an escalating alternative reinforcer schedule reduces cigarette smoking overall, an escalating and resetting alternative reinforcer schedule may reduce repeated cigarette smoking (i.e., relapse).

Methylphenidate increases cigarette smoking in participants with ADHD.

RATIONALE: Methylphenidate (Ritalin®) is commonly prescribed for behavioral problems associated with attention deficit/hyperactivity disorder (ADHD). The results of previous studies suggest that methylphenidate increases cigarette smoking in participants without psychiatric diagnoses. Whether methylphenidate increases cigarette smoking in participants diagnosed with ADHD is unknown. OBJECTIVE: In this within-subjects, repeated measures experiment, the acute effects of a range of doses of methylphenidate (10, 20, and 40 mg) and placebo were assessed in nine cigarette smokers who were not attempting to quit and met diagnostic criteria for ADHD but no other Axis I psychiatric disorders other than nicotine dependence. METHODS: Each dose of methylphenidate was tested once while placebo was tested twice. One hour after ingesting drug, participants were allowed to smoke ad libitum for 4 h. Measures of smoking included total cigarettes smoked, total puffs, and carbon monoxide levels. Snacks and decaffeinated drinks were available ad libitum; caloric intake during the 4-h smoking session was calculated. RESULTS: Methylphenidate increased the total number of cigarettes smoked, total number of puffs, and carbon monoxide levels. Methylphenidate decreased the number of food items consumed and caloric intake. CONCLUSIONS: The results of this experiment suggest that acutely administered methylphenidate increases cigarette smoking in participants with ADHD, which is concordant with findings from previous studies that tested healthy young adults. These data indicate that clinicians may need to consider non-stimulant options or counsel their patients before starting methylphenidate when managing ADHD-diagnosed individuals who smoke.

Methylphenidate increases choice of cigarettes over money.

INTRODUCTION: Stimulants increase cigarette smoking in the naturalistic environment and laboratory. The effects of methylphenidate on a 9-trial, discrete cigarette versus money ($0.25) choice task were tested to elucidate the mechanisms underlying stimulant-induced increases in smoking. METHODS: Eleven participants who reported smoking 10-20 cigarettes/day completed the study. Four doses of methylphenidate (0, 10, 20, and 40 mg) were administered across 5 experimental sessions, with placebo administered twice. One hour following medication administration and at 30-min intervals thereafter, participants chose between smoking a cigarette and receiving US$0.25. The primary behavioral outcome measure was number of cigarette choices. RESULTS: Methylphenidate increased the number of cigarette choices over money. Puffs per session and carbon monoxide levels increased significantly and caloric intake decreased significantly following methylphenidate administration relative to placebo. CONCLUSIONS: The results of this study suggest that methylphenidate increases the relative reinforcing efficacy of cigarette smoking. Stimulant use may thus be an important consideration for individuals attempting to quit smoking.

A clinical laboratory model for evaluating the acute effects of electronic "cigarettes": nicotine delivery profile and cardiovascular and subjective effects.

BACKGROUND: Electronic "cigarettes" are marketed to tobacco users as potential reduced exposure products (PREP), albeit with little information regarding electronic cigarette user toxicant exposure and effects. This information may be obtained by adapting clinical laboratory methods used to evaluate other PREPs for smokers. METHODS: Thirty-two smokers participated in four independent Latin-square ordered conditions that differed by product: own brand cigarette, "NPRO" electronic cigarettes (NPRO EC; 18 mg cartridge), "Hydro" electronic cigarettes (Hydro EC; 16 mg cartridge), or sham (unlit cigarette). Participants took 10 puffs at two separate times during each session. Plasma nicotine and carbon monoxide (CO) concentration, heart rate, and subjective effects were assessed. RESULTS: Own brand significantly increased plasma nicotine and CO concentration and heart rate within the first five minutes of administration whereas NPRO EC, Hydro EC, and sham smoking did not. Own brand, NPRO EC, and Hydro EC (but not sham) significantly decreased tobacco abstinence symptom ratings and increased product acceptability ratings. The magnitude of symptom suppression and increased acceptability was greater for own brand than for NPRO EC and Hydro EC. CONCLUSIONS: Under these acute testing conditions, neither of the electronic cigarettes exposed users to measurable levels of nicotine or CO, although both suppressed nicotine/tobacco abstinence symptom ratings. IMPACT: This study illustrates how clinical laboratory methods can be used to understand the acute effects of these and other PREPs for tobacco users. The results and methods reported here will likely be relevant to the evaluation and empirically based regulation of electronic cigarettes and similar products.

Stimulant-induced changes in smoking and caloric intake: influence of rate of onset.

Rate-of-onset modulates the subject-rated effects of stimulants. Results of two studies from our laboratory demonstrate that immediate-release methylphenidate increases smoking and decreases caloric intake. Whether rate-of-onset influences the effects of methylphenidate on smoking and eating is unknown. The present experiment examined the influence of a range of doses of immediate- (7.5-30 mg) and sustained-release (18-72 mg) methylphenidate as well as placebo on smoking and eating. Eight cigarette smokers participated. A double-dummy drug administration procedure was used to maintain the double blind because immediate-release methylphenidate produces peak plasma concentrations 1.5-2 h and the sustained-release formulation produces peak plasma concentrations 6-8 h after oral administration. Smoking and eating were assessed for 4 h across the predicted peak effects of both methylphenidate formulations. Measures of smoking included total cigarettes, puffs, and carbon monoxide levels. Snacks and decaffeinated beverages were available ad libitum and caloric intake was monitored during the four-hour smoking session. Immediate- and sustained-release methylphenidate increased smoking and decreased caloric intake. The effects of methylphenidate generally did not vary as a function of formulation. The results of this study may have important implications for the treatment of disorders that require stimulant medications. Smoking should be monitored in patients that are prescribed stimulant medications, regardless of the formulation type.

The influence of acute varenicline administration on smoking and eating behavior in humans.

Varenicline (Chantix) is a novel smoking-cessation agent that acts at a number of nicotinic acetylcholine receptors. The aim of this study was to determine the behavioral effects of acute varenicline administration in human subjects. The effects of doses of varenicline (0.5, 1 and 2 mg), methylphenidate (40 mg; positive control) and placebo were assessed in 8 (7 males, 1 female) cigarette smokers. Staggered, double blind dosing was used to examine eating and smoking behavior during the peak effects of varenicline and methylphenidate. Starting at the published time to peak plasma levels of these drugs, subjects were allowed to smoke and eat ad libitum for 4 h. Acute varenicline was devoid of behavioral effects. Methylphenidate produced prototypical stimulant-like effects (e.g., increased smoking behavior; decreased caloric intake). The present results indicate that acute varenicline administration does not alter smoking behavior although the low number of subjects limits the ability to detect small effects. Future research should examine the effects of chronic varenicline on smoking and eating behavior in humans, particularly using operant techniques to determine whether varenicline alters the reinforcing effects of cigarettes and food in humans.