Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 min nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a 2 h whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular mid-day smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 h smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 h WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21–25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation.     

Relationship between cigarette format and mouth-level exposure to tar and nicotine in smokers of Russian king-size cigarettes

Differences in length and circumference of cigarettes may influence smoker behaviour and exposure to smoke constituents. Superslim king-size (KSSS) cigarettes (17 mm circumference versus 25 mm circumference of conventional king-size [KS] cigarettes), have gained popularity in several countries, including Russia. Some smoke constituents are lower in machine-smoked KSSS versus KS cigarettes, but few data exist on actual exposure in smokers. We investigated mouth-level exposure (MLE) to tar and nicotine in Russian smokers of KSSS versus KS cigarettes and measured smoke constituents under machine-smoking conditions. MLE to tar was similar for smokers of 1 mg ISO tar yield products, but lower for smokers of 4 mg and 7 mg KSSS versus KS cigarettes. MLE to nicotine was lower in smokers of 4 mg KSSS versus KS cigarettes, but not for other tar bands. No gender differences were observed for nicotine or tar MLE. Under International Organization for Standardization, Health Canada Intense and Massachusetts regimes, KSSS cigarettes tended to yield less carbon monoxide, acetaldehyde, nitric oxide, acrylonitrile, benzene, 1,3-butadiene and tobacco-specific nitrosamines, but more formaldehyde, than KS cigarettes. In summary, differences in MLE were observed between cigarette formats, but not systematically across pack tar bands.     

Lack of effect of menthol level and type on smokers’ estimated mouth level exposures to tar and nicotine and perceived sensory characteristics of cigarette smoke

Menthol can reduce sensory irritation and it has been hypothesised that this could result in smokers of mentholated cigarettes taking larger puffs and deeper post-puff inhalations thereby obtaining higher exposures to smoke constituents than smokers of non-mentholated cigarettes. The aim of our study was to use part-filter analysis methodology to assess the effects of cigarette menthol loading on regular and occasional smokers of mentholated cigarettes. We measured mouth level exposure to tar and nicotine and investigated the effects of mentholation on smokers’ sensory perceptions such as cooling and irritation. Test cigarettes were produced containing no menthol and different loadings of synthetic and natural l-menthol at 1 and 4 mg ISO tar yields. A target of 100 smokers of menthol cigarettes and 100 smokers who predominantly smoked non-menthol cigarettes from both 1 and 4 mg ISO tar yield categories were recruited in Poland and Japan. Each subject was required to smoke the test cigarette types of their usual ISO tar yield. There were positive relationships between menthol loading and the perceived ‘strength of menthol taste’ and ‘cooling’ effect. However, we did not see marked menthol-induced reductions in perceived irritation or menthol-induced increases in mouth level exposure to tar and nicotine.     

Effect of cigarette smoke on protein synthesis in brain and liver

The rates of protein synthesis in brain and liver were determined in 2 inbred mouse strains (BALB/c and CXBH) during 1 hr of smoke exposure, and after 3 and 6 days of cigarette smoke treatment. Exposure to cigarette smoke reduced valine incorporation into brain and liver protein by 12 and 30% respectively. The greatest part of this reduction in synthesis was due to the hypothermie effect of smoke exposure, which was an approx. 8% change in the synthesis rate for each degree of reduction in body temperature, though a significant smoke effect was still evident. Two major components of cigarette smoke, nicotine and carbon monoxide, were individually tested. Injections of nicotine produced a similar inhibition of brain protein synthesis, with no effect on liver protein synthesis. After extraction of nicotine from the smoke by use of a Cambridge filter, only slight inhibition of brain protein synthesis was observed, which was due to the decrease in body temperature; there was still a significant inhibition in the liver. Incorporation measured, not during but after smoke exposure, was still significantly reduced, although reduction in the liver was smaller than that measured during smoke exposure. Carboxyhemoglobin at levels 50% higher than that achieved by smoke exposure had no effect on brain or liver protein synthesis; higher carboxyhemoglobin levels (300–400% higher than levels during smoke exposure) produced inhibition of liver protein synthesis. The results suggest that the slight and significant inhibition of brain protein synthesis is due to nicotine, whereas the effect on the liver is probably due to anoxia. Smoke treatment for 3–6 days suggests that there is no adaptation to these effects. Strain differences in smoke sensitivity are not related to the effect of nicotine on protein synthesis, suggesting that other mechanisms are involved in smoke sensitivity.     

The effect of menthol containing cigarettes on adult smokers’ exposure to nicotine and carbon monoxide

There is limited information comparing biomarkers of exposure (BOE) to cigarette smoke in menthol (MS) and non-menthol cigarette smokers (NMS). Objective: To compare BOE to nicotine and carbon monoxide in MS and NMS. Methods: Cross-sectional, observational, ambulatory, multi-centre study in 3341 adult cigarette smokers. Nicotine equivalents (NE) in 24 h urine, NE/cigarette, COHb and serum cotinine were measured. Statistical analyses included analysis of variance and Wilcoxon test. Results: Analyses of variance revealed no statistically significant effects of mentholated cigarettes on NE/24 h, COHb, serum cotinine and NE/cigarette. On average MS smoked 15.0 and NMS 16.8 cigarettes/day. The unadjusted mean differences were as follows: MS had lower NE/24 h (5.4%) and COHb (3.2%), higher serum cotinine (3.0%) and NE/cigarette (5.7%) than NMS. African-Americans MS smoked 40% fewer cigarettes, showed lower NE/24 h (24%) and COHb (10%) and higher NE/cig (29%) and serum cotinine (8%) levels than their White counterparts. Conclusions: Smoking mentholated cigarettes does not increase daily exposure to smoke constituents as measured by NE and COHb. These findings are consistent with the majority of epidemiological studies indicating no difference in smoking related risks between MS and NMS.     

Preadolescent tobacco smoke exposure leads to acute nicotine dependence but does not affect the rewarding effects of nicotine or nicotine withdrawal in adulthood in rats

Epidemiological studies indicate that parental smoking increases the risk for smoking in children. However, the underlying mechanisms by which parental smoking increases the risk for smoking are not known. The aim of these studies was to investigate if preadolescent tobacco smoke exposure, postnatal days 21-35, affects the rewarding effects of nicotine and nicotine withdrawal in adult rats. The rewarding effects of nicotine were investigated with the conditioned place preference procedure. Nicotine withdrawal was investigated with the conditioned place aversion procedure and intracranial self-stimulation (ICSS). Elevations in brain reward thresholds in the ICSS paradigm reflect a dysphoric state. Plasma nicotine and cotinine levels in the preadolescent rats immediately after smoke exposure were 188 ng/ml and 716 ng/ml, respectively. Preadolescent tobacco smoke exposure led to the development of nicotine dependence as indicated by an increased number of mecamylamine-precipitated somatic withdrawal signs in the preadolescent tobacco smoke exposed rats compared to the control rats. Nicotine induced a similar place preference in adult rats that had been exposed to tobacco smoke or air during preadolescence. Furthermore, mecamylamine induced place aversion in nicotine dependent rats but there was no effect of preadolescent tobacco smoke exposure. Finally, preadolescent tobacco smoke exposure did not affect the elevations in brain reward thresholds associated with precipitated or spontaneous nicotine withdrawal. These studies indicate that passive exposure to tobacco smoke during preadolescence leads to the development of nicotine dependence but preadolescent tobacco smoke exposure does not seem to affect the rewarding effects of nicotine or nicotine withdrawal in adulthood.     

Induction of the drug metabolizing enzyme CYP2D in monkey brain by chronic nicotine treatment

Cytochrome P450 (CYP) 2D6, an enzyme found in the liver and the brain, is involved in the metabolism of numerous centrally acting drugs (e.g. antidepressants, neuroleptics, opiates), endogenous neurochemicals (e.g. catecholamines) and in the inactivation of neurotoxins (e.g. pesticides, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)). Although CYP2D6 is essentially an uninducible enzyme in the liver, we show that smokers have higher CYP2D6 in the brain, especially in the basal ganglia. In order to determine whether nicotine, a component of cigarette smoke, could increase brain CYP2D, African Green monkeys were treated chronically with nicotine (0.05 mg/kg for 2 days, then 0.15 mg/kg for 2 days followed by 0.3 mg/kg for 18 days s.c., b.i.d.). Monkeys treated with nicotine showed significant induction of CYP2D in brain when compared to saline-treated animals as detected by western blotting and immunocytochemistry. No changes in liver CYP2D were observed in nicotine-treated monkeys. Induction was observed in various brain regions including those affected in Parkinson's disease (PD) such as substantia nigra (3-fold, p = 0.01), putamen (2.1-fold, p = 0.001) and brainstem (2.4-fold, p = 0.001), with the caudate nucleus approaching significance (1.6-fold, p = 0.07). Immunocytochemistry revealed that the expression of CYP2D in both saline- and nicotine-treated monkeys is cell-specific particularly in the cerebellum, frontal cortex and hippocampus. These results suggest that monkey brain expresses CYP2D, which is induced in specific cells and brain regions upon chronic nicotine treatment. Smokers, or those using nicotine treatment, may have higher levels of brain CYP2D6 that may result in altered localized CNS drug metabolism and inactivation of neurotoxins.     

Do smokers of specialty and conventional cigarettes differ in their dependence on nicotine?

Specialty cigarettes, bidis and kreteks, have commonly been viewed by adolescent users as being less harmful than conventional cigarettes. Biochemical studies, however, have shown that the concentration and delivery of nicotine from these tobacco products are not insignificant. The current study tested whether the diagnosis and symptoms for nicotine dependence differed among conventional-only smokers (n = 16 959), specialty-only smokers (n = 313), and poly-tobacco smokers (n = 1288) from the 2002 and 2003 National Surveys on Drug Use and Health. Compared with the specialty-only smokers, the conventional-only and poly-tobacco smokers were more dependent on nicotine, assessed by the Nicotine Dependence Syndrome Scale and a single item from the Fagerstrom Test for Nicotine Dependence. However, after accounting for differences in smoking frequency, the specialty-only smokers had significantly greater odds of being nicotine dependent than the conventional-only smokers. The reversed effect was primarily attributed to the specialty-only smokers who smoked less frequently, but reported a shorter time to their first cigarette. These findings suggest that the nicotine acquired from specialty cigarettes may be sufficient in yielding a sense of urgency to smoke.     

Menthol smoking in relation to time to first cigarette and cotinine: Results from a community-based study

Smokers who have their first cigarette shortly after waking, an indicator of nicotine dependence, have substantially higher cotinine levels. There is controversy regarding the role of menthol in nicotine dependence. We hypothesized that menthol smokers have a shorter time to first cigarette (TTFC), and tested whether any statistical association actually reflects increased dependence by measuring nicotine uptake (e.g. cotinine) in the same group of smokers. A cross-sectional community-based study was conducted that included 495 black and white daily cigarette smokers. Results showed a trend between menthol smoking and a shorter TTFC (P < 0.04 in blacks). Menthol was not an independent predictor of cotinine or an effect modifier with TTFC on cotinine levels in blacks and whites. These results show that while menthol in tobacco is associated with an indicator of nicotine dependence in blacks, menthol was not associated with biological uptake of nicotine in black and white smokers.     

Toxicological considerations on the use of propylene glycol as a humectant in cigarettes

Propylene glycol (PG) is a humectant commonly used in cigarettes. Previous toxicological examinations of the effects on the addition of PG to tobacco used mixtures with several other flavoring agents. In the present work, toxicological comparisons were made of experimental cigarettes containing no added PG against otherwise similar cigarettes with three different amounts of PG added to the tobacco. The main toxicological comparison was a sub-chronic inhalation study with mainstream smoke in Sprague–Dawley rats (exposures of 150 mg/m³ of total particulate matter, 6 h exposure per day, for 90 consecutive days). The target PG concentrations in the tobacco of the four cigarette types were 0, 4, 7 and 10%. Additional studies with mainstream smoke were bacterial mutagenicity (5 Salmonella strains, both with and without metabolic activation, particulate phase only), cytotoxicity of both particulate and gas/vapor phases (using the neutral red uptake assay), and analytical chemistry (41 analytes). The graded inclusion of PG into experimental cigarettes resulted in increases in the smoke concentrations of propylene oxide, at very low concentrations. Broadly similar responses were seen across the four cigarette types, and the responses were similar to those previously described in the scientific literature. The addition of PG to experimental cigarettes reduced concentrations of some smoke components (e.g. nicotine), but had minimal effects on the biological responses. Most of the changes produced in the 90-days of exposure were resolved in a 42-day post-inhalation period.     

Factors affecting exposure to nicotine and carbon monoxide in adult cigarette smokers

Exposure to cigarette smoke among smokers is highly variable. This variability has been attributed to differences in smoking behavior as measured by smoking topography, as well as other behavioral and subjective aspects of smoking. The objective of this study was to determine the factors affecting smoke exposure as estimated by biomarkers of exposure to nicotine and carbon monoxide (CO). In a multi-center cross-sectional study of 3585 adult smokers and 1077 adult nonsmokers, exposure to nicotine and CO was estimated by 24 h urinary excretion of nicotine and five of its metabolites and by blood carboxyhemoglobin, respectively. Number of cigarettes smoked per day (CPD) was determined from cigarette butts returned. Puffing parameters were determined through a CreSS® micro device and a 182-item adult smoker questionnaire (ASQ) was administered. The relationship between exposure and demographic factors, smoking machine measured tar yield and CPD was examined in a statistical model (Model A). Topography parameters were added to this model (Model B) which was further expanded (Model C) by adding selected questions from the ASQ identified by a data reduction process. In all the models, CPD was the most important and highest ranking factor determining daily exposure. Other statistically significant factors were number of years smoked, questions related to morning smoking, topography and tar yield categories. In conclusion, the models investigated in this analysis, explain about 30-40% of variability in exposure to nicotine and CO.     

Exposure to chronic intermittent nicotine vapor induces nicotine dependence

Animal models of drug exposure are important tools for the study of the neurobiological mechanisms of nicotine dependence and as preclinical models for medication development. There are few non-invasive animal models of nicotine exposure and currently there is no known animal model of second-hand exposure to nicotine. We hypothesized that chronic administration of nicotine vapors would produce blood levels of nicotine in rodents that are clinically relevant to those observed in human smoking and that rodents exposed to nicotine vapors would develop dependence to nicotine. We developed a system that vaporizes nicotine in the air in a stable, reliable and consistent manner. Intermittent exposure to nicotine vapor (0.2 mg/m³) for 8 or 14 h per day for 7 days produced a concentration of nicotine in the blood of 22 ng/mL. Sixteen hours after removal from nicotine vapors, rats showed significant somatic withdrawal signs precipitated by mecamylamine (1.5 mg/kg). These results provide a new rodent model of nicotine dependence using vapor administration that produces consistent levels of nicotine in the blood that are relevant for both heavy smoking and second-hand smoking, using a non-invasive technique that mimics the intermittent aspect and route of administration in humans.     

Dissociating nicotine and nonnicotine components of cigarette smoking

To dissociate the sensorimotor aspects of cigarette smoking from the pharmacologic effects of nicotine, smokers rated the subjective effects of nicotine-containing or denicotinized cigarettes, and intravenous (IV) nicotine or saline infusions. Three groups of participants (n=20 per group) received either: (1) continuous nicotine, (2) pulsed nicotine, or (3) saline. Each group was exposed to an IV condition once while smoking a denicotinized cigarette and once while not smoking, in a 3x2 mixed design. A fourth group (n=20) received saline while smoking their usual brand of cigarette. The dose and rate of nicotine administration were individualized based on previous measures of ad lib smoke intake. Denicotinized cigarette smoke significantly reduced craving and was rated significantly more satisfying and rewarding than the no-smoking conditions. IV nicotine reduced craving for cigarettes, and increased ratings of lightheadedness and dizziness. However, no significant satisfaction or reward was reported after IV nicotine. The combination of IV nicotine and denicotinized cigarette smoke produced effects similar to those of smoking the usual brand of cigarette. The results suggest that sensorimotor factors are critical in mediating the immediate subjective response to smoking, and that the immediate subjective effects of nicotine administered in doses obtained from cigarette smoking are subtle. Thus, addressing smokers' needs for both for the sensorimotor aspects of smoking as well as for the direct CNS effects of nicotine may be critical in enhancing smoking cessation treatment outcome.     

Population characteristics and cigarette yield as determinants of smoke exposure

Relationships of population characteristics, smoking history, and cigarette yield with smoke exposure as measured by peripheral blood concentrations of thiocyanate, carboxyhemoglobin, nicotine and cotinine were sought in 170 male smokers. This population of smokers had significant elevations of serum thiocyanate, blood carboxyhemoglobin and plasma nicotine and cotinine concentrations as compared with an equal number of age- and sex-matched nonsmokers and these concentrations correlated significantly with past 24-hour cigarette consumption. Although the nicotine yield of the cigarette correlated significantly with plasma cotinine and marginally with plasma nicotine, the reduction in plasma nicotine and cotinine was not proportionate to the reduced yield of the cigarettes, suggesting that smokers partially compensate for the lower yields of their cigarettes. Blood levels of carboxyhemoglobin, nicotine and cotinine were also significantly associated with the weight of the subjects, presumably due to the relationship between weight and the volume of distribution. Univariate and multiple regression analyses provided evidence that coffee and alcohol consumption and years smoked also may be important determinants of smoke exposure.     

Repeated pre-exposure to tobacco smoke potentiates subsequent locomotor responses to nicotine and tobacco smoke but not amphetamine in adult rats

These studies investigated if pre-exposure to tobacco smoke affects the locomotor response to tobacco smoke, nicotine, and amphetamine in adult rats. The rats were habituated to an open field for 3-4 days and then exposed to tobacco smoke for 2 h/day for 13-14 days. The effect of exposure to tobacco smoke on locomotor activity was investigated after 1, 7, and 14 days of smoke exposure and after one 2-hour exposure session that followed a 3-week off period. The effects of tobacco smoke on the locomotor responses to nicotine (0.04 and 0.4 mg/kg, base) and amphetamine (0.1 and 0.5 mg/kg) were investigated on day 14, one day after the last smoke exposure session. The locomotor response to tobacco smoke was increased after 7 and 14 days of smoke exposure and after one exposure session after the 3-week off-period. The acute administration of the high dose of nicotine (0.4 mg/kg) led to a brief period of hypoactivity that was followed by a period of hyperactivity. Pre-exposure to tobacco smoke attenuated the nicotine-induced hypoactivity and potentiated the nicotine-induced hyperactivity. The low dose of nicotine (0.04 mg/kg) did not affect locomotor activity in the control rats but increased the total distance traveled in the tobacco smoke exposed rats. Exposure to tobacco smoke did not affect the locomotor response to amphetamine. These findings indicate that exposure to tobacco smoke leads to tolerance to the depressant effects of nicotine and potentiates the stimulant effects of nicotine and tobacco smoke.     

Influence of cigarette filter ventilation on smokers’ mouth level exposure to tar and nicotine

Cigarette filter ventilation allows air to be drawn into the filter, diluting the cigarette smoke. Although machine smoking reveals that toxicant yields are reduced, it does not predict human yields. The objective of this study was to investigate the relationship between cigarette filter ventilation and mouth level exposure (MLE) to tar and nicotine in cigarette smokers. We collated and reviewed data from 11 studies across 9 countries, in studies performed between 2005 and 2013 which contained data on MLE from 156 products with filter ventilation between 0% and 87%. MLE among 7534 participants to tar and nicotine was estimated using the part-filter analysis method from spent filter tips. For each of the countries, MLE to tar and nicotine tended to decrease as filter ventilation increased. Across countries, per-cigarette MLE to tar and nicotine decreased as filter ventilation increased from 0% to 87%. Daily MLE to tar and nicotine also decreased across the range of increasing filter ventilation. These data suggest that on average smokers of highly ventilated cigarettes are exposed to lower amounts of nicotine and tar per cigarette and per day than smokers of cigarettes with lower levels of ventilation.     

Effects of cigarette nicotine content on smoking behavior of baboons

Human cigarette smokers modify the way in which they smoke cigarettes of differing nicotine content, apparently to maintain nicotine exposure at a preferred level. The effects of changing from moderate to high or low nicotine content cigarettes were examined in 11 baboons (superspecies Papio cynocephalus) trained to smoke cigarettes for water rewards. Relative to the moderate nicotine content cigarette, the animals took significantly (p < .05) more puffs on the high nicotine content cigarette, and the puffs on the high nicotine cigarette were significantly larger in volume. The animals made the same number of puffs, relative to the moderate nicotine content cigarette, on the low nicotine content cigarette, but the volume of the puffs was significantly smaller. The cotinine output in urine varied significantly and was directly related to cigarette nicotine content; cotinine is the primary metabolite of nicotine. Baboons, like people, prefer high nicotine content cigarettes. Nonhuman primates also regulate nicotine exposure by modification of their puffing behavior. These results indicate that the nonhuman primate also can be used as a model for the investigation of the behavioral aspects of cigarette smoking.     

Self-administration of intravenous nicotine in male and female cigarette smokers.

Although nicotine is the main addictive chemical in tobacco, there have been few studies of pure nicotine self-administration in humans. The goal of this study was to test the parameters of an intravenous (IV) nicotine self-administration model using nicotine doses presumed to be within the range of those of average intake from cigarette smoking. Six male and four female smokers participated in a double-blind, placebo-controlled, crossover study, which consisted of one adaptation and three experimental sessions. In each experimental session, subjects were randomly assigned to one of the three doses of nicotine (0.1, 0.4, or 0.7 mg). The lowest nicotine dose, 0.1 mg, was chosen to be approximately half the amount of nicotine inhaled from one puff of a cigarette. During each experimental session, subjects first sampled the assigned nicotine dose and placebo and then had the opportunity to choose between nicotine and placebo for a total of six choices over a 90-min period. Out of six options, the average (SEM) number of nicotine choices were 3.0 (0.48) for 0.1 mg, 4.7 (0.48) for 0.4 mg and 4.5 (0.46) for 0.7 mg, indicating a significant effect of nicotine dose on nicotine choice. Both the 0.4 and 0.7, but not the 0.1 mg, nicotine doses were preferred to placebo. These higher doses also produced increases in heart rate, blood pressure, and ratings of drug liking and high. Overall, these findings indicate that smokers chose both the 0.4 and the 0.7 mg nicotine doses over placebo. Our model may be useful in the evaluation of the effects of both behavioral and pharmacological manipulations on nicotine self-administration in humans.     

Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a “healthy” tobacco-free alternative

Tobacco smoking using a waterpipe (narghile, hookah, shisha) has become a global epidemic. Unlike cigarette smoking, little is known about the health effects of waterpipe use. One acute effect of cigarette smoke inhalation is dysfunction in autonomic regulation of the cardiac cycle, as indicated by reduction in heart rate variability (HRV). Reduced HRV is implicated in adverse cardiovascular health outcomes, and is associated with inhalation exposure-induced oxidative stress. Using a 32 participant cross-over study design, we investigated toxicant exposure and effects of waterpipe smoking on heart rate variability when, under controlled conditions, participants smoked a tobacco-based and a tobacco-free waterpipe product promoted as an alternative for “health-conscious” users. Outcome measures included HRV, exhaled breath carbon monoxide (CO), plasma nicotine, and puff topography, which were measured at times prior to, during, and after smoking. We found that waterpipe use acutely decreased HRV (p < 0.01 for all measures), independent of product smoked. Plasma nicotine, blood pressure, and heart rate increased only with the tobacco-based product (p < 0.01), while CO increased with both products (p < 0.01). More smoke was inhaled during tobacco-free product use, potentially reflecting attempted regulation of nicotine intake. The data thus indicate that waterpipe smoking acutely compromises cardiac autonomic function, and does so through exposure to smoke constituents other than nicotine.     

ADHD medication reduces cotinine levels and withdrawal in smokers with ADHD

Individuals with ADHD may self-medicate with nicotine, the main psychoactive ingredient in tobacco smoke, in order to reduce symptoms and negative moods associated with ADHD. ADHD medication (e.g., methylphenidate and atomoxetine) may mimic some of the effects of nicotine and may aid smoking cessation in smokers with ADHD. The present study examined if ADHD medication reduces smoking and withdrawal in non-treatment seeking smokers with ADHD. Fifteen adult smokers with ADHD participated in the study, which consisted of an experimental phase and field monitoring phase to examine the acute and extended effects, respectively, of ADHD medication. During the experimental phase, smokers were asked to complete a Continuous Performance Task (CPT) and the Shiffman-Jarvik smoking withdrawal questionnaire during the following four conditions: (1) ADHD medication + cigarette smoking, (2) ADHD medication + overnight abstinence, (3) placebo + cigarette smoking, and (4) placebo + overnight abstinence. During the field monitoring phase, participants were asked to provide salivary cotinine samples and complete electronic diaries about smoking, smoking urge, ADHD symptoms, and stress in everyday life for two days on ADHD medication and for two days on placebo. Results of the experimental phase showed that ADHD medication improved task performance on the CPT and reduced withdrawal during overnight abstinence. During the field monitoring phase, ADHD medication reduced salivary cotinine levels compared to placebo. In addition, the electronic diary revealed that ADHD medication improved difficulty concentrating during no smoking events and stress. The findings of the present study suggest that, along with other strategies, ADHD medication may be used to aid smoking withdrawal and cessation in smokers with ADHD.