Low Nicotine Cigarettes Research Articles

Separate and Combined Effects of Very Low Nicotine Cigarettes and Nicotine Replacement in Smokers with Schizophrenia and Controls

The prevalence of smoking among people with schizophrenia in the United States is about 3 times that of the general population. Novel approaches are needed to reduce rates of smoking-related morbidity and mortality among these smokers. This study used a within-subjects design to investigate the separate and combined effects of sensorimotor replacement for smoking (very low nicotine content [VLNC] cigarettes vs. no cigarettes) and transdermal nicotine replacement (42 mg nicotine [NIC] vs. placebo [PLA] patches) in smokers with schizophrenia (SS; n = 30) and control smokers without psychiatric illness (CS; n = 26). Each session contained a 5-hr controlled administration period in which participants underwent the following conditions, in counterbalanced order: VLNC + NIC, VLNC + PLA, no cigarettes + NIC, no cigarettes + PLA, usual-brand cigarettes + no patches. Next, participants completed measures of cigarette craving, nicotine withdrawal, smoking habit withdrawal, and cigarette subjective effects, followed by a 90-min period of ad libitum usual-brand smoking. Smoking VLNC cigarettes during the controlled administration periods reduced cigarette craving, nicotine withdrawal symptoms, habit withdrawal symptoms, and usual-brand smoking in SS and CS relative to the no cigarette conditions. VLNC cigarettes were well accepted by both groups and did not affect psychiatric symptom levels in SS. Transdermal nicotine significantly reduced cigarette craving but did not affect usual-brand smoking. These findings suggest that reducing the nicotine content of cigarettes to nonaddictive levels may be a promising approach for reducing nicotine dependence among people with schizophrenia.

Nicotine degradation enhancement by Pseudomonas stutzeri ZCJ during aging process of tobacco leaves

Nicotine is a key harmful component of tobacco and cigarettes, and the development of low-nicotine cigarettes is of increasing importance in the market. The objectives of this study are to isolate native nicotine-degrading strains and evaluate their feasibility for nicotine reduction during the aging (or fermentation) of tobacco leaves. A novel nicotine-degrading strain was isolated and identified as Pseudomonas stutzeri ZCJ based on its 16S rDNA sequence and morphological-biochemical characteristics. In submerged cultures, P. stutzeri ZCJ could tolerate 4.5 g/L nicotine and completely degrade 1.5 g/L nicotine within 24 h at 37°C and pH 7.4. The addition of glucose (1 g/L) could improve nicotine degradation by P. stutzeri ZCJ in submerged cultures. After submerged culturing, the cell suspension of P. stutzeri ZCJ could be utilized to improve nicotine reduction in tobacco leaves during solid-state fermentation. The nicotine content of tobacco leaves decreased by as much as 32.24% after 7 days of solid-state fermentation by P. stutzeri ZCJ, suggesting the industrial application potential of the native strain to enhance nicotine degradation during the aging of tobacco leaves.

Empirical analysis of the impact of cigarette excise taxes on cigarette consumption: estimates from recent state-level data

The adverse health effects from cigarette smoking account for an estimated 443,000 deaths annually in the U.S. Given this circumstance, this study has two objectives. First, it uses a state-level panel data set for a recent time frame to investigate the impact of federal plus state cigarette excise taxes (along with a variety of other factors) on the aggregate consumption of cigarettes. The study adopts a state-level panel data series spanning the period 2002 through 2007, which is the most recent panel for which data for all of the variables are available. Consistent with a number of previous studies, the PLS estimates in this study find that the higher the cigarette excise tax, the lower the aggregate volume of cigarettes consumed. Of course, this outcome does not address the practical problem of the substitution of high nicotine cigarettes for low nicotine cigarettes in the presence of a significant cigarette tax hike. This circumstance leads to the second objective of this study, namely, to propose a general template for a different kind of cigarette excise tax, one that is tied directly to each cigarette brand’s nicotine and tar content.

Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler

The Nicotrol® (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChRs). Previous studies examined β2*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of β2*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [123I]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9±6.4% occupancy of β2*-nAChRs 2-5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6±14.1% occupancy 1.5-5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of β2*-nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms.

A Preliminary Contemporary Panel Data Analysis of the Consumption Impact of Cigarette Taxation

The adverse health effects from cigarette smoking account for an estimated 400,000 deaths annually in the U.S. Given this circumstance, the present study has two objectives. First, using a panel data set for a very recent time frame, it seeks to investigate the impact of federal plus state cigarette excise taxes (along with the influence of other factors) on the aggregate consumption of cigarettes. The study adopts a five-year state-level panel data series spanning the period 2002 through 2006. Consistent with certain previous studies, the estimates in this study find that the higher the cigarette excise tax, the lower the aggregate volume of cigarettes consumed. However, this outcome does not address the practical problem of the substitution of high nicotine cigarettes for low nicotine cigarettes in light of a significant cigarette tax hike. This circumstance leads to the second objective of this study, namely, to formally propose a general form/template for a cigarette excise tax that is tied directly to each cigarette brand’s nicotine and tar content.

Smoking Related Factors according to the Nicotine Content

Background: Recently, a variety of cigarettes which contain a low content of nicotine are on the market and the nicotine tends to be reduced continuously. However, studies have not yet fully demonstrated that low-nicotine cigarettes are subservient to quitting smoking. This study was designed to investigate the effects of the nicotine content on smoking attitudes and on the factors associated with successful smoking cessation. Methods: One hundred twenty-fi ve adult smokers, who had undergone a health examination in a general hospital, had their carbon monoxide measured after responding to the questionnaire. The items of questionnaire consisted of the duration of smoking, the age of starting to smoke, the number of attempts to stop smoking, recognition of nicotine dependence, and nicotine dependence score. Results: The subjects consisted of two groups. One group was low nicotine group and the nicotine content was lower than 0.35 mg per cigarette. The other group was high nicotine group and the nicotine content was over 0.35 mg per cigarette. he age was younger and duration of smoking was shorter in low nicotine group. Monthly income, last schooling and number of attempts to stop smoking were higher in low nicotine group. There was no statistical signifi cant differences between the two groups in the frequency of alcohol drinking, the age of starting to smoke, marital status, nicotine dependence, carbon monoxide concentration and recognition of nicotine dependence. Conclusion: As there was no differences in smoking habits which has infl uence on achieving quit smoking of low nicotine group, we made our conclusion that low nicotine cigarette might be unhelpful in quit smoking.

Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette

Our group recently reported that smoking a regular cigarette (1.2-1.4 mg nicotine) resulted in 88% occupancy of brain alpha4beta2* nicotinic acetylcholine receptors (nAChRs). However, this study did not determine whether nicotine inhalation or the many other pharmacological and behavioural factors that occur during smoking resulted in this receptor occupancy. If nicotine is solely responsible for alpha4beta2* nAChR occupancy from smoking, then (as estimated from our previous data) smoking a denicotinized (0.05 mg nicotine) or a low-nicotine (0.6 mg nicotine) cigarette (commonly used for research and clinical purposes) would result in substantial 23% and 78% alpha4beta2* nAChR occupancies, respectively, and a plasma nicotine concentration of 0.87 ng/ml would result in 50% alpha4beta2* nAChR occupancy (EC50). Twenty-four positron emission tomography sessions were performed on tobacco-dependent smokers, using 2-[F-18]fluoro-A-85380 (2-FA), a radiotracer that binds to alpha4beta2* nAChRs. 2-FA displacement was determined from before to 3.1 hours after either: no smoking, smoking a denicotinized cigarette, or smoking a low-nicotine cigarette. Analysis of this PET data revealed that smoking a denicotinized and a low-nicotine cigarette resulted in 26% and 79% alpha4beta2* nAChR occupancies, respectively, across three regions of interest. The EC50 determined from this dataset was 0.75 ng/ml. Given the consistency of findings between our previous study with regular cigarettes and the present study, nicotine inhalation during smoking appears to be solely responsible for alpha4beta2* nAChR occupancy, with other factors (if present at all) having either short-lived or very minor effects. Furthermore, smoking a denicotinized cigarette resulted in substantial nAChR occupancy.

Policy and Health Implications of Using the U.S. Food and Drug Administration Product Design Approach in Reducing Tobacco Product Risk

Purported risk or harm reduction through product design change of cigarettes has occurred in three phases in the U.S. The first phase from the 1940s to the early 1960s included a gradual rise in filtered cigarettes. The second phase, which began in the early 1960s in response to the landmark 1964 U.S. Surgeon General's report that linked smoking with lung cancer and other diseases, included the introduction of purportedly low tar and nicotine cigarettes. Subsequent research found that both filters and low tar and nicotine cigarettes were ineffective approaches to reducing health risks associated with smoking. Despite this, these product design changes were used in tobacco industry marketing campaigns to allay consumer health concerns and stabilize tobacco markets and sales. Since 2004, a new risk or harm reduction phase has occurred with the backing by Philip Morris as well as major U.S. health groups of U.S. Food and Drug Administration legislation that would require disclosure of tobacco ingredients, ban misleading health claims, prohibit or reduce harmful ingredients, and require prior approval of tobacco design, performance changes, and modified risk tobacco products. However, current scientific literature indicates that there is no scientific consensus and little evidence on what tobacco ingredients are linked to particular morbidities and mortalities and at what levels. This will allow the tobacco industry to implicitly or explicitly claim their products are "safer." Instead, health advocates should advocate for scientifically proven policy measures such as smoke free public places or higher tobacco taxes that control and reduce tobacco markets and consumption.

A study investigating the acute dose— response effects of 13 mg and 17 mg Δ 9- tetrahydrocannabinol on cognitive—motor skills, subjective and autonomic measures in regular users of marijuana

Heavy use of marijuana is claimed to damage critical skills related to short-term memory, visual scanning and attention. Motor skills and driving safety may be compromised by the acute effects of marijuana. The aim of this study was to investigate the acute effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol (THC) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana. Fourteen regular users of marijuana were enrolled. Each subject was tested on two separate days. On each test day, subjects smoked two low-nicotine cigarettes, one with and the other without THC. Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day. The sequence of cigarette types was unknown to the subject. During smoking, heart rate and blood pressure were monitored, and the subjects performed a virtual reality maze task requiring attention and motor coordination, followed by 3 other cognitive tasks (Wisconsin Card Sorting Test (WCST), a "gambling" task and estimation of time and distance from an approaching car). After smoking a cigarette with 17 mg THC, regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC; this effect was not seen in patients after they smoked cigarettes with 13 mg THC. Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC. Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC, but not with 13 m THC. Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction, drug "effect" and drug "high". These findings imply that smoking of 17 mg THC results in impairment of cognitive-motor skills that could be important for coordinated movement and driving, whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana.

Toxicological analysis of low-nicotine and nicotine-free cigarettes

Low-nicotine and nicotine-free cigarettes are commercially available under the brand-name Quest ®. Some consumers may believe that these are safer cigarettes, and they may smoke more cigarettes or inhale more smoke to compensate for low nicotine yields. Thus, we have studied the toxicological effects of these two cigarettes and compared them with the Kentucky reference cigarette 2R4F. Also, the availability of nicotine-free cigarettes allows for the assessing the role of nicotine in cigarette smoke. In addition to nicotine, some tobacco-specific nitrosamines, aldehydes, and volatile organic compounds were also reduced in the Quest ® cigarettes compared to the 2R4F. However, aromatic amines were higher in the nicotine-free compared with low nicotine cigarettes. The Ames test revealed that cigarette smoke condensates from the nicotine-free (CSC-F), low nicotine (CSC-L) and 2R4F (CSC-R) cigarettes had a similar mutagenic potency. Exposure to any CSC caused a similar dose-dependent LDH leakage from normal human bronchial epithelial cells. However, CSC-F had more inhibitory effects on the cell growth than CSC-L and CSC-R. Adding nicotine to the CSC-F attenuated this inhibition. Both Quest ® CSCs decreased gap junction intercellular communication and caused cell cycle arrest. CSC exposure increased cytoplasmic nucleosomes, sub-G1/G0 population and apoptotic comet tails. Proapoptotic protein Bax increased independent of p53 induction after exposure to CSC-F. In conclusion, these studies are not consistent with a perception that low-nicotine or nicotine-free cigarettes may have less toxicity in human cells. Nicotine, as it exists in CSC, attenuates cytotoxicity possibly in part through inhibition of apoptotic pathways.

123I]5-IA-85380 SPECT imaging nicotine occupancy of brain β2-nicotinic acetylcholine receptors after smoking low nicotine and nicotine-free cigarettes

123I]5-IA-85380 SPECT imaging nicotine occupancy of brain β2-nicotinic acetylcholine receptors after smoking low nicotine and nicotine-free cigarettes

Effects of Smoking Successive Low- and High-Nicotine Cigarettes on Hypothalamic–Pituitary–Adrenal Axis Hormones and Mood in Men

Smoking one cigarette produces rapid nicotine dose-related increases in hypothalamic-pituitary-adrenal (HPA) axis hormones, mood, and heart rate, but relatively little is known about the effects of smoking several cigarettes successively. Twenty-four healthy adult men who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for nicotine dependence provided informed consent. After overnight abstinence from smoking, men smoked three low- or high-nicotine cigarettes for 4 min each at 60 min intervals. Samples for nicotine and hormone analysis, Visual Analog Scale (VAS) ratings of subjective effects and heart rate were collected at 4, 8, 12, 16, 20, 30, 40, and 50 min after each cigarette. After low-nicotine cigarettes, nicotine levels, adrenocorticotropin hormone, and heart rate did not increase significantly, cortisol and dehydroepiandrosterone decreased significantly, and positive VAS ratings were lower but parallel to ratings after high-nicotine cigarette smoking. After high-nicotine cigarettes, peak nicotine levels increased monotonically. HPA axis hormones increased after smoking, but peak levels did not differ significantly after successive high-nicotine cigarettes. Positive VAS ratings and heart rate increased after each high-nicotine cigarette, but peak levels were lower after smoking the second and third cigarette. 'Craving' decreased significantly after smoking both low- and high-nicotine cigarettes, then gradually increased during the 60 min interval between cigarettes. These data are consistent with clinical reports that the first cigarette after overnight nicotine abstinence is most salient. Tolerance to the subjective and cardiovascular effects of nicotine developed rapidly during repeated cigarette smoking, but nicotine-stimulated increases in HPA axis hormones did not change significantly.

Light cigarette smoking impairs coronary microvascular functions as severely as smoking regular cigarettes

Background:Smoking is the most prevalent and most preventable risk factor for cardiovascular diseases. Smoking low-tar, low-nicotine cigarettes (light cigarettes) would be expected to be less hazardous than smoking regular cigarettes...

Composition and emissions of VOCs in main- and side-stream smoke of research cigarettes

It is well known that mainstream (MS) and sidestream (SS) cigarette smoke contains a vast number of chemical substances. Previous studies have emphasized SS smoke rather than MS smoke to which smokers are exposed, and most have used chamber tests that have several disadvantages such as wall losses. Emissions from standard research cigarettes have been measured, but relatively few constituents have been reported, and only the 1R4F (low nicotine) cigarette type has been tested. This study provides a comprehensive characterization of total, MS and SS smoke emissions for the 1R5F (ultra low nicotine), 2R4F (low nicotine), and 1R3F (standard nicotine) research cigarettes research cigarettes, including emission factors for a number of toxic compounds (e.g., benzene) and tobacco smoke tracers (e.g., 2,5-dimethyl furan). Emissions of volatile organic compounds (VOCs) and particulate matter (PM) are quantified using a dynamic dilution emission measurement system that is shown to produce accurate, rapid and reproducible results for over 30 VOCs and PM. SS and MS emissions were accurately apportioned based on a mass balance of total emissions. As expected, SS emissions greatly exceeded MS emissions. The ultra low nicotine cigarette had lower emissions of most VOCs compared to low and standard nicotine cigarettes, which had similar emissions. Across the three types of cigarettes, emissions of benzene (296–535 μg cig −1), toluene (541–1003 μg cig −1), styrene (90–162 μg cig −1), 2-dimethyl furan (71–244 μg cig −1), naphthalene (15–18 μg cig −1) and other VOCs were generally comparable to or somewhat higher than literature estimates using chamber tests.

Euphoriant effects of nicotine in smokers: fact or artifact?

The claim that nicotine in cigarettes is euphoriant to smokers is largely based on two studies (Pomerleau and Pomerleau, Psychopharmacology, 108:460-465, 1992; Tobacco Control, 3:374, 1994) in which smokers were instructed to respond to sensations of rush, buzz, or high while smoking low-nicotine or regular cigarettes. However, the assumption that these sensations are pleasurable was not tested and may have biased the results. The aim of this study was to re-examine the claim that smoked nicotine is euphoriant to smokers. Study 1 surveyed the frequency and pleasantness of the smoking-related sensations of rush, buzz, and high in a sample of smokers. Study 2 replicated Pomerleau and Pomerleau (Psychopharmacology, 108:460-465, 1992) with two sets of instruction. One set, as in the original study, defined these sensations as pleasurable, whereas the other defined them as unpleasant. Study 1 found that whereas rush and high were perceived as pleasant, buzz was unpleasant to most smokers. Study 2 found that under both sets of instructions, smokers reported more sensations when smoking the regular, as compared to the low-nicotine cigarette. Additionally, the sensations of rush, buzz, and high were rated as more pleasant under the pleasant instructions as compared to the unpleasant instructions. Finally, in the pleasant instructions condition, many participants reported having pressed the button to indicate a pleasurable sensation despite having actually experienced that sensation as unpleasant. Our results suggest that the findings of Pomerleau and Pomerleau (Psychopharmacology, 108:460-465, 1992; Tobacco Control, 3:374, 1994) may have been biased by the experimental instructions and cannot be taken as evidence that smoked nicotine is euphoriant to smokers.

New lower nicotine cigarettes can produce compensatory smoking and increased carbon monoxide exposure

Potential reduced exposure products (PREPs) are marketed as a means to reduce exposure to tobacco toxicants. Quest ® cigarettes, a new type of PREP, use genetically modified tobacco to provide a nicotine step-down approach, and are available as 0.6, 0.3 and 0.05 mg nicotine cigarettes. However, these cigarettes deliver equivalent levels of tar (10 mg). Prior research on low nicotine cigarettes suggests smokers will compensate for lower nicotine delivery by increasing their puffing behavior to extract more nicotine. This study tested the hypothesis that compensatory smoking will occur with this PREP as nicotine levels decrease, increasing exposure to tobacco toxins. Fifty smokers completed a within-subject human laboratory study investigating the effect of cigarette nicotine level on smoking behavior. Cigarette nicotine level was double-blinded and order of presentation counter-balanced. Breath carbon monoxide (CO) boost was used as a biomarker of smoke exposure; total puff volume to assess smoking behavior. Total puff volume was greatest for the 0.05 mg nicotine cigarette and CO boost was moderately greater after smoking the 0.3 and 0.05 mg cigarettes compared to the 0.6 mg nicotine cigarette. These data provide novel behavioral and biochemical evidence of compensatory smoking when smoking lower nicotine cigarettes. Although marketed as a PREP, increases in CO boost suggest this product can potentially be a harm-increasing product.

Precessation treatment with nicotine skin patch facilitates smoking cessation

Nicotine replacement therapy (NRT) is a well-established treatment to aid smoking cessation, and current products recommend using NRT only after quitting smoking. However, theoretical arguments and previous data support the hypothesis that precessation use of NRT might be useful in reducing dependence on inhaled nicotine and serve as a helpful prelude to smoking cessation. The present study explored the use of NRT for 2 weeks before a target quit-smoking date, during which subjects continued to smoke ad libitum. Three experimental conditions varied the nicotine delivery of the cigarettes smoked during these 2 weeks so that we could examine the effects of concurrent nicotine administration on compensatory smoking of low tar and nicotine cigarettes. Subjects smoked (a) their usual brands of cigarettes, (b) conventional low tar and nicotine cigarettes, or (c) denicotinized cigarettes. After the quit date, subjects received pharmacotherapy consisting of various doses of NRT (0, 21, or 42 mg/24-hr) in combination with the nicotinic antagonist mecamylamine (10 mg/day). Results showed that precessation nicotine patch treatment was associated with a significantly higher rate of continuous smoking abstinence at 4 weeks, regardless of cigarette condition. Ad libitum smoking before the target quit date was modulated by nicotine patch treatment, and compensatory increases in smoking low tar and nicotine cigarettes were prevented by concurrent use of nicotine patches. These results suggest that use of NRT before a target quit-smoking date deserves further evaluation as a possible smoking cessation treatment. Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake.

Will the Next Generation of “Safer” Cigarettes Be Safer?

There are three basic means of avoiding smoking-related diseases: never starting to smoke, quitting, and avoiding smoke-filled environments. Recently, a fourth possibility has emerged: use of new, ostensibly less toxic products by smokers who cannot or will not quit, including "reduced toxin" cigarettes and novel smokeless tobacco products. To their purveyors, these new "tobacco harm reduction" (THR) products represent an opportunity for inveterate smokers to reduce their risk of lung cancer and other diseases. To health professionals, the new products pose a myriad of risks. This new generation of THR products is not the first to promise reduced risk, however. Both filtered cigarettes and low tar and nicotine cigarettes were marketed with explicit health themes, ultimately with disastrous results for public health. THR products enter the market subject to no product regulation whatsoever; thus, the opportunity for objective, independent scientific evaluation of their risks and benefits, and for regulation of advertising or sale as a result, is absent. This paper describes the new generation of THR products, discusses potential benefits and risks, examines lessons from the experience with filtered and low tar and nicotine cigarettes, and describes the principal challenges that confront the medical profession, government, and the public in determining what to do with this perplexing array of novel products.

The airway sensory impact of nicotine contributes to the conditioned reinforcing effects of individual puffs from cigarettes

Puffs from cigarettes are the fundamental unit of smoking reward. Here, we examined the extent to which reward from puffs can be derived from the airway sensory effect of nicotine, in the absence of a direct central nervous system effect of nicotine. We did this by assessing the self-reported reward obtained from individual puffs from nicotinized, denicotinized and unlit cigarettes within 7 s of inhalation, which is before nicotine had an opportunity to reach the brain. We also assessed the self-reported strength of airway sensations elicited by the puffs. We found that nicotinized puffs were rated as both stronger and more rewarding than denicotinized and unlit puffs. We also found that the extent to which nicotine elicited reward was directly correlated with the extent to which nicotine elicited airway sensations. This indicates that the airway sensory effects of nicotine contribute to the reward from puffs, above and beyond the reward derived from the airway sensory effects of non-nicotine constituents. These findings have implications for the interpretation of studies that use puffs as experimental units to examine nicotine reward. They also have implications for the use of denicotinized and low nicotine cigarettes as aids to smoking cessation.

Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

The acute effects of smoking a low- or high-nicotine cigarette on hypothalamic-pituitary-adrenal (HPA) hormones, subjective responses, and cardiovascular measures were studied in 20 healthy men who met American Psychiatric Association Diagnostic and Statistical Manual IV criteria for nicotine dependence. Within four puffs (or 2 min) after cigarette smoking began, plasma nicotine levels and heart rate increased significantly (P<0.01), and peak ratings of 'high' and 'rush' on a Visual Analogue Scale were reported. Reports of 'high', 'rush', and 'liking' and reduction of 'craving' were significantly greater after smoking a high-nicotine cigarette than a low-nicotine cigarette (P<0.05). Peak plasma nicotine levels after high-nicotine cigarette smoking (23.9+/-2.6 ng/ml) were significantly greater than after low-nicotine cigarette smoking (3.63+/-0.59 ng/ml) (P<0.001). After smoking a low-nicotine cigarette, adrenocorticotropin hormone (ACTH), cortisol, dehydroepiandrosterone (DHEA), and epinephrine did not change significantly from baseline. After high-nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.88+/-5.34 pmol/l within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r=0.85; P<0.0001), DHEA (r=0.66; P=0.002), and epinephrine (r=0.86; P<0.0001). Cortisol and DHEA increased significantly within 20 min (P<0.05) and reached peak levels of 424+/-48 and 21.13+/-2.55 ng/ml within 60 and 30 min, respectively. Thus cigarette smoking produced nicotine dose-related effects on HPA hormones and subjective and cardiovascular measures. These data suggest that activation of the HPA axis may contribute to the abuse-related effects of cigarette smoking.