Nicotine Reduction Research Articles

Vaporised nicotine and tobacco harm reduction for addressing smoking among people living with HIV: A cross-sectional survey of Australian HIV health practitioners’ attitudes

BackgroundTobacco smoking is a major cause of morbidity and mortality among people living with HIV (PLHIV). Due to the limited success of standard abstinence-focused smoking cessation strategies in this population, there is growing interest in tobacco harm reduction (THR) approaches as an additional strategy to address these high smoking rates. This study explored the attitudes of health practitioners who provide healthcare to PLHIV towards THR. Methods179 Australian health practitioners who provide healthcare to PLHIV completed an online survey that measured their attitudes towards THR approaches, including switching from cigarettes to e-cigarettes or vaporised nicotine products (VNPs). ResultsRespondents supported the concept of THR but were undecided on the role of VNPs. Respondents most commonly reported ‘don’t know’ or ‘undecided’ responses to statements regarding VNPs. More respondents, however, agreed than disagreed that switching from smoking to long-term vaping could reduce risk (36% and 22% respectively) and be an effective strategy to help PLHIV to quit smoking (37% agree and 17% disagree). Only a minority of respondents (20%) agreed that VNPs are too harmful to recommend to patients, however around half (53%) were undecided. ConclusionsDespite supporting the principle of THR, health practitioners may require more evidence and knowledge about VNPs before being willing to consider them as a suitable intervention strategy.

Animal Research on Nicotine Reduction: Current Evidence and Research Gaps.

This review will provide policy makers and clinical researchers interested in nicotine reduction with an overview of the preclinical animal research conducted on nicotine reduction and the regulatory implications of that research. The review also highlights the utility of preclinical research for research questions related to nicotine reduction.

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol

BackgroundThe U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT) in four phases over 34 weeks.MethodsAdult smokers (N = 200) of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General). Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg). After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a) quit smoking with assistance, (b) continue smoking free research cigarettes, or (c) return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 1-hydroxypyrene, oxidative stress biomarkers including 8-isoprostanes, measures of psychiatric symptoms (e.g., depression, anxiety), smoking behavior and dependence (e.g., cigarette consumption, quit attempts), and health effects (e.g., blood pressure, respiratory symptoms).DiscussionResults from this study will inform FDA on the potential effects of regulating the nicotine content of cigarettes and help determine whether smokers with mood and/or anxiety disorders can safely transition to significantly reduced nicotine content cigarettes.Trial registrationTRN: NCT01928758, registered August 21, 2013.

Knowledge about nicotine among HIV-positive smokers: Implications for tobacco regulatory science policy

The present paper describes the general knowledge of smoking and nicotine among a sample of current smokers living with HIV (n=271) who were recruited via Amazon Mechanical Turk. Descriptive statistics were used to report sociodemographic and smoking characteristics, as well as knowledge about smoking and nicotine. The sample was comprised of relatively light smokers, both in terms of cigarettes per day (M=8.1, SD=9.7) and dependence (67.5% had low dependence according to the Heaviness of Smoking Index). The majority of participants correctly identified smoking as being a potential cause of various smoking-related conditions and correctly identified constituents in cigarette smoke. However, a majority of participants also misattributed nicotine as being a potential cause of smoking-related illness. Accurate knowledge about nicotine was low. These misperceptions are of particular concern for vulnerable populations, such as persons living with HIV, who are disproportionately burdened by the prevalence of smoking and associated morbidities and mortality. These misperceptions could have unintended consequences in the wake of a potential nicotine reduction policy, such that reduced nicotine content products are perceived as safer than normal nicotine content products currently available for sale. Additionally, incorrect knowledge about nicotine has implications for the uptake and continued use of nicotine replacement therapy.

Reduced Nicotine Content Expectancies Affect Initial Responses to Smoking.

We sought to determine if negative responses to reduced nicotine content (RNC) cigarettes during open-label trials result from smokers' (negative) expectancies. We examined the effects of nicotine content description - independent of actual nicotine content - on subjective responses (craving reduction, withdrawal suppression, mood changes, and sensory ratings) and smoking behaviors (topography measures and carbon monoxide [CO] boost). Thirty-six 12-hour-abstinent daily smokers completed a 3-session crossover trial. During each session, participants smoked their preferred brand cigarette - blinded and described as containing "usual," "low," and "very low" nicotine content - through a topography device and completed CO and subjective response assessments. Although nicotine content was identical, compared to the "usual" content cigarette, participants experienced less craving reduction after smoking the "very low" nicotine cigarette, and rated its smoke as weaker (p < .05). Participants took shallower puffs of the "low" nicotine cigarette (p < .05), and rated the "low" and "very low" nicotine cigarettes as weaker and too mild (p < .01). Negative responses to RNC cigarettes may be due, in part, to negative expectancies about using cigarettes containing less nicotine. In this context, RNC cigarette marketing and labeling are likely important considerations if a federal nicotine reduction policy is initiated.

How Intravenous Nicotine Administration in Smokers Can Inform Tobacco Regulatory Science.

Reducing the negative health effects caused by tobacco products continues to be a public health priority. The Family Smoking Prevention and Tobacco Control Act of 2009 gives the Food Drug Administration authority to pursue several new strategies, including regulating levels of nicotine and other ingredients in tobacco products. A nicotine reduction strategy proposed by Benowitz and Henningfield aims to reduce the nicotine content of tobacco products to an amount below a threshold that supports neither the development nor maintenance of addiction. Many factors must be considered to determine the viability and efficacy of this approach. For example, the policy should be based on precise information on the dose-dependent effects of nicotine on reinforcement and factors that contribute to individual differences in these effects. However, there have been few studies on these topics in humans. Here, we briefly review nicotine pharmacology and reinforcement then present several studies illustrating the application of intravenous (IV) nicotine delivery to study nicotine reinforcement in humans. We discuss how nicotine delivery by IV infusion may be uniquely suited for studying nicotine's dose-dependent effects, and how this can inform tobacco regulatory science to facilitate the development of effective tobacco control policies.

Reducing the nicotine content of combusted tobacco products sold in New Zealand

Large reductions in nicotine content could dramatically reduce reinforcement from and dependence on cigarettes. In this article, we summarise the potential benefits of reducing nicotine in combusted tobacco and address...

When smokers quit: exposure to nicotine and carcinogens persists from thirdhand smoke pollution

BackgroundOver a 6-month period, we examined tobacco smoke pollutants (also known as thirdhand smoke, THS) that remained in the homes of former smokers and the exposure to these pollutants.Methods90 smokers...

Characterizing the relationship between increases in the cost of nicotine and decreases in nicotine content in adult male rats: implications for tobacco regulation.

A large reduction in the nicotine content of cigarettes may benefit public health by reducing the rate and the prevalence of smoking. A behavioral economics framework suggests that a decrease in nicotine content may be considered an increase in the unit price of nicotine (unit price=reinforcer cost/reinforcer magnitude). Increasing the price of cigarettes (i.e., increasing reinforcer cost) would be considered an equivalent change in unit price to reducing nicotine content (i.e., reducing reinforcer magnitude). The goal of the present experiments was to characterize the relationship between increases in nicotine cost and decreases in nicotine dose. A rat self-administration model was used to assess this relationship across three experiments, with an emphasis on very low nicotine doses to model a potential nicotine reduction policy. Cost was manipulated via changes in the number of responses required to earn an infusion. Results show that increases in the cost of nicotine and decreases in nicotine content were not equivalent manipulations. Nicotine consumption was more sensitive to nicotine dose than to nicotine cost. Nicotine consumption was also not equivalent across a variety of cost and dose combinations forming a single unit price. Results of the present studies suggest that nicotine reduction is likely to have a large impact on nicotine exposure from cigarettes.

Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms.

The FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction. In this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures. Of the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p < .05); among those with CES-D scores ≥ 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D scores than those assigned to NNC cigarettes. Among those in the lowest nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores < 16 and no change in CES-D score for those with baseline CES-D scores ≥ 16. These findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms. This secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity.

Microbial Biofertilizer Decreases Nicotine Content by Improving Soil Nitrogen Supply

Biofertilizers have been widely used in many countries for their benefit to soil biological and physicochemical properties. A new microbial biofertilizer containing Phanerochaete chrysosporium and Bacillus thuringiensis was prepared to decrease nicotine content in tobacco leaves by regulating soil nitrogen supply. Soil NO3--N, NH4+-N, nitrogen supply-related enzyme activities, and nitrogen accumulation in plant leaves throughout the growing period were investigated to explore the mechanism of nicotine reduction. The experimental results indicated that biofertilizer can reduce the nicotine content in tobacco leaves, with a maximum decrement of 16-18% in mature upper leaves. In the meantime, the total nitrogen in mature lower and middle leaves increased with the application of biofertilizer, while an opposite result was observed in upper leaves. Protein concentration in leaves had similar fluctuation to that of total nitrogen in response to biofertilizer. NO3--N content and nitrate reductase activity in biofertilizer-amended soil increased by 92.3 and 42.2%, respectively, compared to those in the control, whereas the NH4+-N and urease activity decreased by 37.8 and 29.3%, respectively. Nitrogen uptake was improved in the early growing stage, but this phenomenon was not observed during the late growth period. Nicotine decrease is attributing to the adjustment of biofertilizer in soil nitrogen supply and its uptake in tobacco, which result in changes of nitrogen content as well as its distribution in tobacco leaves. The application of biofertilizer containing P. chrysosporium and B. thuringiensis can reduce the nicotine content and improve tobacco quality, which may provide some useful information for tobacco cultivation.

The case for the WHO Advisory Note, Global Nicotine Reduction Strategy

Cigarettes are the most addictive tobacco product and also the most deadly, causing the highest rates of tobacco-caused mortality and morbidity in most areas of the world.1 ,2 Although current...

Self-Administered Nicotine Suppresses Body Weight Gain Independent of Food Intake in Male Rats.

The action of nicotine to suppress body weight is often cited as a factor impacting smoking initiation and the failure to quit. Despite the weight-suppressant effects of nicotine, smokers and nonsmokers report equal daily caloric intake. The weight-suppressive effects of nicotine in animal models of smoking are poorly understood. Furthermore, the Food and Drug Administration has authority to implement a policy markedly reducing nicotine levels in cigarettes; such a reduction could reduce smoking behavior, but have detrimental effects on body weight. The aim of this investigation was to examine the effects of self-administered nicotine on body weight and food intake in rats. In Experiment 1, rats with ad libitum access to chow responded for intravenous infusions of nicotine (60 µg/kg/infusion) or saline in daily 1-hour sessions; body weight and 24-hour food intake were measured. Experiment 2 tested the effects of subcutaneous injections of nicotine on food intake. In Experiment 3, rats were food restricted and self-administered nicotine across a range of doses (3.75-60 µg/kg/infusion) while body weight was measured. In Experiment 4, rats self-administered 60 µg/kg/infusion nicotine before reduction to one of several doses (1.875-15 µg/kg/infusion) for 50 days. Self-administered nicotine suppressed weight gain independent of food intake. In food restricted rats, self-administered nicotine dose-dependently suppressed body weight gain. In rats self-administering 60 µg/kg/infusion nicotine, dose reduction increased body weight. Self-administered nicotine, even at low doses, suppressed body independent of food intake; this may have important implications for nicotine reduction policy. The results of the present studies demonstrate that self-administered nicotine suppresses body weight independent of food intake in rats. Further, the present studies establish that self-administered nicotine suppresses body weight even at very low doses and that reduction of nicotine dose results in weight gain. These results have important implications for nicotine reduction policy.

RNA interference of the nicotine demethylase gene CYP82E4v1 reduces nornicotine content and enhances Myzus persicae resistance in Nicotiana tabacum L

The CYP82E4v1 gene was identified to encode nicotine demethylase, which catalyzed the conversion of nicotine to nornicotine. In this study, we constructed CYP82E4v1-RNAi vector and genetically transformed tobacco variety K326. The determination results of nicotine and nornicotine content via HPLC demonstrated that there was significant increase of nicotine content and reduction of nornicotine content in transgenic plants compared with those in wild-type plants. Exogenous application of IAA or GA3 could reduce the nicotine content in tobaccos, while ABA or 6-BA could increase the content of nicotine. And the more significant difference of nicotine content change in transgenic plants. Aphid-inoculation experiment demonstrated the number of aphid population in transgenic plants was significantly lower than wild-type plants at 12 d after aphid-inoculation. Meanwhile, the activity of AOEs and PAL in transgenic and wild-type tobacco plants after aphid-inoculation was measured. At 3 d after aphid-inoculation, both AOEs and PAL activity were significantly higher than controls, including wild-type plants with aphid-inoculation and transgenic plants with mock-inoculation. Also, the relative expression of these genes involved in salicylic acid/jasmonic acid (SA/JA) signaling pathways was analyzed at different stages after aphid-inoculation and the results demonstrated that there was significantly higher expression of JA-induced LOX gene in both transgenic and wild-type plants inoculated by aphid than the non-inoculated ones while no significant difference in the expression of SA-induced PR-1a gene among them was found, which indicated the JA-mediated resistance response was activated during aphid infestation. Moreover, although the expression level of BGL (another JA-induced gene) was less significant between the two inoculated tobaccos, it was significantly higher than the plant without inoculation, which was 1.4 and 2.2 folds higher than the non-inoculated controls respectively. To sum up, the improvement of aphid-resistance in transgenic tobaccos was based on nicotine accumulation which might cause nerve and antifeed toxicity and JA-mediated resistance response by enhancing the activities of AOEs and PAL.

Cigarettes production based on flavored sauced tobacco blend

Complex work on designing cigarettes with adjustable composition cut filler and auxiliary materials are not carried out, therefore, despite the progress made in the field of cigarette, meet the requirements of safety indicators of tobacco smoke, the problem of designing and development of new types of cigarettes on the regulated parameters smoke toxicity remains relevant. Objects of research were cigarettes of different constructions containing tobacco blend which includes recovered tobacco and expanded stem. Additionally, tobacco blend was added by aromatic plant material (anise, fennel, lemon balm, sweet grass). Flavored sauced tobacco blend is prepared by mixing cut tobacco and plant raw materials to provide high fill value, toxicity reduction of tobacco smoke and increased combustibility. The composition of the tobacco blend does not contain nicotine plant material and artificial flavors. Found that nicotine reduction is the result of using no nicotine plant raw materials and increases the storage life of cigarettes is a result of the uniform distribution of plant components, delaying its evaporation.

Cigarettes production based on flavored sauced tobacco blend

Complex work on designing cigarettes with adjustable composition cut filler and auxiliary materials are not carried out, therefore, despite the progress made in the field of cigarette, meet the requirements of safety indicators of tobacco smoke, the problem of designing and development of new types of cigarettes on the regulated parameters smoke toxicity remains relevant. Objects of research were cigarettes of different constructions containing tobacco blend which includes recovered tobacco and expanded stem. Additionally, tobacco blend was added by aromatic plant material (anise, fennel, lemon balm, sweet grass). Flavored sauced tobacco blend is prepared by mixing cut tobacco and plant raw materials to provide high fill value, toxicity reduction of tobacco smoke and increased combustibility. The composition of the tobacco blend does not contain nicotine plant material and artificial flavors. Found that nicotine reduction is the result of using no nicotine plant raw materials and increases the storage life of cigarettes is a result of the uniform distribution of plant components, delaying its evaporation.

En Route for Better From Bad (?): Introducing Reduced Nicotine Cigarettes

Smoking is one of the major modifiable etiological factors of multiple morbidities. Convincing evidences are available to establish the causal influence of smoking on cancers, cardiovascular diseases, respiratory morbidities and reproductive dysfunctions. The main culprit responsible for smoking-associated morbidities and mortality is nicotine. Youngsters accidentally experiment smoking, get addicted to smoking which pushes the into the dark era of associated morbidities. With a view of reducing exposure to toxicants in cigarettes, reducednicotine cigarettes (RNCs) were introduced with a belief that they would reduce the incidence of addiction and thus the incidence of associated morbidities. These RNCs were introduced as a result of nicotine reduction policy implemented by the US government. Recent evidences have demonstrated that RNCs are safer than conventional cigarettes in many aspects. This article describes the challenges involved in effective functioning of nicotine reduction policy and adds a note on future prospects to enhance the outcomes.

Predicted Impact of Nicotine Reduction on Smokers with Affective Disorders.

In 2009 the FDA acquired the authority to reduce the nicotine content in cigarettes if appropriate for public health, prompting research to evaluate the implications of this policy scientifically. Studies in non-psychiatric populations show that reducing the nicotine content of cigarettes to non-addictive levels reduces smoking rates and nicotine dependence. However, few studies have examined this hypothesis in vulnerable populations. In this narrative review we examined the extant literature on the effects of nicotine reduction or cessation on symptoms of withdrawal, as well as psychiatric symptoms, among those with affective disorders. Following initial withdrawal from nicotine, smokers with affective disorders experience more severe mood disruption than smokers without these disorders. Use of very low nicotine content (VLNC) cigarettes during abstinence may help mitigate the mood-disrupting effects of initial abstinence. Once the initial effects of nicotine withdrawal on mood have passed, longer-term abstinence is associated with psychiatric improvement rather than worsening. These findings suggest that if a national nicotine reduction policy were to be implemented, smokers with affective disorders would need additional support to overcome initial withdrawal but that long-term outcomes would likely be positive.

Predictors of the nicotine reinforcement threshold, compensation, and elasticity of demand in a rodent model of nicotine reduction policy

BackgroundThe FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. MethodsThe present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. ResultsConsiderable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. ConclusionsThese findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction.

Prospects for a nicotine-reduction strategy in the cigarette endgame: Alternative tobacco harm reduction scenarios

Some major national and international tobacco control organisations favour mandating a reduction in nicotine content of cigarettes to non-addictive levels as a tobacco control tool. Reducing nicotine content, it is argued, will make tobacco smoking less attractive. The 2009 U.S. Food and Drug Administration's regulation of cigarettes appears to have the power to reduce nicotine to non-addictive levels provided it is not taken to zero. A consideration of the U.S. context, however, raises doubts about (a) whether this will ever be practicable and (b), if practicable, how long it will take to implement. Current versions of the nicotine-reducing strategy propose the systematic, incentivised use of less harmful nicotine/tobacco products as elements of the mandatory cigarette nicotine-reduction strategy. Time will tell if and when mandatory nicotine reduction in tobacco cigarettes will occur and what impact it might have on smoking prevalence. The question posed here is “Why wait?” Resources used in implementing reduction in nicotine content have an opportunity cost. In the meantime, nicotine-maintaining harm reduction strategies can have nearer term effects on tobacco use as an individual and a public health issue.