Pros and Cons of Long-Term use of Nicotine Replacement Therapies: A Qualitative Study

DEFF Research Database (Denmark)

Borup, Gitte; Kaae, Susanne; Nørgaard, Lotte Stig

2016-01-01

, intrapersonal processes, the social environment of smoking vs. NRTs and finances. None of the ex-smokers feared to relapse to smoking, and few were motivated to quit NRTs. Non-nicotinic factors were found to have an important role in developing an addiction to NRTs. The use of NRTs yields some of the expected......, including perceived pros and cons of using NRTs, the risk of relapse to smoking and their motivation to quit using NRTs. The results identified five major themes that entailed pros and cons of the long-term use of NRTs. These were the non-nicotinic factors of NRTs, health risks of NRTs vs. smoking......In the last decade, harm reduction has been increasingly suggested as a method to reduce the harm caused by smoking in smokers who are unable or unwilling to quit all nicotine products. One of these methods includes long-term substitution of tobacco with nicotine replacement therapies (NRTs...

Maternal use of nicotine replacement therapy during pregnancy and offspring birthweight: a study within the Danish National Birth Cohort

DEFF Research Database (Denmark)

Lassen, Tina H; Madsen, Mia; Skovgaard, Lene T

2010-01-01

Smoking is a well-established risk factor for fetal growth restriction and other adverse pregnancy outcomes, and nicotine may be one of the chemical compounds that drive these associations. Nicotine replacement therapy (NRT) is a smoking cessation aid, which can facilitate smoking cessation. It is...

[Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].

Science.gov (United States)

Suemaru, K; Kawasaki, H; Gomita, Y

1997-06-01

The repeated administration of nicotine at small doses, which do not produce whole body tremor or convulsion, causes tremor only in the tail (tail-tremor) of rats. The tremor is accompanied by locomotor hyperactivity without rigidity and immobility of the whole body, suggesting that the nicotine-induced tail-tremor model is useful for studying the mechanism underlying tremor associated with movement. The tail-tremor induced by nicotine was suppressed by mecamylamine, a nicotinic antagonist, but not by atropine or scopolamine, muscalinic antagonists. Moreover, the tail-tremor was suppressed by the beta-blockers propranolol and pindolol, as well as the benzodiazepines diazepam and clonazepam. Tremor at rest is observed only in Parkinson's disease, which is improved with anti-muscalinic drugs. Essential tremor is one of the typical tremors connected with movement (postural and kinetic tremor) and is improved with beta-blocker. These findings and results suggest that nicotine-induced tail-tremor is useful for the study of essential tremor in animal models.

Knowledge and Perceptions Regarding Nicotine Replacement Therapy among Dental Students in Karnataka

OpenAIRE

Ajagannanavar, Sunil Lingaraj; Alshahrani, Obaid Abdullah; Jhugroo, Chitra; Tashery, Hamed Mohammed; Mathews, Jacob; Chavan, Khechari

2015-01-01

Background: Organized dentistry has recognized the role of oral health professionals in discouraging tobacco use. Unexplored level of knowledge regarding the benefits and prescription of nicotine replacement therapy (NRT) have aroused interest among us which initiated us to assess the knowledge and perception of dental students toward NRT among various dental colleges in Karnataka, South India. Materials and Methods: A questionnaire survey was done among 16 selected colleges in Karnataka. It ...

Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse.

Science.gov (United States)

Hall, E S; Wexelblatt, S L; Greenberg, J M

2016-10-01

The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse. The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection. Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (Pdrugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures. Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources.

For Nicotine, Dose Matters | Center for Cancer Research

Science.gov (United States)

Nicotine replacement therapy (NRT) is frequently part of a person’s regimen for smoking cessation. The U.S. Food and Drug Administration has approved use of this approach for 12 weeks in supervised quitting programs. Unfortunately for some patients, though, this length of time is not long enough to break their addiction to tobacco. 

Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse.

Science.gov (United States)

Cross, Sarah J; Lotfipour, Shahrdad; Leslie, Frances M

2017-03-01

Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

Nicotine Vapor Method to Induce Nicotine Dependence in Rodents.

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Kallupi, Marsida; George, Olivier

2017-07-05

Nicotine, the main addictive component of tobacco, induces potentiation of brain stimulation reward, increases locomotor activity, and induces conditioned place preference. Nicotine cessation produces a withdrawal syndrome that can be relieved by nicotine replacement therapy. In the last decade, the market for electronic cigarettes has flourished, especially among adolescents. The nicotine vaporizer or electronic nicotine delivery system is a battery-operated device that allows the user to simulate the experience of tobacco smoking without inhaling smoke. The device is designed to be an alternative to conventional cigarettes that emits vaporized nicotine inhaled by the user. This report describes a procedure to vaporize nicotine in the air to produce blood nicotine levels in rodents that are clinically relevant to those that are observed in humans and produce dependence. We also describe how to construct the apparatus to deliver nicotine vapor in a stable, reliable, and consistent manner, as well as how to analyze air for nicotine content. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study.

Science.gov (United States)

Shahab, Lion; Goniewicz, Maciej L; Blount, Benjamin C; Brown, Jamie; McNeill, Ann; Alwis, K Udeni; Feng, June; Wang, Lanqing; West, Robert

2017-03-21

Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential. To compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT. Cross-sectional study. United Kingdom. The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181). Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs). After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites. Cross-sectional design with self-selected sample. Former

Drug, nicotine, and alcohol use among exercisers: Does substance addiction co-occur with exercise addiction?

Directory of Open Access Journals (Sweden)

Attila Szabo

2018-06-01

Full Text Available Background: Scholastic works suggest that those at risk for exercise addiction are also often addicted to illicit drugs, nicotine, and/or alcohol, but empirical evidence is lacking. Aims: The aim of the present work was to examine the co-occurrence of illicit drug, nicotine, and alcohol use frequency (prevalence of users and severity (level of problem in users among exercisers classified at three levels of risk for exercise addiction: (i asymptomatic, (ii symptomatic, and (iii at-risk. Methods: A sample of 538 regular exercisers were surveyed via the Qualtrics research platform. They completed the (i Drug Use Disorder Identification Test, (ii Fagerström Test for Nicotine Dependence, (iii Alcohol Use Disorder Identification Test, and (iv Exercise Addition Inventory. Results: A large proportion (n=59; 10.97% of the sample was found to be at risk for exercise addiction. The proportion of drug and alcohol users among these participants did not differ from the rest of the sample. However, the incidence of nicotine consumption was lowest among them. The severity of problematic substance use did not differ across the groups. Conclusions: These findings suggest that substance addiction and the risk for exercise addiction are unrelated. In fact, those at risk for exercise addiction exhibited the healthiest profile related to the prevalence of smoking. Keywords: Alcohol drinking, Cigarette smoking, Exercise dependence, Illicit substance use, Physical activity, Sport

Inside-out neuropharmacology of nicotinic drugs.

Science.gov (United States)

Henderson, Brandon J; Lester, Henry A

2015-09-01

Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as "inside-out pharmacology". This term contrasts with the better-known, acute, "outside-in" effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Extended nicotine self-administration increases sensitivity to nicotine, motivation to seek nicotine and the reinforcing properties of nicotine-paired cues.

Science.gov (United States)

Clemens, Kelly J; Lay, Belinda P P; Holmes, Nathan M

2017-03-01

An array of pharmacological and environmental factors influence the development and maintenance of tobacco addiction. The nature of these influences likely changes across the course of an extended smoking history, during which time drug seeking can become involuntary and uncontrolled. The present study used an animal model to examine the factors that drive nicotine-seeking behavior after either brief (10 days) or extended (40 days) self-administration training. In Experiment 1, extended training increased rats' sensitivity to nicotine, indicated by a leftward shift in the dose-response curve, and their motivation to work for nicotine, indicated by an increase in the break point achieved under a progressive ratio schedule. In Experiment 2, extended training imbued the nicotine-paired cue with the capacity to maintain responding to the same high level as nicotine itself. However, Experiment 3 showed that the mechanisms involved in responding for nicotine or a nicotine-paired cue are dissociable, as treatment with the partial nicotine receptor agonist, varenicline, suppressed responding for nicotine but potentiated responding for the nicotine-paired cue. Hence, across extended nicotine self-administration, pharmacological and environmental influences over nicotine seeking increase such that nicotine seeking is controlled by multiple sources, and therefore highly resistant to change. © 2015 Society for the Study of Addiction.

Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats.

Science.gov (United States)

Feltenstein, Matthew W; Ghee, Shannon M; See, Ronald E

2012-03-01

Tobacco addiction is a relapsing disorder that constitutes a substantial worldwide health problem, with evidence suggesting that nicotine and nicotine-associated stimuli play divergent roles in maintaining smoking behavior in men and women. While animal models of tobacco addiction that utilize nicotine self-administration have become more widely established, systematic examination of the multiple factors that instigate relapse to nicotine-seeking have been limited. Here, we examined nicotine self-administration and subsequent nicotine-seeking in male and female Sprague-Dawley rats using an animal model of self-administration and relapse. Rats lever pressed for nicotine (0.03 and 0.05 mg/kg/infusion, IV) during 15 daily 2-h sessions, followed by extinction of lever responding. Once responding was extinguished, we examined the ability of previously nicotine-paired cues (tone+light), the anxiogenic drug yohimbine (2.5mg/kg, IP), a priming injection of nicotine (0.3mg/kg, SC), or combinations of drug+cues to reinstate nicotine-seeking. Both males and females readily acquired nicotine self-administration and displayed comparable levels of responding and intake at both nicotine doses. Following extinction, exposure to the previously nicotine-paired cues or yohimbine, but not the nicotine-prime alone, reinstated nicotine-seeking in males and females. Moreover, when combined with nicotine-paired cues, both yohimbine and nicotine enhanced reinstatement. No significant sex differences or estrous cycle dependent changes were noted across reinstatement tests. These results demonstrate the ability to reinstate nicotine-seeking with multiple modalities and that exposure to nicotine-associated cues during periods of a stressful state or nicotine can increase nicotine-seeking. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

Science.gov (United States)

Wonnacott, Susan

2011-01-01

Parkinson's disease is a debilitating movement disorder characterized by a generalized dysfunction of the nervous system, with a particularly prominent decline in the nigrostriatal dopaminergic pathway. Although there is currently no cure, drugs targeting the dopaminergic system provide major symptomatic relief. As well, agents directed to other neurotransmitter systems are of therapeutic benefit. Such drugs may act by directly improving functional deficits in these other systems, or they may restore aberrant motor activity that arises as a result of a dopaminergic imbalance. Recent research attention has focused on a role for drugs targeting the nicotinic cholinergic systems. The rationale for such work stems from basic research findings that there is an extensive overlap in the organization and function of the nicotinic cholinergic and dopaminergic systems in the basal ganglia. In addition, nicotinic acetylcholine receptor (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for this proposition stems from studies with experimental animal models showing that nicotine protects against neurotoxin-induced nigrostriatal damage and improves motor complications associated with l-DOPA, the “gold standard” for Parkinson's disease treatment. Nicotine interacts with multiple central nervous system receptors to generate therapeutic responses but also produces side effects. It is important therefore to identify the nAChR subtypes most beneficial for treating Parkinson's disease. Here we review nAChRs with particular emphasis on the subtypes that contribute to basal ganglia function. Accumulating evidence suggests that drugs targeting α6β2* and α4β2* nAChR may prove useful in the management of Parkinson's disease. PMID:21969327

Discontinuation of nicotine replacement therapy among smoking-cessation attempters.

Science.gov (United States)

Burns, Emily K; Levinson, Arnold H

2008-03-01

Nicotine replacement therapy (NRT) doubles successful quitting, but more than half of NRT users do not comply with optimal treatment regimens. From the 2005 Colorado state tobacco survey, quit attempters who utilized NRT (N=366) were analyzed in spring 2007. Descriptive and regression analyses were used to examine reasons for discontinuing NRT, length of time on NRT, and quit intentions. The reasons for discontinuing NRT were resuming smoking (34%), side effects (17%), NRT not helping with quitting (14%), quitting smoking (10%), and cost (5%). Poverty, age, and non-Latino minority status were associated with reasons for discontinuation other than quitting smoking. Having side effects was associated with a short duration of NRT use and 95% lower odds of intending to quit in the next month. In the first population-level study examining reasons for discontinuing NRT, general-population smokers who initiate NRT use when attempting to quit are highly likely to discontinue NRT prematurely. Age and culturally-appropriate medication management interventions may increase NRT compliance and improve cessation outcomes.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

2011-11-18

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

International Nuclear Information System (INIS)

Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

2011-01-01

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Directory of Open Access Journals (Sweden)

A. Zago

2012-01-01

Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT) - a study protocol.

Science.gov (United States)

Klonizakis, Markos; Crank, Helen; Gumber, Anil; Brose, Leonie S

2017-04-04

The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or "e-") cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately) combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants' "quit date". Participants will be assessed at baseline, 3 days following their self-determined "quit date", at intervention end (3 months) and 6 months following their "quite date". Findings are expected to give an indication of the cardiovascular effects of e-cigarettes both in the short- and in the medium-term period

Electronic cigarettes: health impact, nicotine replacement therapy, regulations

Directory of Open Access Journals (Sweden)

Zygmunt Zdrojewicz

2017-03-01

Full Text Available While the adverse effects of conventional cigarettes on human health have been thoroughly examined, in the last 15 years we have witnessed the birth of electronic cigarettes. There are many types of these devices available on the market. Studies are still underway to determine their negative impact on the human body. Electronic cigarettes comprise of power supply and a vaporising system. The user inhales the aerosol produced by heating up the liquid containing nicotine. In contrast with conventional cigarettes, the tobacco is not combusted, thus the compositions of the aerosol and cigarette smoke are considerably different. Out of 93 chemical substances present in the e-cigarette smoke, the aerosol contains only acetaldehyde, acetone, acrolein, formaldehyde and nicotine. More toxic substances, such as polycyclic aromatic hydrocarbons and heavy metals, are not present. The amount of evidence suggesting electronic cigarettes’ harmful effects on the human body is constantly increasing. Some reports imply that the electronic cigarettes negatively influence pregnancy, human psyche, respiratory and cardiovascular systems. They might also be involved in oncogenesis. With electronic cigarettes constantly gaining popularity, the question about the adverse effects of passive smoking becomes increasingly more relevant. Although various methods of helping people cease smoking or delivering nicotine to their bodies without burning toxic substances are being explored, electronic cigarettes are not recommended in nicotine substitution therapy. Legal regulations regarding electronic cigarettes are still being worked on. The purpose of this paper is to evaluate the effects electronic cigarettes have on the human’s health.

Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence.

Science.gov (United States)

Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

2017-08-01

Because electronic cigarettes (e-cigs) containing nicotine may relieve smoking abstinence symptoms similar to nicotine replacement therapy medication, we used within-subjects designs to test these effects with a first-generation e-cig in nonquitting and quitting smokers. In Study 1, 28 nontreatment-seeking smokers abstained overnight prior to each of 3 sessions. Minnesota Nicotine Withdrawal Scale (MNWS) withdrawal (and craving item) relief was assessed following 4 exposures (each 10 puffs) over 2 hr to e-cigs that either did (36 mg/ml) or did not (i.e., placebo, 0 mg/ml) contain nicotine or after no e-cig. Relief was greater after nicotine versus placebo e-cig (p < .05) but not after placebo versus no e-cig, showing relief was due to nicotine per se and not simple e-cig use behavior. Using a crossover design in Study 2, smokers preparing to quit soon engaged in 2 experimental 4-day quit periods on separate weeks. In weeks 1 and 3, all received a nicotine or placebo e-cig on Monday to use ad libitum while trying to abstain from smoking on Tuesday through Friday. (Week 2 involved resumption of ad libitum smoking.) MNWS and Questionnaire of Smoking Urges (QSU) craving were assessed at daily visits following 24-hr abstinence. Of 17 enrolled, 12 quit for ≥24 hr at least once, allowing test of relief because of e-cig use on quit days. Withdrawal and craving were reduced because of nicotine versus placebo e-cig use (both p < .05). In sum, compared with placebo e-cigs, nicotine e-cigs can relieve smoking abstinence symptoms, perhaps in a manner similar to Food and Drug Administration-approved nicotine replacement therapy products, although much more research with larger samples is needed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking.

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Islam Gamaleddin

Full Text Available Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2 have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg and CB2 agonist AM1241 (1 to 10 mg/kg on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.

How do consumers perceive differences in risk across nicotine products? A review of relative risk perceptions across smokeless tobacco, e-cigarettes, nicotine replacement therapy and combustible cigarettes.

Science.gov (United States)

Czoli, Christine D; Fong, Geoffrey T; Mays, Darren; Hammond, David

2017-03-01

To systematically review the literature regarding relative risk perceptions (RRPs) across non-combustible nicotine products. MEDLINE and PsycINFO databases were searched for articles published up to October 2014. Of the 5266 records identified, articles not published in English that did not quantitatively assess RRPs across categories of non-combustible nicotine products were excluded, yielding 55 records. One reviewer extracted measures and findings of RRPs for product comparisons of smokeless tobacco (SLT), e-cigarettes (ECs) and nicotine replacement therapy (NRT) to one another, and to combustible cigarettes (CCs). A total of 157 samples from 54 studies were included in the analyses. The accuracy of RRPs differed based on the products being compared: although the accuracy of RRPs was variable across studies, substantial proportions of respondents reported inaccurate beliefs about the relative harmfulness of SLT versus CCs, as well as of ECs versus NRT. In addition, in most studies, respondents did not know the relative harmfulness of SLT versus NRT. In contrast, respondents in many studies correctly perceived NRT and ECs as less harmful than CCs. Cigarette smokers and users of non-combustible nicotine products tended to correctly perceive the relative harmfulness of products more often than non-users. Measures used to assess RRPs varied across studies, with different approaches characterised by certain strengths and limitations. The highly variable and context-specific nature of non-combustible nicotine product RRPs have direct implications for researchers and present several challenges for policymakers working with modified risk products, including issues of measurement, health risk communication and behaviour change. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

21 CFR 172.310 - Aluminum nicotinate.

Science.gov (United States)

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.310 Aluminum nicotinate. Aluminum nicotinate may be safely...

Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT - a study protocol

Directory of Open Access Journals (Sweden)

Markos Klonizakis

2017-04-01

Full Text Available Abstract Background The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or “e-“ cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. Methods This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants’ “quit date”. Discussion Participants will be assessed at baseline, 3 days following their self-determined “quit date”, at intervention end (3 months and 6 months following their “quite date”. Findings are expected to give an indication of the cardiovascular

Nicotine replacement therapy decision based on fuzzy multi-criteria analysis

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Tarmudi, Zamali; Matmali, Norfazillah; Abdullah, Mohd Lazim

2017-08-01

It has been observed that Nicotine Replacement Therapy (NRT) is one of the alternatives to control and reduce smoking addiction among smokers. Since the decision to choose the best NRT alternative involves uncertainty, ambiguity factors and diverse input datasets, thus, this paper proposes a fuzzy multi-criteria analysis (FMA) to overcome these issues. It focuses on how the fuzzy approach can unify the diversity of datasets based on NRT's decision-making problem. The analysis done employed the advantage of the cost-benefit criterion to unify the mixture of dataset input. The performance matrix was utilised to derive the performance scores. An empirical example regarding the NRT's decision-making problem was employed to illustrate the proposed approach. Based on the calculations, this analytical approach was found to be highly beneficial in terms of usability. It was also very applicable and efficient in dealing with the mixture of input datasets. Hence, the decision-making process can easily be used by experts and patients who are interested to join the therapy/cessation program.

Nicotine and tobacco

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... ease your withdrawal symptoms. Health experts warn that e-cigarettes are not a replacement therapy for cigarette smoking. ... not known exactly how much nicotine is in e-cigarette cartridges, because information on labels is often wrong.

Nicotine response and nicotinic receptors in long-sleep and short-sleep mice.

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De Fiebre, C M; Medhurst, L J; Collins, A C

1987-01-01

Nicotine response and nicotinic receptor binding were characterized in long-sleep (LS) and short-sleep (SS) mice which have been selectively bred for differential "sleep-time" following ethanol administration. LS mice are more sensitive than SS mice to nicotine as measured by a battery of behavioral and physiological tests and as measured by sensitivity to nicotine-induced seizures. The greater sensitivity of the LS mice is not due to differences in binding of [3H]nicotine. Unlike inbred mouse strains which differ in sensitivity to nicotine-induced seizures, these selected mouse lines do not differ in levels of binding of [125I]alpha-bungarotoxin (BTX) in the hippocampus. Significant differences in BTX binding were found in the cerebellum and striatum. Although these two mouse lines do not differ in blood levels of nicotine following nicotine administration, they differ slightly in brain levels of nicotine indicating differential distribution of the drug. Since this distribution difference is much smaller than the observed behavioral differences, these mice probably differ in CNS sensitivity to nicotine; however, follow-up studies are necessary to test whether the differential response of these mice is due to subtle differences in distribution of nicotine to the brain.

Design, formulation and evaluation of nicotine chewing gum

OpenAIRE

Abolfazl Aslani; Sahar Rafiei

2012-01-01

Background: Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which satisfy the consumers the most. Materials and Methods: Nicotine, sugar, liquid...

Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.

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Lopez, Alexa A; Hiler, Marzena M; Soule, Eric K; Ramôa, Carolina P; Karaoghlanian, Nareg V; Lipato, Thokozeni; Breland, Alison B; Shihadeh, Alan L; Eissenberg, Thomas

2016-05-01

Electronic cigarettes (ECIGs) aerosolize a liquid that usually contains propylene glycol and/or vegetable glycerin, flavorants, and the dependence-producing drug nicotine in various concentrations. This study examined the extent to which ECIG liquid nicotine concentration is related to user plasma nicotine concentration in ECIG-naïve tobacco cigarette smokers. Sixteen ECIG-naïve cigarette smokers completed four laboratory sessions that differed by the nicotine concentration of the liquid (0, 8, 18, or 36 mg/ml) that was placed into a 1.5 Ohm, dual coil "cartomizer" powered by a 3.3V battery. In each session, participants completed two, 10-puff ECIG use bouts with a 30-second inter-puff interval; bouts were separated by 60 minutes. Venous blood was sampled before and after bouts for later analysis of plasma nicotine concentration; puff duration, volume, and average flow rate were measured during each bout. In bout 1, relative to the 0mg/ml nicotine condition (mean = 3.8 ng/ml, SD = 3.3), plasma nicotine concentration increased significantly immediately after the bout for the 8 (mean = 8.8 ng/ml, SD = 6.3), 18 (mean = 13.2 ng/ml, SD = 13.2), and 36 mg/ml (mean = 17.0 ng/ml, SD = 17.9) liquid concentration. A similar pattern was observed after bout 2. Average puff duration in the 36 mg/ml condition was significantly shorter compared to the 0mg/ml nicotine condition. Puff volume increased during the second bout for 8 and 18 mg/ml conditions. For a given ECIG device, nicotine delivery may be directly related to liquid concentration. ECIG-naïve cigarette smokers can, from their first use bout, attain cigarette-like nicotine delivery profiles with some currently available ECIG products. Liquid nicotine concentration can influence plasma nicotine concentration in ECIG-naïve cigarette smokers, and, at some concentrations, the nicotine delivery profile of a 3.3V ECIG with a dual coil, 1.5-Ohm cartomizer approaches that of a combustible tobacco cigarette in this

The Nicotinic Acetylcholine Receptor as a Target for Antidepressant Drug Development

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Noah S. Philip

2012-01-01

Full Text Available An important new area of antidepressant drug development involves targeting the nicotinic acetylcholine receptor (nAChR. This receptor, which is distributed widely in regions of the brain associated with depression, is also implicated in other important processes that are relevant to depression, such as stress and inflammation. The two classes of drugs that target nAChRs can be broadly divided into mecamylamine- and cytisine-based compounds. These drugs probably exert their effects via antagonism at α4β2 nAChRs, and strong preclinical data support the antidepressant efficacy of both classes when used in conjunction with other primary antidepressants (e.g., monoamine reuptake inhibitors. Although clinical data remain limited, preliminary results in this area constitute a compelling argument for further evaluation of the nAChR as a target for future antidepressant drug development.

Personality Traits and Psychopathology in Nicotine and Opiate Dependents Using the Gateway Drug Theory

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Bahareh Amirabadi

2015-03-01

Full Text Available Objectives: According to the gateway drug theory, tobacco use is a predisposing factor for future substance abuse. This study was conducted to compare nicotine and opiate dependents to identify the differences between their personality traits and psychopathology that makes them turn to other substances after cigarette smoking. Methods: A causal-comparative study was conducted. Three groups were randomly selected: nicotine dependents, opiate dependents and ordinary individuals (non-dependent population. Cloninger’s Temperament and Character Inventory-Revised, the Fagerstrom Test for Nicotine Dependence, Maudsley Addiction Profile, the Beck Depression Inventory, and Beck Anxiety Inventory were used to collect data. Analysis of variance was used to analyze data. Results: Opiate dependents had higher ‘novelty seeking’ and lower ‘cooperativeness’ scores as compared to the other two groups. They also had higher anxiety and depression scores than the other two groups. Discussion: Higher ‘novelty seeking’ and lower ‘cooperativeness’ scores are important personality traits predicting

Opioid Analgesics and Nicotine: More Than Blowing Smoke.

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Yoon, Jin H; Lane, Scott D; Weaver, Michael F

2015-09-01

Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

Repeated nicotine exposure enhances reward-related learning in the rat.

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Olausson, Peter; Jentsch, J David; Taylor, Jane R

2003-07-01

Repeated exposure to addictive drugs causes neuroadaptive changes in cortico-limbic-striatal circuits that may underlie alterations in incentive-motivational processes and reward-related learning. Such drug-induced alterations may be relevant to drug addiction because enhanced incentive motivation and increased control over behavior by drug-associated stimuli may contribute to aspects of compulsive drug-seeking and drug-taking behaviors. This study investigated the consequences of repeated nicotine treatment on the acquisition and performance of Pavlovian discriminative approach behavior, a measure of reward-related learning, in male rats. Water-restricted rats were trained to associate a compound conditioned stimulus (tone+light) with the availability of water (the unconditioned stimulus) in 15 consecutive daily sessions. In separate experiments, rats were repeatedly treated with nicotine (0.35 mg/kg, s.c.) either (1) prior to the onset of training, (2) after each daily training session was completed (ie postsession injections), or (3) received nicotine both before the onset of training as well as after each daily training session. In this study, all nicotine treatment schedules increased Pavlovian discriminative approach behavior and, thus, prior repeated exposure to nicotine, repeated postsession nicotine injections, or both, facilitated reward-related learning.

Reframing the science and policy of nicotine, illegal drugs and alcohol - conclusions of the ALICE RAP Project.

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Anderson, Peter; Berridge, Virginia; Conrod, Patricia; Dudley, Robert; Hellman, Matilda; Lachenmeier, Dirk; Lingford-Hughes, Anne; Miller, David; Rehm, Jürgen; Room, Robin; Schmidt, Laura; Sullivan, Roger; Ysa, Tamyko; Gual, Antoni

2017-01-01

In 2013, illegal drug use was responsible for 1.8% of years of life lost in the European Union, alcohol was responsible for 8.2% and tobacco for 18.2%, imposing economic burdens in excess of 2.5% of GDP. No single European country has optimal governance structures for reducing the harm done by nicotine, illegal drugs and alcohol, and existing ones are poorly designed, fragmented, and sometimes cause harm. Reporting the main science and policy conclusions of a transdisciplinary five-year analysis of the place of addictions in Europe, researchers from 67 scientific institutions addressed these problems by reframing an understanding of addictions.  A new paradigm needs to account for evolutionary evidence which suggests that humans are biologically predisposed to seek out drugs, and that, today, individuals face availability of high drug doses, consequently increasing the risk of harm.  New definitions need to acknowledge that the defining element of addictive drugs is 'heavy use over time', a concept that could replace the diagnostic artefact captured by the clinical term 'substance use disorder', thus opening the door for new substances to be considered such as sugar. Tools of quantitative risk assessment that recognize drugs as toxins could be further deployed to assess regulatory approaches to reducing harm. Re-designed governance of drugs requires embedding policy within a comprehensive societal well-being frame that encompasses a range of domains of well-being, including quality of life, material living conditions and sustainability over time; such a frame adds arguments to the inappropriateness of policies that criminalize individuals for using drugs and that continue to categorize certain drugs as illegal. A health footprint, modelled on the carbon footprint, and using quantitative measures such as years of life lost due to death or disability, could serve as the accountability tool that apportions responsibility for who and what causes drug-related harm.

Long-term effectiveness of mailed nicotine replacement therapy: study protocol of a randomized controlled trial 5-year follow-up.

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Kushnir, Vladyslav; Selby, Peter; Zawertailo, Laurie; Tyndale, Rachel F; Leatherdale, Scott T; Cunningham, John A

2017-07-18

Our group recently completed a randomized controlled trial, evaluating the efficacy of providing 5 weeks of free nicotine replacement therapy (NRT; in the form of the nicotine patch) by expedited postal mail without behavioral assistance to regular adult smokers interested in receiving it. The findings revealed that mailed provision of nicotine patches resulted in more than a doubling of quit rates at a six-month follow-up compared to a no intervention control group. While this trial provided evidence for the effectiveness of mailed nicotine patches in promoting cessation, the findings speak only to the short term effectiveness of this approach. As relapse to smoking is known to occur beyond the 6 month period, it is important to evaluate whether the net benefit of NRT in naturalistic settings can be maintained long-term. The present study aims to perform a 5-year follow-up survey of participants in the original trial to evaluate the long-term effectiveness of mailed NRT. Trained interviewers will contact participants in the randomized controlled trial 5 years post-enrollment. A total of 924 participants will be eligible to be contacted. Interviewers will first assess participants' smoking status and their level of nicotine dependence. Participants reporting not currently smoking will be asked whether they have smoked tobacco, even a puff, in the last 30 days (primary outcome measure: 30-day point prevalence abstinence), past 6 months (secondary outcome measure: prolonged 6-month abstinence), and since the 8-week follow-up survey (secondary outcome measure: > 4 year continuous abstinence). Interviewers will be blind to experimental condition at the time the primary outcome measure will be assessed. It is hypothesized that participants who received nicotine patches at baseline will display significantly higher quit rates at the 5-year follow-up as compared to participants who did not receive nicotine patches at baseline. If the study finds that the mailed

Decreased sensitivity to nicotine-induced seizures as a consequence of nicotine pretreatment in long-sleep and short-sleep mice.

Science.gov (United States)

de Fiebre, C M; Collins, A C

1988-01-01

Male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with a subseizure-producing dose of nicotine (2.0 mg/kg) 7.5, 15 and 30 minutes prior to challenge with seizure-producing doses of this drug. Nicotine pretreated animals were less susceptible to nicotine-induced seizures than were saline pretreated animals. The latency to seizure following nicotine challenge was greater in nicotine pretreated animals than in saline controls. Nicotine pretreated LS mice show a greater decrease in nicotine-induced seizure susceptibility than do nicotine pretreated SS mice. This decrease in seizure susceptibility is consistent with induction of nicotinic receptor desensitization via nicotine pretreatment. It is hypothesized that LS and SS mice might differ in sensitivity to nicotine in part because they differ in baseline levels of desensitized versus functional nicotinic receptors.

The impact of advertising on nicotine replacement therapy demand.

Science.gov (United States)

Tauras, John A; Chaloupka, Frank J; Emery, Sherry

2005-05-01

While much is known about the economic determinants of tobacco use, very little is known about the economic determinants of nicotine replacement therapy (NRT) use. This paper is the first econometric study to examine the impact of advertising on NRT demand. Pooled cross-sectional time-series scanner-based data for 50 major metropolitan markets in the USA covering the period between the second quarter of 1996 and the second quarter of 2002 are used in the analysis. Fixed-effects modeling is employed to estimate the NRT demand equation. The estimates indicate that increased advertising of Nicoderm CQ transdermal patches and Nicotrol transdermal patches increases per-capita sales of established Nicoderm CQ and Nicotrol products, respectively. However, increased advertising of Nicorette polacrilex (gum) was found not to significantly increase sales of established Nicorette products. Moreover, decreases in the price of NRT and increases in the price of cigarettes were found to increase per-capita sales of NRT products. Given the documented efficacy of NRT, measures to increase peoples' awareness of NRT products through advertising, measures to decrease the price of NRT, and measures to increase the price of cigarettes would be effective means to increase the use of NRT, likely leading to decreased cigarette smoking and reductions in the future public health burden caused by tobacco use.

What Are Tobacco, Nicotine, and E-Cigarette Products?

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... Drug Facts / Tobacco, Nicotine, & E-Cigarettes Tobacco, Nicotine, & E-Cigarettes Street names: Chew, Dip, Snuff Print Expand All Revised July 2017 What are tobacco, nicotine, and e-cigarette products? ©Shutterstock/ CatherineL-Prod Also known as: Cigarettes: ...

E-cigarettes for the management of nicotine addiction

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Knight-West O

2016-08-01

Full Text Available Oliver Knight-West, Christopher Bullen The National Institute for Health Innovation, School of Population Health, The University of Auckland, Auckland, New Zealand Abstract: In this review, we discuss current evidence on electronic cigarettes (ECs, a rapidly evolving class of nicotine delivery system, and their role in managing nicotine addiction, specifically in helping smokers to quit smoking and/or reduce the amount of tobacco they smoke. The current evidence base is limited to three randomized trials (only one compares ECs with nicotine replacement therapy and a growing number of EC user surveys (n=6, case reports (n=4, and cohort studies (n=8. Collectively, these studies suggest modest cessation efficacy and a few adverse effects, at least with the short-term use. On this basis, we provide advice for health care providers on providing balanced information for patients who enquire about ECs. More research, specifically well-conducted large efficacy trials comparing ECs with standard smoking cessation management (eg, nicotine replacement therapy plus behavioral support and long-term prospective studies for adverse events, are urgently needed to fill critical knowledge gaps on these products. Keywords: tobacco, smoking, nicotine, electronic cigarettes, cessation, addiction

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

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Wang, Xiao-Fei; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gao, Jun-Tao; Okunola-Bakare, Oluyomi M; Slack, Rachel D; Gardner, Eliot L; Xi, Zheng-Xiong; Newman, Amy Hauck

2015-01-01

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans. PMID:25613829

The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats.

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Randall, Patrick A; Cannady, Reginald; Besheer, Joyce

2016-08-01

Nicotine and alcohol co-use is highly prevalent, and as such, individuals experience the interoceptive effects of both substances together. Therefore, examining sensitivity to a compound nicotine and alcohol (N + A) interoceptive cue is critical to broaden our understanding of mechanisms that may contribute to nicotine and alcohol co-use. This work assessed the ability of a N + A interoceptive cue to gain control over goal-tracking behavior and determined the effects of the α4β2 nicotinic partial agonist and smoking cessation compound varenicline on sensitivity to N + A. Two groups of male Long Evans rats were trained to discriminate N + A (0.4 mg/kg nicotine + 1 g/kg alcohol, intragastric gavage (IG)) from water under two different training conditions using a Pavlovian drug discrimination task. The effects of varenicline (0, 1, 3 mg/kg, intraperitoneally (IP)) administered alone and on sensitivity to N + A and the components were determined. Under both training conditions, N + A rapidly gained control over behavior, with a greater contribution of nicotine to the N + A compound cue. Varenicline fully substituted for the N + A training dose, and varenicline (1 mg/kg) enhanced sensitivity to the lowest N + A dose (0.1 N + 0.1 A). Given the high selectivity of varenicline for the α4β2 receptor, this finding suggests a functional role for α4β2 nicotinic acetylcholine receptors (nAChRs) in modulating sensitivity to N + A. The N + A compound cue is a unique cue that is modulated, in part, by activity at the α4β2 nAChR. These findings advance understanding of the interoceptive effects of nicotine and alcohol in combination and may have implications in relation to their co-use.

Tolerance to and cross tolerance between ethanol and nicotine.

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Collins, A C; Burch, J B; de Fiebre, C M; Marks, M J

1988-02-01

Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.

Endocrinological Responses to the Administration of Nicotine: Interactions with Drug Initiation, Conditioned Effects, and Conditions of Stress, Volume II

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1984-01-07

Benowitz, Kuyt and Jacob, 1982; Feyerabend S Russe l l , 1978). 273 10 Measurement of hematocrit was performed as follows: 1) after centrifugation of...Incentives, Washington, D.C.: Winston. Feyerabend , C. , & Russell, M. A. H. (1978). Effect of urinary pH and nicotine excretion rate can plasma...s Feyerabend , c. (1978). Cigarette smoking: A dependence on high-nicotine boll. Drug Metabolism Review, 8_, 29-57. Russell, M. A. H. , Wilson, C

Mechanisms of metabonomic for a gateway drug: nicotine priming enhances behavioral response to cocaine with modification in energy metabolism and neurotransmitter level.

Directory of Open Access Journals (Sweden)

Hongyu Li

Full Text Available Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

Renal transport and metabolism of nicotinic acid

International Nuclear Information System (INIS)

Schuette, S.; Rose, R.C.

1986-01-01

Renal metabolism and brush-border transport of nicotinic acid were studied in renal cortical slices and brush-border membrane vesicles exposed to a physiological concentration of vitamin (2.2-3.5 microM). Vesicle transport of [ 3 H]nicotinic acid was found to be Na+ dependent and concentrative. The presence of a Na+ gradient resulted in a fivefold increase in the rate of nicotinic acid uptake over that observed with mannitol and caused a transient nicotinic acid accumulation two- to fourfold above the equilibrium value. The effects of membrane potential, pH, and elimination of Na+-H+ exchange were also studied. Cortical slices and isolated tubules exposed to 2.2 microM [ 14 C]nicotinic acid took up vitamin and rapidly metabolized most of it to intermediates in the Preiss-Handler pathway for NAD biosynthesis; little free nicotinic acid was detectable intracellularly. The replacement of Na+ with Li+ in the bathing medium reduced total accumulation of 14 C label primarily as a result of reduced nicotinic acid uptake. Cortical tissue concentrated free nicotinic acid only when the involved metabolic pathways were saturated by levels of nicotinic acid far in excess of what occurs in vivo

Nicotine dependence and psychiatric disorders.

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Salín-Pascual, Rafael J; Alcocer-Castillejos, Natasha V; Alejo-Galarza, Gabriel

2003-01-01

, concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance.

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol

Science.gov (United States)

Versaggi, Cassandra L.; King, Christopher P.; Meyer, Paul J.

2016-01-01

Rationale Some individuals are particularly responsive to reward-associated stimuli (“cues”), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. Objectives To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food predictive cue (“sign-trackers”) or a reward-delivery location (“goal-trackers”). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Methods Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Results Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue, and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Conclusions Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs. PMID:27282365

The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol.

Science.gov (United States)

Versaggi, Cassandra L; King, Christopher P; Meyer, Paul J

2016-08-01

Some individuals are particularly responsive to reward-associated stimuli ("cues"), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ("sign-trackers") or a reward-delivery location ("goal-trackers"). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. Sign-trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue-induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs.

Direct observation of Medicaid beneficiary attempts to fill prescriptions for nicotine replacement medications.

Science.gov (United States)

Richter, Kimber P; Shergina, Elena; Grodie, Amanda; Massey, Justin K; Ellerbeck, Edward F; Applegate, Amanda; Faseru, Babalola

2018-04-21

Although many states have expanded Medicaid coverage of cessation medications, utilization remains low. Anecdotal reports suggest that beneficiaries are at times denied coverage of cessation medications at the pharmacy counter. We conducted an observational community-wide case study of Medicaid beneficiary attempts to fill over-the-counter nicotine replacement therapy at pharmacies. We recruited tobacco-using beneficiaries from a Federally Qualified Health Center, whose providers wrote paper prescriptions for nicotine patches. Study staff escorted beneficiaries to all eligible pharmacies (n = 18) in a Midwestern community to observe fill attempts. Study staff recorded encounters via smartphone into a secure database on a university server. Seven of 18 pharmacies (39%) did not fill the prescription on the day of the attempt. Of these, 6 offered to order the patch for pick-up at a later date. All (4/4) chain pharmacies filled the prescription; 2/3 mass merchant pharmacies failed to fill. Combining successful same-day fills with offers to order for pick-up, 17/18 (94%) would ultimately have been able to obtain patches. This pilot study found that many beneficiaries left pharmacies without a prescription in hand. Successful same-day fills varied markedly by store type. For people with low incomes, transportation presents a major barrier for delayed pick-up. In addition, delays can fuel ambivalence toward quitting. Future research based on this pilot study might address whether patients who fail to secure a same-day prescription ever fill the prescription and, if not, the degree to which this barrier contributes to success or failure in quitting. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

Science.gov (United States)

Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

2013-01-01

Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine.

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Uslaner, Jason M; Vardigan, Joshua D; Drott, Jason M; Uebele, Victor N; Renger, John J; Lee, Ariel; Li, Zhaoxia; Lê, A D; Hutson, Pete H

2010-10-15

Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse. We examined the influence of the novel, potent, and selective T-type calcium channel antagonist [2-(4-cyclopropylphenyl)-N-((1R)-1-{5-[2,2,2-trifluoroethyl]oxo}pyridine-2-yl)ethyl]acetamide] (TTA-A2) (.3, 1, or 3 mg/kg) on motivation for nicotine, as measured by nicotine self-administration on a progressive ratio (PR) schedule, and nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine delivery (n = 11 or 12 Long Evans rats/group). Furthermore, we examined the specificity of the TTA-A2 effects by characterizing its influence on PR responding for food (in the absence or presence of nicotine-potentiated responding), food- versus nicotine-induced cue-potentiated reinstatement for a response previously reinforced by food administration (n = 11 or 12 Wistar Hannover rats/group), and its ability to induce a conditioned place aversion. TTA-A2 dose-dependently decreased self-administration of nicotine on a PR schedule and the ability of both nicotine and a cue paired with nicotine to reinstate responding. The effects were specific for nicotine's incentive motivational properties, as TTA-A2 did not influence responding for food on a PR schedule but did attenuate the ability of nicotine to potentiate responding for food. Likewise, TTA-A2 did not alter food-induced cue-potentiated reinstatement for a response previously reinforced by food but did decrease nicotine-induced cue-potentiated reinstatement. Finally, TTA-A2 did not produce an aversive state, as indicated by a lack of ability to induce conditioned place aversion. These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Nicotine as a discriminative stimulus for ethanol use.

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Ginsburg, Brett C; Levy, Simon A; Lamb, R J

2018-01-01

Abused drugs reinforce behavior; i.e., they increase the probability of the behavior preceding their administration. Abused drugs can also act as discriminative stimuli; i.e., they can set the occasion for responding reinforced by another event. Thus, one abused drug could come to set the occasion for the use of another and this functional relationship may play a role in polysubstance abuse, where common patterns of use could result in this relationship. Here we establish nicotine (0.4mg/kg, ip 5-min pre-session) as a discriminative stimulus for behavior reinforced by ethanol (0.1ml 8% w/v po, versus food) and determine the ability of nicotine (0.02-0.4mg/kg), varenicline (0.1-3.0mg/kg), and ethanol (250 and 500mg/kg) to control responding for ethanol. We compare these results to those from rats where nicotine signaled food was available (and ethanol was not). Nicotine came to function as a discriminative stimulus. Nicotine and varenicline produced dose-dependent increases in responding on the nicotine-appropriate lever while ethanol produced responding on the vehicle-appropriate lever. Whether this responding occurred on the lever that produced ethanol or food access depended on the training condition. These results demonstrate that a drug can come to set the occasion for use of another and suggest that this behavioral mechanism could play an important role in the maintenance of and recovery from polysubstance abuse, depending on the pattern of use. Copyright © 2017 Elsevier B.V. All rights reserved.

General Practitioners' views on the provision of nicotine replacement therapy and bupropion

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West Robert

2001-10-01

Full Text Available Abstract Background Nicotine replacement therapies (NRT and a new drug, bupropion, are licensed in several countries as aids to smoking cessation. General practitioners (GPs play a crucial role in recommending or prescribing these medications. In the UK there has been discussion about whether the medications should be reimbursable by the National Health Service (NHS. This study assessed English GPs' attitudes towards reimbursement of NRT and bupropion. Methods Postal survey of a randomly selected national sample of GPs; 376 GPs completed the questionnaire after one reminder; effective response rate: 53%. There was no difference between the responses of GPs who responded to the initial request and those who responded only after a reminder suggesting minimal bias due to non-response. Results Attitudes of GPs were remarkably divided on most issues relating to the medications. Forty-three percent thought that bupropion should not be on NHS prescription while 42% thought that it should be (15% did not know; Fifty percent thought that NRT should not be on NHS prescription while 42% thought it should be (8% did not know. Requiring that smokers attend behavioural support programmes to be eligible to receive the medications on NHS prescription made no appreciable difference to the GPs' views. GPs were similarly divided on whether having the medications reimbursable would add unacceptably to their workload or offer a welcome opportunity to discuss smoking with their patients. A principal components analysis of responses to the individual questions on NRT and bupropion revealed that GPs' attitudes could be understood in terms of a single 'pro-con' dimension accounting for 53% of the total variance which made no distinction between the two medications. Conclusions GPs in England appear to be divided in their attitudes to medications to aid smoking cessation and appear not to discriminate in their views between different types of medication or different

Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank.

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Escuder-Vieco, Diana; Garcia-Algar, Óscar; Joya, Xavier; Marchei, Emilia; Pichini, Simona; Pacifici, Roberta; Pallás-Alonso, Carmen Rosa

2016-08-01

The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances. The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it. Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom. No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881. Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine. © The Author(s) 2016.

Randomized controlled trial to evaluate tooth stain reduction with nicotine replacement gum during a smoking cessation program

LENUS (Irish Health Repository)

Whelton, Helen

2012-06-13

.011) and 12 weeks (p = 0.003) with greater lightening in the gum-group at each examination period.ConclusionThese results support the efficacy of the tested nicotine replacement gum in stain reduction and shade lightening. These findings may help dentists to motivate those wishing to quit smoking using a nicotine replacement gum.Trial registrationNCT01440985

Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

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Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

2013-01-15

Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells

NARCIS (Netherlands)

Benyó, Zoltán; Gille, Andreas; Bennett, Clare L.; Clausen, Björn E.; Offermanns, Stefan

2006-01-01

The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing, which develops in almost every patient taking nicotinic acid. Nicotinic acid-induced flushing has been

Predictors of treatment success in smoking cessation with varenicline combined with nicotine replacement therapy v varenicline alone

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F Noor

2018-12-01

Full Text Available Background. Identification of the predictors of treatment success in smoking cessation may help healthcare workers to improve the effectiveness of attempts at quitting.Objective. To identify the predictors of success in a randomised controlled trial comparing varenicline alone or in combination with nicotine replacement therapy (NRT.Methods. A post-hoc analysis of the data of 435 subjects who participated in a 24-week, multicentre trial in South Africa was performed. Logistic regression was used to analyse the effect of age, sex, age at smoking initiation, daily cigarette consumption, nicotine dependence, and reinforcement assessment on abstinence rates at 12 and 24 weeks. Point prevalence and continuous abstinence rates were self-reported and confirmed biochemically with exhaled carbon monoxide readings.Results. The significant predictors of continuous abstinence at 12 and 24 weeks on multivariate analysis were lower daily cigarette consumption (odds ratio (OR 1.86, 95% confidence interval (CI 1.21 - 2.87, p=0.005 and OR 1.83, 95% CI 1.12 - 2.98, p=0.02, respectively and older age (OR 1.52, 95% CI 1.00 - 2.31, p=0.049 and OR 1.79, 95% CI 1.13 - 2.84, p=0.01, respectively. There was no difference in the predictors of success in the univariate analysis, except that older age predicted point prevalence abstinence at 12 weeks (OR 1.47, 95% CI 1.00 - 2.15, p=0.049. The findings were inconclusive for an association between abstinence and lower nicotine dependence, older age at smoking initiation and positive reinforcement.Conclusion. Older age and lower daily cigarette consumption are associated with a higher likelihood of abstinence in patients using varenicline, regardless of the addition of NRT.

Cellular, Molecular, and Genetic Substrates Underlying the Impact of Nicotine on Learning

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Gould, Thomas J.; Leach, Prescott T.

2013-01-01

Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: 1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, 2) how nicotine usurps the cellular mechanisms of synaptic plasticity, 3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal

Toward a comprehensive long term nicotine policy.

Science.gov (United States)

Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

2005-06-01

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

Hormones, Nicotine and Cocaine: Clinical Studies

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Mello, Nancy K.

2009-01-01

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

Use of pharmacy data to evaluate smoking regulations' impact on sales of nicotine replacement therapies in New York City.

Science.gov (United States)

Metzger, Kristina B; Mostashari, Farzad; Kerker, Bonnie D

2005-06-01

Recently, New York City and New York State increased cigarette excise taxes and New York City implemented a smoke-free workplace law. To assess the impact of these policies on smoking cessation in New York City, we examined over-the-counter sales of nicotine replacement therapy (NRT) products. Pharmacy sales data were collected in real time as part of nontraditional surveillance activities. We used Poisson generalized estimating equations to analyze the effect of smoking-related policies on pharmacy-specific weekly sales of nicotine patches and gum. We assessed effect modification by pharmacy location. We observed increases in NRT product sales during the weeks of the cigarette tax increases and the smoke-free workplace law. Pharmacies in low-income areas generally had larger and more persistent increases in response to tax increases than those in higher-income areas. Real-time monitoring of existing nontraditional surveillance data, such as pharmacy sales of NRT products, can help assess the effects of public policies on cessation attempts. Cigarette tax increases and smoke-free workplace regulations were associated with increased smoking cessation attempts in New York City, particularly in low-income areas.

NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

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Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

2009-01-01

Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

The α7 nicotinic acetylcholine receptor complex

DEFF Research Database (Denmark)

Thomsen, Morten Skøtt; Mikkelsen, Jens D

2012-01-01

The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds and prote......The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds...

Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.

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Andrew W Bergen

Full Text Available The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine, has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3. Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

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Manoj Misra

2014-10-01

Full Text Available The use of electronic cigarettes (e-cigs continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT products and a nicotine replacement therapy (NRT product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

Use of Electronic Nicotine Delivery Systems Among Adolescents: Status of the Evidence and Public Health Recommendations.

Science.gov (United States)

Kamat, Aarti D; Van Dyke, Alison L

2017-02-01

Although the prevalence of tobacco smoking has been declining in recent years, the use of electronic nicotine delivery systems (ENDS) such as of electronic cigarettes, vaporizers, and hookahs has been steadily rising, especially among adolescents. ENDS are not only advertised to children, but their sale via the Internet has made them easily accessible to youth. In general, children perceive ENDS as safe, or at least safer than smoking traditional combustible tobacco products; however, exposure to nicotine may have deleterious effects on the developing brain. Concern also persists that ENDS may be a "starter" drug that may lead to further tobacco, drug, and/or alcohol use. In contrast to this precautionary stance that is associated with calls for legislative oversight of ENDS marketing and sales, harm reductionists claim that the risks posed by ENDS are minor in comparison with those of combustible tobacco products and that ENDS may be used as a means of nicotine replacement for smoking cessation, despite no concrete evidence to support this assertion. Many medical and health-related organizations have produced position statements concerning ENDS use, including among adolescents. This article summarizes the advantages and disadvantages of using ENDS espoused in these position statements, especially as they relate to use among adolescents. [Pediatr Ann. 2017;46(2):e69-e77.]. Copyright 2017, SLACK Incorporated.

Adverse effects of perinatal nicotine exposure on reproductive outcomes.

Science.gov (United States)

Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

2015-12-01

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women. © 2015 Society for Reproduction and Fertility.

Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice.

Science.gov (United States)

O'Rourke, Kyu Y; Touchette, Jillienne C; Hartell, Elizabeth C; Bade, Elizabeth J; Lee, Anna M

2016-10-01

Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cigarette craving is associated with blunted reward processing in nicotine-dependent smokers.

Science.gov (United States)

Peechatka, Alyssa L; Whitton, Alexis E; Farmer, Stacey L; Pizzagalli, Diego A; Janes, Amy C

2015-10-01

Dysfunctional reward processing leading to the undervaluation of non-drug rewards is hypothesized to play a crucial role in nicotine dependence. However, it is unclear if blunted reward responsivity and the desire to use nicotine are directly linked after a brief period of abstinence. Such an association would suggest that individuals with reduced reward responsivity may be at increased risk to experience nicotine craving. Reward function was evaluated with a probabilistic reward task (PRT), which measures reward responsivity to monetary incentives. To identify whether smoking status influenced reward function, PRT performance was compared between non-depressed, nicotine-dependent smokers and non-smokers. Within smokers, correlations were conducted to determine if blunted reward responsivity on the PRT was associated with increased nicotine craving. Time since last nicotine exposure was standardized to 4h for all smokers. Smokers and non-smokers did not differ in reward responsivity on the PRT. However, within smokers, a significant negative correlation was found between reward responsivity and intensity of nicotine craving. The current findings show that, among smokers, the intensity of nicotine craving is linked to lower sensitivity to non-drug rewards. This finding is in line with prior theories that suggest reward dysfunction in some clinical populations (e.g., depressive disorders, schizophrenia) may facilitate nicotine use. The current study expands on such theories by indicating that sub-clinical variations in reward function are related to motivation for nicotine use. Identifying smokers who show blunted sensitivity to non-drug rewards may help guide treatments aimed at mitigating the motivation to smoke. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice.

Directory of Open Access Journals (Sweden)

Kia J Jackson

Full Text Available The influx of Ca(2+ through calcium-permeable nicotinic acetylcholine receptors (nAChRs leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB, which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/- mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

Chronic oral nicotine increases brain [3H]epibatidine binding and responsiveness to antidepressant drugs, but not nicotine, in the mouse forced swim test

DEFF Research Database (Denmark)

Andreasen T., Jesper; Nielsen, Elsebet O; Redrobe, John P

2009-01-01

Smoking rates among depressed individuals is higher than among healthy subjects, and nicotine alleviates depressive symptoms. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. In mice, acute nicotine administration enhances...... the activity of antidepressants in the mouse forced swim (mFST) and tail suspension tests. Here, we investigated if this action of nicotine is also reflected in a chronic treatment regimen....

Oxytocin attenuates aversive response to nicotine and anxiety-like behavior in adolescent rats.

Science.gov (United States)

Lee, Hyunchan; Jang, Minji; Noh, Jihyun

2017-02-01

Initial tobacco use is initiated with rewarding and aversive properties of nicotine and aversive response to nicotine plays a critical role in nicotine dependency. Decrease of nicotine aversion increases the nicotine use that causes behavioral and neuronal changes of animals. Oxytocin influences drug abuse and reciprocally affect vulnerability to drug use. To assess the effect of oxytocin on initial nicotine aversion and anxiety, we examined voluntary oral nicotine intake and anxiety-like behavior following oxytocin treatment in adolescent rats. Sprague-Dawley male rats (4 weeks old) were used. For oxytocin administration, rats were injected subcutaneously with saline or oxytocin (0.01, 0.1 and 1mg/kg) according to the assigned groups. Voluntary oral nicotine consumption test was performed by two bottle free-choice paradigm. To examine anxiety-like behavior in rats, we performed a light/dark box test. Oxytocin not only significantly increased the nicotine intake but also alleviated nicotine aversion after acclimation to nicotine solution in a concentration dependent manner. Meanwhile, oxytocin significantly reduced anxiety-like behavior. We suggest that oxytocin itself mitigates aversive response toward initial nicotine intake and anxiety-like behavior. These results widen the psychophysiological perspective on oxytocin for better understanding of nicotine addiction related behaviors influenced by diverse social factors. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Slower nicotine metabolism among postmenopausal Polish smokers.

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Kosmider, Leon; Delijewski, Marcin; Koszowski, Bartosz; Sobczak, Andrzej; Benowitz, Neal L; Goniewicz, Maciej L

2018-06-01

A non-invasive phenotypic indicator of the rate of nicotine metabolism is nicotine metabolite ratio (NMR) defined as a ratio of two major metabolites of nicotine - trans-3'-hydroxycotinine/cotinine. The rate of nicotine metabolism has important clinical implications for the likelihood of successful quitting with nicotine replacement therapy (NRT). We conducted a study to measure NMR among Polish smokers. In a cross-sectional study of 180 daily cigarette smokers (42% men; average age 34.6±13.0), we collected spot urine samples and measured trans-3'-hydroxycotinine (3-HC) and cotinine levels with LC-MS/MS method. We calculated NMR (molar ratio) and analyzed variations in NMR among groups of smokers. In the whole study group, an average NMR was 4.8 (IQR 3.4-7.3). The group of women below 51 years had significantly greater NMR compared to the rest of the population (6.4; IQR 4.1-8.8 vs. 4.3; IQR 2.8-6.4). No differences were found among group ages of male smokers. This is a first study to describe variations in nicotine metabolism among Polish smokers. Our findings indicate that young women metabolize nicotine faster than the rest of population. This finding is consistent with the known effects of estrogen to induce CYP2A6 activity. Young women may require higher doses of NRT or non-nicotine medications for most effective smoking cessation treatment. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Trace Amine-Associated Receptor 1 Modulates the Locomotor and Sensitization Effects of Nicotine

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Sukhanov, Ilya; Dorofeikova, Mariia; Dolgorukova, Antonina; Dorotenko, Artem; Gainetdinov, Raul R.

2018-01-01

Trace amine-associated receptor 1 (TAAR1) has emerged as a promising target for addiction treatments because it affects dopamine transmission in the mesolimbic pathway. TAAR1 is involved in the effects of addictive drugs, such as amphetamines, cocaine and ethanol, but the impact of TAAR1 on the effects of nicotine, the psychoactive drug responsible for the development and maintenance of tobacco smoking, has not yet been studied. This study was performed to investigate the possible modulatory action of TAAR1 on the effects of nicotine on locomotor behaviors in rats and mice. Pretreatment with the TAAR1 agonist RO5263397 dose-dependently decreased nicotine-induced hyperlocomotion in rats habituated to locomotor boxes, prevented the development of nicotine sensitization and blocked hypermotility in nicotine-sensitized rats at the highest tested dose (10 mg/kg). The lack of TAAR1 failed to affect the effects of nicotine on the locomotion of mutant mice. Based on the results of the present study, TAAR1 activation attenuates the locomotion-stimulating effects of nicotine on rats. These results further support the previously proposed hypothesis that TAAR1 is a promising target for the prevention and treatment of drug addiction. Further studies aimed at analyzing the effects of TAAR1 agonists on animal models of nicotine addiction are warranted. PMID:29681856

Trace Amine-Associated Receptor 1 Modulates the Locomotor and Sensitization Effects of Nicotine

Directory of Open Access Journals (Sweden)

Ilya Sukhanov

2018-04-01

Full Text Available Trace amine-associated receptor 1 (TAAR1 has emerged as a promising target for addiction treatments because it affects dopamine transmission in the mesolimbic pathway. TAAR1 is involved in the effects of addictive drugs, such as amphetamines, cocaine and ethanol, but the impact of TAAR1 on the effects of nicotine, the psychoactive drug responsible for the development and maintenance of tobacco smoking, has not yet been studied. This study was performed to investigate the possible modulatory action of TAAR1 on the effects of nicotine on locomotor behaviors in rats and mice. Pretreatment with the TAAR1 agonist RO5263397 dose-dependently decreased nicotine-induced hyperlocomotion in rats habituated to locomotor boxes, prevented the development of nicotine sensitization and blocked hypermotility in nicotine-sensitized rats at the highest tested dose (10 mg/kg. The lack of TAAR1 failed to affect the effects of nicotine on the locomotion of mutant mice. Based on the results of the present study, TAAR1 activation attenuates the locomotion-stimulating effects of nicotine on rats. These results further support the previously proposed hypothesis that TAAR1 is a promising target for the prevention and treatment of drug addiction. Further studies aimed at analyzing the effects of TAAR1 agonists on animal models of nicotine addiction are warranted.

Drug Facts

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Full Text Available ... Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What ... Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800- ...

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Full Text Available ... Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs ... Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call ...

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Full Text Available ... Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of ... Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1- ...

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Full Text Available ... Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? ... Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662- ...

Waterpipe tobacco products: nicotine labelling versus nicotine delivery.

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Vansickel, Andrea R; Shihadeh, Alan; Eissenberg, Thomas

2012-05-01

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

Drug: D08669 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 571 ... Nicotinic cholinergic receptor partial agonist Other ... DG01718 ... Drugs for addictive disorder ... DG01715 ... Drugs for nicotine depend...ence ATC code: N07BA03 Chemical group: DG00995 ... Nicotine withdrawal CHRNA4/CHRNB2

78 FR 277 - Food and Drug Administration Actions Related to Nicotine Replacement Therapies and Smoking...

Science.gov (United States)

2013-01-03

... Dependence; Public Hearing; Extension of Comment Period AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public hearing; Extension of comment period. SUMMARY: The Food and Drug Administration (FDA) is... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 15 [Docket No...

Attenuated nicotine‐like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily

Science.gov (United States)

Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

2016-01-01

Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers.

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Brossard, Patrick; Weitkunat, Rolf; Poux, Valerie; Lama, Nicola; Haziza, Christelle; Picavet, Patrick; Baker, Gizelle; Lüdicke, Frank

2017-10-01

Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence 4: Gum - THS (n = 9). Plasma nicotine concentrations were measured in 16 blood samples collected over 24 h after single use. Maximal nicotine concentration (C max ) and area under the curve from start of product use to time of last quantifiable concentration (AUC 0-last ) were similar between THS and CC in both studies, with ratios varying from 88 to 104% for C max and from 96 to 98% for AUC 0-last . Urge-to-smoke total scores were comparable between THS and CC. The THS nicotine pharmacokinetic profile was close to CC, with similar levels of urge-to-smoke. This suggests that THS can satisfy smokers and be a viable alternative to cigarettes for adult smokers who want to continue using tobacco. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Adolescents' understanding and use of nicotine in e-cigarettes.

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Pepper, Jessica K; Farrelly, Matthew C; Watson, Kimberly A

2018-07-01

Nicotine harms adolescent brain development and contributes to addiction. Some adolescents report using nicotine-free e-cigarettes, but the accuracy of their reporting is unclear. We explored adolescents' use of nicotine-free e-cigarettes and understanding of chemicals in e-cigarettes, including nicotine. Using social media, we recruited 1589 US adolescents (aged 15-17) who reported past 30-day use of e-cigarettes in 2016. We assessed perceptions of the nicotine source in e-liquid and whether e-cigarette aerosol is just "water vapor." We explored differences among adolescents who usually used e-cigarettes with nicotine (n = 473) and without nicotine (n = 452). We used weights to calibrate our sample to the Youth Risk Behavior Survey. Twenty-nine percent usually used e-cigarettes without nicotine, 28% with nicotine, 39% with "both," and 5% were "not sure." Few participants (17% of non-nicotine users vs. 34% of nicotine users, p e-cigarette aerosol was just water vapor were more likely to usually use without nicotine. Older adolescents and current tobacco users were less likely to usually use without nicotine. The adolescents who reported usually using e-cigarettes without nicotine had poorer knowledge of e-cigarettes. This lack of understanding could contribute to inaccurate reporting of nicotine use. Most youth thought the nicotine in e-cigarettes was artificial, potentially indicating a belief that this nicotine is "safer." The US Food & Drug Administration will require nicotine warnings on e-cigarettes in 2018; a complementary educational campaign could address youths' misperceptions about nicotine and other chemicals in e-cigarette aerosol. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of chronic inhalation of electronic cigarettes containing nicotine on glial glutamate transporters and α-7 nicotinic acetylcholine receptor in female CD-1 mice.

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Alasmari, Fawaz; Crotty Alexander, Laura E; Nelson, Jessica A; Schiefer, Isaac T; Breen, Ellen; Drummond, Christopher A; Sari, Youssef

2017-07-03

Alteration in glutamate neurotransmission has been found to mediate the development of drug dependence, including nicotine. We and others, through using western blotting, have reported that exposure to drugs of abuse reduced the expression of glutamate transporter-1 (GLT-1) as well as cystine/glutamate antiporter (xCT), which consequently increased extracellular glutamate concentrations in the mesocorticolimbic area. However, our previous studies did not reveal any changes in glutamate/aspartate transporter (GLAST) following exposure to drugs of abuse. In the present study, for the first time, we investigated the effect of chronic exposure to electronic (e)-cigarette vapor containing nicotine, for one hour daily for six months, on GLT-1, xCT, and GLAST expression in frontal cortex (FC), striatum (STR), and hippocampus (HIP) in outbred female CD1 mice. In this study, we also investigated the expression of alpha-7 nicotinic acetylcholine receptor (α-7 nAChR), a major pre-synaptic nicotinic receptor in the glutamatergic neurons, which regulates glutamate release. We found that inhalation of e-cigarette vapor for six months increased α-7 nAChR expression in both FC and STR, but not in the HIP. In addition, chronic e-cigarette exposure reduced GLT-1 expression only in STR. Moreover, e-cigarette vapor inhalation induced downregulation of xCT in both the STR and HIP. We did not find any significant changes in GLAST expression in any brain region. Finally, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques, we detected high concentrations of nicotine and cotinine, a major metabolite of nicotine, in the FC tissues of e-cigarette exposed mice. These data provide novel evidence about the effects of chronic nicotine inhalation on the expression of key glial glutamate transporters as well as α-7 nAChR. Our work may suggest that nicotine exposure via chronic inhalation of e-cigarette vapor may be mediated in part by alterations in the glutamatergic

A systematic review of possible serious adverse health effects of nicotine replacement therapy.

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Lee, Peter N; Fariss, Marc W

2017-04-01

We conducted a systematic literature review to identify and critically evaluate studies of serious adverse health effects (SAHEs) in humans using nicotine replacement therapy (NRT) products. Serious adverse health effects refer to adverse events, leading to substantial disruption of the ability to conduct normal life functions. Strength of evidence evaluations and conclusions were also determined for the identified SAHEs. We evaluated 34 epidemiological studies and clinical trials, relating NRT use to cancer, reproduction/development, CVD, stroke and/or other SAHEs in patients, and four meta-analyses on effects in healthy populations. The overall evidence suffers from many limitations, the most significant being the short-term exposure (≤12 weeks) and follow-up to NRT product use in most of the studies, the common failure to account for changes in smoking behaviour following NRT use, and the sparse information on SAHEs by type of NRT product used. The only SAHE from NRT exposure we identified was an increase in respiratory congenital abnormalities reported in one study. Limited evidence indicated a lack of effect between NRT exposure and SAHEs for CVD and various reproduction/developmental endpoints. For cancer, stroke and other SAHEs, the evidence was inadequate to demonstrate any association with NRT use. Our conclusions agree with recent statements from authoritative bodies.

Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice123

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Storey, Granville P.; Heimbigner, Lauren; Walwyn, Wendy M.; Bamford, Nigel S.

2016-01-01

Abstract Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca2+ influx and desensitizes α4β2*-type nicotinic receptors, reduced amphetamine-seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self-administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following

GLP-1 acts on habenular avoidance circuits to control nicotine intake.

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Tuesta, Luis M; Chen, Zuxin; Duncan, Alexander; Fowler, Christie D; Ishikawa, Masago; Lee, Brian R; Liu, Xin-An; Lu, Qun; Cameron, Michael; Hayes, Matthew R; Kamenecka, Theodore M; Pletcher, Matthew; Kenny, Paul J

2017-05-01

Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered.

Disparities in Access to Over-the-Counter Nicotine Replacement Products in New York City Pharmacies

Science.gov (United States)

Cabral, Lisa; Maantay, Juliana; Peprah, Dorothy; Lounsbury, David; Maroko, Andrew; Murphy, Mary; Shelley, Donna

2009-01-01

Objectives. We surveyed the availability of tobacco products and nonprescription nicotine replacement therapy (NRT) in pharmacies in New York City, stratified by the race, ethnicity, and socioeconomic status (SES) of the surrounding neighborhoods to determine whether disparities in availability existed. Methods. Surveyors visited a random sample of retail pharmacies to record the availability of tobacco products and nonprescription NRT. We used census data and geographic information systems analysis to determine the SES of each neighborhood. We used logistic modeling to explore relations between SES and the availability of NRT and tobacco products. Results. Of 646 pharmacies sampled, 90.8% sold NRT and 46.9% sold cigarettes. NRT and cigarettes were slightly more available in pharmacies in neighborhoods with a higher SES. NRT was more expensive in poorer neighborhoods. Conclusions. Small disparities existed in access to nonprescription NRT and cigarettes. The model did not adequately account for cigarette access, because of availability from other retail outlets. These results may explain some of the excess prevalence of cigarette use in low-SES areas. PMID:19638596

E-Cigarette Liquid Nicotine Ingestion in a Child: Case Report and Discussion.

Science.gov (United States)

Gill, Natasha; Sangha, Gurinder; Poonai, Naveen; Lim, Rodrick

2015-11-01

Nicotine poisoning is well described in the pediatric population, and even small oral doses may result in toxic effects. The source of nicotine is usually tobacco products and nicotine replacement products such as gum and patches. With the more frequent use of novel products such as e-cigarettes, concern has arisen regarding liquid nicotine. As there are no regulations regarding childproof bottling and packaging, there may be increased potential for unintentional ingestion of these colorfully and appealingly packaged products by children. We present and discuss a case of this nature, as we feel emergency physicians should be aware of this new mode of poisoning, and public health efforts should be made to minimize such exposures.

Nicotine Reduction Revisited: Science and Future Directions

Science.gov (United States)

Hatsukami, Dorothy K.; Perkins, Kenneth A.; LeSage, Mark G.; Ashley, David L.; Henningfield, Jack E.; Benowitz, Neal L.; Backinger, Cathy; Zeller, Mitch

2015-01-01

Regulation of nicotine levels in cigarettes and other tobacco products is now possible with the passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009 giving the U.S. Food and Drug Administration authority to regulate tobacco products, and with Articles 9-11 of the World Health Organization Framework Convention on Tobacco Control.[1-2] Both regulatory approaches allow establishing product standards for tobacco constituents, including nicotine. The FSPTCA does not allow nicotine levels to be decreased to zero, although FDA has the authority to reduce nicotine yields to very low, presumably non-addicting levels. The proposal to reduce levels of nicotine to a level that is non-addicting was originally suggested in 1994.[3] Reduction of nicotine in tobacco products could potentially have a profound impact on reducing tobacco-related morbidity and mortality. To examine this issue, two meetings were convened in the United States with non-tobacco-industry scientists of varied disciplines, tobacco control policy-makers and representatives of government agencies. This article provides an overview of the current science in the area of reduced nicotine content cigarettes and key conclusions and recommendations for research and policy that emerged from the deliberations of the meeting members. PMID:20876072

Drug: D05157 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D05157 Drug Nicotine polacrilex (USAN); Nicorette (TN) ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Cyp substrate ... DG01638 ... CYP2A6 substrate Cy

Validation of a LC-MS/MS method for quantifying urinary nicotine, six nicotine metabolites and the minor tobacco alkaloids--anatabine and anabasine--in smokers' urine.

Directory of Open Access Journals (Sweden)

James E McGuffey

Full Text Available Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling--i.e., metabolite ratios. In addition, the minor tobacco alkaloids--anabasine and anatabine--can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1'-N-oxide, anatabine, and anabasine are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76-99%, specificity, accuracy (0-10% bias and reproducibility (2-9% C.V. make this method ideal for large high through-put studies.

Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor (R)-modafinil on co-use of ethanol and nicotine in female P rats.

Science.gov (United States)

Maggio, Sarah E; Saunders, Meredith A; Baxter, Thomas A; Nixon, Kimberly; Prendergast, Mark A; Zheng, Guangrong; Crooks, Peter; Dwoskin, Linda P; Slack, Rachel D; Newman, Amy H; Bell, Richard L; Bardo, Michael T

2018-05-01

Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs. 15%, two-bottle choice), (2) nicotine alone (0.03 mg/kg/infusion, active vs. inactive lever), and (3) concurrent access to both EtOH and nicotine. Using this model, we examined the effects of (1) varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist with high affinity for the α4β2* subtype; (2) r-bPiDI, a subtype-selective antagonist at α6β2* nAChRs; and (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter (DAT). In phases 1 and 2, pharmacologically relevant intake of EtOH and nicotine was achieved. In the concurrent access phase (phase 3), EtOH consumption decreased while nicotine intake increased relative to phases 1 and 2. For drug pretreatments, in the EtOH access phase (phase 1), (R)-modafinil (100 mg/kg) decreased EtOH consumption, with no effect on water consumption. In the concurrent access phase, varenicline (3 mg/kg), r-bPiDI (20 mg/kg), and (R)-modafinil (100 mg/kg) decreased nicotine self-administration but did not alter EtOH consumption, water consumption, or inactive lever pressing. These results indicate that therapeutics which may be useful for smoking cessation via selective inhibition of α4β2* or α6β2* nAChRs, or DAT inhibition, may not be sufficient to treat EtOH and nicotine co-use.

Cardiovascular risks in smokers treated with nicotine replacement therapy: a historical cohort study

Directory of Open Access Journals (Sweden)

Dollerup J

2017-04-01

Full Text Available Jens Dollerup,1 Jørgen Vestbo,2 Tarita Murray-Thomas,3 Alan Kaplan,4 Richard J Martin,5 Emilio Pizzichini,6 Marcia M M Pizzichini,6 Anne Burden,7 Jessica Martin,7 David B Price7,8 1Dollerup Medical Consultancy, Kongens Lyngby, Denmark; 2Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, UK; 3Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency, London, UK; 4Family Physician Airways Group of Canada, Richmond Hill, ON, Canada; 5National Jewish Health, Denver, CO, USA; 6Federal University of Santa Catarina, Santa Catarina, Brazil; 7Observational and Pragmatic Research Institute Pte Ltd, Singapore; 8Centre for Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Previous research suggests exposure to nicotine replacement therapy (NRT may be associated with an increased risk of cardiovascular disease (CVD.Methods: Using data from the United Kingdom’s Clinical Practice Research Datalink, this study aimed to evaluate CVD events and survival among individuals who attempted smoking cessation with the support of NRT compared with those aided by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in 50,214 smokers attempting to quit – 33,476 supported by smoking cessation advice and 16,738 with the support of NRT prescribed by their primary care physician. Patients were matched (2 smoking cessation advice patients:1 NRT patient on demographic and clinical characteristics during a baseline year preceding their quit attempt. Cox proportional hazard regression, conditional negative binomial regression model, and conditional logistic regression were used to analyze data.Results: Mean (standard deviation population age was 47 (11.2 years; 51% were females. Time to first diagnosis of ischemic heart disease (IHD among NRT and smoking cessation advice patients was similar within the first 4 weeks, but

Nicotine inhibits potassium currents in Aplysia bag cell neurons

Science.gov (United States)

White, Sean H.; Sturgeon, Raymond M.

2016-01-01

Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPβS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K+ with Cs+. Consistent with an underlying mechanism of direct inhibition of one or more K+ channels, nicotine was found to rapidly reduce the fast-inactivating A-type K+ current as well as both components of the delayed-rectifier K+ current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K+ channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID:26864763

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges
.

Science.gov (United States)

Sukhija, Manpreet; Srivastava, Reena; Kaushik, Aditya

2018-03-01

Nicotine replacement therapy (NRT) increases the probability of smoking cessation. This study was conducted to determine if three prototype 4-mg nicotine lozenges produced locally in India were bioequivalent to a globally marketed reference product, Nicorette® 4-mg nicotine lozenge. Healthy adult smokers (N = 39) were treated with three prototype 4-mg nicotine lozenges in comparison with a reference 4-mg lozenge in this single-center, randomized, open-label, single-dose, 4-way crossover study. Pharmacokinetic sampling was obtained to test for bioequivalence using maximal plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0-∞, time to maximal plasma concentration (tmax), half-life (T1/2), elimination rate constant (Kel), and safety of the prototype lozenges versus the reference lozenge were compared. Each prototype 4-mg nicotine lozenge was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0-∞. Although tmax; was significantly longer for prototype III, all four lozenges achieved maximum plasma nicotine concentrations at a median of 1.5 hours. The safety profiles of the three prototype 4-mg lozenges did not differ from that of the 4-mg reference product. Each prototype 4-mg nicotine lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro dissolution profiles, these data suggest that performance from the in -vitro method deployed is not a firm predictor of pharmacokinetic behavior.
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First trimester nicotine exposure and the risk of infantile colic

DEFF Research Database (Denmark)

Milidou, Ioanna; Henriksen, Tine Brink; Jensen, Morten Søndergaard

Background: Although prenatal exposure to maternal smoking has been associated with infantile colic (IC), to date no published studies have reported on the relationship between the prenatal use of nicotine replacement therapy (NRT) and IC. Aim: We aimed to assess the relationship between fetal...... exposure to nicotine, coming from both cigarette smoking and use of NRT early in pregnancy, and IC. Methods: The study population consisted of 63,883 pregnancies that resulted in live born singletons enrolled in the Danish National Birth Cohort between 1997 and 2002. Mother’s smoking habits and use of NRT......: The results indicate that prenatal exposure to nicotine from any source during the first trimester of the pregnancy increases the risk of infantile colic....

Age-related changes in functional postsynaptic nicotinic acetylcholine receptor subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction.

Science.gov (United States)

Christensen, Mark H; Kohlmeier, Kristi A

2016-03-01

The earlier an individual initiates cigarette smoking, the higher the likelihood of development of dependency to nicotine, the addictive ingredient in cigarettes. One possible mechanism underlying this higher addiction liability is an ontogenetically differential cellular response induced by nicotine in neurons mediating the reinforcing or euphoric effects of this drug, which could arise from age-related differences in the composition of nicotinic acetylcholine receptor (nAChR) subunits. In the current study, we examined whether the subunit composition of nAChRs differed between neurons within the laterodorsal tegmentum (LDT), a nucleus importantly involved in drug addiction associated behaviours, across two periods of ontogeny in which nicotine-mediated excitatory responses were shown to depend on age. To this end, whole-cell patch-clamp recordings in mouse brain slices from identified LDT neurons, in combination with nAChR subunit-specific receptor antagonists, were conducted. Comparison of the contribution of different nAChR subunits to acetylcholine (ACh)-induced inward currents indicated that the contributions of the β2 and/or β4 and α7 nAChR subunits alter across age. Taken together, we conclude that across a limited ontogenetic period, there is plasticity in the subunit composition of nAChRs in LDT neurons. In addition, our data indicate, for the first time, functional presence of α6 nAChR subunits in LDT neurons within the age ranges studied. Changes in subunit composition of nAChRs across ontogeny could contribute to the age-related differential excitability induced by nicotine. Differences in the subunit composition of nAChRs within the LDT would be expected to contribute to ontogenetic-dependent outflow from the LDT to target regions, which include reward-related circuitry. © 2014 Society for the Study of Addiction.

Key issues surrounding the health impacts of electronic nicotine delivery systems (ENDS) and other sources of nicotine.

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Drope, Jeffrey; Cahn, Zachary; Kennedy, Rosemary; Liber, Alex C; Stoklosa, Michal; Henson, Rosemarie; Douglas, Clifford E; Drope, Jacqui

2017-11-01

Answer questions and earn CME/CNE Over the last decade, the use of electronic nicotine delivery systems (ENDS), including the electronic cigarette or e-cigarette, has grown rapidly. More youth now use ENDS than any tobacco product. This extensive research review shows that there are scientifically sound, sometimes competing arguments about ENDS that are not immediately and/or completely resolvable. However, the preponderance of the scientific evidence to date suggests that current-generation ENDS products are demonstrably less harmful than combustible tobacco products such as conventional cigarettes in several key ways, including by generating far lower levels of carcinogens and other toxic compounds than combustible products or those that contain tobacco. To place ENDS in context, the authors begin by reviewing the trends in use of major nicotine-containing products. Because nicotine is the common core-and highly addictive-constituent across all tobacco products, its toxicology is examined. With its long history as the only nicotine product widely accepted as being relatively safe, nicotine-replacement therapy (NRT) is also examined. A section is also included that examines snus, the most debated potential harm-reduction product before ENDS. Between discussions of NRT and snus, ENDS are extensively examined: what they are, knowledge about their level of "harm," their relationship to smoking cessation, the so-called gateway effect, and dual use/poly-use. CA Cancer J Clin 2017;67:449-471. © 2017 American Cancer Society. © 2017 American Cancer Society.

Design, formulation and evaluation of nicotine chewing gum.

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Aslani, Abolfazl; Rafiei, Sahar

2012-01-01

Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which satisfy the consumers the most. Nicotine, sugar, liquid glucose, glycerin, different sweetening and taste-masking agents, and a flavoring agent were added to the gum bases at appropriate temperature. The medicated gums were cut into pieces of suitable size and coated by acacia aqueous solution (2% w/v), sugar dusting, followed by acacia-sugar-calcium carbonate until a smooth surface was produced. The gums' weight variation and content uniformity were determined. The release of nicotine was studied in pH 6.8 phosphate buffer using a mastication device which simulated the mastication of chewing gum in human. The Latin Square design was used for the evaluation of organoleptic characteristics of the formulations at different stages of development. Most formulations released 79-83% of their nicotine content within 20 min. Nicotine-containing sugar-coated gums in which aspartame as sweetener and cherry and eucalyptus as flavoring agents were incorporated (i.e. formulations F(19-SC) and F(20-SC), respectively) had optimal chewing hardness, adhering to teeth, and plumpness characteristics, as well as the most pleasant taste and highest acceptability to smokers. Taste enhancement of nicotine gums was achieved where formulations comprised aspartame as the sweetener and cherry and eucalyptus as the flavoring agents. Nicotine gums of pleasant taste may, therefore, be used as NRT to assist smokers quit smoking.

Predicting intention to use nicotine replacement therapy in people attending residential treatment for substance dependency.

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Kelly, Peter J; Townsend, Camilla J; Osborne, Briony A; Baker, Amanda L; Deane, Frank P; Keane, Carol; Ingram, Isabella; Lunn, Joanne

2018-02-28

Nicotine Replacement Therapy (NRT) is recommended as a frontline smoking cessation tool for people attending mental health and substance dependence treatment services. Previous research suggests that NRT is underutilized in these settings. To improve the use of NRT amongst people attending residential treatment for substance use disorders (SUDs) it is important that the factors influencing smokers' decisions to use NRT are understood. The study aimed to examine: (1) smoking cessation strategies used by participants in previous quit attempts, (2) participants' attitudes towards NRT (i.e. safety concerns and perceived efficacy), and (3) the predictors of participants' intention to use NRT to support future quit attempts. Participants completed a cross-sectional survey that examined their smoking behaviours, previous experiences using smoking cessation strategies, attitudes and beliefs regarding NRT, and intention to use NRT as part of future quit attempts (N = 218). All participants were attending residential treatment for substance use disorders provided by We Help Ourselves (WHOS), a large provider of specialist alcohol and other drug treatment in Australia. The majority of respondents (98%) reported that they had smoked regularly in their lifetime, and 89% were current smokers. Forty-five percent of the current smokers reported that they had previously used NRT to support a quit attempt, with 54% reporting that they intended to use NRT to support a future quit attempt. Intentions to use NRT were not related to the participants' mental health status or the participants' perceptions regarding the safety or potential drawbacks associated with using NRT. However, participants were more likely to report that they would use NRT to support future quit attempts if they were female, had previously used NRT and perceived NRT to be effective. Improving the use of evidence based smoking cessation strategies within substance use treatment continues to be a priority. To enhance

Effect of MK-801 on the development of nicotine sensitization of nucleus accumbens dopamine release

Energy Technology Data Exchange (ETDEWEB)

Hong, Soo Kyung; Choung, In Soon; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2005-07-01

We have previously found that MK-801, a noncompetitive NMDA receptor antagonist, prevents behavioral sensitization to nicotine. This study aimed to investigate the effect of MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drug on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with MK-801 (0.3 mg/kg, i.p.) or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for 7 consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens and DA release was monitored using in vivo microdialysis. In rats pretreated with chronic nicotine, local nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response 969 {+-} 235% (mean {+-} SEM) of basal level vs. 520 {+-} 93%, P < 0.05). Co-administration of MK-801 with nicotine attenuated an increase of DA release elicited by local nicotine challenge, compared with nicotine alone (maximal DA response 427 {+-} 83% of basal level vs. 969 {+-} 235%, P < 0.01). These results suggest that MK-801 blocks the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of NMDA receptors in the development of behavioral sensitization to nicotine.

Effect of MK-801 on the development of nicotine sensitization of nucleus accumbens dopamine release

International Nuclear Information System (INIS)

Hong, Soo Kyung; Choung, In Soon; Kim, Sang Eun

2005-01-01

We have previously found that MK-801, a noncompetitive NMDA receptor antagonist, prevents behavioral sensitization to nicotine. This study aimed to investigate the effect of MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drug on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with MK-801 (0.3 mg/kg, i.p.) or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for 7 consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens and DA release was monitored using in vivo microdialysis. In rats pretreated with chronic nicotine, local nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response 969 ± 235% (mean ± SEM) of basal level vs. 520 ± 93%, P < 0.05). Co-administration of MK-801 with nicotine attenuated an increase of DA release elicited by local nicotine challenge, compared with nicotine alone (maximal DA response 427 ± 83% of basal level vs. 969 ± 235%, P < 0.01). These results suggest that MK-801 blocks the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of NMDA receptors in the development of behavioral sensitization to nicotine

The potential role of cotinine in the cognitive and neuroprotective actions of nicotine.

Science.gov (United States)

Buccafusco, Jerry J; Terry, Alvin V

2003-05-16

Cotinine is a primary metabolite of nicotine that has been suggested in many studies in animals and in humans to exert measurable effects on aspects of on-going behavior or on cognitive function. Much of the interest in cotinine derives from its long pharmacological half-life (15-19 hours) relative to nicotine (2-3 hours). Despite decades of study focusing on nicotine as the predominant behaviorally active component of tobacco, there continue to be aspects of the pharmacology of the drug that have yet to be explained. For example, nicotine can evoke a protracted behavioral response, i.e., in great excess of the presence of the drug in the plasma. Also, there is often a striking differential between the potency for nicotine-induced behavioral responses in humans and animals, and its potency as a cholinergic agonist, neurochemically. One possibility that may explain one or more of these properties of nicotine is the presence of a long-lived bioactive metabolite or breakdown product of nicotine such as cotinine. Preliminary data in support of this hypothesis are consistent with the ability of cotinine to improve performance accuracy on delayed matching task by macaque monkeys, and in reversing apomorphine-induced deficits in prepulse inhibition of acoustic startle in rats. The drug also was shown to be as potent as nicotine in the ability to act as a cytoprotective agent in cells that express a neuronal cholinergic phenotype. This new appreciation for the role of cotinine in nicotine's actions, and as a pharmacological agent in its own right, particularly in aspects of cognitive function and for neuroprotection, ultimately may be applied towards the treatment of Alzheimer's disease and related disorders, and for various psychiatric syndromes.

Ecological momentary assessment of daily discrimination experiences and nicotine, alcohol, and drug use among sexual and gender minority individuals.

Science.gov (United States)

Livingston, Nicholas A; Flentje, Annesa; Heck, Nicholas C; Szalda-Petree, Allen; Cochran, Bryan N

2017-12-01

Sexual and gender minority (SGM) individuals experience elevated rates of minority stress, which has been linked to higher rates of nicotine and substance use. Research on this disparity to date is largely predicated on methodology that is insensitive to within day SGM-based discrimination experiences, or their relation to momentary nicotine and substance use risk. We address this knowledge gap in the current study using ecological momentary assessment (EMA). Fifty SGM individuals, between 18 and 45 years of age, were recruited from an inland northwestern university, regardless of their nicotine or substance use history, and invited to participate in an EMA study. Each were prompted to provide data, six times daily (between 10:00 a.m. and 10:00 p.m.) for 14 days, regarding SGM-based discrimination, other forms of mistreatment, and nicotine, drug, and alcohol use since their last prompt. Discrimination experiences that occurred since individuals' last measurement prompt were associated with greater odds of nicotine and substance use during the same measurement window. Substance use was also more likely to occur in relation to discrimination reported two measurements prior in lagged models. Relative to other forms of mistreatment, discrimination effects were consistently larger in magnitude and became stronger throughout the day/evening. This study adds to existing minority stress research by highlighting the both immediate and delayed correlates of daily SGM-based discrimination experiences. These results also contribute to our understanding of daily stress processes and provide insight into ways we might mitigate these effects using real-time monitoring and intervention technology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Drug: D03365 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D03365 Drug Nicotine (USP); Habitrol (TN) ... C10H14N2 D03365.gif ... Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Cyp substrate ... DG01892 ... CYP1A2 substra

The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance.

Science.gov (United States)

Pesta, Dominik H; Angadi, Siddhartha S; Burtscher, Martin; Roberts, Christian K

2013-12-13

Caffeine, nicotine, ethanol and tetrahydrocannabinol (THC) are among the most prevalent and culturally accepted drugs in western society. For example, in Europe and North America up to 90% of the adult population drinks coffee daily and, although less prevalent, the other drugs are also used extensively by the population. Smoked tobacco, excessive alcohol consumption and marijuana (cannabis) smoking are addictive and exhibit adverse health effects. These drugs are not only common in the general population, but have also made their way into elite sports because of their purported performance-altering potential. Only one of the drugs (i.e., caffeine) has enough scientific evidence indicating an ergogenic effect. There is some preliminary evidence for nicotine as an ergogenic aid, but further study is required; cannabis and alcohol can exhibit ergogenic potential under specific circumstances but are in general believed to be ergolytic for sports performance. These drugs are currently (THC, ethanol) or have been (caffeine) on the prohibited list of the World Anti-Doping Agency or are being monitored (nicotine) due to their potential ergogenic or ergolytic effects. The aim of this brief review is to evaluate the effects of caffeine, nicotine, ethanol and THC by: 1) examining evidence supporting the ergogenic or ergolytic effects; 2) providing an overview of the mechanism(s) of action and physiological effects; and 3) where appropriate, reviewing their impact as performance-altering aids used in recreational and elite sports.

Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

Science.gov (United States)

Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

2017-12-01

Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

Belief about nicotine Modulates subjective craving and insula activity in Deprived smokers

DEFF Research Database (Denmark)

Gu, X. S.; Lohrenz, Terry; Salas, Ramiro

2016-01-01

Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence...... subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told "nicotine" vs. told "no......, smokers demonstrated significantly reduced craving after smoking when told "nicotine in cigarette" but showed no change in craving when told "no nicotine." Second, neural activity in the insular cortex related to craving was only significant when smokers were told "nicotine" but not when told "no nicotine...

Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

Directory of Open Access Journals (Sweden)

Paul Fredrickson

2014-01-01

Full Text Available Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13 analog, blocks behavioral sensitization (an animal model for psychostimulant addiction to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

Role of the dopamine transporter in the action of psychostimulants, nicotine, and other drugs of abuse.

Science.gov (United States)

Zhu, J; Reith, M E A

2008-11-01

A number of studies over the last two decades have demonstrated the critical importance of dopamine (DA) in the behavioral pharmacology and addictive properties of abused drugs. The DA transporter (DAT) is a major target for drugs of abuse in the category of psychostimulants, and for methylphenidate (MPH), a drug used for treating attention deficit hyperactivity disorder (ADHD), which can also be a psychostimulant drug of abuse. Other drugs of abuse such as nicotine, ethanol, heroin and morphine interact with the DAT in more indirect ways. Despite the different ways in which drugs of abuse can affect DAT function, one evolving theme in all cases is regulation of the DAT at the level of surface expression. DAT function is dynamically regulated by multiple intracellular and extracellular signaling pathways and several protein-protein interactions. In addition, DAT expression is regulated through the removal (internalization) and recycling of the protein from the cell surface. Furthermore, recent studies have demonstrated that individual differences in response to novel environments and psychostimulants can be predicted based on individual basal functional DAT expression. Although current knowledge of multiple factors regulating DAT activity has greatly expanded, many aspects of this regulation remain to be elucidated; these data will enable efforts to identify drugs that might be used therapeutically for drug dependence therapeutics.

Alcohol, cannabis, nicotine, and caffeine use and symptom distress in schizophrenia.

Science.gov (United States)

Hamera, E; Schneider, J K; Deviney, S

1995-09-01

The high prevalence of substance use, e.g., alcohol and illegal and nonprescribed drugs, in schizophrenia is widely recognized. One explanation for this high prevalence is that substance use may be a self-initiated method for managing symptoms. To test whether the intake of four substances--alcohol, cannabis, nicotine, and caffeine--would increase with increases in symptom distress, daily self-reports of symptom distress and substance intake over 12 weeks were analyzed with pooled time series analyses. Compliance with neuroleptic medication was added to the analyses to control for any changes in prescribed medication compliance while using nonprescribed drugs or alcohol. Of the four substances studied, only nicotine was significantly related to symptom distress. Higher distress with prodromal symptoms was related to decreases in nicotine use. Analysis of caffeine did not meet the criteria for significance but does provide direction for further research. Higher distress, with neurotic symptoms, was related to increases in caffeine use. Further research is needed to clarify the relationship between nicotine and symptoms.

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

Science.gov (United States)

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

The effects of nicotine on ethanol-induced conditioned taste aversions in Long-Evans rats.

Science.gov (United States)

Rinker, Jennifer A; Busse, Gregory D; Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

2008-04-01

Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter of which is reportedly affected by polydrug use. Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine's impact on ethanol's aversive effects within a conditioned taste aversion design. Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment 2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment 3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally, nicotine's effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined. Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination. These data demonstrate that nicotine may interact with ethanol, increasing ethanol's aversive effects. Although the rewarding effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered nicotine. It is more likely attributable to nicotine-related changes in ethanol's rewarding effects.

Reframing the science and policy of nicotine, illegal drugs and alcohol – conclusions of the ALICE RAP Project [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Peter Anderson

2017-03-01

Full Text Available In 2013, illegal drug use was responsible for 1.8% of years of life lost in the European Union, alcohol was responsible for 8.2% and tobacco for 18.2%, imposing economic burdens in excess of 2.5% of GDP. No single European country has optimal governance structures for reducing the harm done by nicotine, illegal drugs and alcohol, and existing ones are poorly designed, fragmented, and sometimes cause harm. Reporting the main science and policy conclusions of a transdisciplinary five-year analysis of the place of addictions in Europe, researchers from 67 scientific institutions addressed these problems by reframing an understanding of addictions.  A new paradigm needs to account for evolutionary evidence which suggests that humans are biologically predisposed to seek out drugs, and that, today, individuals face availability of high drug doses, consequently increasing the risk of harm.  New definitions need to acknowledge that the defining element of addictive drugs is ‘heavy use over time’, a concept that could replace the diagnostic artefact captured by the clinical term ‘substance use disorder’, thus opening the door for new substances to be considered such as sugar. Tools of quantitative risk assessment that recognize drugs as toxins could be further deployed to assess regulatory approaches to reducing harm. Re-designed governance of drugs requires embedding policy within a comprehensive societal well-being frame that encompasses a range of domains of well-being, including quality of life, material living conditions and sustainability over time; such a frame adds arguments to the inappropriateness of policies that criminalize individuals for using drugs and that continue to categorize certain drugs as illegal. A health footprint, modelled on the carbon footprint, and using quantitative measures such as years of life lost due to death or disability, could serve as the accountability tool that apportions responsibility for who and what

Nicotine poisoning

Science.gov (United States)

Nicotine is found in: Chewing tobacco Cigarettes E-cigarettes Liquid nicotine Nicotine gum (Nicorette) Nicotine patches (Habitrol, Nicoderm) Pipe tobacco Some insecticides Tobacco leaves Note: This list may not be all-inclusive.

Sales of Nicotine-Containing Electronic Cigarette Products: United States, 2015.

Science.gov (United States)

Marynak, Kristy L; Gammon, Doris G; Rogers, Todd; Coats, Ellen M; Singh, Tushar; King, Brian A

2017-05-01

To assess the proportion of electronic cigarette (e-cigarette) products sold in the United States that contain nicotine according to retail scanner data. We obtained unit sales data from January 11, 2015, to December 12, 2015, from The Nielsen Company for convenience stores; supermarkets; mass merchandisers; drug, club, and dollar stores; and Department of Defense commissaries. The data did not include purchases from tobacco specialty shops, "vape shops," or online sources. Nicotine content was assessed by product type (disposables, rechargeables, and refills), region, and flavor status based on nicotine strength listed in the Universal Product Codes. For the 36.7% of entries lacking nicotine content information, we conducted Internet searches by brand, product, and flavor. In 2015, 99.0% of e-cigarette products sold contained nicotine, including 99.0% of disposables, 99.7% of rechargeables, and 98.8% of refills. Overall, 98.7% of flavored e-cigarette products and 99.4% of nonflavored e-cigarette products contained nicotine. In 2015, almost all e-cigarette products sold in US convenience stores and other assessed channels contained nicotine. Public Health Implications. Findings reinforce the importance of warning labels for nicotine-containing products, ingredient reporting, and restrictions on sales to minors.

Use of Nicotine in Electronic Nicotine and Non-Nicotine Delivery Systems by US Adults, 2015.

Science.gov (United States)

Weaver, Scott R; Kemp, Catherine B; Heath, J Wesley; Pechacek, Terry F; Eriksen, Michael P

Nicotine in electronic nicotine and non-nicotine delivery systems (ENDS/ENNDS) may present a risk of harm to those with cardiovascular disease and the fetuses of pregnant women. We assessed the extent to which adult users of ENDS/ENNDS used these products with nicotine. We obtained data for this study from a national probability survey of 6051 US adults that was conducted in August and September 2015. Of 399 adult ENDS/ENNDS users who were current smokers, 337 (80.7%) used ENDS/ENNDS containing nicotine, whereas only 29 of 71 (36.9%) ENDS/ENNDS users who were never smokers used ENDS/ENNDS containing nicotine. Assessments of the population health impact of ENDS/ENNDS use among never smokers should take into account the extent to which use involves nicotine.

Testing environment shape differentially modulates baseline and nicotine-induced changes in behavior: Sex differences, hypoactivity, and behavioral sensitization.

Science.gov (United States)

Illenberger, J M; Mactutus, C F; Booze, R M; Harrod, S B

2018-02-01

In those who use nicotine, the likelihood of dependence, negative health consequences, and failed treatment outcomes differ as a function of gender. Women may be more sensitive to learning processes driven by repeated nicotine exposure that influence conditioned approach and craving. Sex differences in nicotine's influence over overt behaviors (i.e. hypoactivity or behavioral sensitization) can be examined using passive drug administration models in male and female rats. Following repeated intravenous (IV) nicotine injections, behavioral sensitization is enhanced in female rats compared to males. Nonetheless, characteristics of the testing environment also mediate rodent behavior following drug administration. The current experiment used a within-subjects design to determine if nicotine-induced changes in horizontal activity, center entries, and rearing displayed by male and female rats is detected when behavior was recorded in round vs. square chambers. Behaviors were recorded from each group (males-round: n=19; males-square: n=18; females-square: n=19; and females-round: n=19) immediately following IV injection of saline, acute nicotine, and repeated nicotine (0.05mg/kg/injection). Prior to nicotine treatment, sex differences were apparent only in round chambers. Following nicotine administration, the order of magnitude for the chamber that provided enhanced detection of hypoactivity or sensitization was contingent upon both the dependent measure under examination and the animal's biological sex. As such, round and square testing chambers provide different, and sometimes contradictory, accounts of how male and female rats respond to nicotine treatment. It is possible that a central mechanism such as stress or cue sensitivity is impacted by both drug exposure and environment to drive the sex differences observed in the current experiment. Until these complex relations are better understood, experiments considering sex differences in drug responses should balance

Structural Studies of Nicotinic Acetylcholine Receptors

DEFF Research Database (Denmark)

Shahsavar, Azadeh; Gajhede, Michael; Kastrup, Jette

2016-01-01

Nicotinic acetylcholine receptors (nAChRs) are members of the pentameric ligand-gated ion channel superfamily that play important roles in control of neurotransmitter release in the central and peripheral nervous system. These receptors are important therapeutic targets for development of drugs...

Orbitofrontal participation in sign- and goal-tracking conditioned responses: Effects of nicotine.

Science.gov (United States)

Stringfield, Sierra J; Palmatier, Matthew I; Boettiger, Charlotte A; Robinson, Donita L

2017-04-01

Pavlovian conditioned stimuli can acquire incentive motivational properties, and this phenomenon can be measured in animals using Pavlovian conditioned approach behavior. Drugs of abuse can influence the expression of this behavior, and nicotine in particular exhibits incentive amplifying effects. Both conditioned approach behavior and drug abuse rely on overlapping corticolimbic circuitry. We hypothesize that the orbitofrontal cortex (OFC) regulates conditioned approach, and that one site of nicotine action is in the OFC where it reduces cortical output. To test this, we repeatedly exposed rats to 0.4 mg/kg nicotine (s.c.) during training and then pharmacologically inactivated the lateral OFC or performed in vivo electrophysiological recordings of lateral OFC neurons in the presence or absence of nicotine. In Experiment 1, animals were trained in a Pavlovian conditioning paradigm and behavior was evaluated after inactivation of the OFC by microinfusion of the GABA agonists baclofen and muscimol. In Experiment 2, we monitored phasic firing of OFC neurons during Pavlovian conditioning sessions. Nicotine reliably enhanced conditioned responding to the conditioned cue, and inactivation of the OFC reduced conditioned responding, especially the sign-tracking response. OFC neurons exhibited phasic excitations to cue presentation and during goal tracking, and nicotine acutely blunted this phasic neuronal firing. When nicotine was withheld, both conditioned responding and phasic firing in the OFC returned to the level of controls. These results suggest that the OFC is recruited for the expression of conditioned responses, and that nicotine acutely influences this behavior by reducing phasic firing in the OFC. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Activity and Enthalpy of Vaporization of Nicotine from Tobacco at Moderate Temperatures

Directory of Open Access Journals (Sweden)

St.Charles F. Kelley

2016-01-01

Full Text Available The vapor pressure of nicotine has been reported for unprotonated nicotine and for nicotine-water solutions. Yet no published values exist for nicotine in any commercially relevant matrix or for protonated forms (e.g., tobacco, smoke, electronic cigarette solutions, nicotine replacement products, nicotine salts. Therefore a methodology was developed to measure nicotine activity (defined as the vapor pressure from a matrix divided by the vapor pressure of pure nicotine. The headspace concentration of nicotine was measured for pure nicotine and tobacco stored at 23, 30, and 40 °C which allowed for conversion to vapor pressure and nicotine activity and for the estimation of enthalpy of vaporization. Burley, Flue-cured, Oriental, and cigarette blends were tested. Experiments were conducted with pure nicotine initially until the storage and sampling techniques were validated by comparison with previously published values. We found that the nicotine activity from tobacco was less than 1% with Burley > Flue-cured > Oriental. At 23 °C the nicotine vapor pressure averaged by tobacco type was 0.45 mPa for Oriental tobacco, 1.8 mPa for Flue-cured, 13 mPa for Burley while pure nicotine was 2.95 Pa. In general, the nicotine activity increased as the (calculated unprotonated nicotine concentration increased. The nicotine enthalpy of vaporization from tobacco ranged from 77 kJ/mol to 92 kJ/mol with no obvious trends with regard to tobacco origin, type, stalk position or even the wide range of nicotine activity. The mean value for all tobacco types was 86.7 kJ/mol with a relative standard deviation of 6.5% indicating that this was an intrinsic property of the nicotine form in tobacco rather than the specific tobacco properties. This value was about 30 kJ/mol greater than that of pure nicotine and is similar to the energy needed to remove a proton from monoprotonated nicotine.

Drug: D06282 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available C4H6O6 D06282.gif ... Neuropsychiatric agent ... DG01571 ... Nicotinic cholinergic receptor partial agonist Other ... DG01718 ... Drugs... for addictive disorder ... DG01715 ... Drugs for nicotine dependence Therapeutic category: 7990 A

Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

Science.gov (United States)

Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

2017-06-01

Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward-associated memory in rats.

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Fang, Qin; Li, Fang-Qiong; Li, Yan-Qin; Xue, Yan-Xue; He, Ying-Ying; Liu, Jian-Feng; Lu, Lin; Wang, Ji-Shi

2011-10-01

Exposure to cues previously associated with drug intake leads to relapse by activating previously acquired memories. Based on previous findings, in which cannabinoid CB(1) receptors were found to be critically involved in specific aspects of learning and memory, we investigated the role of CB(1) receptors in nicotine reward memory using a rat conditioned place preference (CPP) model. In Experiment 1, rats were trained for CPP with alternating injections of nicotine (0.5mg/kg, s.c.) and saline to acquire the nicotine-conditioned memory. To examine the effects of rimonabant on the reconsolidation of nicotine reward memory, rats were administered rimonabant (0, 0.3, and 3.0mg/kg, i.p.) immediately after reexposure to the drug-paired context. In Experiment 2, rats were trained for CPP similarly to Experiment 1. To examine the effects of rimonabant on the reinstatement of nicotine reward memory, rimonabant (0, 0.3, and 3.0mg/kg, i.p.) was administered before the test of nicotine-induced CPP reinstatement. In Experiment 3, to evaluate whether rimonabant itself produces a reward memory, rats were trained for CPP with alternating injections of different doses of rimonabant (0, 0.3, and 3.0mg/kg) and saline. Rimonabant at a dose of 3.0mg/kg significantly disrupted the reconsolidation of nicotine memory and significantly blocked the reinstatement of nicotine-induced CPP. However, rimonabant itself did not produce CPP. These findings provide clear evidence that CB(1) receptors play a role in nicotine reward memory, suggesting that CB(1) receptor antagonists may be a potential target for managing nicotine addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of nicotine on homeostatic and hedonic components of food intake.

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Stojakovic, Andrea; Espinosa, Enma P; Farhad, Osman T; Lutfy, Kabirullah

2017-10-01

Chronic tobacco use leads to nicotine addiction that is characterized by exaggerated urges to use the drug despite the accompanying negative health and socioeconomic burdens. Interestingly, nicotine users are found to be leaner than the general population. Review of the existing literature revealed that nicotine affects energy homeostasis and food consumption via altering the activity of neurons containing orexigenic and anorexigenic peptides in the brain. Hypothalamus is one of the critical brain areas that regulates energy balance via the action of these neuropeptides. The equilibrium between these two groups of peptides can be shifted by nicotine leading to decreased food intake and weight loss. The aim of this article is to review the existing literature on the effect of nicotine on food intake and energy homeostasis and report on the changes that nicotine brings about in the level of these peptides and their receptors that may explain changes in food intake and body weight induced by nicotine. Furthermore, we review the effect of nicotine on the hedonic aspect of food intake. Finally, we discuss the involvement of different subtypes of nicotinic acetylcholine receptors in the regulatory action of nicotine on food intake and energy homeostasis. © 2017 Society for Endocrinology.

Review of the Scientific Literature and Preparation of an Annotated Bibliography on Effects of Cigarette Smoking and Nicotine on Human Performance. Volume 2

Science.gov (United States)

1985-01-01

RUSSELL N A H, CARRUTHERS M E, FEYERABEND C 222 EFFECT OF NICOTINE REPLACEMENT ON THE CIGARETTE WITHDRAWAL SYNDROME BRITISH JOURNAL ADDICTION 79:215-219...RUSSELL M A, JARVIS M J, FEYERABEND C 147 DOES SWITCHING TO AN ULTRA LOW NICOTINE CIGARETTE INDUCE NICOTINE WITHDRAWAL EFFECTS? PSYCHOPHARMACOLOGY, 84:120

Ethical and policy issues in using vaccines to treat and prevent cocaine and nicotine dependence.

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Hall, Wayne; Gartner, Coral

2011-05-01

To describe the rationale of vaccines against cocaine and nicotine, to review progress in developing and trialing vaccines to treat dependence on these drugs and to discuss some of the ethical issues that may arise from their use in legally coerced addiction treatment or for prevention of addiction in adolescents. Several randomized controlled trials of cocaine and nicotine vaccines for relapse prevention have produced mixed results. The studies demonstrate that it is possible to raise antibodies to cocaine and nicotine in humans. In abstinent patients who show high levels of drug antibodies, the rewarding effects of these drugs are attenuated. Phase 2 trials have not found nicotine vaccines to be superior to placebo because only a third of those vaccinated develop sufficient levels of antibody to block the effects of nicotine. Vaccines are a novel approach to relapse prevention that need to more reliably induce immunity in a larger proportion of vaccinated patients if they are to protect against relapse after achieving abstinence. Vaccines are unlikely to prevent addiction in adolescents. Their use under legal coercion should only be considered after considerable experience with their use in voluntary patients.

New trends in the treatment of nicotine addiction.

Science.gov (United States)

Sliwińska-Mossoń, Mariola; Zieleń, Iwona; Milnerowicz, Halina

2014-01-01

The aim of this study was to discuss the therapeutic substances used to treat nicotine addiction, not registered in Poland. This paper presents the results of the latest clinical trials and the possibility of their use in the treatment of nicotine addiction. The first two discussed drugs clonidine and nortriptyline are recommended by clinical practice guidelines AHRQ (Agency for Healthcare Research and Quality) as the substance of the second line in the fight against addiction. Nortriptyline belongs to tricyclic antidepressants. Its mechanism of action is the inhibition of the reuptake of norepinephrine. It is suggested as the antagonist of activity of nicotinic receptors. The results confirm its efficacy in the treatment of nicotine addiction, but many side effects limit its use. Clonidine acts presumably by inhibition of sympathetic hyperactivity characteristic of symptoms associated with nicotine rehab. The remaining compounds under discussion, such as: venlafaxine, fluoxetine, moclobemide and rimonabant, are not registered in any country with an indication to use in the treatment of nicotine addiction, however, due to the mechanism in which they act, the possibility of their use in the treatment of this disease is considered. The possibility of using anxiolytics such as: buspirone, diazepam, meprobamate and beta-blockers: metoprolol and oxprenolol is also considered in order to treat the anxiety appearing as one of the symptoms of abstinence. An interesting proposal to combat nicotine addiction are vaccines--NicVAX, CYT002-NicQb and TA-NIC. Currently, they are in clinical phase I and II of their development. Their operation would be based on the induction of specific antibodies that bind nicotine in the plasma, thus prevent it reaching the nicotinic receptors. Preliminary results confirm the possible positive effects in the prevention and treatment of nicotine addiction.

Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

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Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

2009-01-01

Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of β2-containing nicotinic receptors with dihydro-β-erythrodine (DHβE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal α7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical α7 and β2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHβE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHβE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHβE infusion potentiated clozapine-induced memory impairment, whereas previously the memory

Chronic underactivity of medial frontal cortical beta2-containing nicotinic receptors increases clozapine-induced working memory impairment in female rats.

Science.gov (United States)

Levin, Edward D; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N Channelle

2009-03-17

Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of beta2-containing nicotinic receptors with dihydro-beta-erythrodine (DHbetaE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal alpha7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical alpha7 and beta2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHbetaE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHbetaE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHbetaE infusion potentiated clozapine-induced memory impairment, whereas previously

Effect of nicotine replacement therapy on cardiovascular outcomes after acute coronary syndromes.

Science.gov (United States)

Woolf, Kevin J; Zabad, Mohammed Nour; Post, Jennifer M; McNitt, Scott; Williams, Geoffrey C; Bisognano, John D

2012-10-01

The optimal approach to encourage smoking cessation after acute coronary syndrome (ACS) remains unclear. The safety of nicotine replacement therapy (NRT) after ACS is not well established. The aim of the present study was to determine the relationship between NRT use and adverse cardiovascular outcomes after ACS. Using a pre-existing database, 663 smokers with ACS were identified. The patients were separated into the NRT (n = 184) or control (n = 479) groups according to whether NRT was prescribed on hospital discharge. Multivariate logistic regression analysis was used to account for the baseline differences between the 2 groups. Of the 663 patients, 202 had adverse events in the first year after ACS. No significant differences were seen with NRT use for the 1-year combined end point of death, myocardial infarction), repeat revascularization, or rehospitalization for angina, congestive heart failure or arrhythmia (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.61 to 1.30, p = 0.54). There were no differences in the individual 1-year end points of death (odds ratio 0.80, 95% confidence interval 0.33 to 1.91, p = 0.61), myocardial infarction (odds ratio 0.90, 95% confidence interval 0.40 to 2.06, p = 0.80), repeat revascularization (odds ratio 0.77, 95% confidence interval 0.44 to 1.36, p = 0.37), or rehospitalization for angina, congestive heart failure, or arrhythmia (odds ratio 1.01, 95% confidence interval 0.66 to 1.53, p = 0.97). In conclusion, NRT use was not associated with an increased risk of adverse cardiovascular events in the first year after ACS. Copyright © 2012 Elsevier Inc. All rights reserved.

Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.

Science.gov (United States)

Lesage, Elise; Aronson, Sarah E; Sutherland, Matthew T; Ross, Thomas J; Salmeron, Betty Jo; Stein, Elliot A

2017-06-01

Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline

US smokers' reactions to a brief trial of oral nicotine products

Directory of Open Access Journals (Sweden)

Mahoney Martin C

2011-01-01

Full Text Available Abstract Background It has been suggested that cigarette smokers will switch to alternative oral nicotine delivery products to reduce their health risks if informed of the relative risk difference. However, it is important to assess how smokers are likely to use cigarette alternatives before making predictions about their potential to promote individual or population harm reduction. Objectives This study examines smokers' interest in using a smokeless tobacco or a nicotine replacement product as a substitute for their cigarettes. Methods The study included 67 adult cigarette smokers, not currently interested in quitting, who were given an opportunity to sample four alternative oral nicotine products: 1 Camel Snus, 2 Marlboro Snus, 3 Stonewall dissolvable tobacco tablets, and 4 Commit nicotine lozenges. At visit 1, subjects were presented information about the relative benefits/risks of oral nicotine delivery compared to cigarettes. At visit 2, subjects were given a supply of each of the four products to sample at home for a week. At visit 3, subjects received a one-week supply of their preferred product to see if using such products reduced or eliminated cigarette use. Results After multiple product sampling, participants preferred the Commit lozenges over the three smokeless tobacco products (p = 0.011. Following the one week single-product trial experience, GEE models controlling for gender, age, level of education, baseline cigarettes use, and alternative product chosen, indicated a significant decline in cigarettes smoked per day across one week of single-product sampling (p Conclusions Findings from this study show that smokers, who are currently unwilling to make a quit attempt, may be willing to use alternative products in the short term as a temporary substitute for smoking. However, this use is more likely to be for partial substitution (i.e. they will continue to smoke, albeit at a lower rate rather than complete substitution. Of the

Cigarette nicotine yields and nicotine intake among Japanese male workers

OpenAIRE

Ueda, K; Kawachi, I; Nakamura, M; Nogami, H; Shirokawa, N; Masui, S; Okayama, A; Oshima, A

2002-01-01

Objectives: To analyse brand nicotine yield including "ultra low" brands (that is, cigarettes yielding ≤ 0.1 mg of nicotine by Federal Trade Commission (FTC) methods) in relation to nicotine intake (urinary nicotine, cotinine and trans-3'-hydroxycotinine) among 246 Japanese male smokers.

Nicotine Lozenges

Science.gov (United States)

Nicotine lozenges are used to help people stop smoking. Nicotine lozenges are in a class of medications called smoking cessation aids. They work by providing nicotine to your body to decrease the withdrawal symptoms ...

Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

Science.gov (United States)

Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

2006-01-01

CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

Effects of nicotine gum on psychomotor performance in smokers and non-smokers.

Science.gov (United States)

Hindmarch, I; Kerr, J S; Sherwood, N

1990-01-01

Two experiments were conducted to investigate the effects of nicotine on human performance. In the first study six smokers, who had been allowed to smoke normally prior to testing, completed a battery of psychometric tests (choice reaction time, memory scanning, tracking and flicker fusion threshold) at set points over 4 h after chewing 0, 2, or 4 mg nicotine polacrilex gum. A second study followed a similar design, but used five non-smoker volunteers who were required to chew only the 0 or 2 mg nicotine gum. Blood nicotine levels following the gum were measured in all subjects. The results indicate that additional nicotine improved both the speed and accuracy of motor activity among the smokers, but did not enhance central cognitive processes. No drug effects were found in the non-smoker study.

Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities.

Science.gov (United States)

Baz-Lomba, Jose Antonio; Salvatore, Stefania; Gracia-Lor, Emma; Bade, Richard; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; van Nuijs, Alexander; Ort, Christoph; Plósz, Benedek G; Ramin, Pedram; Reid, Malcolm; Rousis, Nikolaos I; Ryu, Yeonsuk; de Voogt, Pim; Bramness, Jorgen; Thomas, Kevin

2016-10-01

Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE) has been shown to be a reliable approach complementing such surveys. This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison. High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data. This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.

Emerging nicotine delivery products. Implications for public health.

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Benowitz, Neal L

2014-02-01

The idea of clean nicotine delivery systems that would satisfy nicotine craving and promote smoking cessation has been considered as a possible public health tool for many years. Nicotine medications have been useful for smoking cessation but have not found widespread popularity among smokers, perhaps because of slow nicotine delivery and other sensory characteristics that differ from cigarettes. Traditional smokeless tobacco delivers as much nicotine as cigarettes and has been advocated for harm reduction but contains carcinogenic nitrosamines and has not been proven to promote cessation. Furthermore, there is concern that dual use of smokeless tobacco and cigarettes may inhibit quitting smoking. Newer oral dissolvable tobacco products contain lower levels of toxicants than other smokeless tobacco but also deliver much less nicotine and have not been popular with consumers. Electronic cigarettes that aerosolize nicotine without generating toxic tobacco combustion products have become quite popular and hold promise as a way to attract smokers away from cigarettes, although efficacy in promoting smoking cessation has not yet been demonstrated. There are concerns about safety of long-term use, and there is evidence that youth, including nonsmokers, are taking up e-cigarette use. E-cigarettes are marketed for use when one cannot smoke conventional cigarettes, and such use might result in more persistent cigarette smoking. Although their benefits and risks are being vigorously debated, e-cigarettes or other clean nicotine delivery devices could play an important role as an adjunct to a U.S. Food and Drug Administration regulatory intervention to make cigarettes less addictive and in this context could contribute to the end of cigarette smoking and smoking-induced disease.

The Effect of Nicotine Dependence on Psychopathology in Patients with Schizophrenia

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Anne Yee

2015-01-01

Full Text Available Introduction. Our study aims to determine the prevalence of nicotine dependence and investigate the effect of nicotine dependence on psychopathology among schizophrenia patients. Methods. A cross-sectional study was carried out in an outpatient psychiatric clinic at a general hospital in Malaysia. 180 recruited subjects were administered the Malay version of Mini International Neuropsychiatric Interview (MINI, the Positive and Negative Symptom Scale (PANSS, and the Malay version of Fagerstrom Test for Nicotine Dependence (FTND-M questionnaires. Results. The prevalence of nicotine dependence among the subjects was 38.1% (n=69 and they were mainly composed of male gender, Malay ethnicity, being treated with atypical antipsychotics, and taking other illicit drugs or alcohol. Subjects with severe nicotine dependence scored less in the negative subscale of PANSS compared with the nonsmokers (P=0.011. On performing the hierarchy multiple regressions, dependence status still significantly predicted negative scores after adjusting the confounders (t=-2.87, P=0.005. Conclusion. The rate of nicotine use disorder among schizophrenia patients in this study is higher than that of the general population in Malaysia. The significant association between nicotine dependence and negative psychopathology symptoms will help the healthcare practitioners in their management of nicotine dependence among schizophrenia patients.

Evaluation of nicotine in tobacco-free-nicotine commercial products.

Science.gov (United States)

Hellinghausen, Garrett; Lee, Jauh T; Weatherly, Choyce A; Lopez, Diego A; Armstrong, Daniel W

2017-06-01

Recently, a variety of new tobacco-free-nicotine, TFN, products have been commercialized as e-liquids. Tobacco-derived nicotine contains predominantly (S)-(-)-nicotine, whereas TFN products may not. The TFN products are said to be cleaner, purer substances, devoid of toxic components that come from the tobacco extraction process. A variety of commercial tobacco and TFN products were analyzed to identify the presence and composition of each nicotine enantiomer. A rapid and effective enantiomeric separation of nicotine has been developed using a modified macrocyclic glycopeptide bonded to superficially porous particles. The enantiomeric assay can be completed in nicotine, which is present in much greater quantities in commercial TFN products compared to commercial tobacco-derived products. Such studies are required by the FDA for new enantiomeric pharmacological products. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Real-time UV imaging of nicotin release from transdermal patch

DEFF Research Database (Denmark)

Østergaard, Jesper; Meng-Lund, Emil; Larsen, Susan Weng

2010-01-01

PURPOSE: This study was conducted to characterize UV imaging as a platform for performing in vitro release studies using Nicorette® nicotine patches as a model drug delivery system. METHODS: The rate of nicotine release from 2 mm diameter patch samples (Nicorette®) into 0.067 M phosphate buffer, p......H 7.40, was studied by UV imaging (Actipix SDI300 dissolution imaging system) at 254 nm. The release rates were compared to those obtained using the paddle-over-disk method. RESULTS: Calibration curves were successfully established which allowed temporally and spatially resolved quantification...... of nicotine. Release profiles obtained from UV imaging were in qualitative agreement with results from the paddle-over-disk release method. CONCLUSION: Visualization as well as quantification of nicotine concentration gradients was achieved by UV imaging in real time. UV imaging has the potential to become...

E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices.

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Steinberg, Michael B; Zimmermann, Mia Hanos; Delnevo, Cristine D; Lewis, M Jane; Shukla, Parth; Coups, Elliot J; Foulds, Jonathan

2014-11-01

Novel nicotine delivery products, such as electronic cigarettes (e-cigarettes), have dramatically grown in popularity despite limited data on safety and benefit. In contrast, the similar U.S. Food and Drug Administration (FDA)-approved nicotine inhaler is rarely utilized by smokers. Understanding this paradox could be helpful to determine the potential for e-cigarettes as an alternative to tobacco smoking. To compare the e-cigarette with the nicotine inhaler in terms of perceived benefits, harms, appeal, and role in assisting with smoking cessation. A cross-over trial was conducted from 2012 to 2013 PARTICIPANTS/INTERVENTIONS: Forty-one current smokers age 18 and older used the e-cigarette and nicotine inhaler each for 3 days, in random order, with a washout period in between. Thirty-eight participants provided data on product use, perceptions, and experiences. The Modified Cigarette Evaluation Questionnaire (mCEQ) measured satisfaction, reward, and aversion. Subjects were also asked about each product's helpfulness, similarity to cigarettes, acceptability, image, and effectiveness in quitting smoking. Cigarette use was also recorded during the product-use periods. The e-cigarette had a higher total satisfaction score (13.9 vs. 6.8 [p e-cigarette received higher ratings for helpfulness, acceptability, and "coolness." More subjects would use the e-cigarette to make a quit attempt (76 %) than the inhaler (24 %) (p e-cigarette vs. 10 % (4/38) using the inhaler (p = 0.18). The e-cigarette was more acceptable, provided more satisfaction, and had higher perceived benefit than the inhaler during this trial. E-cigarettes have the potential to be important nicotine delivery products owing to their high acceptance and perceived benefit, but more data are needed to evaluate their actual efficacy and safety. Providers should be aware of these issues, as patients will increasingly inquire about them.

The nicotinic acetylcholine receptors of the parasitic nematode Ascaris suum: formation of two distinct drug targets by varying the relative expression levels of two subunits.

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Sally M Williamson

2009-07-01

Full Text Available Parasitic nematodes are of medical and veterinary importance, adversely affecting human health and animal welfare. Ascaris suum is a gastrointestinal parasite of pigs; in addition to its veterinary significance it is a good model of the human parasite Ascaris lumbricoides, estimated to infect approximately 1.4 billion people globally. Anthelmintic drugs are essential to control nematode parasites, and nicotinic acetylcholine receptors (nAChRs on nerve and muscle are the targets of cholinergic anthelmintics such as levamisole and pyrantel. Previous genetic analyses of nematode nAChRs have been confined to Caenorhabditis elegans, which is phylogenetically distinct from Ascaris spp. and many other important parasites. Here we report the cloning and expression of two nAChR subunit cDNAs from A. suum. The subunits are very similar in sequence to C. elegans UNC-29 and UNC-38, are expressed on muscle cells and can be expressed robustly in Xenopus oocytes to form acetylcholine-, nicotine-, levamisole- and pyrantel-sensitive channels. We also demonstrate that changing the stoichiometry of the receptor by injecting different ratios of the subunit cRNAs can reproduce two of the three pharmacological subtypes of nAChR present in A. suum muscle cells. When the ratio was 5:1 (Asu-unc-38ratioAsu-unc-29, nicotine was a full agonist and levamisole was a partial agonist, and oocytes responded to oxantel, but not pyrantel. At the reverse ratio (1:5 Asu-unc-38ratioAsu-unc-29, levamisole was a full agonist and nicotine was a partial agonist, and the oocytes responded to pyrantel, but not oxantel. These results represent the first in vitro expression of any parasitic nicotinic receptor and show that their properties are substantially different from those of C. elegans. The results also show that changing the expression level of a single receptor subunit dramatically altered the efficacy of some anthelmintic drugs. In vitro expression of these subunits may permit the

Sleep quality during exam stress: the role of alcohol, caffeine and nicotine.

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Zunhammer, Matthias; Eichhammer, Peter; Busch, Volker

2014-01-01

Academic exam stress is known to compromise sleep quality and alter drug consumption in university students. Here we evaluated if sleeping problems and changes in legal drug consumption during exam stress are interrelated. We used the Pittsburgh Sleep Quality Index (PSQI) to survey sleep quality before, during, and after an academic exam period in 150 university students in a longitudinal questionnaire study. Self-reports of alcohol, caffeine, and nicotine consumption were obtained. The Perceived Stress Questionnaire (PSQ-20) was used as a measure of stress. Sleep quality and alcohol consumption significantly decreased, while perceived stress and caffeine consumption significantly increased during the exam period. No significant change in nicotine consumption was observed. In particular, students shortened their time in bed and showed symptoms of insomnia. Mixed model analysis indicated that sex, age, health status, as well as the amounts of alcohol and caffeine consumed had no significant influence on global sleep quality. The amount of nicotine consumed and perceived stress were identified as significant predictors of diminished sleep quality. Nicotine consumption had a small-to-very-small effect on sleep quality; perceived stress had a small-to-moderate effect. In conclusion, diminished sleep quality during exam periods was mainly predicted by perceived stress, while legal drug consumption played a minor role. Exam periods may pose an interesting model for the study of stress-induced sleeping problems and their mechanisms.

Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum

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Feyerabend, C.; Russell, M. A. H.

1978-01-01

1 Plasma nicotine levels produced by chewing nicotine gum were compared with those obtained by cigarette smoking under conditions of controlled urinary pH. 2 Although absorption was slower, plasma levels comparable to cigarette smoking were built up on 4 mg (but not 2 mg) nicotine gum. 3 Urinary excretion of nicotine was influenced markedly by pH and the rate of urine flow. 4 Plasma nicotine was higher under alkaline compared to acidic conditions (P < 0.001) but the rate of urinary nicotine excretion appeared to have little effect on the plasma level.

Nicotine during pregnancy: changes induced in neurotransmission, which could heighten proclivity to addict and induce maladaptive control of attention.

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Kohlmeier, K A

2015-06-01

Prenatal exposure to nicotine, occurring either via maternal smoking or via use of transdermal nicotine patches to facilitate cigarette abstinence by pregnant women, is associated with ∼ 13% of pregnancies worldwide. Nicotine exposure during gestation has been correlated with several negative physiological and psychosocial outcomes, including heightened risk for aberrant behaviors involving alterations in processing of attention as well as an enhanced liability for development of drug dependency. Nicotine is a terotogen, altering neuronal development of various neurotransmitter systems, and it is likely these alterations participate in postnatal deficits in attention control and facilitate development of drug addiction. This review discusses the alterations in neuronal development within the brain's major neurotransmitter systems, with special emphasis placed on alterations within the laterodorsal tegmental nucleus, in light of the role this cholinergic nucleus plays in attention and addiction. Changes induced within this nucleus by gestational exposure to nicotine, in combination with changes induced in other brain regions, are likely to contribute to the transgenerational burden imposed by nicotine. Although neuroplastic changes induced by nicotine are not likely to act in isolation, and are expected to interact with epigenetic changes induced by preconception exposure to drugs of abuse, unraveling these changes within the developing brain will facilitate eventual development of targeted treatments for the unique vulnerability for arousal disorders and development of addiction within the population of individuals who have been prenatally exposed to nicotine.

Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.

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Poirier, Guillaume L; Huang, Wei; Tam, Kelly; DiFranza, Joseph R; King, Jean A

2017-09-01

Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine's effects on functional brain networks in an animal model of ADHD. Awake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction. Relative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit. In the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits. Nicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that

CHRNA3 genotype, nicotine dependence, lung function and disease in the general population

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Kaur-Knudsen, Diljit; Nordestgaard, Børge G; Bojesen, Stig E

2012-01-01

The CHRNA3 rs1051730 polymorphism has been associated to chronic obstructive pulmonary disease (COPD), lung cancer and nicotine dependence in case-control studies with high smoking exposure; however, its influence on lung function and COPD severity in the general population is largely unknown. We...... genotyped 57,657 adult individuals from the Copenhagen General Population Study, of whom 34,592 were ever-smokers. Information on spirometry, hospital admissions, smoking behaviour and use of nicotinic replacement therapy was recorded. In homozygous (11%), heterozygous (44%) and noncarrier (45%) ever...

Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

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Kendler, Kenneth S; Myers, John; Prescott, Carol A

2007-11-01

Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence

Coordination Driven Capture of Nicotine Inside a Mesoporous MOF.

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Balestri, Davide; Capucci, Davide; Demitri, Nicola; Bacchi, Alessia; Pelagatti, Paolo

2017-06-30

Metal organic frameworks (MOFs) are a wide class of crystalline porous polymers studied in many fields, ranging from catalysis to gas storage. In the past few years, MOFs have been studied for the encapsulation of organic or organometallic molecules and for the development of potential drug carriers. Here, we report on the study of two structurally-related mesoporous Cu-MOFs, namely PCN-6 and PCN-6' (PCN stands for Porous Coordination Network), for nicotine trapping. Nicotine is a well-known alkaloid liquid molecule at room temperature, whose crystalline structure is still unknown. In this work, the loading process was monitored by electron ionization mass spectrometry by using a direct insertion probe (DIP-EI/MS), infrared (IR), and ultraviolet/visible (UV/VIS) analysis. Both nuclear magnetic resonance (NMR) spectroscopy and thermogravimetric (TGA) analysis showed evidence that nicotine trapping reaches remarkable uptakes up to 40 wt %. In the case of PCN-6@nicotine, X-ray structural resolution revealed that the guest uptake is triggered by coordination of the pyridine ring of nicotine to the copper nuclei of the paddle-wheel units composing the framework of PCN-6.

Coordination Driven Capture of Nicotine Inside a Mesoporous MOF

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Davide Balestri

2017-06-01

Full Text Available Metal organic frameworks (MOFs are a wide class of crystalline porous polymers studied in many fields, ranging from catalysis to gas storage. In the past few years, MOFs have been studied for the encapsulation of organic or organometallic molecules and for the development of potential drug carriers. Here, we report on the study of two structurally-related mesoporous Cu-MOFs, namely PCN-6 and PCN-6′ (PCN stands for Porous Coordination Network, for nicotine trapping. Nicotine is a well-known alkaloid liquid molecule at room temperature, whose crystalline structure is still unknown. In this work, the loading process was monitored by electron ionization mass spectrometry by using a direct insertion probe (DIP-EI/MS, infrared (IR, and ultraviolet/visible (UV/VIS analysis. Both nuclear magnetic resonance (NMR spectroscopy and thermogravimetric (TGA analysis showed evidence that nicotine trapping reaches remarkable uptakes up to 40 wt %. In the case of PCN-6@nicotine, X-ray structural resolution revealed that the guest uptake is triggered by coordination of the pyridine ring of nicotine to the copper nuclei of the paddle-wheel units composing the framework of PCN-6.

The α7 nicotinic acetylcholine receptor complex

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Thomsen, Morten S; Mikkelsen, Jens D

2012-01-01

The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds and prote......The α7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds...... in diseases such as schizophrenia and Alzheimer's disease. Furthermore, α7 nAChR agonists and allosteric modulators differentially alter expression and functionality of the α7 nAChR with repeated administration, which suggests that there may be fundamentally different outcomes of long-term administration...... with these different types of compounds. Finally, we describe the special case of Aβ1-42 binding to the α7 nAChR, which may pose a unique challenge to drug development of α7 nAChR-specific ligands for Alzheimer's disease. Hopefully, a greater knowledge of the many factors influencing α7 nAChR function as well...

E-Cigarette Users' Attitudes on the Banning of Sales of Nicotine E-Liquid, Its Implication on E-Cigarette Use Behaviours and Alternative Sources of Nicotine E-Liquid.

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Wong, Li Ping; Alias, Haridah; Agha Mohammadi, Nasrin; Ghadimi, Azadeh; Hoe, Victor Chee Wai

2017-12-01

The banning of sales of nicotine e-liquid in e-cigarette shops has been implemented in several states in Malaysia. The distribution of nicotine e-liquid can only be allowed by licensed pharmacies or registered medical practitioners. This study aimed to evaluate e-cigarette users' responses to the control policy in a cross-sectional survey of 851 e-cigarette users by utilizing a self-report questionnaire that assessed (1) attitudes on regulation policy of e-cigarette banning; (2) e-cigarette use behaviors; and (3) sources of e-liquid after the regulation policy has been implemented. Participants from the state of Selangor where the banning policy was implemented were surveyed. The majority (95.8%) opposed the banning and believed e-cigarettes should be sold to anyone aged 18 years or above as with tobacco cigarettes, only a minority believed that nicotine e-liquid should only be available for sale over the counter in pharmacy stores (14.6%) and in clinics with a doctor's prescription (11.8%). The majority (44.2%) reported that they would continue their e-cigarette use as before the banning policy, while 20% plan to completely stop e-cigarette usage without replacing it with any alternatives. The vast majority (87.9%) was still able to obtained nicotine e-liquid from e-cigarette shops in spite of the ban and the second most common source was from online purchase (63.1%). The sales of nicotine e-liquid from black-market were evidenced as many reported obtaining zero nicotine e-liquid from the black market (54.4%). Self- or home-made (30.8%) nicotine e-liquid was also reported. Majority of respondents that self-made e-liquid were from the average monthly income group (below MYR3000). Obtaining nicotine from the pharmacy was least preferred (21.4%). Provision of professional advice to nicotine e-liquid users along with the ban may lessen the likelihood of users switching to tobacco cigarettes or other nicotine alternatives. Banning of sales of nicotine e-liquid in e

Stimulus properties of nicotine, amphetamine, and chlordiazepoxide as positive features in a pavlovian appetitive discrimination task in rats.

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Palmatier, Matthew I; Wilkinson, Jamie L; Metschke, Dawn M; Bevins, Rick A

2005-04-01

Recent experiments from our laboratory have demonstrated that drug states can signal when environmental cues will be followed by rewarding outcomes (ie Pavlovian conditioning). However, little is known about the generality of this approach and whether it can be used for studying the pharmacological properties of drug states. Accordingly, the present experiments tested the pharmacological specificity of nicotine (0.4 mg/kg), amphetamine (1 mg/kg), and chlordiazepoxide (CDP, 5 mg/kg) in this Pavlovian drug discrimination procedure. Following drug administration, presentation of a conditional stimulus (CS) was followed by brief access to sucrose. When saline was administered, the same CS was presented but sucrose was withheld. In substitution tests, rats in each condition received varying doses of all training drugs and caffeine. Anticipatory food seeking developed during the CS on drug sessions but not on saline sessions for all drug features (ie drug state-specific conditional response (CR)). In generalization tests, this CR decreased as a function of decreases in the training dose. Median effective doses (ED50s) were calculated for nicotine (0.054 mg/kg), amphetamine (0.26 mg/kg), and CDP (2.48 mg/kg). No compound tested substituted for the CDP training drug. Partial substitution was evident between nicotine and amphetamine; CDP did not substitute for either of these drug features. Caffeine fully substituted for nicotine (ED50 = 15.45 mg/kg) and amphetamine (ED50 = 3.70 mg/kg), but not for CDP. These results are consistent with the hypothesis that drug states can occasion appetitive Pavlovian CRs in a pharmacologically specific manner.

Acute effects of nicotine amplify accumbal neural responses during nicotine-taking behavior and nicotine-paired environmental cues.

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Karine Guillem

Full Text Available Nicotine self-administration (SA is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present study, Long-Evans rats were trained to self-administer nicotine. During SA sessions each press of a lever was followed by an intravenous infusion of nicotine (30 µg/kg paired with a combined light-tone cue. Extracellular recordings of single-neuron activity showed that 20% of neurons exhibited a phasic change in firing during the nicotine-directed operant, the light-tone cue, or both. The phasic change in firing for 98% of neurons was an increase. Sixty-two percent of NAc neurons additionally or alternatively showed a sustained decrease in average firing during the SA session relative to a presession baseline period. These session decreases in firing were significantly less prevalent in a group of neurons that were activated during either the operant or the cue than in a group of neurons that were nonresponsive during those events (referred to as task-activated and task-nonactivated neurons, respectively. Moreover, the session decrease in firing was dose-dependent for only the task-nonactivated neurons. The data of the present investigation provide supportive correlational evidence for two hypotheses: (1 excitatory neurophysiological mechanisms mediate the NAc role in cue-maintenance of nicotine SA, and (2 a differential nicotine-induced inhibition of task-activated and task-nonactivated neurons mediates the NAc role in nicotine-induced amplification of cue effects on nicotine SA.

Effects of nicotine and nicotine expectancy on attentional bias for emotional stimuli.

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Adams, Sally; Attwood, Angela S; Munafò, Marcus R

2015-06-01

Nicotine's effects on mood are thought to enhance its addictive potential. However, the mechanisms underlying the effects of nicotine on affect regulation have not been reliably demonstrated in human laboratory studies. We investigated the effects of nicotine abstinence (Experiment 1), and nicotine challenge and expectancy (Experiment 2) on attentional bias towards facial emotional stimuli differing in emotional valence. In Experiment 1, 46 nicotine-deprived smokers were randomized to either continue to abstain from smoking or to smoke immediately before testing. In Experiment 2, 96 nicotine-deprived smokers were randomized to smoke a nicotinized or denicotinized cigarette and to be told that the cigarette did or did not contain nicotine. In both experiments participants completed a visual probe task, where positively valenced (happy) and negatively valenced (sad) facial expressions were presented, together with neutral facial expressions. In Experiment 1, there was evidence of an interaction between probe location and abstinence on reaction time, indicating that abstinent smokers showed an attentional bias for neutral stimuli. In Experiment 2, there was evidence of an interaction between probe location, nicotine challenge and expectation on reaction time, indicating that smokers receiving nicotine, but told that they did not receive nicotine, showed an attentional bias for emotional stimuli. Our data suggest that nicotine abstinence appears to disrupt attentional bias towards emotional facial stimuli. These data provide support for nicotine's modulation of attentional bias as a central mechanism for maintaining affect regulation in cigarette smoking. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use and compulsive smoking

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Ami eCohen

2013-06-01

Full Text Available Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake.

Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities

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Jose Antonio Baz-Lomba

2016-10-01

Full Text Available Abstract Background Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE has been shown to be a reliable approach complementing such surveys. Method This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison. Results High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data. Conclusions This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.

Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

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Zarrelli, Armando, E-mail: zarrelli@unina.it [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); Isidori, Marina; Lavorgna, Margherita [Department of Life Sciences, II University of Naples, Caserta (Italy); Passananti, Monica; Previtera, Lucio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy)

2012-06-01

Nicotine, the main alkaloid of tobacco, is a non- prescription drug to which all members of a tobacco-smoking society are exposed either through direct smoke inhalation or through second-hand passive 'smoking'. Nicotine is also commercially available in some pharmaceutical products and is used worldwide as a botanical insecticide in agriculture. Nicotine dynamics in indoor and outdoor environments as well as the human excretions and the manufacturing process are responsible for its entry in the environment through municipal and industrial wastewater discharges. The presence of nicotine in surface and ground waters points out that it survives a conventional treatment process and persists in potable-water supplies. Complete removal of nicotine is instead reported when additional chlorination steps are used. In this paper a simulation of STP chlorination of nicotine and a genotoxic evaluation of its main degradation products are reported. Under laboratory conditions removal of nicotine seems not to be due to mineralization but to transformation in oxidized and chlorinated products. The by-products have been isolated after fractionation by diverse chromatographic procedures and their structures determined using mass spectrometry and {sup 1}H and {sup 13}C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: Black-Right-Pointing-Pointer Processes of chlorination in the treatment of raw water. Black-Right-Pointing-Pointer STP chlorination of nicotine. Black-Right-Pointing-Pointer Genotoxic evaluation of main degradation products of nicotine.

Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

International Nuclear Information System (INIS)

Zarrelli, Armando; DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio; Isidori, Marina; Lavorgna, Margherita; Passananti, Monica; Previtera, Lucio

2012-01-01

Nicotine, the main alkaloid of tobacco, is a non- prescription drug to which all members of a tobacco-smoking society are exposed either through direct smoke inhalation or through second-hand passive ‘smoking’. Nicotine is also commercially available in some pharmaceutical products and is used worldwide as a botanical insecticide in agriculture. Nicotine dynamics in indoor and outdoor environments as well as the human excretions and the manufacturing process are responsible for its entry in the environment through municipal and industrial wastewater discharges. The presence of nicotine in surface and ground waters points out that it survives a conventional treatment process and persists in potable-water supplies. Complete removal of nicotine is instead reported when additional chlorination steps are used. In this paper a simulation of STP chlorination of nicotine and a genotoxic evaluation of its main degradation products are reported. Under laboratory conditions removal of nicotine seems not to be due to mineralization but to transformation in oxidized and chlorinated products. The by-products have been isolated after fractionation by diverse chromatographic procedures and their structures determined using mass spectrometry and 1 H and 13 C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: ► Processes of chlorination in the treatment of raw water. ► STP chlorination of nicotine. ► Genotoxic evaluation of main degradation products of nicotine.

Nicotinic plant poisoning.

Science.gov (United States)

Schep, Leo J; Slaughter, Robin J; Beasley, D Michael G

2009-09-01

A wide range of plants contain nicotinic and nicotinic-like alkaloids. Of this diverse group, those that have been reported to cause human poisoning appear to have similar mechanisms of toxicity and presenting patients therefore have comparable toxidromes. This review describes the taxonomy and principal alkaloids of plants that contain nicotinic and nicotinic-like alkaloids, with particular focus on those that are toxic to humans. The toxicokinetics and mechanisms of toxicity of these alkaloids are reviewed and the clinical features and management of poisoning due to these plants are described. This review was compiled by systematically searching OVID MEDLINE and ISI Web of Science. This identified 9,456 papers, excluding duplicates, all of which were screened. Reviewed plants and their principal alkaloids. Plants containing nicotine and nicotine-like alkaloids that have been reported to be poisonous to humans include Conium maculatum, Nicotiana glauca and Nicotiana tabacum, Laburnum anagyroides, and Caulophyllum thalictroides. They contain the toxic alkaloids nicotine, anabasine, cytisine, n-methylcytisine, coniine, n-methylconiine, and gamma-coniceine. These alkaloids act agonistically at nicotinic-type acetylcholine (cholinergic) receptors (nAChRs). The nicotinic-type acetylcholine receptor can vary both in its subunit composition and in its distribution within the body (the central and autonomic nervous systems, the neuromuscular junctions, and the adrenal medulla). Agonistic interaction at these variable sites may explain why the alkaloids have diverse effects depending on the administered dose and duration of exposure. Nicotine and nicotine-like alkaloids are absorbed readily across all routes of exposure and are rapidly and widely distributed, readily traversing the blood-brain barrier and the placenta, and are freely distributed in breast milk. Metabolism occurs predominantly in the liver followed by rapid renal elimination. Following acute exposure

In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

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André Luís Morais Ruela

2013-09-01

Full Text Available The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC. The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.

Neuropharmacological Consequences of Variant Drugs

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Mahnoor Amjad Butt

2017-11-01

Full Text Available Neuropharmacological effects deals with the influence of drugs on nervous system which harvest the changes in mood, behavioral action of an individual. The drugs are characterized by the chemical substances that communicate with the neurons which have different impacts on nervous system. It may either conducts the abusive or pleasure response which depends on the neural chemicals activity and concerns with the licit and illicit drugs. The elucidation of drugs via LC/MS shows its exertion on the brain components. The computational model helps in the identification of signaling pathways that trigger or inhibit the neurotransmitters. The licit drugs have indisputable responses on CNS. It imparts neuroprotection by either stimulating or inhibiting the receptor, by down regulation yield antinociceptors. However, the illicit drugs have negative acknowledgment on the body as in nicotine the fewer amounts provides benefits but in higher amount mimics the activity of brain receptors and replaces it. Many other drugs induce neurodegenerative disorders. Due to advances in field of neuropharmacology innumerable drugs are available for feasible treatment. The main objective of this review is neuropharmacological consequences in correlation to licit and illicit drugs that what type of responses generated by using these drugs, the neurodegenerative disorders, and their restoration via current treatment.

Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

NARCIS (Netherlands)

Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

2011-01-01

The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

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Sleep quality during exam stress: the role of alcohol, caffeine and nicotine.

Directory of Open Access Journals (Sweden)

Matthias Zunhammer

Full Text Available Academic exam stress is known to compromise sleep quality and alter drug consumption in university students. Here we evaluated if sleeping problems and changes in legal drug consumption during exam stress are interrelated. We used the Pittsburgh Sleep Quality Index (PSQI to survey sleep quality before, during, and after an academic exam period in 150 university students in a longitudinal questionnaire study. Self-reports of alcohol, caffeine, and nicotine consumption were obtained. The Perceived Stress Questionnaire (PSQ-20 was used as a measure of stress. Sleep quality and alcohol consumption significantly decreased, while perceived stress and caffeine consumption significantly increased during the exam period. No significant change in nicotine consumption was observed. In particular, students shortened their time in bed and showed symptoms of insomnia. Mixed model analysis indicated that sex, age, health status, as well as the amounts of alcohol and caffeine consumed had no significant influence on global sleep quality. The amount of nicotine consumed and perceived stress were identified as significant predictors of diminished sleep quality. Nicotine consumption had a small-to-very-small effect on sleep quality; perceived stress had a small-to-moderate effect. In conclusion, diminished sleep quality during exam periods was mainly predicted by perceived stress, while legal drug consumption played a minor role. Exam periods may pose an interesting model for the study of stress-induced sleeping problems and their mechanisms.

Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

International Nuclear Information System (INIS)

Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U.

2007-01-01

Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers

A comparison of the development of tolerance to ethanol and cross-tolerance to nicotine after chronic ethanol treatment in long- and short-sleep mice.

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de Fiebre, C M; Collins, A C

1993-09-01

Previous studies have shown that inbred mouse strains differ in the development of tolerance to both nicotine and ethanol, indicating that genetic factors regulate tolerance development. Those mouse strains that are most sensitive to an acute challenge dose of either drug develop the most tolerance to that drug. The ethanol-sensitive long-sleep (LS) mice are more sensitive to several behavioral and physiological effects of nicotine than are the ethanol-resistant short-sleep (SS) mice. The experiments reported here assessed whether the LS and SS mice develop tolerance to ethanol after chronic treatment with ethanol-containing liquid diets and whether cross-tolerance to nicotine also developed. Tolerance and cross-tolerance were measured by assessing the effects of acute challenge doses of drug on Y-maze crossing and rearing activities, heart rate and body temperature. The LS mice developed tolerance to ethanol's effects on three of the four measures and were cross-tolerant to nicotine on all of the measures. In contrast, the SS mice developed tolerance to ethanol for only two of the measures, but failed to develop cross-tolerance to any action of nicotine. These findings support the hypothesis that ethanol and nicotine share sites of action and that common genes regulate responses to these two drugs. Evidence suggests that tolerance to nicotine may be related to an up-regulation of brain nicotinic receptors, at least in some inbred mouse strains, but chronic ethanol treatment did not reproducibly change either [3H]nicotine or alpha-[125I]bungarotoxin binding. Therefore, other mechanisms must underlie the tolerance and cross-tolerance that was seen.

Modelling a budgetary impact analysis for funding drug-based smoking cessation therapies for patients with major depressive disorder in Spain.

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Rejas-Gutiérrez, J; Bruguera, E; Cedillo, S

2017-09-01

Smoking is associated with high healthcare resource utilisation and cost to society. Patients with major depressive disorder (MDD) exhibit high susceptibility to nicotine dependence. Varenicline, bupropion and nicotine replacement therapy are all indicated for smoking cessation; however funding by the Spanish national health system (SNHS) is limited. We modelled a budgetary impact analysis (BIA) to estimate the impact of the SNHS funding drug-based therapies for smoking cessation in smokers with MDD. The BIA compared the current unfunded scenario versus a funded scenario (varenicline, bupropion, nicotine replacement therapy combined with medical follow-up and counselling) using the Spanish SNHS and societal perspectives. The BIA design was a hybrid model using a decision tree algorithm (population size: smokers with MDD) and Markov chains (smoking cessation attempts) over a 5-year horizon. Smoking cessation drug efficacy was derived from clinical trials, and smoking cessation costs avoided were taken from an analysis of the Spanish National Health Survey. Results were shown as incremental cost savings. Scenarios and threshold univariate sensitivity analyses tested model robustness. The funded scenario resulted in an increase of 43,478 cessation attempts and 8930 fewer smokers after 5 years compared to the unfunded scenario. The cost of funding was €25.3 million and costs avoided were €26.5 million. There was a cumulative 5-year incremental cost saving of €1.2 million to Spanish society. Results were robust using alternative scenarios. Funding smoking cessation drugs in patients with MDD is of economic benefit to Spain and could produce net savings from the third year of implementation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Simultaneous multiplexed quantification of nicotine and its metabolites using surface enhanced Raman scattering.

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Alharbi, Omar; Xu, Yun; Goodacre, Royston

2014-10-07

The detection and quantification of xenobiotics and their metabolites in man is important for drug dosing, therapy and for substance abuse monitoring where longer-lived metabolic products from illicit materials can be assayed after the drug of abuse has been cleared from the system. Raman spectroscopy offers unique specificity for molecular characterization and this usually weak signal can be significantly enhanced using surface enhanced Raman scattering (SERS). We report here the novel development of SERS with chemometrics for the simultaneous analysis of the drug nicotine and its major xenometabolites cotinine and trans-3'-hydroxycotinine. Initial experiments optimized the SERS conditions and we found that when these three determinands were analysed individually that the maximum SERS signals were found at three different pH. These were pH 3 for nicotine and pH 10 and 11 for cotinine and trans-3'-hydroxycotinine, respectively. Tertiary mixtures containing nicotine, cotinine and trans-3'-hydroxycotinine were generated in the concentration range 10(-7)-10(-5) M and SERS spectra were collected at all three pH values. Chemometric analysis using kernel-partial least squares (K-PLS) and artificial neural networks (ANNs) were conducted and these models were validated using bootstrap resampling. All three analytes were accurately quantified with typical root mean squared error of prediction on the test set data being 5-9%; nicotine was most accurately predicted followed by cotinine and then trans-3'-hydroxycotinine. We believe that SERS is a powerful approach for the simultaneous analysis of multiple determinands without recourse to lengthy chromatography, as demonstrated here for the xenobiotic nicotine and its two major xenometabolites.

Examination of the effects of varenicline, bupropion, lorcaserin, or naltrexone on responding for conditioned reinforcement in nicotine-exposed rats.

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Guy, Elizabeth G; Fisher, Daniel C; Higgins, Guy A; Fletcher, Paul J

2014-12-01

Smoking tobacco remains one of the leading causes of preventable deaths in North America. Nicotine reinforces smoking behavior, in part, by enhancing the reinforcing properties of reward-related stimuli, or conditioned stimuli (CSs), associated with tobacco intake. To investigate how pharmaceutical interventions may affect this property of nicotine, we examined the effect of four US Food and Drug Administration (FDA) approved drugs on the ability of nicotine to enhance operant responding for a CS as a conditioned reinforcer. Thirsty rats were exposed to 13 Pavlovian sessions where a CS was paired with water delivery. Nicotine (0.4 mg/kg) injections were administered before each Pavlovian session. Then, in separate groups of rats, the effects of varenicline (1 mg/kg), bupropion (10 and 30 mg/kg), lorcaserin (0.6 mg/kg), and naltrexone (2 mg/kg), and their interaction with nicotine on responding for conditioned reinforcement were examined. Varenicline and lorcaserin each reduced nicotine-enhanced responding for conditioned reinforcement, whereas naltrexone had a modest effect of reducing response enhancements by nicotine. In contrast, bupropion enhanced the effect of nicotine on this measure. The results of these studies may inform how pharmaceutical interventions can affect smoking cessation attempts and relapse through diverse mechanisms, either substituting for, or interacting with, the reinforcement-enhancing properties of nicotine.

Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation

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Tasnim S. Mohamed

2015-11-01

Full Text Available Nicotine addiction, the result of tobacco use, leads to over six million premature deaths world-wide, a number that is expected to increase by a third within the next two decades. While more than half of smokers want and attempt to quit, only a small percentage of smokers are able to quit without pharmacological interventions. Therefore, over the past decades, researchers in academia and the pharmaceutical industry have focused their attention on the development of more effective smoking cessation therapies, which is now a growing 1.9 billion dollar market. Because the role of neuronal nicotinic acetylcholine receptors (nAChR in nicotine addiction is well established, nAChR based therapeutics remain the leading strategy for smoking cessation. However, the development of neuronal nAChR drugs that are selective for a nAChR subpopulation is challenging, and only few neuronal nAChR drugs are clinically available. Among the many neuronal nAChR subtypes that have been identified in the brain, the α4β2 subtype is the most abundant and plays a critical role in nicotine addiction. Here, we review the role of neuronal nAChRs, especially the α4β2 subtype, in the development and treatment of nicotine addiction. We also compare available smoking cessation medications and other nAChR orthosteric and allosteric ligands that have been developed with emphasis on the difficulties faced in the development of clinically useful compounds with high nAChR subtype selectivity.

A Role for Matrix Metalloproteinases in Nicotine-Induced Conditioned Place Preference and Relapse in Adolescent Female Rats

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Reka Natarajan

2013-01-01

Full Text Available Reconfiguration of extracellular matrix proteins appears to be necessary for the synaptic plasticity that underlies memory consolidation. The primary candidates involved in controlling this process are a family of endopeptidases called matrix metalloproteinases (MMPs; however, the potential role of MMPs in nicotine addiction-related memories has not been adequately tested. Present results indicate transient changes in hippocampal MMP-2, -3, and -9 expression following context dependent learning of nicotine-induced conditioned place preference (CPP. Members of a CPP procedural control group also indicated similar MMP changes, suggesting that memory activation occurred in these animals as well. However, hippocampal MMP-9 expression was differentially elevated in members of the nicotine-induced CPP group on days 4 and 5 of training. Inhibition of MMPs using a broad spectrum MMP inhibitor (FN439 during nicotine-induced CPP training blocked the acquisition of CPP. Elevations in hippocampal and prefrontal cortex MMP-3 expression—but not MMP-2 and -9—accompanied reactivation of a previously learned drug related memory. Decreases in the actin regulatory cytoskeletal protein cortactin were measured in the HIP and PFC during the initial two days of acquisition of CPP; however, no changes were seen following re-exposure to the drug related environment. These results suggest that MMP-9 may be involved in facilitating the intracellular and extracellular events required for the synaptic plasticity underlying the acquisition of nicotine-induced CPP. Furthermore, MMP-3 appears to be important during re-exposure to the drug associated environment. However, rats introduced into the CPP apparatus and given injections of vehicle rather than nicotine during training also revealed a pattern of MMP expression similar to nicotine-induced CPP animals.

Cost-effectiveness of varenicline for smoking cessation

DEFF Research Database (Denmark)

Keiding, Hans

2009-01-01

Smoking cessation therapies are among the most cost-effective preventive healthcare measures. Varenicline is a relatively new drug developed especially for this purpose, and it has been shown to achieve better quit rates than nicotine replacement therapies and the non-nicotine-based drug, bupropion...

Weight gain and cardiovascular risk factors during smoking cessation with bupropion or nicotine.

Science.gov (United States)

Botella-Carretero, J I; Escobar-Morreale, H F; Martín, I; Valero, A M; Alvarez, F; García, G; Varela, C; Cantarero, M

2004-03-01

Weight gain is frequent after smoking cessation, and may limit patient's will to quit and long-term success. Nicotine and bupropion are effective drugs for smoking withdrawal. However, their influence on weight gain, insulin resistance and other cardiovascular risk factors, as well as possible differences in obese and lean subjects, have not been fully evaluated. We randomised 25 lean and 25 obese smokers to receive either bupropion or nicotine patches. Clinical evaluation and lipid profile were performed at baseline and after treatment. Insulin resistance was also assessed at the end. Weight, BMI, waist-to-hip ratio, and diastolic blood pressure increased (p < 0.005), whereas lipid profile improved (p < 0.001) after smoking cessation independently of obesity at baseline or drug used. Obese patients had higher insulin resistance at the end (p < 0.05) regardless of drug used. Weight gain was inversely related to age (beta= - 0.125, R = 0.38, p = 0.046), and insulin resistance was related to obesity at baseline (beta = 0.85, R = 0.46, p = 0.02). In conclusion, weight gain after smoking cessation is not dependent on obesity or drug taken. A beneficial lipid profile is achieved after quitting smoking with either bupropion or nicotine patch in both obese and lean subjects.

Dorsal-CA1 Hippocampal Neuronal Ensembles Encode Nicotine-Reward Contextual Associations.

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Xia, Li; Nygard, Stephanie K; Sobczak, Gabe G; Hourguettes, Nicholas J; Bruchas, Michael R

2017-06-06

Natural and drug rewards increase the motivational valence of stimuli in the environment that, through Pavlovian learning mechanisms, become conditioned stimuli that directly motivate behavior in the absence of the original unconditioned stimulus. While the hippocampus has received extensive attention for its role in learning and memory processes, less is known regarding its role in drug-reward associations. We used in vivo Ca 2+ imaging in freely moving mice during the formation of nicotine preference behavior to examine the role of the dorsal-CA1 region of the hippocampus in encoding contextual reward-seeking behavior. We show the development of specific neuronal ensembles whose activity encodes nicotine-reward contextual memories and that are necessary for the expression of place preference. Our findings increase our understanding of CA1 hippocampal function in general and as it relates to reward processing by identifying a critical role for CA1 neuronal ensembles in nicotine place preference. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of the rewarding properties of nicotine and caffeine by implementation of a five-choice conditioned place preference task in zebrafish.

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Faillace, M P; Pisera-Fuster, A; Bernabeu, R

2018-06-08

The rewarding properties of drugs in zebrafish can be studied using the conditioned place preference (CPP) paradigm. Most devices that have been used for CPP consist of two-half tanks with or without a central chamber. Here we evaluated the rewarding effects of nicotine and caffeine using a tank with five arms distributed radially from a central chamber that we have denoted Fish Tank Radial Maze (FTRM). Zebrafish were trained to associate nicotine or caffeine with a coloured arm. In testing sessions to assess CPP induction, between two and five different arms were available to explore. We found that when offering the two arms, one of them associated to the drug mediating conditioning for 14 days, zebrafish showed nicotine-induced CPP but not caffeine-induced CPP. When zebrafish had the option to explore drug-paired arms together with new coloured arms as putative distractors, the nicotine-CPP strength was maintained for at least three days. The presence of novel environments induced caffeine-CPP, which was still positive after three days of testing sessions. Complementary behavioural data supported these findings. Nicotine-CPP was prevented by the histone deacetylase inhibitor phenylbutyrate administered during conditioning; however, there were no effects on caffeine-CPP. The specific acetylation of lysine 9 in histone 3 (H3-K9) was increased in nicotine-conditioned zebrafish brains. This study suggests that novel environmental cues facilitate drug-environment associations, and hence, the use of drugs of abuse. Copyright © 2018 Elsevier Inc. All rights reserved.

Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice

NARCIS (Netherlands)

Hanson, Julien; Gille, Andreas; Zwykiel, Sabrina; Lukasova, Martina; Clausen, Björn E.; Ahmed, Kashan; Tunaru, Sorin; Wirth, Angela; Offermanns, Stefan

2010-01-01

The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein-coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of

Nicotine chewing gum (2 mg, 4 mg) and cigarette smoking: comparative effects upon vigilance and heart rate.

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Parrott, A C; Winder, G

1989-01-01

Sixteen male smokers, abstinent the morning before testing, were assessed under four conditions: placebo chewing gum, 2 mg nicotine chewing gum, 4 mg nicotine gum, and cigarette smoking. Placebo gum was administered in the cigarette condition, while sham smoking occurred in the gum conditions. Pre-drug administration and post-drug difference scores were calculated for each assessment measure: rapid visual information processing (RVIP), memory for new information, and heart rate. Nicotine raised heart rate in a significant monotonic dose-related manner (P less than 0.001): placebo +0.2; 2 mg gum +5.1; 4 mg gum +9.8; cigarette +17.5 bpm. Rapid visual information processing target detections were also significantly related to dose (P less than 0.01), with this increased vigilance significant under 4 mg nicotine gum and cigarette smoking. Memory task performance was not significantly affected. Self-reported feelings of alertness/energy were higher while smoking than under placebo or 4 mg gum. Complaints about the taste of the 4 mg nicotine gum were frequent.

Comparison of effect of nicotine and levamisole and ivermectin on mortality of leech

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Mahmoud Bahmani

2014-02-01

Full Text Available Objective: To study the effect of different doses of nicotine on Limnatis in comparison with levamisole and ivermectin. Methods: In this interventional experimental study in July 2012, the amount of 61 mature leeches of Limnatis nilotica species were collected and anti-parasitic effects of drug treatments using anti-leech method were assessed. So that, a leech was placed in the dishes with 600 mL spring water and leech's paralysis and death time were recorded accurately for 720 min. A total of 9 replicates were considered for each treatment. Six drug treatments were considered. Pharmacological treatments include nicotine (5, 1 0 and 20 mg doses, levamisole (1 0 mg, ivermectin (10 mg and distilled water. Data were analyzed using the Sigma ASA 2 software and pair t-test method with less than 0.05 confidence levels. Results: The results of present study show that doses of 5, 10 and 20 mg of nicotine, with time average of 2.44依0.52, 1.88依0.78 and 1.55依0.72 min cause to death of leeches. Ivermectin and levamisole cause to death of leeches, averaging 7.44依1.12 and 14.66依5.09 min, respectively. Distilled water treatment has been reported as an ineffective group. Data analysis showed that the group receiving 5 mg nicotine, had minimum time of death and there are statistical differences among all groups (P>0.05, but there are not significant differences between treatments receiving 10 mg nicotine, with 5 and 20 mg nicotine treatments. Conclusions: It appears that nicotine compound as the effective substance of tobacco plant has the strong anti-leech effect on Limnatis nilotica species and can be used as leech purposes in the future.

Inhibition of monoacylglycerol lipase (MAGL) enhances cue-induced reinstatement of nicotine-seeking behavior in mice.

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Trigo, Jose M; Le Foll, Bernard

2016-05-01

Tobacco smoking is still a major population health issue. The endocannabinoid system has been shown to control drug-seeking behaviors. There are two main endocannabinoids: anandamide degraded by fatty acid amide hydrolase (FAAH) and 2-arachidonoylglycerol (2-AG) degraded by monoacylglycerol lipase (MAGL). The role of MAGL has only been explored recently, and so far, no study have been performed to evaluate the effects of MAGL inhibitor on nicotine reinforcing properties and cue-induced reinstatement of nicotine seeking. Here, we investigated the effects of the MAGL inhibitor JZL184 on nicotine self-administration under fixed and progressive-ratio schedules of reinforcement and on cue-induced reinstatement of nicotine seeking in mice. We also evaluated the effects of JZL184 on food self-administration for possible non-specific effects. JZL184 (0, 8, and 16 mg/kg) did not affect food taking, nicotine taking, or motivation for nicotine. MAGL inhibition by JZL184 (16 mg/kg) increased reinstatement of previously extinguished nicotine seeking induced by presentation of nicotine-associated cues, but did not produce reinstatement on its own. This study implicates involvement of 2-AG in nicotine-seeking behaviors.

The Influence of Puff Characteristics, Nicotine Dependence, and Rate of Nicotine Metabolism on Daily Nicotine Exposure in African American Smokers.

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Ross, Kathryn C; Dempsey, Delia A; St Helen, Gideon; Delucchi, Kevin; Benowitz, Neal L

2016-06-01

African American (AA) smokers experience greater tobacco-related disease burden than Whites, despite smoking fewer cigarettes per day (CPD). Understanding factors that influence daily nicotine intake in AA smokers is an important step toward decreasing tobacco-related health disparities. One factor of interest is smoking topography, or the study of puffing behavior. (i) to create a model using puff characteristics, nicotine dependence, and nicotine metabolism to predict daily nicotine exposure, and (ii) to compare puff characteristics and nicotine intake from two cigarettes smoked at different times to ensure the reliability of the puff characteristics included in our model. Sixty AA smokers smoked their preferred brand of cigarette at two time points through a topography device. Plasma nicotine, expired CO, and changes in subjective measures were measured before and after each cigarette. Total nicotine equivalents (TNE) was measured from 24-hour urine collected during ad libitum smoking. In a model predicting daily nicotine exposure, total puff volume, CPD, sex, and menthol status were significant predictors (R(2) = 0.44, P smokers. Cancer Epidemiol Biomarkers Prev; 25(6); 936-43. ©2016 AACR. ©2016 American Association for Cancer Research.

Enriched environment palliates nicotine-induced addiction and associated neurobehavioral deficits in rats.

Science.gov (United States)

Nawaz, Amber; Batool, Zehra; Ahmed, Saara; Tabassum, Saiqa; Khaliq, Saima; Mehdi, Bushra Jabeen; Sajid, Irfan; Ahmad, Shoaib; Saleem, Sadia; Naqvi, Fizza; Naqvi, Faizan; Haider, Saida

2017-11-01

This study was designed to investigate the role of enriched environment in preventing and/or reducing the neurobehavioral deficits produced after nicotine administration in albino Wistar rats. Equal numbers of rat in two groups were either placed in social environment (control group) or social along with physically enriched environment for four weeks before the administration of nicotine. Exposure to different environmental conditions was followed by the intraperitoneal injection of nicotine at the dose of 0.6 mg/kg for seven consecutive days during which addictive behavior was monitored using conditioned placed preference paradigm. Behavioral responses to locomotor activity, anxiety and retention of short term memory were investigated in control and nicotine injected groups exposed to different environments. Results of this study showed that the rats pre-exposed to physical along with social enrichment exhibited a decrease in drug seeking behavior, hyper locomotion, anxiogenic effects along with improvement of working memory as compared to control and nicotine injected groups that were kept in social environment alone. This behavioral study suggests that the exposure to physical enrichment along with socialization in young age can later reduce the chances of compulsive dependence on nicotine and related neurobehavioral deficits.

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Behavioral and Physiological Responses to Nicotine Patch Administration Among Nonsmokers Based on Acute and Chronic Secondhand Tobacco Smoke Exposure.

Science.gov (United States)

Okoli, Chizimuzo; Kodet, Jonathan; Robertson, Heather

2016-01-01

Despite the large amount that is known about the physical health effects of secondhand tobacco smoke (SHS) exposure, little is known about the behavioral health effects. Nicotine, the principle psychoactive substance in SHS, elicits subjective mood and physiological responses in nonsmokers. However, no studies have examined the subjective mood or physiological responses to nicotine in nonsmokers while accounting for prior chronic or acute SHS exposure. A 7-mg nicotine patch was administered to 17 adult nonsmokers for 2 hr. Main outcome measures obtained at ½ hr, 1 hr, and 2 hr were subjective behavioral drug effects (based on eleven 10-cm Visual Analog Scales [VASs]) and the physiological measures of heart rate, blood pressure, and serum nicotine levels. Analysis of outcome data was based on participants' chronic (using hair nicotine) or acute (using saliva cotinine) SHS exposure. Greater chronic SHS exposure was negatively associated with pleasurable responses to nicotine administration ("drug feels good" score at 2-hr time point, Spearman's ρ = -.65, p < .004), whereas greater acute SHS exposure was associated with positive responses ("like feeling of drug" score at 2-hr time point, Spearman's ρ = .63, p < .01). There were no associations between chronic or acute exposure and physiological changes in response to nicotine administration. The findings of this study may be useful in providing preliminary empirical data for future explorations of the mechanism whereby SHS exposure can influence behavioral outcomes in nonsmokers. Such studies can inform future interventions to reduce the physical and behavioral health risks associated with SHS exposure. © The Author(s) 2015.

Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

Science.gov (United States)

Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

2014-04-01

The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Nicotine delivery to users from cigarettes and from different types of e-cigarettes.

Science.gov (United States)

Hajek, Peter; Przulj, Dunja; Phillips, Anna; Anderson, Rebecca; McRobbie, Hayden

2017-03-01

Delivering nicotine in the way smokers seek is likely to be the key factor in e-cigarette (EC) success in replacing cigarettes. We examined to what degree different types of EC mimic nicotine intake from cigarettes. Twelve participants ('dual users' of EC and cigarettes) used their own brand cigarette and nine different EC brands. Blood samples were taken at baseline and at 2-min intervals for 10 min and again at 30 min. Eleven smokers provided usable data. None of the EC matched cigarettes in nicotine delivery (C max  = 17.9 ng/ml, T max  = 4 min and AUC 0->30  = 315 ng/ml/min). The EC with 48 mg/ml nicotine generated the closest PK profile (C max  = 13.6 ng/ml, T max  = 4 min, AUC 0->30  = 245 ng/ml/min), followed by a third generation EC using 20 mg/ml nicotine (C max  = 11.9 ng/ml, T max  = 6 min, AUC 0->30  = 232 ng/ml/min), followed by the tank system using 20 mg/ml nicotine (C max  = 9.9 ng/ml, T max  = 6 min, AUC 0->30  = 201 ng/ml/min). Cig-a-like PK values were similar, ranging from C max 7.5 to 9.7 ng/ml, T max 4-6 min, and AUC 0->30 144 to 173 ng/ml/min. Moderate differences in e-liquid nicotine concentrations had little effect on nicotine delivery, e.g. the EC with 24 mg/ml cartridge had the same PK profile as ECs with 16 mg/ml cartridges. Using similar strength e-liquid, the tank EC provided significantly more nicotine than cig-a-like ECs. EC brands we tested do not deliver nicotine as efficiently as cigarettes, but newer EC products deliver nicotine more efficiently than cig-a-like brands. Moderate variations in nicotine content of e-liquid have little effect on nicotine delivery. Smokers who are finding cig-a-like EC unsatisfactory should be advised to try more advanced systems.

Moderation of Nicotine Effects on Covert Orienting of Attention Tasks by Poor Placebo Performance and Cue Validity

Science.gov (United States)

Gilbert, David G.; Rzetelny, Adam; Rabinovich, Norka E.

2016-01-01

Introduction and Rationale Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement. Method The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task. Results Compared to a placebo patch, a 14 mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance. Conclusions These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine’s effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement. PMID:27461547

The ''in vivo'' distribution of carbon 11 labeled-nicotine in animals. A method suitable for use in man

International Nuclear Information System (INIS)

Maziere, M.; Berger, G.; Plummer, D.; Comar, D.; Masse, R.

1978-01-01

A method is described to label nicotine with carbon 11. A hundred millicuries can be obtained, in 45 minutes, with a high specific activity. This labeling of nicotine has allowed an ''in vivo'' study of the distribution of this very toxic drug in animals. Five minutes after injection in rabbits or monkeys, it was shown with a gamma camera or with a positron camera that the radioactivity was very rapidly distributed throughout the tissues especially in brain, lungs and kidneys. 11 C-nicotine readily penetrates the blood-brain barrier and the brain radioactivity decreases very sharply with time. The eyes however retained activity, possibly in the retina. Unfortunately the monkey is not the ideal subject for 11 C-nicotine brain study because: the brain is small, considering the resolution of the cameras and the cerebral lobes are also quite overlaped in this animal; Japanese authors have shown that compared with dogs the nicotine brain uptake is lower, due to the high affinity of nicotine for skeletal muscle which occupies approximately forty to fifty % of the body weight of the monkey. Also in monkeys, the nicotine destruction is faster than in dogs because there is a higher enzyme nicotine metabolizing activity in the liver of this animal. The differences observed between various animals studies using nicotine indicate that we should not draw any firm conclusions about the behaviour of this drug in humans. In order to do so, examinations must be conducted in man and the method described in spite of its limitations provides a means for such a study

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

Science.gov (United States)

Karatayev, Olga; Lukatskaya, Olga; Moon, Sang-Ho; Guo, Wei-Ran; Chen, Dan; Algava, Diane; Abedi, Susan; Leibowitz, Sarah F.

2015-01-01

Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes

Nicotine delivery efficiency of first- and second-generation e-cigarettes and its impact on relief of craving during the acute phase of use.

Science.gov (United States)

Rüther, Tobias; Hagedorn, Dieter; Schiela, Konstantin; Schettgen, Thomas; Osiander-Fuchs, Helga; Schober, Wolfgang

2018-03-01

Knowledge about the change in blood nicotine concentrations during the first five minutes (acute phase) of e-cigarette vaping is important to determine whether the used product has a dependence potential or may be an efficient nicotine replacement product. To address this issue, we monitored blood nicotine levels during the acute phase in volunteers using disposable cigalikes (CLs) and a tank model (TM) and compared them with blood nicotine levels in subjects using a tobacco cigarette (TC). In parallel, heart rate changes were continually measured and withdrawal symptoms and craving were assessed with the Questionnaire on Smoking Urges before and immediately after the vaping/smoking sessions. Additionally, at the end of each session negative health effects were rated on a visual analog scale. After five minutes of e-cigarette or TC use, the mean nicotine plasma concentrations were as follows: CLs, 5.5ng/ml; TM, 9.3ng/ml; TC, 17.1ng/ml. Nicotine levels increased significantly faster in the first 4min of consuming a TC than with the CLs and the TM. The highest rate of increase in nicotine concentration was found with the TC (6.8ng/ml) and TM (2.3ng/ml) between the 1st and 2nd minute, whereas the CLs showed comparatively small changes in the amount delivered over the five minutes. Withdrawal and craving for smoking decreased with the TM by the same amount as with the TC, even though less nicotine was delivered to the blood and considerably fewer side effects occurred. The heart rate of TM users was also markedly lower than that of the TC users. Unlike CLs, TM e-cigarettes represent an effective source of nicotine and might be used as an alternative nicotine replacement product to aid smoking cessation. However, nicotine plasma levels observed in TM users after short-time vaping have also the potential to produce and sustain nicotine addiction. Copyright © 2017 Elsevier GmbH. All rights reserved.

Gutkha Addiction: Nicotine Dependence or a Conditioned Reflex?

OpenAIRE

Joshi, Prathamesh Satish; Prashant, M C; Nagpal, Neelu; Patil, Atulkumar A; Ahuja, Rinky; Mathur, Vidhi

2015-01-01

Background: A pre-packaged mixture of areca nut, tobacco, slaked lime, catechu, and flavoring agents is popularly known as Gutkha. Aim of study is to analyze the addiction biology of Gutkha chewing and to assess efficacy of a cessation program based on nicotine replacement therapy (NRT). Materials and Methods: Patterns of addiction of 400 Gutkha chewers were analyzed with a questionnaire-based survey. Urine cotinine levels of 60 subjects undergoing NRT were periodically estimated using gas ch...

Nicotine Withdrawal Disrupts Contextual Learning but Not Recall of Prior Contextual Associations: Implications for Nicotine Addiction

OpenAIRE

Portugal, George S.; Gould, Thomas J.

2008-01-01

Interactions between nicotine and learning could contribute to nicotine addiction. Although previous research indicates that nicotine withdrawal disrupts contextual learning, the effects of nicotine withdrawal on contextual memories acquired before withdrawal are unknown. The present study investigated whether nicotine withdrawal disrupted recall of prior contextual memories by examining the effects of nicotine withdrawal on recall of nicotine conditioned place preference (CPP) and contextual...

Thermochemical Properties of Nicotine Salts

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Riggs DM

2014-12-01

Full Text Available The thermal gravimetric analysis (TGA and differential scanning calorimetry (DSC results presented in this report clearly show that the thermal stability and the endothermic peak nicotine release temperatures are different for different nicotine salts and these temperatures appear to be linked to the general microstructural details of the salt itself. In addition, the peak nicotine release temperatures are highly dependent upon the sample size used. The heat of vaporization for neat (non-protonated nicotine is also sample-size dependent. The TGA data showed that the least stable of the salts tested at elevated temperatures was the liquid salt nicotine triacetate followed by the crystalline materials (e.g., nicotine gallate and finally, the amorphous salts (e.g., nicotine alginate. The DSC results revealed that the liquid and crystalline salts exhibit nicotine release endotherms that are strongly related to the sample weight being tested. The amorphous salts show nicotine endotherm peak temperatures that are nearly independent of the sample weight. The range of peak nicotine release temperatures varied depending upon the specific salts and the sample size from 83 oC to well over 200 oC. Based on these results, the evolution of nicotine from the nicotine salt should be expected to vary based on the composition of the salt, the details of its microstructure, and the amount of nicotine salt tested.

Behavioral desensitization to nicotine is enhanced differentially by ethanol in long-sleep and short-sleep mice.

Science.gov (United States)

de Fiebre, C M; Collins, A C

1989-01-01

In order to assess the anticonvulsant potency of ethanol, male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with ethanol 7.5 min prior to challenge with an ED80 dose of nicotine (LS: 4.25 mg/kg; SS: 6.25 mg/kg). LS mice were more sensitive to the anticonvulsant effects of ethanol than were SS mice. In order to assess the effect of ethanol on the nicotine-induced behavioral desensitization to nicotine observed previously in these mice, animals were pretreated with saline, nonanticonvulsant doses of ethanol (0.25 g/kg, 0.75 g/kg or 1.5 g/kg), a subseizure-producing dose of nicotine (2.0 mg/kg) or a combination of these two drugs 15 or 30 min prior to nicotine challenge. Ethanol enhanced the nicotine-induced behavioral desensitization in both mouse lines; however, this effect was seen at lower ethanol doses and was more pronounced in LS mice. Ethanol pretreatment did not affect brain nicotine concentrations; therefore, the ethanol effect probably involves changes in brain sensitivity to nicotine.

Smoking and nicotine in inflammatory bowel disease: good or bad for cytokines?

Directory of Open Access Journals (Sweden)

F. J. Zijlstra

1998-01-01

Full Text Available Smoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis and Crohn's disease respectively. Transdermal application of nicotine had similar effects in ulcerative colitis and therefore was considered to be an effective basic drug which could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid resistant ulcerative colitis. In this communication the short-term use of nicotine in ulcerative colitis is reviewed.

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers

OpenAIRE

Van Overmeire, Ilse P. I.; De Smedt, Tom; Dendale, Paul; Nackaerts, Kristiaan; Vanacker, Hilde; Vanoeteren, Jan F. A.; Van Laethem, Danny M. G.; Van Loco, Joris; De Cremer, Koen A. J.

2016-01-01

Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerstrom Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual F...

Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report.

Science.gov (United States)

Ramôa, Carolina P; Hiler, Marzena M; Spindle, Tory R; Lopez, Alexa A; Karaoghlanian, Nareg; Lipato, Thokozeni; Breland, Alison B; Shihadeh, Alan; Eissenberg, Thomas

2016-04-01

Electronic cigarettes (ECIGs) aerosolise a liquid that usually contains propylene glycol and/or vegetable glycerine, flavourants and the dependence-producing drug, nicotine, in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration and plasma nicotine concentration and puffing behaviour in experienced ECIG users. Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil 'cartomiser' loaded with 1 mL of a flavoured propylene glycol/vegetable glycerine liquid to complete four sessions, at least 2 days apart, that differed by nicotine concentration (0, 8, 18 or 36 mg/mL). In each session, participants completed two 10-puff ECIG-use bouts (30 s puff interval) separated by 60 min. Venous blood was sampled to determine plasma nicotine concentration. Puff duration, volume and average flow rate were measured. Immediately after bout 1, mean plasma nicotine concentration was 5.5 ng/mL (SD=7.7) for 0 mg/mL liquid, with significantly (pcombustible cigarette. The rationale for this higher level of nicotine delivery is uncertain. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking.

Science.gov (United States)

Ross, Kathryn C; Gubner, Noah R; Tyndale, Rachel F; Hawk, Larry W; Lerman, Caryn; George, Tony P; Cinciripini, Paul; Schnoll, Robert A; Benowitz, Neal L

2016-09-01

Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity. Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers. There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites. The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure. Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed. The results indicated that rate of nicotine metabolism was a more important factor influencing nicotine intake in White smokers. Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine. However, this relationship was not found in African Americans. Overall there was a greater step-down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic Nicotine Treatment During Adolescence Attenuates the Effects of Acute Nicotine in Adult Contextual Fear Learning.

Science.gov (United States)

Holliday, Erica D; Gould, Thomas J

2017-01-01

Adolescent onset of nicotine abuse is correlated with worse chances at successful abstinence in adulthood. One reason for this may be due to enduring learning deficits resulting from nicotine use during adolescence. Previous work has indicated that chronic nicotine administration beginning in late adolescence (PND38) caused learning deficits in contextual fear when tested in adulthood. The purpose of this study was to determine if chronic nicotine treatment during adolescence would alter sensitivity to nicotine's cognitive enhancing properties in adulthood. C57BL/6J mice received saline or chronic nicotine (12.6mg/kg/day) during adolescence (postnatal day 38) or adulthood (postnatal day 54) for a period of 12 days. Following a 30-day protracted abstinence, mice received either an acute injection of saline or nicotine (0.045, 0.18, and 0.36mg/kg) prior to training and testing a mouse model of contextual fear. It was found that chronic nicotine administration in adult mice did not alter sensitivity to acute nicotine following a protracted abstinence. In adolescent mice, chronic nicotine administration disrupted adult learning and decreased sensitivity to acute nicotine in adulthood as only the highest dose tested (0.36mg/kg) was able to enhance contextual fear learning. These results suggest that adolescent nicotine exposure impairs learning in adulthood, which could increase the risk for continued nicotine use in adulthood by requiring administration of higher doses of nicotine to reverse learning impairments caused by adolescent nicotine exposure. Results from this study add to the growing body of literature suggesting chronic nicotine exposure during adolescence leads to impaired learning in adulthood and demonstrates that nicotine exposure during adolescence attenuates the cognitive enhancing effects of acute nicotine in adulthood, which suggests altered cholinergic function. © The Author 2016. Published by Oxford University Press on behalf of the Society for

The 5-HT2C receptor agonist lorcaserin reduces nicotine self-administration, discrimination, and reinstatement: relationship to feeding behavior and impulse control.

Science.gov (United States)

Higgins, Guy A; Silenieks, Leo B; Rossmann, Anne; Rizos, Zoe; Noble, Kevin; Soko, Ashlie D; Fletcher, Paul J

2012-04-01

Lorcaserin ((1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl) is a selective 5-HT(2C) receptor agonist with clinical efficacy in phase-III obesity trials. Based on evidence that this drug class also affects behaviors motivated by drug reinforcement, we compared the effect of lorcaserin on behavior maintained by food and nicotine reinforcement, as well as the stimulant and discriminative stimulus properties of nicotine in the rat. Acutely administered lorcaserin (0.3-3 mg/kg, subcutaneous (SC)) dose dependently reduced feeding induced by 22-h food deprivation or palatability. Effects up to 1 mg/kg were consistent with a specific effect on feeding motivation. Lorcaserin (0.6-1 mg/kg, SC) reduced operant responding for food on progressive and fixed ratio schedules of reinforcement. In this dose range lorcaserin also reversed the motor stimulant effect of nicotine, reduced intravenous self-administration of nicotine, and attenuated the nicotine cue in rats trained to discriminate nicotine from saline. Lorcaserin also reduced the reinstatement of nicotine-seeking behavior elicited by a compound cue comprising a nicotine prime and conditioned stimulus previously paired with nicotine reinforcement. Lorcaserin did not reinstate nicotine-seeking behavior or substitute for a nicotine cue. Finally, lorcaserin (0.3-1 mg/kg) reduced nicotine-induced increases in anticipatory responding, a measure of impulsive action, in rats performing the five-choice serial reaction time task. Importantly, these results indicate that lorcaserin, and likely other selective 5-HT(2C) receptor agonists, similarly affect both food- and nicotine-motivated behaviors, and nicotine-induced impulsivity. Collectively, these findings highlight a therapeutic potential for 5-HT(2C) agonists such as lorcaserin beyond obesity into addictive behaviors, such as nicotine dependence.

The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance

OpenAIRE

Pesta, Dominik H; Angadi, Siddhartha S; Burtscher, Martin; Roberts, Christian K

2013-01-01

Abstract Caffeine, nicotine, ethanol and tetrahydrocannabinol (THC) are among the most prevalent and culturally accepted drugs in western society. For example, in Europe and North America up to 90% of the adult population drinks coffee daily and, although less prevalent, the other drugs are also used extensively by the population. Smoked tobacco, excessive alcohol consumption and marijuana (cannabis) smoking are addictive and exhibit adverse health effects. These drugs are not only com...

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro.

Science.gov (United States)

Ying, Xiaozhou; Zhang, Wei; Cheng, Shaowen; Nie, Pengfei; Cheng, Xiaojie; Shen, Yue; Wang, Wei; Xue, Enxing; Chen, Qingyu; Kou, Dongquan; Peng, Lei; Zhang, Yu; Lu, Chuanzhu

2012-11-01

Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10(-7), 10(-6) and 10(-5) M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro. BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue. The cell viability was not significantly impaired until up to a concentration of 10(-5) M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10(-6) M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10(-5) M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10(-7) and 10(-6) M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10(-7)-10(-5) M nicotine (P < 0.05). It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.

Role of endocannabinoids in regulating drug dependence

Directory of Open Access Journals (Sweden)

Daniela Parolaro

2007-01-01

Full Text Available Daniela Parolaro, Daniela Vigano’, Natalia Realini, Tiziana RubinoNeuroscience Center, DBSF, University of Insubria, Busto Arsizio, ItalyAbstract: This review will discuss the latest knowledge of how the endocannabinoid system might be involved in treating addiction to the most common illicit drugs. Experimental models are providing increasing evidence for the pharmacological management of endocannabinoid signaling not only to block the direct reinforcing effects of cannabis, opioids, nicotine and ethanol, but also for preventing relapse to the various drugs of abuse, including opioids, cocaine, nicotine, alcohol and metamphetamine. Preclinical and clinical studies suggest that the endocannabinoid system can be manipulated by the CB1 receptor antagonist SR141716A, that might constitute a new generation of compounds for treating addiction across different classes of abused drugs.Keywords: Endocannabinoids, drug dependence, opioids, nicotine, alcohol, psychostimulants

Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of cocaine and nicotine place preference

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Ream eAl-Hasani

2013-08-01

Full Text Available Stress increases the risk of drug abuse, causes relapse to drug seeking, and potentiates the rewarding properties of both nicotine and cocaine. Understanding the mechanisms by which stress regulates the rewarding properties of drugs of abuse provides valuable insight into potential treatments for drug abuse. Prior reports have demonstrated that stress causes dynorphin release, activating kappa-opioid receptors (KOR in monoamine circuits resulting in both potentiation and reinstatement of cocaine and nicotine conditioned place preference. Here we report that kappa-opioid dependent reinstatement of cocaine and nicotine place preference is reduced when the mice are exposed to a randomized chronic mild stress regime prior to training in a conditioned place preference-reinstatement paradigm. The chronic mild stress schedule involves seven different stressors (removal of nesting for 24hr, 5min forced swim stress at 15°C, 8hr food and water deprivation, damp bedding overnight, white noise, cage tilt and disrupted home cage lighting rotated over a three-week period. This response is KOR-selective, because chronic mild stress does not protect against cocaine or nicotine drug-primed reinstatement. This protection from reinstatement is also observed following sub-chronic social defeat stress, where each mouse is placed in an aggressor mouse home cage for a period of 20 min over five days. In contrast, a single acute stressor resulted in a potentiation of KOR-induced reinstatement, similarly to previously reported. Prior studies have shown that stress alters sensitivity to opioids and prior stress can influence the pharmacodynamics of the opioid receptor system. Together, these findings suggest that exposure to different forms of stress may cause a dysregulation of kappa opioid circuitry and that changes resulting from mild stress can have protective and adaptive effects against drug relapse.

A synthetic combinatorial strategy for developing a-conotoxin analogs as potent a7 nicotinic acetylcholine receptor antagonists

DEFF Research Database (Denmark)

Armishaw, Christopher J; Singh, Narender; Medina-Franco, Jose L

2010-01-01

alpha-Conotoxins are peptide neurotoxins isolated from venomous cone snails that display exquisite selectivity for different subtypes of nicotinic acetylcholine receptors (nAChR). They are valuable research tools that have profound implications in the discovery of new drugs for a myriad of neurop......alpha-Conotoxins are peptide neurotoxins isolated from venomous cone snails that display exquisite selectivity for different subtypes of nicotinic acetylcholine receptors (nAChR). They are valuable research tools that have profound implications in the discovery of new drugs for a myriad...

Electronic Nicotine Delivery Systems.

Science.gov (United States)

Walley, Susan C; Jenssen, Brian P

2015-11-01

Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control. Copyright © 2015 by the American Academy of Pediatrics.

Evaluating psychological markers for human nicotine dependence: tobacco choice, extinction, and Pavlovian-to-instrumental transfer.

Science.gov (United States)

Hogarth, Lee; Chase, Henry W

2012-06-01

Individual differences in drug dependence may be mediated by several abnormalities in associative learning, including perseveration of drug-seeking following contingency change, greater control over drug-seeking by Pavlovian stimuli, or greater sensitivity to drug reinforcement establishing higher rates of drug-seeking. To evaluate these three candidate markers for nicotine dependence, Experiment 1 contrasted daily (N = 22) and nondaily smoker groups (N = 22) on a novel instrumental learning task, where one S+ was first trained as a predictor of tobacco reward before being extinguished. Experiment 2 compared daily (N = 18) and nondaily smoker groups (N = 18) on a concurrent-choice task for tobacco and chocolate reward before an extinction test in which the tobacco response was extinguished, followed by a Pavlovian-to-instrumental transfer test, wherein the impact of tobacco and chocolate cues on concurrent choice was measured (gender was balanced within each smoker group). The results showed no group difference in sensitivity to extinction of either the stimulus-drug or response-drug contingency in Experiments 1 and 2, respectively, nor did groups show a difference in Pavlovian-to-instrumental transfer of control over tobacco choice. By contrast, nicotine-dependence status was marked by a higher frequency of tobacco choice in the concurrent-choice procedure, and this choice preference was associated with subjective craving (gender did not affect any behavioral measure). These results favor the view that nicotine dependence in this sample is not determined by individual predilection for perseveration or stimulus-control over drug-seeking, but by greater sensitivity to reinforcement of instrumental drug choice. Value-based decision theories of dependence are discussed.

Brain nicotinic acetylcholine receptors are involved in stress-induced potentiation of nicotine reward in rats.

Science.gov (United States)

Javadi, Parastoo; Rezayof, Ameneh; Sardari, Maryam; Ghasemzadeh, Zahra

2017-07-01

The aim of the present study was to examine the possible role of nicotinic acetylcholine receptors of the dorsal hippocampus (CA1 regions), the medial prefrontal cortex or the basolateral amygdala in the effect of acute or sub-chronic stress on nicotine-induced conditioned place preference. Our results indicated that subcutaneous administration of nicotine (0.2 mg/kg) induced significant conditioned place preference. Exposure to acute or sub-chronic elevated platform stress potentiated the response of an ineffective dose of nicotine. Pre-conditioning intra-CA1 (0.5-4 µg/rat) or intra-medial prefrontal cortex (0.2-0.3 µg/rat) microinjection of mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist) reversed acute stress-induced potentiation of nicotine reward as measured in the conditioned place preference paradigm. By contrast, pre-conditioning intra-basolateral amygdala microinjection of mecamylamine (4 µg/rat) potentiated the effects of acute stress on nicotine reward. Our findings also showed that intra-CA1 or intra-medial prefrontal cortex, but not intra-basolateral amygdala, microinjection of mecamylamine (4 µg/rat) prevented the effect of sub-chronic stress on nicotine reward. These findings suggest that exposure to elevated platform stress potentiates the rewarding effect of nicotine which may be associated with the involvement of nicotinic acetylcholine receptors. It seems that there is a different contribution of the basolateral amygdala, the medial prefrontal cortex or the CA1 nicotinic acetylcholine receptors in stress-induced potentiation of nicotine-induced conditioned place preference.

Effects of nicotine on visuo-spatial selective attention as indexed by event-related potentials.

Science.gov (United States)

Meinke, A; Thiel, C M; Fink, G R

2006-08-11

Nicotine has been shown to specifically reduce reaction times to invalidly cued targets in spatial cueing paradigms. In two experiments, we used event-related potentials to test whether the facilitative effect of nicotine upon the detection of invalidly cued targets is due to a modulation of perceptual processing, as indexed by early attention-related event-related potential components. Furthermore, we assessed whether the effect of nicotine on such unattended stimuli depends upon the use of exogenous or endogenous cues. In both experiments, the electroencephalogram was recorded while non-smokers completed discrimination tasks in Posner-type paradigms after chewing a nicotine polacrilex gum (Nicorette 2 mg) in one session and a placebo gum in another session. Nicotine reduced reaction times to invalidly cued targets when cueing was endogenous. In contrast, no differential effect of nicotine on reaction times was observed when exogenous cues were used. Electrophysiologically, we found a similar attentional modulation of the P1 and N1 components under placebo and nicotine but a differential modulation of later event-related potential components at a frontocentral site. The lack of a drug-dependent modulation of P1 and N1 in the presence of a behavioral effect suggests that the effect of nicotine in endogenous visuo-spatial cueing tasks is not due to an alteration of perceptual processes. Rather, the differential modulation of frontocentral event-related potentials suggests that nicotine acts at later stages of target processing.

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers.

Science.gov (United States)

Van Overmeire, Ilse P I; De Smedt, Tom; Dendale, Paul; Nackaerts, Kristiaan; Vanacker, Hilde; Vanoeteren, Jan F A; Van Laethem, Danny M G; Van Loco, Joris; De Cremer, Koen A J

2016-09-01

Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerström Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual FTND items. Urine samples and questionnaire data of 239 daily smokers were obtained. Nicotine, cotinine and hydroxycotinine urinary levels were determined by UPLC MS/MS.Multiple linear regression models were developed to explore the relationship between nicotine, cotinine, hydroxycotinine levels and separate FTND scores (for all six items). We found significant correlations between the different urinary biomarker concentrations, and the FTND score. The time before the first cigarette after waking (TTFC) was significantly associated with the nicotine, cotinine and hydroxycotinine concentrations. No association was found between the ratio of hydroxycotinine to cotinine and either the FTND or the CPD. A model including four FTND questions, sex, age, and the cotinine concentration, accounted for 45% of the variance of CPD. There are significant relationships between urinary levels of nicotine, cotinine, and hydroxycotinine and the FTND score. Especially the FTND question about TTFC is relevant for explaining the biomarker concentrations. CPD (below 15) was significantly explained by four FTND dependence items and urinary cotinine levels in a regression model. We investigated associations between urinary levels of nicotine, cotinine, and hydroxycotinine in daily smokers and the FTND scores for nicotine dependence. We did not find association between the hydroxycotinine/cotinine ratio and CPD. We developed a model that explains the cigarettes smoked daily (CPD) in a group of light

Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research.

Science.gov (United States)

Dursun, S M; Kutcher, S

1999-02-01

Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.

78 FR 19718 - Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use

Science.gov (United States)

2013-04-02

... nicotine lozenge and mini-lozenge were approved directly for OTC use in 2002 and 2009, respectively. \\1\\ A... the Agency's Adverse Event Reporting System and to the Substance Abuse and Mental Health Services...

Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

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Jennifer E Bruin

Full Text Available Nicotine replacement therapy (NRT is currently recommended as a safe smoking cessation aid for pregnant women. However, fetal and neonatal nicotine exposure in rats causes mitochondrial-mediated beta cell apoptosis at weaning, and adult-onset dysglycemia, which we hypothesize is related to progressive mitochondrial dysfunction in the pancreas. Therefore in this study we examined the effect of fetal and neonatal exposure to nicotine on pancreatic mitochondrial structure and function during postnatal development. Female Wistar rats were given saline (vehicle control or nicotine bitartrate (1 mg/kg/d via subcutaneous injection for 2 weeks prior to mating until weaning. At 3-4, 15 and 26 weeks of age, oral glucose tolerance tests were performed, and pancreas tissue was collected for electron microscopy, enzyme activity assays and islet isolation. Following nicotine exposure mitochondrial structural abnormalities were observed beginning at 3 weeks and worsened with advancing age. Importantly the appearance of these structural defects in nicotine-exposed animals preceded the onset of glucose intolerance. Nicotine exposure also resulted in significantly reduced pancreatic respiratory chain enzyme activity, degranulation of beta cells, elevated islet oxidative stress and impaired glucose-stimulated insulin secretion compared to saline controls at 26 weeks of age. Taken together, these data suggest that maternal nicotine use during pregnancy results in postnatal mitochondrial dysfunction that may explain, in part, the dysglycemia observed in the offspring from this animal model. These results clearly indicate that further investigation into the safety of NRT use during pregnancy is warranted.

Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes.

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Amber N Brown

Full Text Available Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.

Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats

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Sanchez, Victoria; Moore, Catherine F; Brunzell, Darlene H; Lynch, Wendy J

2013-01-01

Rationale Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population. Objectives To determine if wheel running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence. Methods Male adolescent rats (n = 55) were trained to self-administer saline or nicotine infusions (5 or 10 μg/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30. After 5 days, access was extended to 23-hr/day with unlimited infusions for a total of 10 days. After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2-hr/day. Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm. Results Intake was higher at the 10 μg/kg dose as compared to the 5 μg/kg dose; however, intake did not differ within doses prior to wheel assignment. Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect. Nicotine led to modest, but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise. Conclusions Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction. PMID:23371488

Electronic cigarettes and nicotine clinical pharmacology.

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Schroeder, Megan J; Hoffman, Allison C

2014-05-01

To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

Electronic cigarettes and nicotine clinical pharmacology

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Schroeder, Megan J; Hoffman, Allison C

2014-01-01

Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

Nicotinic receptor blockade decreases fos immunoreactivity within orexin/hypocretin-expressing neurons of nicotine-exposed rats.

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Simmons, Steven J; Gentile, Taylor A; Mo, Lili; Tran, Fionya H; Ma, Sisi; Muschamp, John W

2016-11-01

Tobacco smoking is the leading cause of preventable death in the United States. Nicotine is the principal psychoactive ingredient in tobacco that causes addiction. The structures governing nicotine addiction, including those underlying withdrawal, are still being explored. Nicotine withdrawal is characterized by negative affective and cognitive symptoms that enhance relapse susceptibility, and suppressed dopaminergic transmission from ventral tegmental area (VTA) to target structures underlies behavioral symptoms of nicotine withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking smokers at one-year post-cessation, and new targets are needed to more effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade, which is commonly used to precipitate withdrawal, on orexin neurons remain poorly investigated and present an attractive target for intervention. The present study sought to investigate the effects of nicotinic receptor blockade on hypothalamic orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate groups of rats were treated with either chronic nicotine or saline for 7-days at which point effects of mecamylamine or saline on somatic signs and anxiety-like behavior were assessed. Finally, tissue from rats was harvested for immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that nicotinic receptor blockade leads to reduced orexin cell activity, as indicated by lowered Fos-immunoreactivity, and suggest that this underlying cellular activity may be associated with symptoms of nicotine withdrawal as effects were most prominently observed in rats given chronic nicotine. We conclude from this study that orexin transmission becomes suppressed in rats upon nicotinic receptor blockade, and that behavioral symptoms associated

Isolating behavioral mechanisms of intertemporal choice: nicotine effects on delay discounting and amount sensitivity.

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Locey, Matthew L; Dallery, Jesse

2009-03-01

Many drugs of abuse produce changes in impulsive choice, that is, choice for a smaller-sooner reinforcer over a larger-later reinforcer. Because the alternatives differ in both delay and amount, it is not clear whether these drug effects are due to the differences in reinforcer delay or amount. To isolate the effects of delay, we used a titrating delay procedure. In phase 1, 9 rats made discrete choices between variable delays (1 or 19 s, equal probability of each) and a delay to a single food pellet. The computer titrated the delay to a single food pellet until the rats were indifferent between the two options. This indifference delay was used as the starting value for the titrating delay for all future sessions. We next evaluated the acute effects of nicotine (subcutaneous 1.0, 0.3, 0.1, and 0.03 mg/kg) on choice. If nicotine increases delay discounting, it should have increased preference for the variable delay. Instead, nicotine had very little effect on choice. In a second phase, the titrated delay alternative produced three food pellets instead of one, which was again produced by the variable delay (1 s or 19 s) alternative. Under this procedure, nicotine increased preference for the one pellet alternative. Nicotine-induced changes in impulsive choice are therefore likely due to differences in reinforcer amount rather than differences in reinforcer delay. In addition, it may be necessary to include an amount sensitivity parameter in any mathematical model of choice when the alternatives differ in reinforcer amount.

Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

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Moheimani, Roya S; Bhetraratana, May; Peters, Kacey M; Yang, Benjamin K; Yin, Fen; Gornbein, Jeffrey; Araujo, Jesus A; Middlekauff, Holly R

2017-09-20

Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

'Real-world' compensatory behaviour with low nicotine concentration e-liquid: subjective effects and nicotine, acrolein and formaldehyde exposure.

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Dawkins, Lynne; Cox, Sharon; Goniewicz, Maciej; McRobbie, Hayden; Kimber, Catherine; Doig, Mira; Kośmider, Leon

2018-06-07

To compare the effects of i) high versus low nicotine concentration e-liquid, ii) fixed versus adjustable power and iii) the interaction between the two on: a) vaping behaviour, b) subjective effects, c) nicotine intake, and d) exposure to acrolein and formaldehyde in e-cigarette users vaping in their everyday setting. Counterbalanced, repeated measures with four conditions: i) low nicotine (6 mg/mL)/fixed power; ii) low nicotine/adjustable power; iii) high nicotine (18 mg/mL)/fixed power; iv) high nicotine/adjustable power. London and the South East, England. Twenty experienced e-cigarette users (recruited between September 2016 and February 2017) vaped ad libitum using an eVic Supreme™ with a 'Nautilus Aspire' tank over four weeks (one week per condition). Puffing patterns (daily puff number [PN], puff duration [PD], inter-puff interval [IPI]), mL of e-liquid consumed, changes to power (where permitted), and subjective effects (urge to vape, nicotine withdrawal symptoms) were measured in each condition. Nicotine intake was measured via salivary cotinine. 3-hydroxypropylmercapturic acid (3-HPMA), a metabolite of the toxicant acrolein, and formate, a metabolite of the carcinogen formaldehyde, were measured in urine. There was a significant nicotine concentration x power interaction for PD (p<0.01). PD was longer with low nicotine/fixed power compared with i) high nicotine/fixed power (p< 0.001 and ii) low nicotine/adjustable power (p< 0.01). PN and liquid consumed were higher in the low versus high nicotine condition (main effect of nicotine, p<0.05). Urge to vape and withdrawal symptoms were lower, and nicotine intake was higher, in the high nicotine condition (main effects of nicotine: p<0.01). Whilst acrolein levels did not differ, there was a significant nicotine x power interaction for formaldehyde (p<0.05). Use of a lower nicotine concentration e-liquid may be associated with compensatory behaviour (e.g., higher number and duration of puffs) and increases

Glutamatergic transmission in drug reward: implications for drug addiction

OpenAIRE

D'Souza, Manoranjan S.

2015-01-01

Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades...

Nicotine reduction as an increase in the unit price of cigarettes: a behavioral economics approach.

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Smith, Tracy T; Sved, Alan F; Hatsukami, Dorothy K; Donny, Eric C

2014-11-01

Urgent action is needed to reduce the harm caused by smoking. Product standards that reduce the addictiveness of cigarettes are now possible both in the U.S. and in countries party to the Framework Convention on Tobacco Control. Specifically, standards that required substantially reduced nicotine content in cigarettes could enable cessation in smokers and prevent future smoking among current non-smokers. Behavioral economics uses principles from the field of microeconomics to characterize how consumption of a reinforcer changes as a function of the unit price of that reinforcer (unit price=cost/reinforcer magnitude). A nicotine reduction policy might be considered an increase in the unit price of nicotine because smokers are paying more per unit of nicotine. This perspective allows principles from behavioral economics to be applied to nicotine reduction research questions, including how nicotine consumption, smoking behavior, use of other tobacco products, and use of other drugs of abuse are likely to be affected. This paper reviews the utility of this approach and evaluates the notion that a reduction in nicotine content is equivalent to a reduction in the reinforcement value of smoking-an assumption made by the unit price approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats.

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Noori, Negin; Bangash, Mohammad Yasan; Motaghinejad, Majid; Hosseini, Pantea; Noudoost, Behshad

2014-01-01

Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment. Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20(th) and 25(th) days. The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

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

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Grebenstein, Patricia E; Burroughs, Danielle; Roiko, Samuel A; Pentel, Paul R; LeSage, Mark G

2015-06-01

The 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. The 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. Considerable 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. These 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Science.gov (United States)

Grebenstein, Patricia E.; Burroughs, Danielle; Roiko, Samuel A.; Pentel, Paul R.; LeSage, Mark G.

2015-01-01

Background The 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. Methods The 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. Results Considerable 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. Conclusions These 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. PMID:25891231

Chronic Nicotine Exposure Initiated in Adolescence and Unpaired to Behavioral Context Fails to Enhance Sweetened Ethanol Seeking

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Aric C. Madayag

2017-08-01

Full Text Available Nicotine use in adolescence is pervasive in the United States and, according to the Gateway Hypothesis, may lead to progression towards other addictive substances. Given the prevalence of nicotine and ethanol comorbidity, it is difficult to ascertain if nicotine is a gateway drug for ethanol. Our study investigated the relationship between adolescent exposure to nicotine and whether this exposure alters subsequent alcohol seeking behavior. We hypothesized that rats exposed to nicotine beginning in adolescence would exhibit greater alcohol seeking behavior than non-exposed siblings. To test our hypothesis, beginning at P28, female rats were initially exposed to once daily nicotine (0.4 mg/kg, SC or saline for 5 days. Following these five initial injections, animals were trained to nose-poke for sucrose reinforcement (10%, w/v, gradually increasing to sweetened ethanol (10% sucrose; 10% ethanol, w/v on an FR5 reinforcement schedule. Nicotine injections were administered after the behavioral sessions to minimize acute effects of nicotine on operant self-administration. We measured the effects of nicotine exposure on the following aspects of ethanol seeking: self-administration, naltrexone (NTX-induced decreases, habit-directed behavior, motivation, extinction and reinstatement. Nicotine exposure did not alter self-administration or the effectiveness of NTX to reduce alcohol seeking. Nicotine exposure blocked habit-directed ethanol seeking. Finally, nicotine did not alter extinction learning or cue-induced reinstatement to sweetened ethanol seeking. Our findings suggest that nicotine exposure outside the behavioral context does not escalate ethanol seeking. Further, the Gateway Hypothesis likely applies to scenarios in which nicotine is either self-administered or physiologically active during the behavioral session.

Enhancement of a visual reinforcer by D-amphetamine and nicotine in adult rats: relation to habituation and food restriction.

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Wright, Jennifer M; Ren, Suelynn; Constantin, Annie; Clarke, Paul B S

2018-03-01

Nicotine and D-amphetamine can strengthen reinforcing effects of unconditioned visual stimuli. We investigated whether these reinforcement-enhancing effects reflect a slowing of stimulus habituation and depend on food restriction. Adult male rats pressed an active lever to illuminate a cue light during daily 60-min sessions. Depending on the experiment, rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg IP) and nicotine (0.025-0.2 mg/kg SC) or with the tobacco constituent norharman (0.03-10 μg/kg IV). Experiment 1 tested for possible reinforcement-enhancing effects of D-amphetamine and norharman. Experiment 2 investigated whether nicotine and amphetamine inhibited the spontaneous within-session decline in lever pressing. Experiment 3 assessed the effects of food restriction. Amphetamine (0.25-1 mg/kg) and nicotine (0.1 mg/kg) increased active lever pressing specifically (two- to threefold increase). The highest doses of nicotine and amphetamine also affected inactive lever responding (increase and decrease, respectively). With the visual reinforcer omitted, responding was largely extinguished. Neither drug appeared to slow habituation, as assessed by the within-session decline in lever pressing, and reinforcement-enhancing effects still occurred if the drugs were given after this decline had occurred. Food restriction enhanced the reinforcement-enhancing effect of amphetamine but not that of nicotine. Responding remained goal-directed after several weeks of testing. Low doses of D-amphetamine and nicotine produced reinforcement enhancement even in free-feeding subjects, independent of the spontaneous within-session decline in responding. Reinforcement enhancement by amphetamine, but not nicotine, was enhanced by concurrent subchronic food restriction.

Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol.

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Becker, Jérôme A J; Kieffer, Brigitte L; Le Merrer, Julie

2017-09-01

Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse. © 2016 Society for the Study of Addiction.

Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement

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Yu Liu

2008-01-01

Full Text Available The conditioned place preference (CPP model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

Rapid detection of nicotine from breath using desorption ionisation on porous silicon.

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Guinan, T M; Abdelmaksoud, H; Voelcker, N H

2017-05-04

Desorption ionisation on porous silicon (DIOS) was used for the detection of nicotine from exhaled breath. This result represents proof-of-principle of the ability of DIOS to detect small molecular analytes in breath including biomarkers and illicit drugs.

Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence

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Prevost A Toby

2010-11-01

Full Text Available Abstract Background The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication. The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy (NRT of informing smokers that their oral dose of NRT has been tailored to a DNA analysis. Hypotheses to be tested are as follows: IAdherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA (genotype, compared to one tailored to nicotine dependence questionnaire score (phenotype. II Amongst smokers who fail to quit at six months, motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype. Methods/Design An open label, parallel groups randomised trial in which 630 adult smokers (smoking 10 or more cigarettes daily using National Health Service (NHS stop smoking services in primary care are randomly allocated to one of two groups: i. NRT oral dose tailored by DNA analysis (OPRM1 gene (genotype, or ii. NRT oral dose tailored by nicotine dependence questionnaire score (phenotype The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt, with the secondary outcome being motivation to make another quit attempt, amongst smokers not abstinent at six months. Other outcomes include adherence to NRT in the first seven days and biochemically validated smoking abstinence at six months. The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5% difference in mean proportion of NRT consumed using a two-tailed test at the 5% level of significance between groups. The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent samples t-test and by estimating the 95

Drugs + HIV, Learn the Link

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Full Text Available ... Bath Salts) Tobacco/Nicotine and E-Cigs Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults ... 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction have been linked with HIV/AIDS since the ...

Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

Directory of Open Access Journals (Sweden)

Nicole M Mantella

Full Text Available Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1 or orosensory-mediated responses to nicotine solutions (Experiment 2 were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are

Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

Science.gov (United States)

Mantella, Nicole M; Youngentob, Steven L

2014-01-01

Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

Insight into nicotine addiction

Directory of Open Access Journals (Sweden)

Sahil Handa

2017-01-01

Full Text Available The emergence of the epidemic of nicotine addiction in India and other nations is a global public health tragedy of untoward proportions. Smoking or chewing tobacco can seriously affect general, as well as oral health. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke and addiction to nicotine is the proximate cause of these diseases. This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. The pharmacologic reasons for nicotine use are an enhancement of mood, either directly or through relief of withdrawal symptoms and augmentation of mental or physical functions. Tobacco cessation is necessary to reduce morbidity and mortality related to tobacco use. Strategies for tobacco cessation involves 5A's and 5R's approach and pharmacotherapy. Dental professionals play an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. Dentists are in a unique position to educate and motivate patients concerning the hazards of tobacco to their oral and systemic health, and to provide intervention programs as a part of routine patient care.

Surveillance of smokeless tobacco nicotine, pH, moisture, and unprotonated nicotine content.

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Richter, Patricia; Spierto, Francis W

2003-12-01

Smokeless tobacco is a complex chemical mixture, including not only the components of the tobacco leaf but also chemicals added during the manufacturing process. Smokeless tobacco contains the addictive chemical nicotine and more than 20 cancer-causing chemicals, including the potent tobacco-specific nitrosamines. The National Toxicology Program of the National Institutes of Health has concluded that oral use of smokeless tobacco is a human carcinogen. Therefore, smokeless tobacco is not a safe alternative to cigarettes. In fact, smokeless tobacco use begins primarily during early adolescence and can lead to nicotine dependence and increased risk of becoming a cigarette smoker. Under the Comprehensive Smokeless Tobacco Health Education Act of 1986 (15 U.S.C. 4401 et seq., Pub. L. 99-252), tobacco manufacturers report annually to the Centers for Disease Control and Prevention (CDC) on the total nicotine, unprotonated nicotine, pH, and moisture content of their smokeless tobacco products. This information is considered "trade secret," or confidential, in accordance with 5 U.S.C. 552(b)(4) and 18 U.S.C. 1905 and cannot be released to the public. In an effort to provide consumers and researchers with information on the nicotine content of smokeless tobacco, CDC arranged for the analysis of popular brands of smokeless tobacco. The results of this CDC study show that pH is a primary factor in the amount of nicotine that is in the most readily absorbable, unprotonated form. Furthermore, this study found that the brands of moist snuff smokeless tobacco with the largest amount of unprotonated nicotine also are the most frequently sold brands.

Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain

Directory of Open Access Journals (Sweden)

Anat eBiegon

2012-11-01

Full Text Available Cigarette smoking continues to be a major public health problem, and while smoking rates in men have shown some decrease over the last few decades, smoking rates among girls and young women are increasing. Practically all of the important aspects of cigarette smoking are sexually dimorphic. Women become addicted more easily than men, while finding it harder to quit. Nicotine replacement appears to be less effective in women. This may be linked to the observation that women are more sensitive than men to non-nicotine cues or ingredients in cigarettes. The reasons for these sex differences are mostly unknown. Several lines of evidence suggest that many of the reported sex differences related to cigarette smoking may stem from the inhibitory effects of nicotine and other tobacco alkaloids on estrogen synthesis via the enzyme aromatase (cyp19a gene product. Aromatase is the last enzyme in estrogen biosynthesis, catalyzing the conversion of androgens to estrogens. This review provides a summary of experimental evidence supporting brain aromatase as a potential mediator and/or modulator of nicotine actions in the brain, contributing to sex differences in smoking behavior. Additional research on the interaction between tobacco smoke, nicotine and aromatase may help devise new, sex specific methods for prevention and treatment of smoking addiction.

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

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Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.

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McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E; Kozink, Rachel V; Addicott, Merideth A; Sweitzer, Maggie M; Westman, Eric C; Van Wert, Dana M

2016-07-01

Smoking abstinence impairs executive function, which may promote continued smoking behavior and relapse. The differential influence of nicotine and non-nicotine (i.e. sensory, motor) smoking factors and related neural substrates is not known. In a fully factorial, within-subjects design, 33 smokers underwent fMRI scanning following 24 hours of wearing a nicotine or placebo patch while smoking very low nicotine content cigarettes or remaining abstinent from smoking. During scanning, blood oxygenation level-dependent (BOLD) signal was acquired while participants performed a verbal N-back task. Following 24-hour placebo (versus nicotine) administration, accuracy on the N-back task was significantly worse and task-related BOLD signal lower in dorsomedial frontal cortex. These effects were observed irrespective of smoking. Our data provide novel evidence that abstinence-induced deficits in working memory and changes in underlying brain function are due in large part to abstinence from nicotine compared with non-nicotine factors. This work has implications both for designing interventions that target abstinence-induced cognitive deficits and for nicotine-reduction policy. © 2015 Society for the Study of Addiction.

Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

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Sudakov, S K; Bogdanova, N G

2016-10-01

The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

Energy Technology Data Exchange (ETDEWEB)

Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Roskams, Tania [Department of Morphology and Molecular Pathology, University of Leuven (Belgium); Oben, Jude A., E-mail: j.oben@ucl.ac.uk [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Department of Gastroenterology and Hepatology, Guy' s and St Thomas' Hospital, London SE1 7EH (United Kingdom)

2012-01-06

Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

International Nuclear Information System (INIS)

Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI; Roskams, Tania; Oben, Jude A.

2012-01-01

Highlights: ► Cigarette smoke may induce liver fibrosis via nicotine receptors. ► Nicotine induces proliferation of hepatic stellate cells (HSCs). ► Nicotine activates hepatic fibrogenic pathways. ► Nicotine receptor antagonists attenuate HSC proliferation. ► Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine – which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed – RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-α2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-β1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type (α1, β1, delta and epsilon) and neuronal type (α3, α6, α7, β2 and β4) nAChR subunits at the mRNA level. Among these subunits, α3, α7, β1 and ε were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-α2 and TGF-β1 mRNA expression were significantly upregulated by nicotine and inhibited by mecamylamine. α1 and α3-nAChR mRNA expression was significantly upregulated in NASH fibrosis compared to normal livers. Conclusion: Nicotine at levels in smokers’ blood is pro-fibrogenic, through

A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

Energy Technology Data Exchange (ETDEWEB)

Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles

2013-02-01

The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.

Nicotine-magnesium aluminum silicate microparticle surface modified with chitosan for mucosal delivery

DEFF Research Database (Denmark)

Kanjanakawinkul, Watchara; Rades, Thomas; Puttipipatkhachorn, Satit

2013-01-01

Magnesium aluminum silicate (MAS), a negatively charged clay, and nicotine (NCT), a basic drug, can interact electrostatically to form microparticles. Chitosan (CS) was used for the surface modification of the microparticles, and a lyophilization method was used to preserve the original particle...

The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction.

Science.gov (United States)

Selya, Arielle S; Dierker, Lisa; Rose, Jennifer S; Hedeker, Donald; Mermelstein, Robin J

2017-07-07

remains unclear. The use of e-cigarettes as a quit aid was not associated with reductions in conventional smoking, consistent with most other quit aids in this sample except for nicotine replacement therapy, which was only effective for the most dependent smokers. Notably, these findings highlight the necessity of accounting for smokers' nicotine dependence levels when examining tobacco use patterns. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain indices of nicotine's effects on attentional bias to smoking and emotional pictures and to task-relevant targets.

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Gilbert, David G; Sugai, Chihiro; Zuo, Yantao; Rabinovich, Norka E; McClernon, F Joseph; Froeliger, Brett

2007-03-01

Aversive and smoking-related stimuli are related to smoking urges and relapse and can be potent distractors of selective attention. It has been suggested that the beneficial effect of nicotine replacement therapy may be mediated partly by the ability of nicotine to reduce distraction by such stimuli and thereby to facilitate attention to task-relevant stimuli. The present study tested the hypothesis that nicotine reduces distraction by aversive and smoking-related stimuli as indexed by the parietal P3b brain response to a task-relevant target digit. We assessed the effect of nicotine on distraction by emotionally negative, positive, neutral, and smoking-related pictures immediately preceding target digits during a rapid visual information processing task in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included two experimental sessions. After overnight smoking deprivation (12+ hr), active nicotine patches were applied to participants during one of the sessions and placebo patches were applied during the other session. Nicotine enhanced P3b responses associated with target digits immediately subsequent to negative emotional pictures bilaterally and subsequent to smoking-related pictures only in the right hemisphere. No effects of nicotine were observed for P3bs subsequent to positive and neutral distractor pictures. Another measure of attention, contingent negative variation amplitude in anticipation of the target digits also was increased by nicotine, especially in the left hemisphere and at posterior sites. Together, these findings suggest that nicotine reduces the distraction by emotionally negative and smoking-related stimuli and promotes attention to task-related stimuli by modulating somewhat lateralized and task-specific neural networks.

Low Nicotine Content Descriptors Reduce Perceived Health Risks and Positive Cigarette Ratings in Participants Using Very Low Nicotine Content Cigarettes.

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Denlinger-Apte, Rachel L; Joel, Danielle L; Strasser, Andrew A; Donny, Eric C

2017-10-01

Understanding how smokers perceive reduced nicotine content cigarettes will be important if the FDA and global regulatory agencies implement reduced nicotine product standards for cigarettes. Prior research has shown that some smokers incorrectly believe "light" cigarettes are less harmful than regular cigarettes. Similar misunderstandings of health risk could also apply to reduced nicotine cigarettes. To date, most studies of reduced nicotine cigarettes have blinded subjects to the nicotine content. Therefore, little is known about how smokers experience reduced nicotine content cigarettes when they are aware of the reduced content, and how use may be impacted. The present study was a within-subjects experiment with 68 adult daily smokers who smoked two identical very low nicotine content Quest 3 (0.05 mg nicotine yield) cigarettes. Subjects were told that one cigarette contained "average" nicotine content, and the other contained "very low" nicotine content. After smoking each cigarette, subjects completed subjective measures about their smoking experience. Subjects rated the "very low" nicotine cigarette as less harmful to their health overall compared to the "average" nicotine cigarette; this effect held true for specific smoking-related diseases. Additionally, they rated the "very low" nicotine cigarette as having less desirable subjective effects than the "average" nicotine cigarette and predicted having greater interest in quitting smoking in the future if only the "very low" nicotine cigarette was available. Explicit knowledge of very low nicotine content changes smokers' perceptions of very low nicotine content cigarettes, resulting in reduced predicted harm, subjective ratings and predicted future use. Before a reduced nicotine product standard for cigarettes can be implemented, it is important to understand how product information impacts how smokers think about and experience very low nicotine content cigarettes. Prior research has shown that smokers

Nicotine concentration of e-cigarettes used by adolescents.

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Morean, Meghan E; Kong, Grace; Cavallo, Dana A; Camenga, Deepa R; Krishnan-Sarin, Suchitra

2016-10-01

E-cigarettes are popular among youth, but little is known about the nicotine concentrations of e-liquids used by adolescents. In Spring, 2014, we conducted cross-sectional surveys in four Connecticut high schools and two middle schools. Among past-30-day e-cigarette users (n=513, 45% female, mean age 15.9 [SD=1.4]), we examined what nicotine concentration adolescents typically used in their e-cigarettes (range 0-30mg/mL and "I don't know"). We first examined whether age, sex, smoking status, e-cigarette use frequency, and/or e-cigarette acquisition source were associated with using nicotine-free e-liquid, nicotine e-liquid, or not knowing the e-liquid nicotine concentration. Among nicotine users (n=185), we then examined whether the aforementioned variables were associated with using higher nicotine concentrations. Adolescents reported using nicotine-free e-liquid (28.5%), nicotine e-liquid (37.4%), or not knowing their e-liquid nicotine concentration (34.1%). Nicotine users comprised more smokers and heavier e-cigarette users compared to nicotine-free e-liquid users and those who did not know their nicotine concentration. Nicotine users also comprised more males and were more likely to purchase e-cigarettes online or from tobacco shops compared to those who did not know their nicotine concentration. Among nicotine users, cigarette smoking, male sex, and purchasing e-cigarettes from tobacco shops predicted using higher nicotine concentrations. Adolescents reported using e-liquids with variable nicotine concentrations. Smokers, males, and those who purchased their own e-cigarettes reported using the highest nicotine levels. Of concern, many adolescents were unaware of the nicotine concentration in their e-liquid, raising concerns about inadvertent nicotine exposure among youth. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neonatal Nicotine Exposure Increases Excitatory Synaptic Transmission and Attenuates Nicotine-stimulated GABA release in the Adult Rat Hippocampus

Science.gov (United States)

Damborsky, Joanne C.; Griffith, William H.; Winzer-Serhan, Ursula H.

2014-01-01

Developmental exposure to nicotine has been linked to long-lasting changes in synaptic transmission which may contribute to behavioral abnormalities seen in offspring of women who smoke during pregnancy. Here, we examined the long-lasting effects of developmental nicotine exposure on glutamatergic and GABAergic neurotransmission, and on acute nicotine-induced glutamate and GABA release in the adult hippocampus, a structure important in cognitive and emotional behaviors. We utilized a chronic neonatal nicotine treatment model to administer nicotine (6 mg/kg/day) to rat pups from postnatal day (P) 1–7, a period that falls developmentally into the third human trimester. Using whole-cell voltage clamp recordings from CA1 pyramidal neurons in hippocampal slices, we measured excitatory and inhibitory postsynaptic currents in neonatally control- and nicotine-treated young adult males. Neonatal nicotine exposure significantly increased AMPA receptor-mediated spontaneous and evoked excitatory signaling, with no change in glutamate release probability in adults. Conversely, there was no increase in spontaneous GABAergic neurotransmission in nicotine-males. Chronic neonatal nicotine treatment had no effect on acute nicotine-stimulated glutamate release in adults, but acute nicotine-stimulated GABA release was significantly attenuated. Thus, neonatal nicotine exposure results in a persistent net increase in excitation and a concurrent loss of nicotinic acetylcholine receptor (nAChR)-mediated regulation of presynaptic GABA but not glutamate release, which would exacerbate excitation following endogenous or exogenous nAChR activation. Our data underscore an important role for nAChRs in hippocampal excitatory synapse development, and suggest selective long-term changes at specific presynaptic nAChRs which together could explain some of the behavioral abnormalities associated with maternal smoking. PMID:24950455

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Is nicotine replacement therapy overvalued in smoking cessation? Analysis of smokers' and quitters' communication in social media.

Science.gov (United States)

Kurko, Terhi; Linden, Kari; Kolstela, Maija; Pietilä, Kirsi; Airaksinen, Marja

2015-12-01

Internet discussion forums provide new, albeit less used data sources for exploring personal experiences of illness and treatment strategies. To gain an understanding of how discussion forum participants value nicotine replacement therapy (NRT) in smoking cessation (SC). Finnish national Internet-based discussion forum, STUMPPI, supporting SC and consisting of ten free discussion areas, each with a different focus. The analysis was based on STUMPPI forum participants' postings (n = 24 481) in five discussion areas during January 2007-January 2012. Inductive content analysis of the postings concerning NRT use or comparing NRT to other SC methods. Three major themes related to NRT in SC emerged from the discussions. These were as follows: (I) distrust and negative attitude towards NRT; (II) neutral acceptance of NRT as a useful SC method; and (III) trust on the crucial role of NRT and other SC medicines. The negative attitude was related to following perceptions: NRT use maintains tobacco dependence, fear of NRT dependence or experience of not gaining help from NRT use. NRT was perceived to be useful particularly in the initiation of SC attempts and in dealing with physiological dependence. The most highlighted factors of successful quitting were quitters' own psychological empowerment and peer support from the discussion community. The majority of STUMPPI forum participants had low or balanced expectations towards the role of NRT in SC. More research from the smokers' and quitters' perspective is needed to assess the real value of NRT compared to other methods in SC. © 2014 John Wiley & Sons Ltd.

Neuronal nicotinic acetylcholine receptors: Common molecular substrates of nicotine and alcohol dependence

Directory of Open Access Journals (Sweden)

Linzy M. Hendrickson

2013-04-01

Full Text Available Alcohol and nicotine are often co-abused. As many as 80-95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs, ligand-gated cation channels normally activated by endogenous acetylcholine (ACh, ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA which project to the nucleus accumbens (NAc. Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from preclinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence.

Genotoxicity study on nicotine and nicotine-derived nitrosamine by accelerator mass spectrometry

International Nuclear Information System (INIS)

Li, X.S.; Wang, H.F.; Shi, J.Y.; Wang, X.Y.; Liu, Y.F.; Li, K.; Lu, X.Y.; Wang, J.J.; Liu, K.X.; Guo, Z.Y.

1997-01-01

The authors have studied DNA adduction with 14 C-labelled nicotine and nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by accelerator mass spectrometry (AMS) in mouse liver at doses equivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 μg to 4.0 x 10 2 μg·kg -1 , and from 0.1 μg to 2.0 x 10 4 μg·kg -1 , respectively. In the exposure of mice to either nicotine or NNK, the number of DNA adducts increased linearly with increasing dose. The detection limit of DNA adducts was 1 adduct per 10 11 nucleotide molecules. This limit is 1-4 orders of magnitude lower than that of other techniques used for quantification of DNA adducts. The results of the animal experiments enabled us to speculate that nicotine is a potential carcinogen. According to the procedure for 14 C-labelled-NNK synthesis, the authors discuss the ultimate chemical speciation of NNK bound to DNA. From the animal tests the authors derived a directly perceivable relation between tobacco consumption and DNA adduction as the carcinogenic risk assessment

Pathogenesis of Abdominal Aortic Aneurysms: Role of Nicotine and Nicotinic Acetylcholine Receptors

Directory of Open Access Journals (Sweden)

Zong-Zhuang Li

2012-01-01

Full Text Available Inflammation, proteolysis, smooth muscle cell apoptosis, and angiogenesis have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs, although the well-defined initiating mechanism is not fully understood. Matrix metalloproteinases (MMPs such as MMP-2 and -9 and other proteinases degrading elastin and extracellular matrix are the critical pathogenesis of AAAs. Among the risk factors of AAAs, cigarette smoking is an irrefutable one. Cigarette smoke is practically involved in various aspects of the AAA pathogenesis. Nicotine, a major alkaloid in tobacco leaves and a primary component in cigarette smoke, can stimulate the MMPs expression by vascular SMCs, endothelial cells, and inflammatory cells in vascular wall and induce angiogenesis in the aneurysmal tissues. However, for the inflammatory and apoptotic processes in the pathogenesis of AAAs, nicotine seems to be moving in just the opposite direction. Additionally, the effects of nicotine are probably dose dependent or associated with the exposure duration and may be partly exerted by its receptors—nicotinic acetylcholine receptors (nAChRs. In this paper, we will mainly discuss the pathogenesis of AAAs involving inflammation, proteolysis, smooth muscle cell apoptosis and angiogenesis, and the roles of nicotine and nAChRs.

Common biology of craving across legal and illegal drugs - a quantitative meta-analysis of cue-reactivity brain response.

Science.gov (United States)

Kühn, Simone; Gallinat, Jürgen

2011-04-01

The present quantitative meta-analysis set out to test whether cue-reactivity responses in humans differ across drugs of abuse and whether these responses constitute the biological basis of drug craving as a core psychopathology of addiction. By means of activation likelihood estimation, we investigated the concurrence of brain regions activated by cue-induced craving paradigms across studies on nicotine, alcohol and cocaine addicts. Furthermore, we analysed the concurrence of brain regions positively correlated with self-reported craving in nicotine and alcohol studies. We found direct overlap between nicotine, alcohol and cocaine cue reactivity in the ventral striatum. In addition, regions of close proximity were observed in the anterior cingulate cortex (ACC; nicotine and cocaine) and amygdala (alcohol, nicotine and cocaine). Brain regions of concurrence in drug cue-reactivity paradigms that overlapped with brain regions of concurrence in self-reported craving correlations were found in the ACC, ventral striatum and right pallidum (for alcohol). This first quantitative meta-analysis on drug cue reactivity identifies brain regions underlying nicotine, alcohol and cocaine dependency, i.e. the ventral striatum. The ACC, right pallidum and ventral striatum were related to drug cue reactivity as well as self-reported craving, suggesting that this set of brain regions constitutes the core circuit of drug craving in nicotine and alcohol addiction. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats.

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Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L

2014-11-01

Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by

Mecamylamine, dihydro-β-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine

Science.gov (United States)

Struthers, Amanda M.; Wilkinson, Jamie L.; Dwoskin, Linda P.; Crooks, Peter A.; Bevins, Rick A.

2009-01-01

Current smokers express the desire to quit. However, the majority find it difficult to remain abstinent. As such, research efforts continually seek to develop more effective treatment. One such area of research involves the interoceptive stimulus effects of nicotine as either a discriminative stimulus in an operant drug discrimination task, or more recently as a conditional stimulus (CS) in a discriminated goal-tracking task. The present work investigated the potential role nicotinic acetylcholine receptors in the CS effects of nicotine (0.4 mg/kg) using antagonists with differential selectivity for β2*, α7*, α6β2*, and α3β4* receptors. Methyllycaconitine (MLA) had no effect on nicotine-evoked conditioned responding. Mecamylamine and dihydro-β-erythroidine (DHβE) dose dependently blocked responding evoked by the nicotine CS. In a time-course assessment of mecamylamine and DHβE, each blocked conditioned responding when given 5 min before testing and still blocked conditioned responding when administered 200 min before testing. Two novel bis-picolinium analogs (N, N’-(3, 3′-(dodecan-1,12-diyl)-bis-picolinium dibromide [bPiDDB], and N, N’-(decan-1,10-diyl)-bis-picolinium diiodide [bPiDI]) did not block nicotine-evoked conditioned responding. Finally, pretreatment with low dose combinations of mecamylamine, dextromethorphan, and/or bupropion were used to target α3β4* receptors. No combination blocked conditioned responding evoked by the training dose of nicotine. However, a combination of mecamylamine and dextromethorphan partially blocked nicotine-evoked conditioned responding to a lower dose of nicotine (0.1 mg/kg). These results indicate that β2* and potentially α3β4* nicotinic acetylcholine receptors play a role in the CS effects of nicotine and are potential targets for the development of nicotine cessation aids. PMID:19778551

The impact of TV mass media campaigns on calls to a National Quitline and the use of prescribed nicotine replacement therapy: a structural vector autoregression analysis.

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Haghpanahan, Houra; Mackay, Daniel F; Pell, Jill P; Bell, David; Langley, Tessa; Haw, Sally

2017-07-01

To estimate (1) the immediate impact; (2) the cumulative impact; and (3) the duration of impact of Scottish tobacco control TV mass media campaigns (MMCs) on smoking cessation activity, as measured by calls to Smokeline and the volume of prescribed nicotine replacement therapy (NRT). Multivariate time-series analysis using secondary data on population level measures of exposure to TV MMCs broadcast and smoking cessation activity between 2003 and 2012. Population of Scotland. Adult television viewer ratings (TVRs) as a measure of exposure to Scottish mass media campaigns in the adult population; monthly calls to NHS Smokeline; and the monthly volume of prescribed NRT as measured by gross ingredient costs (GIC). Tobacco control TVRs were associated with an increase in calls to Smokeline but not an increase in the volume of prescribed NRT. A 1 standard deviation (SD) increase of 194 tobacco control TVRs led to an immediate and significant increase of 385.9 [95% confidence interval (CI) = 171.0, 600.7] calls to Smokeline (unadjusted model) within 1 month. When adjusted for seasonality the impact was reduced, but the increase in calls remained significant (226.3 calls, 95% CI = 37.3, 415.3). The cumulative impact on Smokeline calls remained significant for 6 months after broadcast in the unadjusted model and 18 months in the adjusted model. However, an increase in tobacco control TVRs of 194 failed to have a significant impact on the GIC of prescribed NRT in either the unadjusted (£1361.4, 95% CI = -£9138.0, £11860.9) or adjusted (£6297.1, 95% CI = -£2587.8, £15182.1) models. Tobacco control television mass media campaigns broadcast in Scotland between 2003 and 2012 were effective in triggering calls to Smokeline, but did not increase significantly the use of prescribed nicotine replacement therapy by adult smokers. The impact on calls to Smokeline occurred immediately within 1 month of broadcast and was sustained for at least 6 months. © 2017 The

Habenular expression of rare missense variants of the β4 nicotinic receptor subunit alters nicotine consumption

Directory of Open Access Journals (Sweden)

Marta A Ślimak

2014-01-01

Full Text Available The CHRNA5-CHRNA3-CHRNB4 gene cluster, encoding the α5, α3 and β4 nicotinic acetylcholine receptor (nAChR subunits, has been linked to nicotine dependence. The habenulo-interpeduncular (Hb-IPN tract is particularly enriched in α3β4 nAChRs. We recently showed that modulation of these receptors in the medial habenula (MHb in mice altered nicotine consumption. Given that β4 is rate-limiting for receptor activity and that single nucleotide polymorphisms (SNPs in CHRNB4 have been linked to altered risk of nicotine dependence in humans, we were interested in determining the contribution of allelic variants of β4 to nicotine receptor activity in the MHb. We screened for missense SNPs with allele frequencies > 0.0005 and introduced the corresponding substitutions in Chrnb4. Fourteen variants were analyzed by co-expression with α3. We found that β4A90I and β4T374I variants, previously shown to associate with reduced risk of smoking, and an additional variant β4D447Y, significantly increased nicotine-evoked current amplitudes, while β4R348C, the mutation most frequently encountered in sporadic amyotrophic lateral sclerosis (sALS, showed reduced nicotine currents. We employed lentiviruses to express β4 or β4 variants in the MHb. Immunoprecipitation studies confirmed that β4 lentiviral-mediated expression leads to specific upregulation of α3β4 but not β2 nAChRs in the Mhb. Mice injected with the β4-containing virus showed pronounced aversion to nicotine as previously observed in transgenic Tabac mice overexpressing Chrnb4 at endogenous sites including the MHb. Habenular expression of the β4 gain-of-function allele T374I also resulted in strong aversion, while transduction with the β4 loss-of function allele R348C failed to induce nicotine aversion. Altogether, these data confirm the critical role of habenular β4 in nicotine consumption, and identify specific SNPs in CHRNB4 that modify nicotine-elicited currents and alter nicotine

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On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl.

Science.gov (United States)

Shin, Soo Hyeon; Ghosh, Priyanka; Newman, Bryan; Hammell, Dana C; Raney, Sam G; Hassan, Hazem E; Stinchcomb, Audra L

2017-09-01

At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

Looking for boomerang effects: a pre-post experimental study of the effects of exposure of youth to television advertising for nicotine replacement therapy and Zyban.

Science.gov (United States)

Durkin, Sarah; Wakefield, Melanie; Spittal, Matt

2006-12-01

In the context of concerns about unintended "boomerang" influences of advertising, this study aimed to examine effects of nicotine replacement therapy (NRT) and Zyban advertising on youth perceptions of the ease of quitting, health risks of smoking and future intentions to smoke. 718 youth aged 14-16years were randomly allocated to view four television ads promoting either: NRT; Zyban; non-pharmaceutical cessation services (telephone Quitline); or non-cessation messages on sun protection. Questionnaire measures were administered before and after viewing ads. There were no effects of advertising exposure on perceived health effects of smoking or intentions to smoke. Compared with the sun protection ads, but not the Quitline ads, those exposed to NRT ads reported stronger perceptions about the ease of quitting, but non-susceptible non-smokers primarily drove this difference. This study suggests that exposure to NRT and Zyban advertising in an experimental context does not reliably influence youth smoking-related beliefs, especially those vulnerable to becoming regular smokers.

NICOTINE EFFECTS ON THE MOTOR ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

Science.gov (United States)

Several studies in the literature have shown that exposure of mice and rats to nicotine early in development alters its effects when the rodents are subsequently challenged with nicotine. Anatoxin-a is a nicotinic agonist produced by several genera of cyanobacteria, and has caus...

Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

International Nuclear Information System (INIS)

El-Mas, Mahmoud M.; Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

2012-01-01

We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE 2 ) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS PE and BRS SNP ). Nicotine (100 μg/kg i.v.) reduced BRS SNP in OVX rats but not in proestrus or OVXE 2 rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS PE was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS SNP interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS SNP attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E 2 against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

Assessment of nicotine concentration in electronic nicotine delivery system (ENDS) liquids and precision of dosing to aerosol.

Science.gov (United States)

Kosmider, Leon; Sobczak, Andrzej; Szołtysek-Bołdys, Izabela; Prokopowicz, Adam; Skórka, Agnieszka; Abdulafeez, Oluyadi; Koszowski, Bartosz

2015-01-01

Global use of electronic nicotine delivery systems (ENDS; also called electronic cigarettes, e-cigarettes) has increased dramatically in recent years. However, due to the limited safety studies and growing concerns on the potential toxicity from long term use of ENDS, many national and international governments have employed regulatory measures to curtail its use. One of the most significant challenges regulators of ENDS encounter is the lack of quality standards to assess ENDS, e-liquid (solution used with ENDS which contain nicotine--a highly toxic and addictive substance), and amount of nicotine delivery to aerosol during ENDS use. Aims of the study were to (1) measure and compare nicotine concentration in e-liquids to values reported by manufacturers on packaging labels; (2) assess the precision of nicotine delivery from tank during aerosol formation. Methods: Nine popular Polish e-liquids (based on the market share data from October 2014) were purchased for the study. The labelled nicotine concentration for the selected e-liquids ranged between 11-25 mg/mL. All e-liquids were aerosolized in the laboratory using a smoking simulation machine (Palaczbot). Each e-liquid was aerosolized in a series of 6 consecutive bouts. A single bout consisted of 15 puffs with the following puff topography: 65 mL puff volume, 2.8 sec. puff duration, and 19 sec. interpuff interval. A total of 90 puffs were generated from each e-liquid. Nicotine content in the e-liquids and the aerosol generated were determined by gas chromatography with thermionic sensitive detection (GC-TSD). For seven of nine analyzed e-liquids, the difference between measured and manufacturer labeled nicotine concentration was less than 10%. Nicotine dose in aerosol per bout ranged between 0.77-1.49 mg (equivalent to one-half the nicotine a smoker inhales from a single combustible cigarette). Our analysis showed the high consistency between the labeled and measured nicotine concentration for popular on the

Dianicline, a novel α4β2 nicotinic acetylcholine receptor partial agonist, for smoking cessation: a randomized placebo-controlled clinical trial

DEFF Research Database (Denmark)

Tonstad, Serena; Holme, Ingar; Tønnesen, Philip

2011-01-01

Dianicline is a α4β2 nicotinic acetylcholine receptor partial agonist, a class of drugs that includes varenicline and cytisine. Varenicline is efficacious for smoking cessation, while cytisine has not been studied systematically. The efficacy of dianicline has not been previously tested in an ade......Dianicline is a α4β2 nicotinic acetylcholine receptor partial agonist, a class of drugs that includes varenicline and cytisine. Varenicline is efficacious for smoking cessation, while cytisine has not been studied systematically. The efficacy of dianicline has not been previously tested...

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

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Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models

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Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

Science.gov (United States)

Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

2017-09-01

Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

Measurement of nicotine in household dust

International Nuclear Information System (INIS)

Kim, Sungroul; Aung, Ther; Berkeley, Emily; Diette, Gregory B.; Breysse, Patrick N.

2008-01-01

An analytical method of measuring nicotine in house dust was optimized and associations among three secondhand smoking exposure markers were evaluated, i.e., nicotine concentrations of both house dust and indoor air, and the self-reported number of cigarettes smoked daily in a household. We obtained seven house dust samples from self-reported nonsmoking homes and 30 samples from smoking homes along with the information on indoor air nicotine concentrations and the number of cigarettes smoked daily from an asthma cohort study conducted by the Johns Hopkins Center for Childhood Asthma in the Urban Environment. House dust nicotine was analyzed by isotope dilution gas chromatography-mass spectrometry (GC/MS). Using our optimized method, the median concentration of nicotine in the dust of self-reported nonsmoking homes was 11.7 ng/mg while that of smoking homes was 43.4 ng/mg. We found a substantially positive association (r=0.67, P<0.0001) between house dust nicotine concentrations and the numbers of cigarettes smoked daily. Optimized analytical methods showed a feasibility to detect nicotine in house dust. Our results indicated that the measurement of nicotine in house dust can be used potentially as a marker of longer term SHS exposure

Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization.

Science.gov (United States)

Zhao, Zongmin; Hu, Yun; Harmon, Theresa; Pentel, Paul; Ehrich, Marion; Zhang, Chenming

2017-09-01

A lipid-polymeric hybrid nanoparticle-based next-generation nicotine nanovaccine was rationalized in this study to combat nicotine addiction. A series of nanovaccines, which had nicotine-haptens localized on carrier protein (LPKN), nanoparticle surface (LPNK), or both (LPNKN), were designed to study the impact of hapten localization on their immunological efficacy. All three nanovaccines were efficiently taken up and processed by dendritic cells. LPNKN induced a significantly higher immunogenicity against nicotine and a significantly lower anti-carrier protein antibody level compared to LPKN and LPNK. Meanwhile, it was found that the anti-nicotine antibodies elicited by LPKN and LPNKN bind nicotine stronger than those elicited by LPKN, and LPNK and LPNKN resulted in a more balanced Th1-Th2 immunity than LPKN. Moreover, LPNKN exhibited the best ability to block nicotine from entering the brain of mice. Collectively, the results demonstrated that the immunological efficacy of the hybrid nanoparticle-based nicotine vaccine could be enhanced by modulating hapten localization, providing a promising strategy to combatting nicotine addiction. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of co-administration of opium and morphine with nicotine during pregnancy on spatial learning and memory of adult male offspring rats.

Science.gov (United States)

Sepehri, Gholamreza; Parsania, Shahrnaz; Hajzadeh, Mousa-Al-Reza; Haghpanah, Tahereh; Sheibani, Vahid; Divsalar, Kouros; Shekarforoush, Shahnaz; Afarinesh, Mohammad Reza

2014-09-01

Smoking opium/cigarette is a global health concern. The aim of this study was to examine learning and memory of rat male offsprings whose mothers had been exposed to either opium or morphine with nicotine during pregnancy. Wistar rats were used for the experiments. In the female rats, opium, morphine and nicotine dependencies were induced by daily injections of drug solution for 10 days before mating. Spatial memory was tested by Morris water maze test in male pups at the postnatal day 60. The duration that took until the rats found the platform in the maze and also their swimming speed were recorded. An increase in the platform finding duration was observed for the pups of dependent mothers in comparison with the control in the training trial (Popium/morphine and nicotine significantly decreased the time spent in the trigger zone to find the hidden platform (Peffect on the swimming speed in the probe test. However, no significant difference was observed in the learning and memory behavior of offspring whose mothers received morphine, opium, nicotine or the co-administration of either morphine or opium with nicotine. The present study showed that the opium, morphine and nicotine abuse and co-administration of opium/morphine with nicotine during pregnancy may cause deficits in spatial learning of male rat offspring. Based on our data, no synergistic effects of co-drug administration were observed on learning and memory in male rat offspring.

Novel Anti-Nicotine Vaccine Using a Trimeric Coiled-Coil Hapten Carrier.

Directory of Open Access Journals (Sweden)

Keith D Miller

Full Text Available Tobacco addiction represents one of the largest public health problems in the world and is the leading cause of cancer and heart disease, resulting in millions of deaths a year. Vaccines for smoking cessation have shown considerable promise in preclinical models, although functional antibody responses induced in humans are only modestly effective in preventing nicotine entry into the brain. The challenge in generating serum antibodies with a large nicotine binding capacity is made difficult by the fact that this drug is non-immunogenic and must be conjugated as a hapten to a protein carrier. To circumvent the limitations of traditional carriers like keyhole limpet hemocyanin (KLH, we have synthesized a short trimeric coiled-coil peptide (TCC that creates a series of B and T cell epitopes with uniform stoichiometry and high density. Here we compared the relative activities of a TCC-nic vaccine and two control KLH-nic vaccines using Alum as an adjuvant or GLA-SE, which contains a synthetic TLR4 agonist formulated in a stable oil-in-water emulsion. The results showed that the TCC's high hapten density correlated with a better immune response in mice as measured by anti-nicotine Ab titer, affinity, and specificity, and was responsible for a reduction in anti-carrier immunogenicity. The Ab responses achieved with this synthetic vaccine resulted in a nicotine binding capacity in serum that could prevent >90% of a nicotine dose equivalent to three smoked cigarettes (0.05 mg/kg from reaching the brain.

High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction.

Science.gov (United States)

Kutlu, Munir Gunes; Holliday, Erica; Gould, Thomas J

2016-02-01

Previously, studies from our lab have shown that while acute nicotine administered prior to training and testing enhances contextual fear conditioning, acute nicotine injections prior to extinction sessions impair extinction of contextual fear. Although there is also strong evidence showing that the acute nicotine's enhancing effects on contextual fear conditioning require high-affinity α4β2 nicotinic acetylcholine receptors (nAChRs), it is unknown which nAChR subtypes are involved in the acute nicotine-induced impairment of contextual fear extinction. In this study, we investigated the effects of acute nicotine administration on contextual fear extinction in knock-out (KO) mice lacking α4, β2 or α7 subtypes of nAChRs and their wild-type (WT) littermates. Both KO and WT mice were first trained and tested for contextual fear conditioning and received a daily contextual extinction session for 4 days. Subjects received intraperitoneal injections of nicotine (0.18 mg/kg) or saline 2-4 min prior to each extinction session. Our results showed that the mice that lack α4 and β2 subtypes of nAChRs showed normal contextual fear extinction but not the acute nicotine-induced impairment while the mice that lack the α7 subtype showed both normal contextual extinction and nicotine-induced impairment of contextual extinction. In addition, control experiments showed that acute nicotine-induced impairment of contextual fear extinction persisted when nicotine administration was ceased and repeated acute nicotine administrations alone did not induce freezing behavior in the absence of context-shock learning. These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction. Copyright © 2015 Elsevier Inc. All rights reserved.

Nicotine permeability across the buccal TR146 cell culture model and porcine buccal mucosa in vitro

DEFF Research Database (Denmark)

Nielsen, Hanne Mørck; Rassing, Margrethe Rømer

2002-01-01

The present study was conducted to investigate and compare the effect of pH and drug concentration on nicotine permeability across the TR146 cell culture model and porcine buccal mucosa in vitro. As a further characterization of the TR146 cell culture model, it was explored whether the results were...... comparable for bi-directional and uni-directional transport in the presence of a transmembrane pH gradient. Nicotine concentrations between 10(-5) and 10(-2) M were applied to the apical side of the TR146 cell culture model or the mucosal side of porcine buccal mucosa. Buffers with pH values of 5.5, 7.......4 and 8.1 were used to obtain different fractions of non- and mono-ionized nicotine. The apparent permeability (P(app)) of nicotine across both models increased significantly with increasing pH, and the P(app) values obtained with the two models could be correlated in a linear manner. With increasing...

Impulsive behavior and nicotinic acetylcholine receptors.

Science.gov (United States)

Ohmura, Yu; Tsutsui-Kimura, Iku; Yoshioka, Mitsuhiro

2012-01-01

Higher impulsivity is thought to be a risk factor for drug addiction, criminal involvement, and suicide. Excessive levels of impulsivity are often observed in several psychiatric disorders including attention-deficit/hyperactivity disorder and schizophrenia. Previous studies have demonstrated that nicotinic acetylcholine receptors (nAChRs) are involved in impulsive behavior. Here, we introduce recent advances in this field and describe the role of the following nAChR-related brain mechanisms in modulating impulsive behavior: dopamine release in the ventral striatum; α4β2 nAChRs in the infralimbic cortex, which is a ventral part of the medial prefrontal cortex (mPFC); and dopamine release in the mPFC. We also suggest several potential therapeutic drugs to address these mechanisms in impulsivity-related disorders and explore future directions to further elucidate the roles of central nAChRs in impulsive behavior.

A pilot study on nicotine residues in houses of electronic cigarette users, tobacco smokers, and non-users of nicotine-containing products.

Science.gov (United States)

Bush, Derek; Goniewicz, Maciej L

2015-06-01

Nicotine deposited on the surfaces has been shown to react with airborne chemicals leading to formation of carcinogens and contributing to thirdhand exposure. While prior studies revealed nicotine residues in tobacco smokers' homes, none have examined the nicotine residue in electronic cigarette (e-cigarette) users' homes. We measured nicotine on the surfaces in households of 8 e-cigarette users, 6 cigarette smokers, and 8 non-users of nicotine-containing products in Western New York, USA. Three surface wipe samples were taken from the floor, wall and window. Nicotine was extracted from the wipes and analyzed using gas chromatography. Half of the e-cigarette users' homes had detectable levels of nicotine on surfaces whereas nicotine was found in all of the tobacco cigarette smokers' homes. Trace amounts of nicotine were also detected in half of the homes of non-users of nicotine-containing products. Nicotine levels in e-cigarette users homes was significantly lower than that found in cigarette smokers homes (average concentration 7.7±17.2 vs. 1303±2676 μg/m2; pe-cigarette users and non-users (p>0.05). Nicotine is a common contaminant found on indoor surfaces. Using e-cigarettes indoors leads to significantly less thirdhand exposure to nicotine compared to smoking tobacco cigarettes. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebellar nicotinic cholinergic receptors are intrinsic to the cerebellum: implications for diverse functional roles.

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Turner, Jill R; Ortinski, Pavel I; Sherrard, Rachel M; Kellar, Kenneth J

2011-12-01

Although recent studies have delineated the specific nicotinic subtypes present in the mammalian cerebellum, very little is known about their location or function within the cerebellum. This is of increased interest since nicotinic receptors (nAChRs) in the cerebellum have recently been implicated in the pathology of autism spectrum disorders. To begin to better understand the roles of these heteromeric nAChRs in the cerebellar circuitry and their therapeutic potential as targets for drug development, we used various chemical and stereotaxic lesion models in conjunction with slice electrophysiology to examine how specific heteromeric nAChR subtypes may influence the surrounding cerebellar circuitry. Using subunit-specific immunoprecipitation of radiolabeled nAChRs in the cerebella following N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, p-chloroamphetamine, and pendunculotomy lesions, we show that most, if not all, cerebellar nicotinic receptors are present in cells within the cerebellum itself and not in extracerebellar afferents. Furthermore, we demonstrate that the β4-containing, but not the β2-containing, nAChRs intrinsic to the cerebellum can regulate inhibitory synaptic efficacy at two major classes of cerebellar neurons. These tandem findings suggest that nAChRs may present a potential drug target for disorders involving the cerebellum.

Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

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Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

2010-03-30

Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

Nicotine, adolescence, and stress: A review of how stress can modulate the negative consequences of adolescent nicotine abuse.

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Holliday, Erica; Gould, Thomas J

2016-06-01

In order to continue the decline of smoking prevalence, it is imperative to identify factors that contribute to the development of nicotine and tobacco addiction, such as adolescent initiation of nicotine use, adolescent stress, and their interaction. This review highlights the biological differences between adolescent and adults in nicotine use and resulting effects, and examines the enduring consequences of adolescent nicotine administration. A review of both clinical and preclinical literature indicates that adolescent, but not adult, nicotine administration leads to increased susceptibility for development of long-lasting impairments in learning and affect. Finally, the role stress plays in normal adolescent development, the deleterious effects stress has on learning and memory, and the negative consequences resulting from the interaction of stress and nicotine during adolescence is reviewed. The review concludes with ways in which future policies could benefit by addressing adolescent stress as a means of reducing adolescent nicotine abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

Addictive drugs and their relationship with infectious diseases.

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Friedman, Herman; Pross, Susan; Klein, Thomas W

2006-08-01

The use of drugs of abuse, both recreationally and medicinally, may be related to serious public health concerns. There is a relationship between addictive drugs of abuse such as alcohol and nicotine in cigarette smoke, as well as illegal drugs such as opiates, cocaine and marijuana, and increased susceptibility to infections. The nature and mechanisms of immunomodulation induced by such drugs of abuse are described in this review. The effects of opiates and marijuana, using animal models as well as in vitro studies with immune cells from experimental animals and humans, have shown that immunomodulation induced by these drugs is mainly receptor-mediated, either directly by interaction with specific receptors on immune cells or indirectly by reaction with similar receptors on cells of the nervous system. Similar studies also show that cocaine and nicotine have marked immunomodulatory effects, which are mainly receptor-mediated. Both cocaine, an illegal drug, and nicotine, a widely used legal addictive component of cigarettes, are markedly immunomodulatory and increase susceptibility to infection. The nature and mechanism of immunomodulation induced by alcohol, the most widely used addictive substance of abuse, are similar but immunomodulatory effects, although not receptor-mediated. The many research studies on the effects of these drugs on immunity and increased susceptibility to infectious diseases, including AIDS, are providing a better understanding of the complex interactions between immunity, infections and substance abuse.

Vitamin E Nicotinate

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Kimbell R. Duncan

2017-03-01

Full Text Available Vitamin E refers to a family of compounds that function as lipid-soluble antioxidants capable of preventing lipid peroxidation. Naturally occurring forms of vitamin E include tocopherols and tocotrienols. Vitamin E in dietary supplements and fortified foods is often an esterified form of α-tocopherol, the most common esters being acetate and succinate. The vitamin E esters are hydrolyzed and converted into free α-tocopherol prior to absorption in the intestinal tract. Because its functions are relevant to many chronic diseases, vitamin E has been extensively studied in respect to a variety of diseases as well as cosmetic applications. The forms of vitamin E most studied are natural α-tocopherol and the esters α-tocopheryl acetate and α-tocopheryl succinate. A small number of studies include or focus on another ester form, α-tocopheryl nicotinate, an ester of vitamin E and niacin. Some of these studies raise the possibility of differences in metabolism and in efficacy between vitamin E nicotinate and other forms of vitamin E. Recently, through metabolomics studies, we identified that α-tocopheryl nicotinate occurs endogenously in the heart and that its level is dramatically decreased in heart failure, indicating the possible biological importance of this vitamin E ester. Since knowledge about vitamin E nicotinate is not readily available in the literature, the purpose of this review is to summarize and evaluate published reports, specifically with respect to α-tocopheryl nicotinate with an emphasis on the differences from natural α-tocopherol or α-tocopheryl acetate.

Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors.

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Melis, Miriam; Pillolla, Giuliano; Luchicchi, Antonio; Muntoni, Anna Lisa; Yasar, Sevil; Goldberg, Steven R; Pistis, Marco

2008-12-17

Nicotine stimulates the activity of mesolimbic dopamine neurons, which is believed to mediate the rewarding and addictive properties of tobacco use. Accumulating evidence suggests that the endocannabinoid system might play a major role in neuronal mechanisms underlying the rewarding properties of drugs of abuse, including nicotine. Here, we investigated the modulation of nicotine effects by the endocannabinoid system on dopamine neurons in the ventral tegmental area with electrophysiological techniques in vivo and in vitro. We discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme that catabolizes fatty acid ethanolamides, among which the endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced excitation of dopamine cells. Importantly, this effect was mimicked by the administration of the FAAH substrates oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules structurally related to AEA, but devoid of affinity for cannabinoid receptors. They blocked the effects of nicotine by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor involved in several aspects of lipid metabolism and energy balance. Activation of PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might lead to phosphorylation and negative regulation of neuronal nicotinic acetylcholine receptors. These data indicate for the first time that the anorexic lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of PPAR-alpha in the brain and provide a potential new target for the treatment of nicotine addiction.

Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors

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Petersen, Ida Nymann; Crestey, François; Jensen, Anders A

2015-01-01

Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers...

Differential effects of psychomotor stimulants on attentional performance in rats: nicotine, amphetamine, caffeine and methylphenidate.

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Bizarro, L; Patel, S; Murtagh, C; Stolerman, I P

2004-05-01

Nicotine can improve attentional performance in the rat as assessed by a modified five-choice serial reaction time task (5-CSRTT), but it is not known if the effect is shared with other psychomotor stimulants. This study compared the effects of nicotine, amphetamine, caffeine and methylphenidate on performance in the 5-CSRTT and determined whether presenting stimuli at unpredictable times by using variable inter-trial intervals (ITI) influenced the sensitivity of the task to the drugs. One group of male hooded rats was trained to obtain food reinforcers by nose-poking in response to 1 s light stimuli presented randomly in one of five apertures, with fixed ITI; for a second group of rats, ITI varied randomly (n=12 per group). As observed previously, nicotine (tested in doses of 0.05-0.2 mg/kg) produced dose-related improvements in accuracy, reduced omission errors and response latencies, but increased anticipatory responding. Amphetamine (0.1-0.8 mg/kg) and methylphenidate (2.5-10 mg/kg) increased accuracy and reduced response latency, and decreased anticipatory responding. Caffeine (2.5-20 mg/kg) did not improve performance except at a small dose that decreased omission errors only. Training at different levels of stimulus predictability influenced performance in the undrugged state but had little impact on profiles of responses to the drugs. The findings with methylphenidate support the potential value of the 5-CSRTT for testing drugs that may be useful in the treatment of attention deficit hyperactivity disorder.

Nicotine Contamination in Particulate Matter Sampling

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Eric Garshick

2009-02-01

Full Text Available We have addressed potential contamination of PM2.5 filter samples by nicotine from cigarette smoke. We collected two nicotine samples – one nicotine sampling filter was placed in-line after the collection of PM2.5 and the other stood alone. The overall correlation between the two nicotine filter levels was 0.99. The nicotine collected on the “stand-alone” filter was slightly greater than that on the “in-line” filter (mean difference = 1.10 μg/m3, but the difference was statistically significant only when PM2.5 was low (≤ 50 μg/m3. It is therefore important to account for personal and secondhand smoke exposure while assessing occupational and environmental PM.

Views and Preferences for Nicotine Products as an Alternative to Smoking: A Focus Group Study of People Living with Mental Disorders

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Carla Meurk

2016-11-01

Full Text Available Aims and Background: People living with mental disorders experience a disproportionately higher burden of tobacco-related disease than the general population. Long-term substitution with less harmful nicotine products could reduce the tobacco-related harm among this population. This study investigated the views and preferences of people with mental health disorders about different nicotine products and their use as long-term substitutes for cigarettes. Methods: Semi-structured focus group discussion followed by a brief questionnaire. The discussion transcripts were analysed for content and themes and quantitative data summarised with descriptive statistics. Results: Twenty-nine participants took part in four focus groups. Vaping devices were the most acceptable nicotine products discussed; however preferences for nicotine products were individual and varied along aesthetic, pragmatic, sensory and symbolic dimensions. The concept of tobacco harm reduction was unfamiliar to participants, however they generally agreed with the logic of replacing cigarettes with less harmful nicotine products. Barriers to activating tobacco harm reduction included the symbolism of smoking and quitting; the importance placed on health; the consumer appeal of alternatives; and cost implications. Discussion and Conclusions: Engaging this population in tobacco harm reduction options will require communication that challenges black and white thinking (a conceptual framework in which smoking cigarettes or quitting all nicotine are the only legitimate options as in practice this serves to support the continuance of smoking. Consumers should be encouraged to trial a range of nicotine products to find the most acceptable alternative to smoking that reduces health harms. Providing incentives to switch to nicotine products could help overcome barriers to using less harmful nicotine products among mental health consumers.

Hypocretin/orexin signaling in the hypothalamic paraventricular nucleus is essential for the expression of nicotine withdrawal.

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Plaza-Zabala, Ainhoa; Flores, África; Maldonado, Rafael; Berrendero, Fernando

2012-02-01

Hypocretin (orexin) signaling is involved in drug addiction. In this study, we investigated the role of these hypothalamic neuropeptides in nicotine withdrawal by using behavioral and neuroanatomical approaches. Nicotine withdrawal syndrome was precipitated by mecamylamine (2 mg/kg, subcutaneous) in C57BL/6J nicotine-dependent mice (25 mg/kg/day for 14 days) pretreated with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 (5 and 10 mg/kg, intraperitoneal), the hypocretin receptor 2 antagonist TCSOX229 (5 and 10 mg/kg, intraperitoneal), and in preprohypocretin knockout mice. c-Fos expression was analyzed in several brain areas related to nicotine dependence by immunofluorescence techniques. Retrograde tracing with rhodamine-labeled fluorescent latex microspheres was used to determine whether the hypocretin neurons project directly to the paraventricular nucleus of the hypothalamus (PVN), and SB334867 was locally administered intra-PVN (10 nmol/side) to test the specific involvement of Hcrtr-1 in this brain area during nicotine withdrawal. Somatic signs of nicotine withdrawal were attenuated in mice pretreated with SB334867 and in preprohypocretin knockout mice. No changes were found in TCSOX229 pretreated animals. Nicotine withdrawal increased the percentage of hypocretin cells expressing c-Fos in the perifornical, dorsomedial, and lateral hypothalamus. In addition, the increased c-Fos expression in the PVN during withdrawal was dependent on hypocretin transmission through Hcrtr-1 activation. Hypocretin neurons directly innervate the PVN and the local infusion of SB334867 into the PVN decreased the expression of nicotine withdrawal. These data demonstrate that hypocretin signaling acting on Hcrtr-1 in the PVN plays a crucial role in the expression of nicotine withdrawal. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task demands.

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Hahn, B; Shoaib, M; Stolerman, I P

2002-07-01

Beneficial effects of nicotine on cognitive processes including attention have potential therapeutic uses and have been proposed as incentives for tobacco smoking. To establish task conditions under which the effects of nicotine on attention are obtained reliably and to characterise such effects further. Rats were trained in a modified version of the five-choice serial reaction time task (5-CSRTT) to detect 1-s light stimuli with greater than 70% accuracy and fewer than 20% omission errors. Nicotine was tested under different task requirements by varying signal event rate, stimulus duration and stimulus predictability, and by introducing white-noise distractors. Nicotine (0.05-0.2 mg/kg, s.c.) repeatedly improved accuracy and reduced omission errors and reaction times, leading to increases in numbers of reinforcers earned. Anticipatory responding was increased. Parametric modifications intended to increase demands on sustained attention did not affect performance in a manner suggesting that this subtype of attention was being taxed, and the effects of nicotine were not more marked under such conditions. Shorter stimulus durations impaired performance, but this manipulation weakened the effect of nicotine on accuracy. In contrast, the presence of noise distractors facilitated the effects of nicotine to the extent that distractor-induced impairments were abolished by the drug. The 5-CSRTT can provide a sensitive rodent model for the attention-enhancing effects of nicotine. Changes made to the procedure may have increased its sensitivity to nicotine, particularly with respect to accuracy. There were indications that the effects of nicotine were largest on processes of selective attention or on disengaging attention from irrelevant events and shifting it to behaviourally significant stimuli.

Effect of Oxidative Phytochemicals on Nicotine-stressed UMNSAH/DF-1 Cell Line

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Amlan Chakraborty

2014-04-01

Full Text Available Nicotine is a parasympathomimetic alkaloid found in the nightshade family of plants (Solanaceae and is a cholinergic drug. It acts directly by stimulating the nicotinic or muscarinic receptors or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or by other mechanisms. 3% of tobacco or one cigarette yields 1 mg of nicotine. As nicotine enters the body, it disturbs the healthy functioning of the body. In this study, we isolated UMNSAH/DF-1 cell line from Gallus gallus. For this, 9±2 day old chicken embryo was taken. This was followed by the extraction of nicotine (1 mg/ml from cigarette. The cells were then given nicotine stress and were observed for blackening after 24 h of incubation under 40× resolution of microscope. It was found that this blackening of the cells was permanent even after a wash with 1× phosphate-buffered saline (PBS followed by replenishing the medium. The phytochemicals extracted were from the dried powder, which included Curcuma longa (薑黃 Jiāng Huáng; Turmeric 40 mg/ml, Azadirachta indica (neem 50 mg/ml, Cinnamomum tamala (bay leaf 30 mg/ml, Camellia sinensis (綠茶 Lǜ Chá; Green Tea 100 mg/ml, and Ocimum sanctum (tulsi 30 mg/ml. When applied to nicotine-stressed cells, it was observed that ursolic acid in neem recovered 70%, followed by 65% recovery by tulsi (having triterpenoid, 50% recovery by the catechins in Ca. sinensis, and very little recovery shown by Ci. tamala. Due to the yellow coloration of the cells by Cu. longa, much could not be inferred, although it was inferable that it had resulted in little effects. Mixtures of these phytochemicals were used, and it was found that neem: tulsi diluted in 3:1 ratio was highly effective and cell recovery was almost 80%. 68% was recovered by tulsi: green tea in a ratio 1:3 and 42% by turmeric:green tea in a ratio of 1:5.

Effect of a nicotine vaccine on nicotine binding to the beta2-nAChRs in vivo in human tobacco smokers

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Esterlis, Irina; Hannestad, Jonas O.; Perkins, Evgenia; Bois, Frederic; D’Souza, D. Cyril; Tyndale, Rachel F.; Seibyl, John P.; Hatsukami, Dorothy M.; Cosgrove, Kelly P.; O’Malley, Stephanie S.

2013-01-01

Objective Nicotine acts in the brain to promote smoking in part by binding to the beta2-containing nicotinic acetylcholine receptors (β2*-nAChRs) and acting in the mesolimbic reward pathway. The effects of nicotine from smoking one tobacco cigarette are significant (80% of β2*-nAChRs occupied for >6h). This likely contributes to the maintenance of smoking dependence and low cessation outcomes. Development of nicotine vaccines provides potential for alternative treatments. We used [123I]5IA-85380 SPECT to evaluate the effect of 3′-AmNic-rEPA on the amount of nicotine that binds to the β2*-nAChRs in the cortical and subcortical regions in smokers. Method Eleven smokers (36years (SD=13); 19cig/day (SD=11) for 10years (SD=7) who were dependent on nicotine (Fagerström Test of Nicotine Dependence score =5.5 (SD=3); plasma nicotine 9.1 ng/mL (SD=5)) participated in 2 SPECT scan days: before and after immunization with 4–400μg doses of 3′-AmNic-rEPA. On SPECT scan days, 3 30-min baseline emission scans were obtained, followed by administration of IV nicotine (1.5mg/70kg) and up to 9 30-min emission scans. Results β2*-nAChR availability was quantified as VT/fP and nicotine binding was derived using the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding (F=5.19, df=1,10, p=0.05). Significant positive correlations were observed between nicotine bound to β2*-nAChRs and nicotine injected before but not after vaccination (p=0.05 vs. p=0.98). There was a significant reduction in the daily number of cigarettes and desire for a cigarette (p=.01 and p=.04, respectively). Conclusions This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between nicotine administered vs. nicotine available to occupy β2*-nAChRs. PMID:23429725

Ever Use of Nicotine and Nonnicotine Electronic Cigarettes Among High School Students in Ontario, Canada.

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Hamilton, Hayley A; Ferrence, Roberta; Boak, Angela; Schwartz, Robert; Mann, Robert E; O'Connor, Shawn; Adlaf, Edward M

2015-10-01

There are limited data on the use of electronic cigarettes (e-cigarettes) among youth, particularly with regard to the use of nicotine versus nonnicotine products. This study investigates ever use of nicotine and nonnicotine e-cigarettes and examines the demographic and behavioral correlates of e-cigarette use in Ontario, Canada. Data for 2,892 high school students were derived from the 2013 Ontario Student Drug Use and Health Survey. This province-wide school-based survey is based on a 2-stage cluster design. Bivariate and multivariate analyses were used to investigate the factors associated with ever use of e-cigarettes. Ever use of e-cigarettes was derived from the question, "Have you ever smoked at least one puff from an electronic cigarette?" All analyses included appropriate adjustments for the complex study design. Fifteen percent of high school students reported using e-cigarettes in their lifetime. Most students who ever used e-cigarettes reported using e-cigarettes without nicotine (72%), but 28% had used e-cigarettes with nicotine. Male, White/Caucasian, and rural students, as well as those with a history of using tobacco cigarettes, were at greater odds of e-cigarette use. Seven percent of students who had never smoked a tobacco cigarette in their lifetime reported using an e-cigarette. Five percent of those who had ever used an e-cigarette had never smoked a tobacco cigarette. More students reported ever using e-cigarettes without nicotine than with nicotine in Ontario, Canada. This underscores the need for greater knowledge of the contents of both nicotine and nonnicotine e-cigarettes to better guide public health policies. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Métodos para abandono do tabagismo e tratamento da dependência da nicotina Methods for smoking cessation and treatment of nicotine dependence

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Aracy Pereira Silveira Balbani

2005-12-01

symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy and second-line (clonidine and nortriptyline drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinence and current therapy with MAO inhibitors. Nicotine replacement therapy can be done with patches or gums. Counseling groups and behavioral interventions are efficacious. The effects of acupuncture on smoking cessation are not fully elucidated. Prompt smoking cessation or gradual reduction strategies have similar success rates.

Sex differences in the effect of wheel running on subsequent nicotine-seeking in a rat adolescent-onset self-administration model

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Sanchez, Victoria; Moore, Catherine F; Brunzell, Darlene H; Lynch, Wendy J

2014-01-01

Rationale Wheel running attenuates nicotine-seeking in male adolescent rats; however it is not known if this effect extends to females. Objective To determine if wheel running during abstinence would differentially attenuate subsequent nicotine-seeking in male and female rats that had extended access to nicotine self-administration during adolescence. Methods Male (N = 49) and female (N = 43) adolescent rats self-administered saline or nicotine (5μg/kg) under an extended access (23-hour) paradigm. Following the last self-administration session, rats were moved to polycarbonate cages for an abstinence period where they either had access to a locked or unlocked running wheel for 2-hours/day. Subsequently, nicotine-seeking was examined under a within-session extinction/cue-induced reinstatement paradigm. Due to low levels of nicotine-seeking in females in both wheel groups, additional groups were included that were housed without access to a running wheel during abstinence. Results Females self-administered more nicotine as compared to males; however, within males and females, intake did not differ between groups prior to wheel assignment. Compared to saline controls, males and females that self-administered nicotine showed a significant increase in drug-seeking during extinction. Wheel running during abstinence attenuated nicotine-seeking during extinction in males. In females, access to either locked or unlocked wheels attenuated nicotine-seeking during extinction. While responding was reinstated by cues in both males and females, levels were modest and not significantly affected by exercise in this adolescent-onset model. Conclusions While wheel running reduced subsequent nicotine-seeking in males, access to a wheel, either locked or unlocked, was sufficient to suppress nicotine-seeking in females. PMID:24271035

A man before his time: Russell's insights into nicotine, smoking, treatment and curbing the smoking problem.

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McNeill, Ann; Robson, Debbie

2018-04-01

This narrative review aimed to provide a brief overview of five key research 'classics' produced by the innovative and radical thought leader, Professor Michael Anthony Hamilton Russell (1932-2009), drawing upon his other work wherever feasible. Narrative review. From more than 250 publications, we selected papers we considered seminal texts, published in 1971, 1976, 1978, 1979 and 1991. Russell was among the first researchers to explain that smoking was a dependence disorder caused by the drug nicotine decades before this was recognized formally. He therefore saw quickly the importance of delivering nicotine in a less harmful format as a way of controlling nicotine withdrawal when stopping smoking, first studying nicotine gum. In addition to pharmacotherapies, Russell's research also explored the role of behavioural support, particularly the role of general practitioners (GPs), alone as well as supported by specialist clinics; this research underpinned initiatives in England to reimburse doctors for giving advice to smokers, and to provide a national network of smoking cessation services. Research on nicotine uptake from other delivery systems and routes led Russell to theorize that the speed and dose of delivery impacted upon the effectiveness of a product to act as a substitute for smoking. He commented on the addictiveness of the high nicotine boli delivered in quick succession when smoking cigarettes and argued that alternative recreational nicotine delivery systems would need to be promoted actively to smokers in order for them to compete with cigarettes, a forerunner for contemporary debates on electronic cigarettes. The legacy of Russell's landmark research is seen in present-day nicotine science, policy and discourse. © 2017 Society for the Study of Addiction.

Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex.

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Kroemer, Nils B; Wuttig, Franziska; Bidlingmaier, Martin; Zimmermann, Ulrich S; Smolka, Michael N

2015-07-01

Endocrine signals such as ghrelin and leptin are known to modulate the mesocorticolimbic dopaminergic system and, consequently, show associations with food and drug reward. In animal models, nicotine was demonstrated to reduce body weight by attenuating food intake and effects of leptin and ghrelin are partly modulated by nicotinic acetylcholine receptors which hint at potential interactions. However, the neuropharmacological modulation of endocrine signals by nicotine in healthy humans remains to be tested experimentally. We used functional magnetic resonance imaging to investigate food-cue reactivity after an overnight fast and following a caloric load (oral glucose tolerance test, OGTT) in 26 healthy normal-weight never-smokers. Moreover, we administered either nicotine (2 mg) or placebo gums using a randomized cross-over design and assessed blood plasma levels of ghrelin and leptin. During fasting, nicotine administration decreased correlations with ghrelin levels in the mesocorticolimbic system whereas correlations with leptin were increased. After the OGTT, nicotine increased the modulatory effects of ghrelin and leptin on food-cue reactivity, particularly in the ventromedial prefrontal cortex (vmPFC) and the amygdala. Critically, this led to an indirect modulation of the behavioral 'appetizer effect' (i.e. cue-induced increases in subjective appetite) by homeostatic feedback signals via food-cue reactivity in vmPFC. We conclude that nicotine enhances the effect of ghrelin and leptin in the valuation and relevance network which might, in turn, reduce appetite. This highlights that amplifying the impact of homeostatic signals such as ghrelin and leptin in normal-weight individuals might hint at a mechanism contributing to nicotine's anorexic potential. © 2014 Society for the Study of Addiction.

In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence.

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Jackson, Asti; Bagdas, Deniz; Muldoon, Pretal P; Lichtman, Aron H; Carroll, F Ivy; Greenwald, Mark; Miles, Michael F; Damaj, M Imad

2017-05-15

Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric α7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-α (PPARα) has been implicated as a downstream signaling target of the α7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPARα as a possible mediator of the effect of α7 nAChR activation in nicotine dependence. Our results demonstrate the PPARα antagonist GW6471 blocks actions of the α7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that α7 nAChR activation attenuates nicotine CPP in a PPARα-dependent manner. To evaluate PPARα activation in nicotine dependence we used the selective and potent PPARα agonist, WY-14643 and the clinically used PPARα activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPARα in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPARα plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of α7 nAChRs in nicotine dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nicotine-induced activation of caudate and anterior cingulate cortex in response to errors in schizophrenia.

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Moran, Lauren V; Stoeckel, Luke E; Wang, Kristina; Caine, Carolyn E; Villafuerte, Rosemond; Calderon, Vanessa; Baker, Justin T; Ongur, Dost; Janes, Amy C; Evins, A Eden; Pizzagalli, Diego A

2018-03-01

Nicotine improves attention and processing speed in individuals with schizophrenia. Few studies have investigated the effects of nicotine on cognitive control. Prior functional magnetic resonance imaging (fMRI) research demonstrates blunted activation of dorsal anterior cingulate cortex (dACC) and rostral anterior cingulate cortex (rACC) in response to error and decreased post-error slowing in schizophrenia. Participants with schizophrenia (n = 13) and healthy controls (n = 12) participated in a randomized, placebo-controlled, crossover study of the effects of transdermal nicotine on cognitive control. For each drug condition, participants underwent fMRI while performing the stop signal task where participants attempt to inhibit prepotent responses to "go (motor activation)" signals when an occasional "stop (motor inhibition)" signal appears. Error processing was evaluated by comparing "stop error" trials (failed response inhibition) to "go" trials. Resting-state fMRI data were collected prior to the task. Participants with schizophrenia had increased nicotine-induced activation of right caudate in response to errors compared to controls (DRUG × GROUP effect: p corrected  state functional connectivity analysis, relative to controls, participants with schizophrenia had significantly decreased connectivity between the right caudate and dACC/bilateral dorsolateral prefrontal cortices. In sum, we replicated prior findings of decreased post-error slowing in schizophrenia and found that nicotine was associated with more adaptive (i.e., increased) post-error reaction time (RT). This proof-of-concept pilot study suggests a role for nicotinic agents in targeting cognitive control deficits in schizophrenia.

Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy

Science.gov (United States)

Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

2017-01-01

Introduction Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. Methods and analysis The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. Ethics and dissemination This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11–1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants

Nicotine transport in lung and non-lung epithelial cells.

Science.gov (United States)

Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

2017-11-01

Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacological receptors of nematoda as target points for action of antiparasitic drugs

Directory of Open Access Journals (Sweden)

Trailović Saša M.

2010-01-01

Full Text Available Cholinergic receptors of parasitic nematodes are one of the most important possible sites of action of antiparasitic drugs. This paper presents some of our own results of electrophysiological and pharamcological examinations of nicotinic and muscarinic receptors of nematodes, as well as data from literature on a new class of anthelmintics that act precisely on cholinergic receptors. The nicotinic acetylcholine receptor (nAChR is located on somatic muscle cells of nematodes and it is responsible for the coordination of parasite movement. Cholinomimetic anthelmintics act on this receptor, as well as acetylcholine, an endogenic neurotransmitter, but they are not sensitive to enzyme acetylcholineesterase which dissolves acetylcholine. As opposed to the nicotinic receptor of vertebra, whose structure has been examined thoroughly, the stoichiometry of the nicotinic receptor of nematodes is not completely known. However, on the grounds of knowledge acquired so far, a model has been constructed recently of the potential composition of a type of nematodes nicotinic receptor, as the site of action of anthelmintics. Based on earlier investigations, it is supposed that a conventional muscarinic receptor exists in nematodes as well, so that it can also be a new pharamocological target for the development of antinematode drugs. The latest class of synthesized anthelmintics, named aminoacetonitriles (AAD, act via the nicotinic receptor. Monepantel is the first drug from the AAD group as a most significant candidate for registration in veterinary medicine. Even though several groups of cholinomimetic anthelmintics (imiodazothiazoles, tetrahydropyrimidines, organophosphat anthelmintics have been in use in veterinary practice for many years now, it is evident that cholinergic receptors of nematodes still present an attractive place in the examinations and development of new antinematode drugs. .

The effects of nicotine in the neonatal quinpirole rodent model of psychosis: Neural plasticity mechanisms and nicotinic receptor changes.

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Peterson, Daniel J; Gill, W Drew; Dose, John M; Hoover, Donald B; Pauly, James R; Cummins, Elizabeth D; Burgess, Katherine C; Brown, Russell W

2017-05-15

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal's lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking. Copyright © 2017. Published by Elsevier B.V.

Compound list: nicotinic acid [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available nicotinic acid NIC 00081 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Hum...an/in_vitro/nicotinic_acid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/R...at/in_vitro/nicotinic_acid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat.../in_vivo/Liver/Single/nicotinic_acid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosc

Discriminating nicotine and non-nicotine containing e-liquids using infrared spectroscopy.

Science.gov (United States)

Deconinck, E; Bothy, J L; Barhdadi, S; Courselle, P

2016-02-20

In a few countries, including Belgium, nicotine-containing e-cigarettes and e-liquids are considered medicines, and therefore cannot freely be sold, but should be distributed in a pharmacy. The fact that in the neighbouring countries these products are freely available, poses a problem for custom personnel, the more the nicotine content of the products is not always labelled, especially when they are bought through internet. Therefore there is a need for easy-to-use equipment and methods to perform a first on site screening of intercepted samples, both for border control as to check label compliance of the sample. The use of attenuated total reflectance-infrared spectroscopy (ATR-IR) and near infrared spectroscopy (NIR), combined with chemometrics was evaluated for the discrimination between nicotine containing and non-nicotine containing samples. It could be concluded that both ATR-IR and NIR could be used for the discrimination when combined with the appropriate chemometric techniques. The presented techniques do not need sample preparation and result in models with a minimum of false negative samples. If a large enough training set can be established the interpretation can be fully automated, making the presented approach suitable for on-site screening of e-liquid samples. Copyright © 2015 Elsevier B.V. All rights reserved.

MOLECULAR GENE CLONING OF NICOTINE-DEHIDROGENASE FROM THE pAO1 MEGAPLASMID OF ARTHROBACTER NICOTINOVORANS

Directory of Open Access Journals (Sweden)

Andreea Andrei

2013-10-01

Full Text Available 6-hydroxi-L-nicotine (6HNic has an important potential as a drug for neuro-degenerative disorders and a  suitable simple and reliable method for obtaining contaminant-free 6HNic preparations is required. Here, we envision the in-vitro production of 6HNic by using purified nicotine-dehydrogenase (NDH followed by HPLC or capillary electrophoresis techniques and we focus on the isolation and cloning of the three genes coding the NDH enzyme.  A PCR protocol was established for easy amplification and the DNA fragment containing the ndhLSM genes was directionally cloned into the pART2 vector.

Use of nonsteroidal anti-inflammatory drugs prior to chronic renal replacement therapy initiation

DEFF Research Database (Denmark)

Kristensen, Søren Lund; Fosbøl, Emil L; Kamper, Anne-Lise

2012-01-01

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study......, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT). METHODS: Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis...

In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

International Nuclear Information System (INIS)

Kassiou, Michael; Eberl, Stefan; Meikle, Steven R.; Birrell, Alex; Constable, Chris; Fulham, Michael J.; Wong, Dean F.; Musachio, John L.

2001-01-01

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[ 123 I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[ 123 I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V d ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V d was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V d or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment

Promise and deceit: pharmakos, drug replacement therapy, and the perils of experience.

Science.gov (United States)

Meyers, Todd

2014-06-01

The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie-its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy "tricking" or lying to the brain)-has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.

Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

Energy Technology Data Exchange (ETDEWEB)

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

2012-02-01

We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE{sub 2}) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS{sub PE} and BRS{sub SNP}). Nicotine (100 μg/kg i.v.) reduced BRS{sub SNP} in OVX rats but not in proestrus or OVXE{sub 2} rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS{sub PE} was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS{sub SNP} interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS{sub SNP} attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E{sub 2} against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

Impact of acetylcholine and nicotine on human osteoclastogenesis in vitro.

Science.gov (United States)

Ternes, Sebastian; Trinkaus, Katja; Bergen, Ivonne; Knaack, Sven; Gelinsky, Michael; Kilian, Olaf; Heiss, Christian; Lips, Katrin Susanne

2015-11-01

Recent studies showed that the non-neuronal cholinergic system (NNCS) is taking part in bone metabolism. Most studies investigated its role in osteoblasts, but up to now, the involvement of the NNCS in human osteoclastogenesis remains relatively unclear. Thus, aim of the present study was to determine whether the application of acetylcholine (ACh, 10(−4) M), nicotine (10(−6) M), mineralized collagen membranes or brain derived neurotrophic factor (BDNF, 40 ng/mL) influences the mRNA regulation of molecular components of the NNCS and the neurotrophin family during osteoclastogenesis. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of young healthy donors (n = 8) and incubated with bone fragments and osteoclast differentiation media for 21 days. All the results are based on the measurement of RNA. Real-time RT-PCR analysis demonstrated a down-regulation of nicotinic acetylcholine receptor (nAChR) subunit α2 and muscarinic acetylcholine receptor (mAChR) M3by osteoclastogenesis while BDNF mRNA expression was not regulated. Application of ACh, nicotine, BDNF or collagen membranes did not affect osteoclastic differentiation.No regulation was detected for nAChR subunit α7, tropomyosin-related kinase receptor B (TrkB), and cholineacetyl transferase (ChAT). Taken together, we assume that the transcriptional level of osteoclastogenesis of healthy young humans is not regulated by BDNF, ACh, and nicotine. Thus, these drugs do not seem to worsen bone degradation and might therefore be suitable as modulators of bone substitution materials if having a positive effect on bone formation.

In vivo human buccal permeability of nicotine

DEFF Research Database (Denmark)

Adrian, Charlotte L; Olin, Helle B D; Dalhoff, Kim

2006-01-01

The aim was to examine the in vivo buccal pH-dependent permeability of nicotine in humans and furthermore compare the in vivo permeability of nicotine to previous in vitro permeability data. The buccal permeability of nicotine was examined in a three-way cross-over study in eight healthy non......-smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of nicotine (P(app)) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine....... The disappearance rate of nicotine increased significantly as the pH increased, which resulted in P(app) values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(-4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R(2)=0.993) was obtained between the P...

Bioelectronic sniffer for nicotine using enzyme inhibition.

Science.gov (United States)

Mitsubayashi, Kohji; Nakayama, Kazumi; Taniguchi, Midori; Saito, Hirokazu; Otsuka, Kimio; Kudo, Hiroyuki

2006-07-28

A novel bioelectronic sniffer for nicotine in the gas phase was developed with enzyme inhibition principle to butyrylcholinesterase activity. The bioelectronic devices for nicotine in the gas and liquid phases were constructed using a Clark-type dissolved oxygen electrode and a membrane immobilized butyrylcholinesterase and choline oxidase. After the assessment of the sensor performances to choline and butyrylcholine as pre-examinations, the characteristics of the biosensor and bio-sniffer for nicotine were evaluated in the liquid and gas phases, respectively. The sensor signal of the bio-devices with 300 micromol l(-1) of butyrylcholine decreased quickly following application of nicotine and reached to the steady-state current, thus relating the concentration of nicotine in the liquid and gas phases. The biosensor was used to measure nicotine solution from 10 to 300 micromol l(-1). In the gas-phase experiment, the current signal of the bio-sniffer was also found to be linearly to the nicotine concentration over the range of 10.0-1000 ppb including 75.0 ppb as threshold limit value (TLV) by American Conference of Governmental Industrial Hygienists (ACGIH).

A hierarchical instrumental decision theory of nicotine dependence.

Science.gov (United States)

Hogarth, Lee; Troisi, Joseph R

2015-01-01

It is important to characterize the learning processes governing tobacco-seeking in order to understand how best to treat this behavior. Most drug learning theories have adopted a Pavlovian framework wherein the conditioned response is the main motivational process. We favor instead a hierarchical instrumental decision account, wherein expectations about the instrumental contingency between voluntary tobacco-seeking and the receipt of nicotine reward determines the probability of executing this behavior. To support this view, we review titration and nicotine discrimination research showing that internal signals for deprivation/satiation modulate expectations about the current incentive value of smoking, thereby modulating the propensity of this behavior. We also review research on cue-reactivity which has shown that external smoking cues modulate expectations about the probability of the tobacco-seeking response being effective, thereby modulating the propensity of this behavior. Economic decision theory is then considered to elucidate how expectations about the value and probability of response-nicotine contingency are integrated to form an overall utility estimate for that option for comparison with qualitatively different, nonsubstitute reinforcers, to determine response selection. As an applied test for this hierarchical instrumental decision framework, we consider how well it accounts for individual liability to smoking uptake and perseveration, pharmacotherapy, cue-extinction therapies, and plain packaging. We conclude that the hierarchical instrumental account is successful in reconciling this broad range of phenomenon precisely because it accepts that multiple diverse sources of internal and external information must be integrated to shape the decision to smoke.

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation.

Science.gov (United States)

Lam, Sum; Patel, Priti N

2007-01-01

Tobacco smoking remains a significant health problem in the United States. It has been associated with staggering morbidity and mortality, specifically due to malignancies and cardiovascular disease. Smoking cessation can be difficult and frequently requires pharmacologic interventions in addition to nonpharmacologic measures. Previously available agents are nicotine replacement products and bupropion, which increased quit rates by about 2-fold compared with placebo. Varenicline is the first drug in a new class known as the selective alpha4beta2 nicotinic receptor partial agonists. In several randomized, double-blind, 52-week clinical trials involving healthy chronic smokers, varenicline demonstrated superiority to placebo and bupropion in terms of efficacy measures. Additionally, it improved tobacco withdrawal symptoms and reinforcing effects of smoking in relapsed patients. Patients should start therapy in combination with tobacco cessation counseling 1 week before quit date and continue the regimen for 12 weeks. The dose of varenicline should be titrated to minimize nausea. The recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week maintenance therapy may be considered for those who achieve abstinence. The most common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is a breakthrough in the management of tobacco addiction and has demonstrated good efficacy in motivated quitters. It also provides an option for smokers who cannot tolerate other pharmacologic interventions.

Nicotine adsorption on single wall carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Girao, Eduardo C. [Departamento de Fisica, Universidade Federal do Ceara, Caixa Postal 6030, Campus do Pici, 60455-900 Fortaleza, Ceara (Brazil); Fagan, Solange B.; Zanella, Ivana [Area de Ciencias Tecnologicas, Centro Universitario Franciscano - UNIFRA, 97010-032 Santa Maria, RS (Brazil); Filho, Antonio G. Souza, E-mail: agsf@fisica.ufc.br [Departamento de Fisica, Universidade Federal do Ceara, Caixa Postal 6030, Campus do Pici, 60455-900 Fortaleza, Ceara (Brazil)

2010-12-15

This work reports a theoretical study of nicotine molecules interacting with single wall carbon nanotubes (SWCNTs) through ab initio calculations within the framework of density functional theory (DFT). Different adsorption sites for nicotine on the surface of pristine and defective (8,0) SWCNTs were analyzed and the total energy curves, as a function of molecular position relative to the SWCNT surface, were evaluated. The nicotine adsorption process is found to be energetically favorable and the molecule-nanotube interaction is intermediated by the tri-coordinated nitrogen atom from the nicotine. It is also predicted the possibility of a chemical bonding between nicotine and SWCNT through the di-coordinated nitrogen.

Hypnotherapy is more effective than nicotine replacement therapy for smoking cessation: results of a randomized controlled trial.

Science.gov (United States)

Hasan, Faysal M; Zagarins, Sofija E; Pischke, Karen M; Saiyed, Shamila; Bettencourt, Ann Marie; Beal, Laura; Macys, Diane; Aurora, Sanjay; McCleary, Nancy

2014-02-01

The efficacy of pharmacotherapy for smoking cessation is well documented. However, due to relapse rates and side effects, hypnotherapy is gaining attention as an alternative treatment option. The aim of this one-center randomized study was to compare the efficacy of hypnotherapy alone, as well as hypnotherapy with nicotine replacement therapy (NRT), to conventional NRT in patients hospitalized with a cardiac or pulmonary illness. We evaluated self-reported and biochemically verified 7-day prevalence smoking abstinence rates at 12 and 26 weeks post-hospitalization. Patients (n=164) were randomized into one of three counseling-based treatment groups: NRT for 30 days (NRT; n=41), a 90-min hypnotherapy session (H; n=39), and NRT with hypnotherapy (HNRT; n=37). Treatment groups were compared to a "self-quit" group of 35 patients who refused intervention. Hypnotherapy patients were more likely than NRT patients to be nonsmokers at 12 weeks (43.9% vs. 28.2%; p=0.14) and 26 weeks after hospitalization (36.6% vs. 18.0%; p=0.06). Smoking abstinence rates in the HNRT group were similar to the H group. There was no difference in smoking abstinence rates at 26 weeks between "self quit" and participants in any of the treatment groups. In multivariable regression analysis adjusting for diagnosis and demographic characteristics, H and HNRT were over three times more likely than NRT participants to abstain at 26-weeks post-discharge (RR=3.6; p=0.03 and RR=3.2; p=0.04, respectively). Hypnotherapy is more effective than NRT in improving smoking abstinence in patients hospitalized for a smoking-related illness, and could be an asset to post-discharge smoking cessation programs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stable isotope studies of nicotine kinetics and bioavailability

International Nuclear Information System (INIS)

Benowitz, N.L.; Jacob, P. III; Denaro, C.; Jenkins, R.

1991-01-01

The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine

Characterization and Genome Analysis of a Nicotine and Nicotinic Acid-Degrading Strain Pseudomonas putida JQ581 Isolated from Marine.

Science.gov (United States)

Li, Aiwen; Qiu, Jiguo; Chen, Dongzhi; Ye, Jiexu; Wang, Yuhong; Tong, Lu; Jiang, Jiandong; Chen, Jianmeng

2017-05-31

The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In this study, a nicotine and NA-degrading bacterium-strain JQ581-was isolated from sediment from the East China Sea and identified as a member of Pseudomonas putida based on morphology, physio-biochemical characteristics, and 16S rDNA gene analysis. The relationship between growth and nicotine/NA degradation suggested that strain JQ581 was a good candidate for applications in the bioaugmentation treatment of nicotine/NA contamination. The degradation intermediates of nicotine are pseudooxynicotine (PN) and 3-succinoyl-pyridine (SP) based on UV, high performance liquid chromatography, and liquid chromatography-mass spectrometry analyses. However, 6-hydroxy-3-succinoyl-pyridine (HSP) was not detected. NA degradation intermediates were identified as 6-hydroxynicotinic acid (6HNA). The whole genome of strain JQ581 was sequenced and analyzed. Genome sequence analysis revealed that strain JQ581 contained the gene clusters for nicotine and NA degradation. This is the first report where a marine-derived Pseudomonas strain had the ability to degrade nicotine and NA simultaneously.

Transdermal nicotine absorption handling e-cigarette refill liquids.

Science.gov (United States)

Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese

2016-02-01

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids. Copyright © 2015 Elsevier Inc. All rights reserved.

Behavioral Pharmacology of Human Drug Dependence

Science.gov (United States)

1981-07-01

1978. pp. 1-37. Pickens, I., Thompson, T., and Muchow, D.C. Cannabis and phenoy- olidine self-adinistration by animals. In: Goldberg, L., and...phenyl- ethylamines: cocaine, caffeine , and nicotine. Cocaine maintained high levels of self-infusion performance through a broader range of doses than...any of the 16 other drugs tested (0.032-3.2 mg/kg). Figure 2 shows that mean levels of self-infusion of both nicotine and caffeine were within the

Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

Science.gov (United States)

Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

2016-03-01

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (pdextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

Energy Technology Data Exchange (ETDEWEB)

Saylor, Kyle, E-mail: saylor@vt.edu; Zhang, Chenming, E-mail: chzhang2@vt.edu

2016-09-15

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

International Nuclear Information System (INIS)

Saylor, Kyle; Zhang, Chenming

2016-01-01

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.

Monitoring nicotine intake from e-cigarettes: measurement of parent drug and metabolites in oral fluid and plasma.

Science.gov (United States)

Papaseit, Esther; Farré, Magí; Graziano, Silvia; Pacifici, Roberta; Pérez-Mañá, Clara; García-Algar, Oscar; Pichini, Simona

2017-03-01

Electronic cigarettes (e-cig) known as electronic nicotine devices recently gained popularity among smokers. Despite many studies investigating their safety and toxicity, few examined the delivery of e-cig-derived nicotine and its metabolites in alternative biological fluids. We performed a randomized, crossover, and controlled clinical trial in nine healthy smokers. Nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (3-HCOT) were measured in plasma and oral fluid by liquid chromatography-tandem mass spectrometry after consumption of two consecutive e-cig administrations or two consecutive tobacco cigarettes. NIC and its metabolites were detected both in oral fluid and plasma following both administration conditions. Concentrations in oral fluid resulted various orders of magnitude higher than those observed in plasma. Oral fluid concentration of tobacco cigarette and e-cig-derived NIC peaked at 15 min after each administration and ranged between 1.0 and 1396 μg/L and from 0.3 to 860 μg/L; those of COT between 52.8 and 110 μg/L and from 33.8 to 94.7 μg/L; and those of 3-HCOT between 12.4 and 23.5 μg/L and from 8.5 to 24.4 μg/L. The oral fluid to plasma concentration ratio of both e-cig- and tobacco cigarette-derived NIC peaked at 15 min after both administrations and correlated with oral fluid NIC concentration. The obtained results support the measurement of NIC and metabolites in oral fluid in the assessment of intake after e-cig use and appear to be a suitable alternative to plasma when monitoring nicotine delivery from e-cig for clinical and toxicological studies.

Positron emission tomography (PET) imaging of nicotine-induced dopamine release in squirrel monkeys using [18F]Fallypride.

Science.gov (United States)

Naylor, Jennifer E; Hiranita, Takato; Matazel, Katelin S; Zhang, Xuan; Paule, Merle G; Goodwin, Amy K

2017-10-01

Nicotine, the principal psychoactive tobacco constituent, is thought to produce its reinforcing effects via actions within the mesolimbic dopamine (DA) system. The objective of the current study was to examine the effect of nicotine on DA D 2 /D 3 receptor availability in the nonhuman primate brain with the use of the radioligand [ 18 F]fallypride and positron emission tomography (PET). Ten adult male squirrel monkeys were used in the current study. Each subject underwent two PET scans, one with an injection (IV) of saline and subsequently one with an injection of nicotine (0.032mg/kg). The DA D 2 /D 3 antagonist, [ 18 F]fallypride, was delivered IV at the beginning of each scan, and nicotine or saline was delivered at 45min into the scan. Regions of interest (ROI) were drawn on specific brain regions and these were used to quantify standard uptake values (SUVs). The SUV is defined as the average concentration of radioactivity in the ROI x body weight/injected dose. Using the cerebellum as a reference region, SUV ratios (SUV ROI /SUV cerebellum ) were calculated to compare saline and nicotine effects in each ROI. Two-way repeated ANOVA revealed a significant decrease of SUV ratios in both striatal and extrastriatal regions following an injection of nicotine during the PET scans. Like other drugs of abuse, these results indicate that nicotine administration may produce DA release, as suggested by the decrease in [ 18 F]fallypride signal in striatal regions. These findings from a nonhuman primate model provide further evidence that the mesolimbic DA system is affected by the use of products that contain nicotine. Published by Elsevier B.V.

REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

Science.gov (United States)

Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

2015-01-01

Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

Reinforcement enhancing effects of acute nicotine via electronic cigarettes.

Science.gov (United States)

Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

2015-08-01

Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. We assessed acute effects of nicotine via electronic cigarettes ("e-cigarettes") on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled "36mg/ml") or placebo ("0″) e-cigarette, or no e-cigarette use. A fourth session involved smoking one's own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Detoxification and elimination of nicotine by nectar-feeding birds.

Science.gov (United States)

Lerch-Henning, S; Du Rand, E E; Nicolson, S W

2017-05-01

Many dilute nectars consumed by bird pollinators contain secondary metabolites, potentially toxic chemicals produced by plants as defences against herbivores. Consequently, nectar-feeding birds are challenged not only by frequent water excess, but also by the toxin content of their diet. High water turnover, however, could be advantageous to nectar consumers by enabling them to excrete secondary metabolites or their transformation products more easily. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences osmoregulation in white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens. We also examined the metabolic fate of nicotine in these two species to shed more light on the post-ingestive mechanisms that allow nectar-feeding birds to tolerate nectar nicotine. A high concentration of nicotine (50 µM) decreased cloacal fluid output and increased its osmolality in both species, due to reduced food intake that led to dehydration. White-eyes excreted a higher proportion of the ingested nicotine-containing diet than sunbirds. However, sugar concentration did not affect nicotine detoxification and elimination. Both species metabolised nicotine, excreting very little unchanged nicotine. Cape white-eyes mainly metabolised nicotine through the cotinine metabolic pathway, with norcotinine being the most abundant metabolite in the excreta, while white-bellied sunbirds excreted mainly nornicotine. Both species also utilized phase II conjugation reactions to detoxify nicotine, with Cape white-eyes depending more on the mercapturic acid pathway to detoxify nicotine than white-bellied sunbirds. We found that sunbirds and white-eyes, despite having a similar nicotine tolerance, responded differently and used different nicotine-derived metabolites to excrete nicotine.

Understanding and use of nicotine replacement therapy and nonpharmacologic smoking cessation strategies among Chinese and Vietnamese smokers and their families.

Science.gov (United States)

Tsang, Icarus K; Tsoh, Janice Y; Wong, Ching; Le, Khanh; Cheng, Joyce W; Nguyen, Anthony N; Nguyen, Tung T; McPhee, Stephen J; Burke, Nancy J

2014-02-20

Population-based studies have reported high rates of smoking prevalence among Chinese and Vietnamese American men. Although nicotine replacement therapy (NRT) is effective, recommended, and accessible without prescription, these populations underuse NRT for smoking cessation. The aim of this study was to assess understanding and use of NRT and nonpharmacologic treatments among Chinese and Vietnamese American male smokers and their families. In-depth qualitative interviews were conducted with 13 smoker-family pairs, followed by individual interviews with each participant. A total of 39 interviews were conducted in Vietnamese or Chinese, recorded, translated, and transcribed into English for analysis. Four themes were identified: use and understanding of NRT, nonpharmacologic strategies, familial and religious approaches, and willpower. Both smokers and their family members believed strongly in willpower and a sense of personal responsibility as the primary drivers for stopping smoking. Lack of these 2 qualities keeps many Chinese and Vietnamese men from using NRT to quit smoking. Those who do use NRT often use it incorrectly, following their own preferences rather than product instructions. Our findings indicate the importance of culturally appropriate patient education about NRT. It may be necessary to teach smokers and their families at an individual level about NRT as a complementary approach that can strengthen their resolve to quit smoking. At a community level, public health education on the indication and appropriate use of evidence-based smoking cessation resources, such as NRT, would be an important component of effective tobacco control.

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

Science.gov (United States)

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-11-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

Short- and long-term effects of nicotine and the histone deacetylase inhibitor phenylbutyrate on novel object recognition in zebrafish.

Science.gov (United States)

Faillace, M P; Pisera-Fuster, A; Medrano, M P; Bejarano, A C; Bernabeu, R O

2017-03-01

Zebrafish have a sophisticated color- and shape-sensitive visual system, so we examined color cue-based novel object recognition in zebrafish. We evaluated preference in the absence or presence of drugs that affect attention and memory retention in rodents: nicotine and the histone deacetylase inhibitor (HDACi) phenylbutyrate (PhB). The objective of this study was to evaluate whether nicotine and PhB affect innate preferences of zebrafish for familiar and novel objects after short- and long-retention intervals. We developed modified object recognition (OR) tasks using neutral novel and familiar objects in different colors. We also tested objects which differed with respect to the exploratory behavior they elicited from naïve zebrafish. Zebrafish showed an innate preference for exploring red or green objects rather than yellow or blue objects. Zebrafish were better at discriminating color changes than changes in object shape or size. Nicotine significantly enhanced or changed short-term innate novel object preference whereas PhB had similar effects when preference was assessed 24 h after training. Analysis of other zebrafish behaviors corroborated these results. Zebrafish were innately reluctant or prone to explore colored novel objects, so drug effects on innate preference for objects can be evaluated changing the color of objects with a simple geometry. Zebrafish exhibited recognition memory for novel objects with similar innate significance. Interestingly, nicotine and PhB significantly modified innate object preference.

Intersubunit bridge formation governs agonist efficacy at nicotinic acetylcholine alpha4beta2 receptors

DEFF Research Database (Denmark)

Rohde, Line Aagot Hede; Ahring, Philip Kiær; Jensen, Marianne Lerbech

2012-01-01

The a4ß2 subtype of the nicotinic acetylcholine receptor (nAChR) has been pursued as a drug target for treatment of psychiatric and neurodegenerative disorders and smoking cessation aids for decades. Still, a thorough understanding of structure-function relationships of a4ß2 agonists is lacking...

Airborne Nicotine, Secondhand Smoke, and Precursors to Adolescent Smoking.

Science.gov (United States)

McGrath, Jennifer J; Racicot, Simon; Okoli, Chizimuzo T C; Hammond, S Katharine; O'Loughlin, Jennifer

2018-01-01

Secondhand smoke (SHS) directly increases exposure to airborne nicotine, tobacco's main psychoactive substance. When exposed to SHS, nonsmokers inhale 60% to 80% of airborne nicotine, absorb concentrations similar to those absorbed by smokers, and display high levels of nicotine biomarkers. Social modeling, or observing other smokers, is a well-established predictor of smoking during adolescence. Observing smokers also leads to increased pharmacological exposure to airborne nicotine via SHS. The objective of this study is to investigate whether greater exposure to airborne nicotine via SHS increases the risk for smoking initiation precursors among never-smoking adolescents. Secondary students ( N = 406; never-smokers: n = 338, 53% girls, mean age = 12.9, SD = 0.4) participated in the AdoQuest II longitudinal cohort. They answered questionnaires about social exposure to smoking (parents, siblings, peers) and known smoking precursors (eg, expected benefits and/or costs, SHS aversion, smoking susceptibility, and nicotine dependence symptoms). Saliva and hair samples were collected to derive biomarkers of cotinine and nicotine. Adolescents wore a passive monitor for 1 week to measure airborne nicotine. Higher airborne nicotine was significantly associated with greater expected benefits ( R 2 = 0.024) and lower expected costs ( R 2 = 0.014). Higher social exposure was significantly associated with more temptation to try smoking ( R 2 = 0.025), lower aversion to SHS ( R 2 = 0.038), and greater smoking susceptibility ( R 2 = 0.071). Greater social exposure was significantly associated with more nicotine dependence symptoms; this relation worsened with higher nicotine exposure (cotinine R 2 = 0.096; airborne nicotine R 2 = 0.088). Airborne nicotine exposure via SHS is a plausible risk factor for smoking initiation during adolescence. Public health implications include limiting airborne nicotine through smoking bans in homes and cars, in addition to stringent restrictions

Nicotine pharmacokinetics and its application to intake from smoking.

Science.gov (United States)

Feyerabend, C; Ings, R M; Russel, M A

1985-01-01

Five subjects were given 25 micrograms/kg nicotine intravenously over 1 min, before and after a loading period involving the smoking of six cigarettes. Plasma nicotine concentrations declined in a biphasic manner, the half-lives of the initial and terminal phases averaging 9 min and 133 min respectively. Terminal half-lives before and after the loading period were essentially the same suggesting the absence of saturation kinetics at nicotine concentrations that build up during smoking. The plasma clearance of nicotine and the volume of distribution were very high averaging 915 ml/min and 1731, respectively. Two approaches were used to calculate the nicotine intake from smoking. The average dose of nicotine absorbed from one cigarette was 1.06 mg which was 82% of the standard machine-smoked yield of 1.3 mg. To illustrate their potential use in 'nicotine titration' studies, these approaches were used to compare nicotine intake from smoking a high (2.4 mg) and low (0.6 mg) nicotine cigarette. The dose of nicotine absorbed averaged 1.14 mg and 0.86 mg per cigarette respectively, being 48% and 143% of the machine-smoked yields. PMID:3986082

Rheological, mechanical and membrane penetration properties of novel dual drug systems for percutaneous delivery.

Science.gov (United States)

Woolfson, A D; Malcolm, R K; Campbell, K; Jones, D S; Russell, J A

2000-07-03

In this study it has been demonstrated that mixtures of two solid drugs, ibuprofen and methyl nicotinate, with different but complementary pharmacological activities and which exist as a single liquid phase over a wide composition range at skin temperature, can be formulated as o/w emulsions without the use of an additional hydrophobic carrier. These novel dual drug systems provided significantly enhanced in vitro penetration rates through a model lipophilic barrier membrane compared to conventional individual formulations of each active. Thus, for ibuprofen, drug penetration flux enhancements of three- and 10-fold were observed when compared to an aqueous ibuprofen suspension and a commercial alcohol-based ibuprofen formulation, respectively. Methyl nicotinate penetration rates were shown to be similar for aqueous gels and emulsified systems. Mechanisms explaining these observations are proposed. Novel dual drug formulations of ibuprofen and methyl nicotinate, formulated within the liquid range at skin temperature, were investigated by oscillatory rheology and texture profile analysis, demonstrating the effects of drug and viscosity enhancer concentrations, and disperse phase type upon the rheological, mechanical and drug penetration properties of these systems.

an appraisal of psychotropic drugs and their consequences among

African Journals Online (AJOL)

user

2017-01-01

Jan 1, 2017 ... workers are familiar with the legal and addiction aspect of psychotropic drugs, many ... Psychotropic drugs revolutionized the treatment of psychological disorders. .... Nicotine is an alkaloid found in the nightshade family of.

NICOTINE EFFECTS ON THE ACTIVITY OF MICE EXPOSED PRENATALLY TO THE NICOTINIC AGONIST ANATOXIN-A.

Science.gov (United States)

Considerable research has shown long-lasting effects of early exposure in experimental animals to nicotine. Anatoxin-a is produced by cyanobacteria and has been shown to be a potent nicotinic agonist. This experiment evaluated the motor activity of adult mice, and their respons...

Effect of nicotine on negative affect among more impulsive smokers.

Science.gov (United States)

Doran, Neal; McChargue, Dennis; Spring, Bonnie; VanderVeen, Joe; Cook, Jessica Werth; Richmond, Malia

2006-08-01

In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity x Condition (nicotinized vs. de-nicotinized) x Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation.

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

Science.gov (United States)

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin

International Nuclear Information System (INIS)

Clarke, P.B.; Schwartz, R.D.; Paul, S.M.; Pert, C.B.; Pert, A.

1985-01-01

Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists [ 3 H]nicotine and [ 3 H]acetylcholine ([ 3 H]ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, [ 125 I]-alpha-bungarotoxin([ 125 I]BTX), which acts as a nicotinic antagonist at the neuromuscular junction. Binding studies employing brain homogenates indicate that the regional distributions of both [ 3 H]nicotine and [ 3 H]ACh differ from that of [ 125 I]BTX. The possible relationship between brain sites bound by [ 3 H]nicotine and [ 3 H]ACh has not been examined directly. The authors have used the technique of autoradiography to produce detailed maps of [ 3 H]nicotine, [ 3 H]ACh, and [ 125 I]BTX labeling; near-adjacent tissue sections were compared at many levels of the rat brain. The maps of high affinity agonist labeling are strikingly concordant, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area. The pattern of [ 125 I]BTX binding is strikingly different, the only notable overlap with agonist binding being the cerebral cortex (layer I) and superior colliculus. [ 125 I]BTX binding is also dense in the inferior colliculus, cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually absent in thalamus. Various lines of evidence suggest that the high affinity agonist-binding sites in brain correspond to nicotinic cholinergic receptors similar to those found at autonomic ganglia; BTX-binding sites may also serve as receptors for nicotine and are possibly related to neuromuscular nicotinic cholinoceptors

Nicotine and endogenous opioids: neurochemical and pharmacological evidence.

Science.gov (United States)

Hadjiconstantinou, Maria; Neff, Norton H

2011-06-01

Although the mesolimbic dopamine hypothesis is the most influential theory of nicotine reward and reinforcement, there has been a consensus that other neurotransmitter systems contribute to the addictive properties of nicotine as well. In this regard, the brain opioidergic system is of interest. Striatum is rich in opioid peptides and opioid receptors, and striatal opioidergic neurons are engaged in a bidirectional communication with midbrain dopaminergic neurons, closely regulating each other's activity. Enkephalins and dynorphins exert opposing actions on dopaminergic neurons, increasing and decreasing dopamine release respectively, and are components of circuits promoting positive or negative motivational and affective states. Moreover, dopamine controls the synthesis of striatal enkephalins and dynorphins. Evidence suggests that opioidergic function is altered after nicotine and endogenous opioids are involved in nicotine's behavioral effects. 1) The synthesis and release of β-endorphin, met-enkephalin and dynorphin in brain, especially nucleus accumbens (NAc), are altered after acute or chronic nicotine treatment and during nicotine withdrawal. 2) Although opioid receptor binding and mRNA do not appear to change in the striatum during nicotine withdrawal, the activity of κ-opioid (KOPr) and δ-opioid (DOPr) receptors is attenuated in NAc. 3) The nicotine withdrawal syndrome reminisces that of opiates, and naloxone precipitates some of its somatic, motivational, and affective signs. 4) Genetic and pharmacological studies indicate that μ-opioid (MOPr) receptors are mainly involved in nicotine reward, while DOPrs contribute to the emotional and KOPrs to the aversive responses of nicotine. 5) Finally, MOPrs and enkephalin, but not β-endorphin or dynorphin, are necessary for the physical manifestations of nicotine withdrawal. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier

Nicotine Analysis in Several Non-Tobacco Plant Materials

Directory of Open Access Journals (Sweden)

Moldoveanu Serban C.

2016-04-01

Full Text Available Present study describes the determination of nicotine in various plant samples with a low content of this compound. Nicotine is found naturally in plants from the Solanaceae family. The plants from Nicotiana genus contain large levels of nicotine. However, only low levels are present in plants from Solanum genus including potato, tomato, eggplant, and from Capsicum genus, which are used as food. Because the levels of nicotine in these materials are in the range of parts per billion, the measurements are difficult and the results are very different from study to study. The present study evaluated the level of nicotine in a number of plants (fruits, roots, leaves, tubers from Solanaceae family (not including Nicotiana genus and from several other vegetables commonly used as food. The analysis consisted of the treatment of plant material with an aqueous solution 5% NaOH at 70°C for 30 min, followed by extraction with TBME containing d3-nicotine as an internal standard. The TBME organic layer was analyzed on a 7890B/7000C GC-MS/MS system with a 30 m × 0.25 mm, 0.25 μm film CAM column. The MS/MS system worked in MRM positive ionization mode monitoring the transition 162 - 84 for nicotine and 165 - 87 for d3-nicotine. Particular attention was given to the preservation of the intact levels of nicotine in the plant material. The plant material was analyzed as is, without drying and with minimal exposure to contaminations. Separately, the moisture of the plant material was measured in order to report the nicotine level on a dry-basis. Levels of nicotine around 180 ng/g dry material were obtained for tomatoes and eggplant (fruit and lower levels were obtained for green pepper and potato. Similar levels to that in the tomato fruit were detected in tomato leaves. Materials from other plant families also showed traces of nicotine. [Beitr. Tabakforsch. Int. 27 (2016 54-59

Nicotine-selective radiation-induced poly(acrylamide/maleic acid) hydrogels

International Nuclear Information System (INIS)

Saraydin, D.; Karadag, E.; Caldiran, Y.; Gueven, O.

2001-01-01

Nicotine-selective poly(acrylamide/maleic acid) (AAm/MA) hydrogels prepared by γ-irradiation were used in experiments on swelling, diffusion, and interactions of the pharmaceuticals nicotine, nicotinic acid, nicotinamide, and nikethamide. For AAm/MA hydrogel containing 60 mg maleic acid and irradiated at 5.2 kGy, the studies indicated that swelling increased in the following order; nicotine>nicotinamide>nikethamide>nicotinic acid>water. Diffusions of water and the pharmaceuticals within the hydrogels were found to be non-Fickian in character. AAm/MA hydrogel sorbed only nicotine and did not sorb nicotinamide, nikethamide and nicotinic acid in the binding experiments. S-type adsorption in Giles's classification system was observed. Some binding and thermodynamic parameters for AAm/MA hydrogel-nicotine system were calculated using the Scatchard method. The values of adsorption heat and free energy of this system were found to be negative whereas adsorption entropy was found to be positive. (author)

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

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Suarez, S.V.; Changeux, J.P.; Granon, S. [Unite de Neurobiologie Integrative du Systeme Cholinergique, URA CNRS 2182, Institut Pasteur, Departement de Neuroscience, 25 rue du Dr Roux, 75015 Paris (France); Amadon, A.; Giacomini, E.; Le Bihan, D. [Service Hospitalier Frederic Joliot, 4 place du general Leclerc, 91400 Orsay (France); Wiklund, A. [Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm (Sweden)

2009-07-01

Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity {beta}2-containing nicotinic receptors ({beta}2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the {beta}2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and {beta}2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, {beta}2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via {alpha}7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on {beta}2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study

International Nuclear Information System (INIS)

Suarez, S.V.; Changeux, J.P.; Granon, S.; Amadon, A.; Giacomini, E.; Le Bihan, D.; Wiklund, A.

2009-01-01

Rationale: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity β2-containing nicotinic receptors (β2*nAChRs) are located. Objectives We intend to see which brain circuits are activated when nicotine is given in animals naive for nicotine and whether the β2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. Materials and methods: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and β2 knockout (KO) mice. Results: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, β2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via α7 nicotinic receptors. Conclusions: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on β2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice. (authors)

Pavlovian Extinction of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats Varies as a Function of Context

Science.gov (United States)

Troisi, Joseph R., II

2011-01-01

Operant extinction contingencies can undermine the discriminative stimulus effects of drugs. Here, nicotine (0.4 mg/kg) and ethanol (0.8 g/kg) first functioned as either an S[superscript D] or S[superscript Delta], in a counterbalanced one-lever go/no-go (across sessions) operant drug discrimination procedure. Pavlovian extinction in the training…

Cholinergic modulation of dopamine pathways through nicotinic acetylcholine receptors.

NARCIS (Netherlands)

de Kloet, S.F.; Mansvelder, H.D.; de Vries, T.J.

2015-01-01

Nicotine addiction is highly prevalent in current society and is often comorbid with other diseases. In the central nervous system, nicotine acts as an agonist for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location and receptor composition. Although nicotinic receptors are

The metabolic fate of nectar nicotine in worker honey bees.

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du Rand, Esther E; Pirk, Christian W W; Nicolson, Susan W; Apostolides, Zeno

2017-04-01

Honey bees (Apis mellifera) are generalist pollinators that forage for nectar and pollen of a very large variety of plant species, exposing them to a diverse range of secondary metabolites produced as chemical defences against herbivory. Honey bees can tolerate high levels of many of these toxic compounds, including the alkaloid nicotine, in their diet without incurring apparent fitness costs. Very little is known about the underlying detoxification processes mediating this tolerance. We examined the metabolic fate of nicotine in newly emerged worker bees using radiolabeled nicotine and LC-MS/MS analysis to determine the kinetic distribution profile of nicotine as well as the absence or presence and identity of any nicotine-derived metabolites. Nicotine metabolism was extensive; virtually no unmetabolised nicotine were recovered from the rectum. The major metabolite found was 4-hydroxy-4-(3-pyridyl) butanoic acid, the end product of 2'C-oxidation of nicotine. It is the first time that 4-hydroxy-4-(3-pyridyl) butanoic acid has been identified in an insect as a catabolite of nicotine. Lower levels of cotinine, cotinine N-oxide, 3'hydroxy-cotinine, nicotine N-oxide and norcotinine were also detected. Our results demonstrated that formation of 4-hydroxy-4-(3-pyridyl) butanoic acid is quantitatively the most significant pathway of nicotine metabolism in honey bees and that the rapid excretion of unmetabolised nicotine does not contribute significantly to nicotine tolerance in honey bees. In nicotine-tolerant insects that do not rely on the rapid excretion of nicotine like the Lepidoptera, it is possible that the 2'C-oxidation of nicotine is the conserved metabolic pathway instead of the generally assumed 5'C-oxidation pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nicotine increases brain functional network efficiency.

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Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

2012-10-15

Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism.

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Rahman, Shafiqur; Engleman, Eric A; Bell, Richard L

2016-01-01

Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The cellular and molecular mechanisms of alcohol reward and addiction are still not well understood. Emerging evidence indicates that unlike other drugs of abuse, such as nicotine, cocaine, or opioids, alcohol targets numerous channel proteins, receptor molecules, and signaling pathways in the brain. Previously, research has identified brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric ligand-gated cation channels expressed in the mammalian brain, as critical molecular targets for alcohol abuse and dependence. Genetic variations encoding nAChR subunits have been shown to increase the vulnerability to develop alcohol dependence. Here, we review recent insights into the rewarding effects of alcohol, as they pertain to different nAChR subtypes, associated signaling molecules, and pathways that contribute to the molecular mechanisms of alcoholism and/or comorbid brain disorders. Understanding these cellular changes and molecular underpinnings may be useful for the advancement of brain nicotinic-cholinergic mechanisms, and will lead to a better translational and therapeutic outcome for alcoholism and/or comorbid conditions. Copyright © 2016. Published by Elsevier Inc.

Agonist and antagonist effects of tobacco-related nitrosamines on human α4β2 nicotinic acetylcholine receptors.

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Simone eBrusco

2015-09-01

Full Text Available Regulation of the ‘neuronal’ nicotinic acetylcholine receptors (nAChRs is implicated in both tobacco addiction and smoking-dependent tumor promotion. Some of these effects are caused by the tobacco-derived N-nitrosamines, which are carcinogenic compounds that avidly bind to nAChRs. However, the functional effects of these drugs on specific nAChR subtypes are largely unknown. By using patch-clamp methods, we tested 4-(methylnitrosamine-1-(3-pyridyl-1-butanone (NNK and N’-nitrosonornicotine (NNN on human α4β2 nAChRs. These latter are widely distributed in the mammalian brain and are also frequently expressed outside the nervous system. NNK behaved as a partial agonist, with an apparent EC50 of 16.7 μM. At 100 μM, it activated 16 % of the maximal current activated by nicotine. When NNK was co-applied with nicotine, it potentiated the currents elicited by nicotine concentrations ≤ 100 nM. At higher concentrations of nicotine, NNK always inhibited the α4β2 nAChR. In contrast, NNN was a pure inhibitor of this nAChR subtype, with IC50 of approximately 1 nM in the presence of 10 μM nicotine. The effects of both NNK and NNN were mainly competitive and largely independent of Vm. The different actions of NNN and NNK must be taken into account when interpreting their biological effects in vitro and in vivo.

Detection of methamphetamine in the presence of nicotine using in situ chemical derivatization and ion mobility spectrometry.