2005 — 2012 |
Heishman, Stephen |
Z01Activity Code Description: Undocumented code - click on the grant title for more information. ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Cue-Reactivity and Attention in Smokers and Nonsmokers @ National Institute On Drug Abuse
One of the most common symptoms reported by people attempting to quit smoking is craving for cigarettes. Laboratory and clinical studies have shown that reports of tobacco craving increase during periods of abstinence and that craving predicts relapse in smokers trying to quit. Thus, tobacco craving appears to play a significant role in the maintenance of nicotine dependence and treatment outcome. The primary objective of this study was to compare the effectiveness of active imagery versus in vivo cues in eliciting self-report and physiological responses indicative of tobacco craving. This study will also examine the effect of nicotine deprivation on cue-elicited craving, the duration of craving responses after cue manipulation, and the effect of nicotine deprivation on the attentional blink task. This study will establish a human laboratory model for investigating self-report and physiological responses to smoking cues. This model will be used in future studies to compare responses among various smoker groups (e.g., nicotine-dependent smokers, occasional smokers, former smokers) and smokers with co-morbid disorders, such as depression and schizophrenia. Smokers attend two experimental sessions, one in which they are at least 12 hours nicotine deprived and one in which they have been smoking normally. Never-smokers attend one experimental session. Experimental sessions begin with performance of the attentional blink task, which reflects a failure of the visual system to detect two target stimuli presented in rapid succession. This will be followed by four experimental trials, which will be presented in random order;each trial will last 30 minutes. The four trials are: 1) imagery script consisting of smoking descriptors, 2) imagery script with no smoking descriptors, 3) in vivo smoking cues, and 4) in vivo neutral cues. Participants will complete self-report measures of craving and have physiological measures taken immediately and 5, 10, 20, and 30 minutes after script or cue exposure. There will be a 5-10 minute rest period between trials. Primary outcome measures include self-report (Tobacco Craving Questionnaire and Visual Analog Scale questions) and physiological (heart rate, blood pressure, finger temperature, and skin conductance) variables. A secondary outcome measure is the number of correct target detections on the attentional blink task.
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1 |
2007 — 2012 |
Heishman, Stephen |
Z01Activity Code Description: Undocumented code - click on the grant title for more information. ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Effect of Nicotine and/or Tobacco Withdrawal On Cognition and Brain Function @ National Institute On Drug Abuse
It is not clear whether symptoms of tobacco withdrawal are due to lack of nicotine or tobacco. Through the use of denicotinized and nicotinized research cigarettes, we can identify whether symptoms are due to the absence of nicotine or tobacco. Smokers completely abstinent from cigarettes have changes in HPA (hypothalamo-pituitary-adrenal) and HPT (hypothalamo-pituitary-thyroid) axes which parallel withdrawal symptoms, measures of mood, and diminished cognitive performance. Monoamine oxidase (MAO) activities which are reduced in chronic smokers return to normal during tobacco abstinence. Nicotinized cigarettes may prevent these neuroendocrine and MAO changes. Smoking denicotinized cigarettes would not prevent changes related to lack of nicotine, but may continue to inhibit MAO activities thought to be related to some components of smoke. Brain activity that underlies behavioral and cognitive changes related to nicotine exposure may be altered in smokers as a function of state (non-abstinent, abstinent, after abstinence) and as compared to nonsmokers. In this study, we compare the effects of tobacco abstinence or smoking denicotinized research cigarettes to smoking ad libitum nicotinized research cigarettes on the following measures: withdrawal symptoms and quality of sleep;MAO-A and MAO-B activities;hormonal responses (HPA, HPT);mood, cognitive and psychometric performance;functional brain activity, and physiological responses. Research participants are men who are at least 18 years old, report smoking at least 15 cigarettes per day, have not used any illicit drug except marijuana in the past year, have no history of drug or alcohol dependence, and have already experienced tobacco withdrawal symptoms when they had no access to cigarettes. Smokers are randomized into one of 3 groups: a) complete tobacco abstinence for 8 days;b) denicotinized research cigarettes for 8 days, or c) control group smoking nicotinized research cigarettes during the entire study (16 days). Because there are few studies comparing functional brain activity in smokers and nonsmokers, a group of nonsmokers will serve as a control group for the brain imaging studies. Assessments will be performed before, during 8 days of complete abstinence/denicotinized cigarette use, and after subjects resume nicotinized cigarette smoking. Identification of hormonal and MAO changes in association with mood and performance alterations may facilitate the development of new treatments (e.g. thyroid hormones or MAOIs) for smoking cessation. If denicotinized cigarettes can antagonize symptoms of smoking abstinence, they can be developed as a non-nicotinic treatment for tobacco dependence. This study is ongoing, and no results are available yet.
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1 |
2007 — 2012 |
Heishman, Stephen J. |
Z01Activity Code Description: Undocumented code - click on the grant title for more information. ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Effect of Nicotine On Elements of Attention in Smokers and Nonsmokers @ National Institute On Drug Abuse
Many cigarette smokers report that smoking helps them stay alert and improves their concentration. Early research tended to support the idea that smoking enhanced human performance; however, many of these studies only demonstrated that smoking reversed withdrawal-induced performance deficits in nicotine-dependent individuals. More recent research has indicated that smoking or nicotine can truly enhance certain aspects of attention and memory. We have recently completed the first of a planned series of studies investigating the effect of varying doses of intranasal nicotine on attention and cognition. This initial study was designed to determine whether we could achieve dose-related effects of nicotine (0, 1, 2, mg) in a single test session. Nicotine dose-dependently increased subjective ratings of alert, head rush, and stimulated, and decreased ratings of relaxed, urge to smoke, and drowsy. Nicotine also increased heart rate and blood pressure. Nicotine dose-dependently increased correct responses and decreased omission errors on a test of sustained attention. Accuracy on an arithmetic test was also enhanced by nicotine in a dose-related manner. In both tests, there was no difference between 12-hr tobacco-deprived and nondeprived conditions. In future studies, we will use this dosing paradigm to investigate the effect of nicotine in smokers and nonsmokers on the various elements of attention: encode, focus/execute, shift, sustain, and stabilize.
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1 |
2008 — 2009 |
Heishman, Stephen |
Z01Activity Code Description: Undocumented code - click on the grant title for more information. ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Neurocognitive/Affective Correlates of Tobacco Dependence in Adolescent Smokers @ National Institute On Drug Abuse
Tobacco addiction is the leading cause of morbidity and mortality in the United States. Because tobacco use typically begins among adolescents and many teenagers try to quit, experience withdrawal and fail, a better understanding of tobacco withdrawal and effective interventions to treat tobacco dependence and withdrawal among young smokers are critically needed. In adult smoking cessation studies tobacco dependence and withdrawal include changes in affect and cognition. Change in negative affect was a significant mediator of the effects of bupropion, a non-nicotine pharmacological agent. This study will examine how tobacco dependence and withdrawal influence cognitive and affective states in adolescent smokers. It will also evaluate whether the effects of tobacco withdrawal in adolescent smokers are reduced by treatment with bupropion, which is also used in mood disorders and childhood ADHD, and is currently approved for adult smoking cessation treatment. This 10-week study consists of an unassisted (pretrial) acute tobacco withdrawal (AW) phase and a 7-week randomized double-blind placebo-controlled trial of bupropion (300 mgday) for tobacco dependence. Neuropsychological examinations will be conducted at baseline, during acute withdrawal, and during treatment (including early withdrawal) with bupropion. We expect smoking cessation in approximately 25% of the active medication group and significant overall smoking reduction. We postulate that bupropion will also reduce the irritability, depressed mood and anxiety symptoms that typically occur during tobacco withdrawal. We expect to observe optimal cognitive performance, (i.e., attention, memory), and affective state during satiety, impairment during pre-treatment abstinence, and intermediate level cognitive performance in the abstinent active-treatment group. Because limited data are available on cognitive tasks in adolescent smokers, a non-smoking group will be included in order to establish the validity and appropriateness of our paradigm with a normative sample. The main potential risks of this study are linked to the medication, which was found to be safe in several adult trials. A potential benefit of this study is the improvement in health status due to cessation or reduction of tobacco exposure in adolescents. This study will also determine the effects of tobacco withdrawal on cognitive and affective states and how they can be addressed early in the addictive cycle.No findings have yet emerged from this study as we have just started recruiting. We are examining the relationship between parental allowance of smoking in the home and adolescents smoking behavior. Adolescents (n=408) who were allowed to smoke at home smoked more cigarettes per day and had higher scores on the Fagerstrom Test of Nicotine Dependence than those not allowed to smoke at home. We are exploring the relationships between baseline motivation and also in-treatment motivation fluctuations and point prevalence abstinence. We are also exploring relationships between: -impulsivity and smoking trajectory (time progression from first puff to first cigarette) -impulsivity including subscales (nonplanning, cognitive, and motor impulsivity) and number of smoking lapses -depressive symptoms and smoking. We are also examining the reasons for adolescent relapse to smoking after a quit attempt.
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0.915 |
2009 — 2011 |
Heishman, Stephen |
ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Breath Co and Cotinine as Biomarkers to Distinguish Smokers From Nonsmokers @ National Institute On Drug Abuse
The purpose of this study is to determine a breath carbon monoxide (CO) cutoff level that optimally discriminates between heavy and light smokers and nonsmokers who are and who are not exposed to environmental tobacco smoke. Breath CO will be compared against cotinine concentration, which is the gold standard in verifying smoking status. The study will include four groups: 1) 55 smokers reporting >10 cigarettes per day, 2) 55 smokers reporting ≤10 cigarettes per day, 3) 55 nonsmokers reporting regular environmental exposure to tobacco smoke, and 4) 55 nonsmokers reporting limited or no environmental exposure to tobacco smoke (total of 110 smokers and 110 nonsmokers). Outcome measures include: 1) breath CO;2) semiquantitative salivary cotinine;3) quantitative salivary nicotine, cotinine, and 3-hydroxycotinine;4) semiquantitative urinary cotinine;5) quantitative urinary nicotine, cotinine, norcotinine, and 3-hydroxycotinine;and 6) self-reported smoking variables. During this past year, we have completed about 75% of subject testing. Because study enrollment is ongoing, we have no findings to report at this time.
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0.915 |
2009 — 2012 |
Heishman, Stephen |
ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Effects of Smoking On Opioid Receptor Binding: a Pet Imaging Study @ National Institute On Drug Abuse
Tobacco smoking is the leading preventable cause of morbidity and mortality in the world, yet despite decades of public awareness campaigns on the adverse health consequences of smoking, 21.5% of adults in the U.S. are daily smokers. The reinforcing effects of nicotine are mediated in part via its effects on α4β2 nicotinic acetylcholine receptors, which result in activation of dopamine (DA) cells and increased release of DA in the nucleus accumbens (NAc). In fact, the ability of most addictive drugs to increase DA in the NAc is believed to be a common mechanism through which drugs of abuse exert their reinforcing effects. However, preclinical studies have shown that nicotine also results in release of endogenous opioids, which is also likely to contribute to its reinforcing effects because nicotine is not reinforcing in mice that do not express mu-opioid receptors. Thus, a more complete understanding of the acute and chronic effects of nicotine on the endogenous opioid system in humans might provide improved strategies for medication development for the treatment of nicotine dependence. In this study, we propose to investigate whether nicotine at the dose delivered through a cigarette (1-2 mg) will increase the release of endogenous opioids. We will also determine whether smokers have adaptations in the opioid system compared with nonsmokers. We will test 20 smokers and 20 nonsmokers. Outcome measures include: 1) displacement of 11Ccarfentanil binding, secondary to the release of endorphins by nicotine;2) upregulation of 11Ccarfentanil specific binding in smokers compared with nonsmokers;3) 11Ccarfentanil specific binding as a function of the mu-opioid receptor A118G polymorphism;and 4) correlation between self-report measures of nicotine effect and 11Ccarfentanil binding profile. During the past year, we have initiated the study and completed testing of three subjects. Because study enrollment is ongoing, we have no findings to report at this time.
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0.915 |
2009 — 2010 |
Heishman, Stephen |
ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Tobacco Craving and Cigarette Reinforcement in Adolescent Smokers @ National Institute On Drug Abuse
Tobacco smoking is the leading preventable cause of morbidity and mortality in the world, yet despite public health efforts to dissuade youth from experimenting with tobacco, about 4.5 million adolescents in the U.S. are cigarette smokers. Every day more than 4,000 young people under 18 years try smoking while another 1,000 who have already experimented with cigarettes become regular smokers. The purpose of this study is to determine the effects of smoking versus neutral cues in adolescents who smoke on 1) craving, mood, and autonomic responsivity and 2) the relative reinforcing efficacy of tobacco cigarettes. We will test 25 adolescent smokers. During cue trials, primary measures include craving (TCQ-SF, VAS), mood (mood form, VAS), and autonomic (heart rate, blood pressure, skin conductance) responsivity. During self-administration trials, primary measures include breakpoint (final ratio completed), total number of responses, and number of cigarette puffs earned and taken. Secondary measures include baseline smoking history, mood, tobacco craving, smoking expectancies, nicotine dependence, and urinary cotinine and 3-hydroxycotinine. During the past year, we have initiated the study and completed testing of two subjects. Because study enrollment is ongoing, we have no findings to report at this time.
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0.915 |
2009 — 2013 |
Heishman, Stephen |
ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Tobacco Craving and Cigarette Reinforcement in Normal and Schizophrenic Smokers @ National Institute On Drug Abuse
Tobacco smoking is the leading preventable cause of morbidity and mortality in the world, yet despite decades of public awareness campaigns on the adverse health consequences of smoking, 21.5% of adults in the U.S. are daily smokers. In contrast with the general population, people with schizophrenia have a much higher prevalence of smoking with reported rates of 70-90%. Environmental smoking cues have been shown to play an important role in the maintenance of nicotine addiction and in relapse to smoking. Few studies, however, have investigated whether smokers with schizophrenia show an exaggerated attentional bias or cue reactivity response to enviornmental smoking cues. Another biobehavioral factor central to addiction is the rewarding or reinforcing effect of pychoactive drugs. If initial drug use leads to increased frequency of use, then the drug is referred to, in operant conditioning terms, as a reinforcing stimulus. One defining characteristic of an addictive drug is that it positively reinforces drug-seeking and drug-taking behavior. The purpose of this study is to determine the effects of smoking versus neutral cues on schizophrenia patients who smoke on 1) craving, mood, and autonomic responsivity and 2) the relative reinforcing efficacy of tobacco cigarettes. We will test 22 patients with schizophrenia who smoke and 22 smokers without schizophrenia. During cue trials, primary measures include craving (TCQ-SF, VAS), mood (mood form, VAS), and autonomic (heart rate, blood pressure, skin conductance) responsivity. During self-administration trials, primary measures include breakpoint (final ratio completed), total number of responses, and number of cigarette puffs earned and taken. Secondary measures include baseline smoking history, mood, tobacco craving, nicotine dependence, and urinary cotinine and 3-hydroxycotinine. During the past year, we have initiated the study and completed testing of 10 smokers without schizophrenia and 8 smokers with schizophreniz. Because study enrollment is ongoing, we have no findings to report at this time.
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0.915 |
2011 — 2013 |
Heishman, Stephen |
ZIAActivity Code Description: Undocumented code - click on the grant title for more information. |
Nicotine Reinforcement and Smoking-Cue Reactivity: Association With Genetics @ National Institute On Drug Abuse
In this study, we will investigate potential associations between several genetic polymorphisms and nicotine addiction. We will examine the relative reinforcing efficacy between nicotine (Nic) and denicotinized (Denic) cigarettes using the forced-choice procedure and operant responding (drug seeking) under a progressive ratio schedule of reinforcement. We will also investigate reactivity to smoking cues. We hypothesize that: 1) In the forced-choice procedure, Nic cigarettes will result in more choices for cigarette puffs than Denic cigarettes. 2) In the PR operant response procedure, Nic cigarettes will result in greater responding and thus a higher breakpoint than Denic cigarettes. 3) Smoking cues will evoke greater self-reported tobacco craving and autonomic reactivity compared with neutral cues. 4) Genetic variants will influence choice for cigarettes puffs, breakpoint values, and cue-reactivity. Specifically, we hypothesize that the C/T variant for CB1R, the Ser9Gly variant for DRD3, and increased CYP2A6 activity will be associated with greater choices for cigarettes puffs, higher breakpoint values, and greater reactivity to smoking cues. Subject enrollment was completed this past year. Data re currently being analyzed for reports.
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0.915 |