To determine if the mu opioid receptor gene (OPRM1) A118G polymorphism moderates the subjective-rewarding effects of intravenous (IV) nicotine in male and female smokers. The subjective effects of nicotine will be measured with a Drug Effects Questionnaire, including the ratings of "good effects" and "drug liking". We hypothesize that smokers with the AG/GG genotype for the OPRM1 A118G will have attenuated subjective-rewarding effects from IV nicotine when compared to those with AA genotype.

NCT00969137

Conditions

1. Nicotine Dependence

Interventions

1. Drug: saline
2. Drug: Nicotine

MeSH:Tobacco Use Disorder

In addition, the association of the G398A polymorphism of the CHRNA5 gene (rs16969968) with maximal response to nicotinic agonists justifies examination of this SNP as a moderator of IV nicotine sensitivity in humans (Bierut et al. 2008).

The frequency of rs16969968 SNP ranges from 35%-42% among those of European ancestry, making it feasible to examine this variation in our subject sample.

Background: - The risk for becoming addicted to drugs varies from person to person, even among those using similar drugs in a similar way. Researchers do not fully understand why some people become addicted to drugs and others do not. Studies suggest that under certain life circumstances, some genes may increase the risk for addiction. This study will use genetic information, computer tasks, magnetic resonance imaging (MRI), and other tests to see what brain networks may be related to drug addiction. Objectives: - To better understand brain networks that may be related to susceptibility to drug addiction. Eligibility: - Healthy non-smoking volunteers between 18 and 55 years of age. Design: - This study will have one screening visit and four all-day study visits. For male participants, the visits will be about 7 days apart over 5 to 7 weeks. Female participants will have the visits scheduled to coordinate with their menstrual cycle. - This study involves small doses of three approved drugs: two oral dopamine drugs and a nicotine patch. For each scanning session, participants will have three study drugs. However, only one pill or patch will be the real drug; the other two will be placebos. Some participants may have only placebos during a visit. - Participants will be screened with a physical exam and medical history. Blood and urine samples will be taken. Other tests will be given to ensure that participants are not smoking or using drugs while they are in the study. - During the all-day scanning visits, participants will receive two pills and one patch in the morning and they will be trained on simple computer tasks. In the afternoon, participants will have MRI scans and we will measure their brain activity while they rest and while they perform computer tasks in the scanner. Participants will also answer questionnaires during the scanning visits.

NCT01924468

Conditions

1. Nicotine Dependence

Interventions

1. Drug: Oral methylphenidate and Oral haloperidol

MeSH:Tobacco Use Disorder

The impact of rs16969968 genotype on the BOLD fMRI signal and functional connectivity (FC) within and between the three networks of interests (SN, ECN, DMN) at rest and during task performance.. null.

While we will target the A/A homozygotes and G/G homozygotes at the rs16969968 locus, we will also allow A/G heterozygotes to become enrolled in the study.

The enrollment will be open to all racial and ethnic groups, including Caucasians, African Americans, and Asians, as well as Hispanic and non-Hispanics, and we will make an effort to include all racial and ethnic groups as long as all participants meet the rs16969968 genotype criteria.

Justification: The allele frequencies at the rs16969968 locus vary greatly between racial and ethnic groups, making it extremely difficult to ensure a balance of ethnicities across the genotype groups.

In particular, the minor A allele of rs16969968 (the Risk allele in the current study), associated with increased risk of heavy smoking and nicotine dependence, has a frequency of 0.42 in Caucasians, but is very rare in Asians (0.03) and African Americans (0.07) (Saccone et al., 2010b).

Importantly, because the association between the rs16969968 locus and nicotine addiction severity has been demonstrated in all three ethnic groups in a recent meta-analysis (Chen et al., 2012), we argue that the racial and ethnic groups not enrolled in the current study will still benefit from basic, mechanistic knowledge gained from this study if translated to clinical treatment and prevention of nicotine abuse and dependence in the future.

Additionally, we will examine ancestry information markers to verify and extend the self-reported ethnic background and to test for possible modulatory effects of specific genetic-ancestry groups with respect to the rs16969968 effects in our data.

The non-synonymous single nucleotide polymorphism (SNP) rs16969968 in the CHRNA5 gene encoding the 5 subunit of nAChRs has been unequivocally associated with smoking behavior and nicotine dependence in genome-wide association studies (GWAS).

We have previously shown that resting-state connectivity of the SN is decreased in smokers and non-smokers with the rs16969968 risk allele.

Consequently, we will employ an integrative imaging pharmacogenetics approach to test for DA mediation of the rs16969968 effects on the SN in healthy non-smoking participants, with the goal of elucidating the neurobiological mechanism underlying the association between this SNP and susceptibility to nicotine dependence without the confound of chronic smoking.

Sixty pre-screened participants will be classified into two equal groups (n = 30 per group) based on their rs16969968 genotype: 1) rs16969968 risk allele homozygotes, or A/A genotype ( Risk Group ); and 2) rs16969968 non-risk allele homozygotes, or G/G genotype ( Non-Risk Group ).

The study will use neuroimaging (fMRI) to assess the impact of rs16969968 genotype and drug condition (MPH vs. haloperidol vs. nicotine vs. placebo) on the SN, ECN, and DMN function at rest and during task performance.

The purpose of the proposal is to identify new predictors of smoking progression in young light smokers (YLS: 18-25 years & cpd < 5) using an 18-month longitudinal design and to relate these predictors of progression to the genetic profile most highly associated with smoking progression. A number of novel predictors will be assessed in 128 YLS. Predictors will include individual differences (IDs) in EEG, reward sensitivity, attentional performance, and mood during abstinence and in response to standardized and to self-selected acute nicotine doses (ANIC), as well as genetically influenced affective traits, and smoking history. The associations of a compelling genetic functional variant polymorphism, rs16969968, in the alpha5 nicotinic receptor subunit will also be related to smoking progression and the novel predictors. The study is expected to provide insights into IDs in mechanisms and predictors that contribute to smoking trajectories in YLS and thereby lead to targeted pharmacotherapy and behavioral interventions for at-risk YLS.

NCT02129387

Conditions

1. Nicotine Dependence

MeSH:Tobacco Use Disorder

The associations of a compelling genetic functional variant polymorphism, rs16969968, in the alpha5 nicotinic receptor subunit will also be related to smoking progression and the novel predictors.

The associations of a compelling genetic functional variant polymorphism, rs16969968, in the alpha5 nicotinic receptor subunit will also be related to smoking progression and the novel predictors.

Background: People with the brain disease AUD (alcohol use disorder) have a serious problem with drinking. Researchers want to study how different people react to alcohol, and how genes affect this. They will focus on a nicotine receptor gene that may increase a person s AUD risk. Objectives: To see if people with variations of a nicotine receptor gene take alcohol differently and have different brain responses to alcohol cues. Eligibility: Healthy adults ages 21 - 60. This study includes smokers and non-smokers. Design: Participants will be screened under another protocol. Participants will have three 9-hour visits. They must have no alcohol or non-prescription drugs before all visits and no food or drink before 2 visits. At every visit, participants will: - Get a light meal - Have breath and urine tests - Get taxi rides there and back At visits 1 and 3, participants will: - Have a thin plastic tube inserted in an arm and connected to a pump for alcohol infusion. - Have sensors on their chest to monitor heart rate. - Sit in a chair for 2.5 hours and get alcohol by pushing a button. Their breath alcohol level will be monitored. - Answer questions about mood and effects of alcohol - Give blood samples - Relax at the clinic while their breath alcohol level drops At visit 2, participants will: - Answer questions and do computer tests - Have an alcoholic drink and a snack - Have a magnetic resonance imaging (MRI) scan. They will lie in a machine that takes pictures of the brain. They will do computer tasks. - Have another drink and snack - Relax until their alcohol level drops Participants will have a follow-up call after each visit....

NCT03294460

Conditions

1. Alcohol Drinking

Interventions

1. Drug: Alcohol (Oral)
2. Drug: Alcohol (IV)
3. Drug: Alcohol (Ethanol)

MeSH:Alcohol Drinking

- Have another drink and snack - Relax until their alcohol level drops Participants will have a follow-up call after each visit.... To examine the effect of CHRNA5 (rs16969968) genetic variation on neural correlates of incentive salience for alcohol, as measured by BOLD response during the Alcohol-Food Incentive Delay (AFID) task using fMRI..

Secondary outcome measures include: (2a) resting state functional connectivity (rsFC) between the regions associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum, and extended amygdala; (2b) preferred rate of self-infusion during the second IV-ASA session.. To examine the effect of CHRNA5 (rs16969968) genetic variation on IV alcohol self-administration, as measured by BrAC exposure (peak BrAC, number of infusions, time to binge-level) in non-smoking, non-dependent drinkers..

Secondary outcome measures include: (2a) resting state functional connectivity (rsFC) between the regions associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum, and extended amygdala; (2b) preferred rate of self-infusion during the second IV-ASA session.. To examine the effect of CHRNA5 (rs16969968) genetic variation on resting-state functional connectivity (rsFC) among brain regions associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum and extended am.... associated with the salience network, including dorsal anterior cingulate cortex, ventral striatum and extended amygdala in non-smoking non-dependent drinkers.. To examine the effect of CHRNA5 (rs16969968) genetic variation on the rate of IV alcohol self-administration, as measured by the preferred rate during the second IV-ASA session in non-smoking, non-dependent drinkers.. null.

There has been a great interest in examining variation in target genes that may play a mechanistic role in the expression of these endophenotypes, such the missense single-nucleotide polymorphism (SNP) in the gene encoding the 5 subunit of the nicotinic acetylcholine receptor (CHRNA5) - rs16969968.

Participants will be stratified into equally-sized groups based on their smoking status (smokers and non-smokers) and rs16969968 genotype: 1).

It has previously been shown that patients with coronary artery disease may have a harder time quitting smoking if they have a specific genetic profile and that these individuals have a better chance at quitting if they receive nicotine replacement therapy. The investigators hypothesize that determining which individuals with coronary artery disease should receive nicotine replacement therapy based on their genotype may improve the number of individuals who are able to quit smoking.This study randomizes treatment to that determined by the patient's genotype compared to standard, non-genotype-guided, treatment.

NCT03383224

Conditions

1. Coronary Artery Disease
2. Smoking Cessation

Interventions

1. Other: genotype-guided therapy
2. Drug: Nicotine patch
3. Behavioral: Smoking cessation counseling

MeSH:Coronary Coronary Artery Disease Myocardial Ischemia Coronary Disease

HPO:Coronary artery atherosclerosis Myocardial infarction

intubated) - Incarcerated - Complications of myocardial infarction (such as shock, hemodynamic instability, life- threatening infection, etc) - Women of child-bearing age with positive pregnancy test or who is breast feeding Coronary Artery Disease Smoking Cessation Coronary Coronary Artery Disease Myocardial Ischemia Coronary Disease In this study, the investigators propose to show the feasibility of incorporating genotype-guided therapy into post-MI smoking cessation therapy and/or smoking cessation therapy in patients with coronary artery disease (CAD) using the CHRNA5 rs16969968 variant as the pilot case.

The investigators propose to genotype ½ of PRISM-GENOMICs patients who are active smokers within 48 hours of admission and to guide their smoking cessation therapy based on CHRNA5 rs16969968 genotype (A allele carriers will be given pharmacologic therapy and GG homozygotes will be given counseling).