Investigation of Cocaine Addiction Using mGluR5 PET and fMRI
Cocaine DependenceThe proposed research program will investigate the changes in brain chemistry and circuitry that 're-wire' the brain during chronic cocaine use, promote relapse, and complicate treatment efforts. Currently-using and non-treatment-seeking individuals with a cocaine use disorder will undergo a cocaine self-administration paradigm 2-5 days prior to completing positron emission tomography (PET) and functional magnetic resonance imaging (fMRI).
PET Assays of Striatal Dopamine Marker in Cocaine Craving
Neural SystemsDrug Abuse1 moreBackground: Cues related to past drug use induce a particular pattern of brain activation, which has been correlated with craving for cocaine in active cocaine abusers. Researchers are interested in determining the role of the brain chemical dopamine in cue-elicited as well as spontaneous craving for cocaine. To study the role of dopamine in cocaine craving, researchers will use positron emission tomography (PET) to compare the neural reactions of cocaine users with those of non-substance-abusing healthy volunteers. Researchers hope that the data gathered from this study will lead to the development of more effective anti-craving medications. Objectives: To clarify the role of dopamine in cue-elicited responses that contribute to cocaine abuse. To determine if PET results of this study differ with various means of administering PET chemicals. Eligibility: - Individuals 21 to 44 years of age who are either current cocaine users (at least twice per week) or healthy volunteers without a history of drug abuse. Design: Cocaine-using participants will enter the inpatient clinical research ward at the National Institute on Drug Abuse (NIDA) Addiction Research Center for 2 nights before the day of the study. In addition, these participants will stay overnight at NIDA the evening after each PET session and will be discharged the following day. Cocaine-using participants will be required to perform a balance test before the study to provide a baseline response in case they require anti-anxiety medications to cope with the effects of the study. Control subjects will not be required to stay overnight and will arrive as outpatients for the PET session. All participants will be required to abstain from alcohol and caffeine consumption from midnight before each study session, and will not be permitted to smoke on the day of testing. - On the day of the study, participants will undergo a practice session to set up the PET scanning equipment. Following the practice session, participants will be shown video recordings of images that are related to nature (e.g., seashells) or to drug abuse (e.g., drug paraphernalia). Participant reactions will be studied through the PET monitoring, and the study will be conducted in two separate PET sessions with a break in between. Individuals in the cocaine-using group may receive anti-anxiety medication if the stimulus cues increase anxiety related to cocaine craving. Different groups of participants will receive different methods of PET chemical administration, and researchers will compare these methods.
Real Time Assessment of Drug Craving, Use, and Abstinence During Outpatient: A Development and Feasibility...
Cocaine AddictionOpiate AddictionBackground: The treatment of addiction often hinges on preventing relapse into drug-using behaviors, which occurs at high rates even after prolonged abstinence. Research has shown that constant reporting through personal data-collection devices, such as electronic diaries, can help prevent relapse and reinforce abstinence. This constant reporting is known as Ecological Momentary Assessment (EMA). The researchers here at NIDA have already completed two major arms of the study, focusing on patterns of craving and drug use during methadone maintenance, and on whether electronic diaries could help remind outpatients to complete treatment tasks. An ongoing arm of the study is examining connections among drug craving/use, stress, and geographical location. Objective: - To investigate the role of stress associated with geographical location in drug craving and use. Eligibility: - Individuals between 18 and 65 years of age or older who are dependent on opioids (cocaine and/or heroin). Design: The study will last 28 weeks. After the initial screening, participants will receive daily methadone and weekly drug counseling sessions that will continue throughout the study. After 3 weeks of methadone treatment, participants will have 15 weeks of EMA in which they will record both event-triggered cravings and daily responses (3 per day). EMA will consist of event-triggered recordings (initiated by participants whenever they use heroin or cocaine, or whenever they feel an urge to do so) and random-signal-triggered recordings (3 per day). During EMA, participants will begin a voucher-based program to encourage abstinence from heroin and cocaine. Participants will also carry global positioning system (GPS) units to record their locations during these 15 weeks, and will complete questionnaires about stress levels at specific intervals during the study. At the end of the study, participants will have the choice of transferring to a community clinic or undergoing an 8-week taper from methadone.
Therapeutic Potential of Kappa-Opioids Against Cocaine - 1
Cocaine-Related DisordersThe purpose of this study is to characterize the effects of enadoline compared to hydromorphone and butorphanol.
Brain Glutamate Receptors and Cocaine Dependence
Drug AbuseCocaine DependenceObjective: Cocaine addiction continues to be an important public health problem with over 1.7 million users in the US alone. Cocaine addiction is characterized by compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. Cocaine addiction may be mediated by neuroadaptations in reward-related learning and memory processes in the mesocorticolimbic dopamine system and glutamatergic corticolimbic circuitry. Metabotropic glutamate subtype 5 receptors (mGluR5) likely play essential roles in mediating some of the actions of drugs of abuse. Animal studies have shown that mGluR5 knock-out or blockade reduces self-administration of cocaine and cocaine-induced hyper-locomotion. However, to what extent mGluR5 are involved in the pathophysiology of cocaine addiction in humans is currently unknown, partly due to the lack of suitable methods to reliably quantify mGluR5 in the living human brain. This protocol aims to determine whether the density of mGluR5 in brain is altered in participants with cocaine addiction compared to healthy controls using positron emission tomography (PET) and the recently developed radiotracer for mGluR5, [18F]SP203. We also aim to determine whether this density is related to genotype, history of cocaine use, and/or craving for cocaine. Study Population: The study populations will consist of healthy adults with no history of substance abuse and a matched group of healthy current primary cocaine dependent male and female participants (20-50 years old.; N=40/group). Design: Density of mGluR5 will be measured in cocaine dependent participants and healthy adults volunteers with PET and (18F)SP203, a radioligand with specificity for mGluR5. All participants will undergo genotyping to identify normal or variant mGluR5 gene associated with drug abuse. The intensity of craving for cocaine will be assessed while watching a video about cocaine use. Outcome measures: Density of mGluR5 will be compared between cocaine dependent participants and healthy controls. In addition, correlation among the genetic polymorphism, the craving response, and the density of mGluR5 will be determined.
Rebalancing the Serotonergic System in Cocaine Dependence
Cocaine DependenceIn the United States, 1.5 million people abuse cocaine leading to a host of negative health and economic consequences, yet no FDA approved treatment exists. To develop effective treatments, the following must be considered: 1) do potential medications ameliorate brain disruptions associated with cocaine use? 2) are multiple, targeted treatments necessary? To meet these goals, innovative multi-modal neuroimaging will be used to determine whether rebalancing the serotonergic (5-HT) system reduces cocaine cue reactivity, impulsivity, and normalizes related neurochemistry and brain connectivity.
tDCS to Reduce Craving in Cocaine Addiction
Cocaine Use DisorderCocaine DependenceTranscranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation in which low level electrical currents are applied to the scalp in order to alter brain function. In the present study, tDCS will be administered with the goal of assessing the tolerability and feasibility of this approach to 1) reduce an individual's level of drug craving and 2) provide evidence to support the use of this device by the patient for future unsupervised stimulation in a non-clinical setting. Research Questions: Can tDCS be used successfully to train cocaine addicted individuals for self-administration purposes? Can active tDCS be used to decrease drug craving in individuals with cocaine use disorders? Does active tDCS outperform sham tDCS in reducing drug craving?
Psychology of Reward and Punishment: Functional and Molecular Brain Imaging and Monoaminergic Correlates...
Cocaine AddictionCocaine AbuseBackground: Brain imaging studies, genetic research, and investigations of stress have provided more information about the role of dopamine in processing reward and punishment, and in vulnerability to substance dependence. Researchers are interested in learning more about how the brain responds to rewards, including drugs of abuse, and how these responses may involve genetic factors or previous stressful events. Researchers intend to use the drug amphetamine to increase levels of dopamine in the brain and study the effects through two kinds of scanning: functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Objectives: To examine the relationship among dopamine function, brain activity, reward processing, genetic profile and exposure to stress in normal healthy adults. To examine the variation in these factors between normal healthy adults and individuals with current cocaine-dependence. Eligibility: - Individuals 18 to 45 years of age who are either current cocaine users or healthy volunteers with no history of substance abuse or dependence. Design: The study will consist of an initial evaluation session and six study visits, four of which will involve fMRI scans (3 hours each) and two of which will involve PET scans (8 to 9 hours each). Cocaine-using participants will enter the inpatient clinical research ward at the National Institute on Drug Abuse Addiction Research Center the night before each scanning session and will be discharged the following day. Healthy volunteer subjects will not be required to stay overnight and will arrive as outpatients for the PET session. Participants will not be released until researchers have determined that participants are not experiencing significant effects of the drug. Initial session (1): Participants will complete questionnaires about past reactions to stressful situations, and will be trained to do thinking tasks that will be performed in fMRI visits. The tasks will be practiced in a mockup of an MRI machine. MRI sessions (2-5): Participants will receive either oral amphetamine or a placebo, and will perform thinking, short-term memory, and reward tasks during MRI scanning as directed by researchers. PET sessions (6-8): Participants will receive either oral amphetamine or a placebo, and will provide blood samples during the PET scanning sessions. Participants will have short breaks during the PET scanning sessions.
A Contribution to the Analysis of the Phenotypic Heterogeneity in Crack/Cocaine Addiction : a Case...
DependenceCocaineThe purpose of this study is to assess the phenotypic candidates symptoms, in patients with crack/cocaine addiction, in terms of clinical comorbidities, dimensions of personality, and neuropsychological evaluations apt to be associated with genetic and genotypic characterisations, notably on the polymorphisms of the genes coding or regulating dopaminergic, norepinephrine and serotoninergic systems.
Impulsivity, Neural Deficits and Cocaine Addiction
Cocaine DependenceThe purpose of this study is to assess neurocognitive and associated neural regions/circuitry disruptions relevant to impulsive relapse in cocaine-addicted subjects, and the relationship of the cognitive and neural mechanisms of impulsivity/decision-making to relapse style.