8 Clinical Trials for Various Conditions
Self-medication of pain with alcohol is a common, yet risky, behavior. Evidence suggests family history of alcoholism may affect the degree to which alcohol use relieves pain, but the independent contributions of expectation and conditioning have not been previously studied. Interactive effects of sex and family history are also currently unclear. This project addresses this gap in knowledge and will inform further research and clinical/translational efforts for reducing risk associated with these behaviors.
Functional neuroimaging of alcoholism vulnerability: glutamate, reward, impulsivity, and Pavlovian-to-instrumental transfer (PIT), part II Saracatinib
The proposed study is the first to explore the contribution of brain glutamate systems, a major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study may lead to an enhanced understanding of the underlying neurobiological mechanism in high risk individuals that may lead to the transition from moderate to excessive use of alcohol.
The aim of the present study is to assess the availability of cannabinoid receptors (CB1R) in the human brain. CB1R are present in everyone's brain, regardless of whether or not someone has used cannabis. The investigators will image brain cannabinoid receptors using Positron Emission Tomography (PET) imaging and the radioligand OMAR, in healthy individuals and several conditions including 1) cannabis use disorders, 2) psychotic disorders, 3) prodrome of psychotic illness and 4) individuals with a family history of alcoholism, 5) Post-Traumatic Stress Disorder 6) Opioid Use Disorder using the PET imaging agent or radiotracer, \[11C\]OMAR. This will allow us to characterize the number and distribution of CB1R in these conditions. It is likely that the list of conditions will be expanded after the collection of pilot data and as new data on cannabinoids receptor function and psychiatric disorders becomes available. Those in the cannabis us disorder arm of the study will have a PET scan on at least three occasions: once while smoking as usual, once after 48-hours of abstinence from cannabis, and a final time after 4 weeks of abstinence. Additional scans may be conducted within the 4 weeks and the last scan may be conducted well beyond 4 weeks. Similarly, while most schizophrenia patients may get scanned just once, a subgroup of patients may get scanned more than once. For example to tease out the effects of medications, unmedicated patients may get scanned while unmedicated and again after treatment with antipsychotic medications. Similarly prodromes may get scanned while in the prodromal stage off medications, on medications and after conversion to schizophrenia.
This project compares Family History Positive (FHP) for alcoholism subjects to matched Family History Negative (FHN) subjects derived from the project Principal Investigator's National Institute on Alcohol Abuse and Alcoholism-funded longitudinal study of drinking behavior in a 2000 college freshman population (known as the Brain and Alcohol Research in College Students study (BARCS)). The age of these subjects is a valuable one at which to capture the transition from harmful use to abuse/dependence. This project explores the effects of memantine in a double-blind, randomized, counterbalanced manner on alcoholism risk-relevant tasks. More specifically, this project studies functional MRI tasks related to different aspects of reward and/or impulsivity-related behavior in different contexts, compares the underlying neural circuitry across tasks, and uses a pharmacologic probe of the glutamatergic system to examine NMDA/DA interactions. The combined measures provide the opportunity to advance our understanding of specific aspects of brain function related to familial alcoholism vulnerability in an already well-characterized population as some members evolve into alcohol abuse. In addition to conventional within-task analyses, functional network connectivity and allied approaches will be used to examine brain networks across tasks. The investigators will study adult male and female subjects in equal numbers who are either offspring of an alcoholic parent or are FHN matched controls. The investigators will recruit and assess a total of 84 (42 FHP and 42 matched FHN) subjects between the ages of 18-21 years on initial BARCS contact. The investigators will use 4 cognitive tasks during the functional MRI (fMRI) which include: 1) a Monetary Incentive Delay Task that distinguishes networks engaged in motivational (anticipation) and consummatory (outcome) components of reward processing; 2) a Go/No-Go Task that measures the ability to inhibit response to a pre-potent stimulus; 3) an Alcohol Cue Reactivity Task that examines Nucleus Accumbens response to alcohol-related versus matched soft drink stimuli; and 4) a Pavlovian-to-Instrumental Transfer (PIT) Task that dissects a component of the Monetary Incentive Delay (MID) Task, and provides an imaging assay of a transfer-like process that can be related to real-world drinking behavior, thus informing upon and extending the key findings from CTNA-2.
Background: - Previous research has shown that a person s genes can influence how they respond to alcohol. But researchers do not yet know all the genes that might be involved. Objectives: - To identify genes that are related to how non-alcoholic individuals respond to alcohol. Eligibility: - Healthy people between 21 and 30 years of age who have no history of alcohol or drug dependence. Design: * The study requires one or two 9-hour visits to the National Institutes of Health Clinical Center. * Participants must not take any medicines (except birth-control pills for women) for at least 3 days before the visit. They must not drink alcohol for at least 2 days before the visit. * Screening includes a medical history, physical exam, and a urine test for drugs of abuse. * Participants will be given alcohol over about 2.5 hours. This will have about the same effect as having three to four drinks. Frequent breathalyzer tests will check breath alcohol level during the infusion. * Before and during the infusion, participants will complete questionnaires about mood and feelings. Other tests will study thinking, balance, judgment, and risk-taking. Blood samples will be collected four times during the infusion. * Participants will have breakfast at the start of the visit (around 8:00 AM). They will have a snack before the start of the alcohol infusion (around 10:45 AM). Lunch will be served after the alcohol infusion is complete (around 2:20 PM). After the tests, those in the study will have to stay in the Clinical Center until their breath alcohol level falls below 0.02%. This can take up to 2.5 hours. A final blood sample will be drawn at that time. Participants will not be able to drive themselves home after the study visits. Also, they should not take any medicines or operate any machinery for at least 2 hours after leaving NIH.
This Project will explore the hypothesis that individuals with a family history positive for alcohol dependence (without any current Axis I disorder, except nicotine dependence), experience an alteration in the reward "valence" (balance of positive and negative effects) of the GABAA receptor agonist barbiturate (thiopental) compared to family history negative age-matched subjects. Further, variation in genes involved in brain GABA function may influence the risk for alcoholism by altering a component of the discriminative stimulus effects of ethanol.
The proposed study is the first to explore the contribution of brain glutamate systems, a major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study may lead to an enhanced understanding of the underlying neurobiological mechanism in high-risk individuals that may lead to the transition from moderate to excessive use of alcohol.