Healthy Volunteer

Background: Malaria is a serious disease caused by parasites spread by mosquitoes. To better diagnose and treat malaria, researchers need to learn more about where the parasites go when they enter a person's body. They want to see if they can locate the malaria parasites in the body using imaging scans. Objective: To learn whether imaging scans can locate parasites in people with malaria. Eligibility: Healthy people aged 18 to 54 years. They must be enrolled in protocol IRB001970 or IRB002627 for controlled malaria infection. Design: Participants will be screened. They will have blood drawn and a physical exam, including an abdominal exam to check the size of their spleen. Participants for this study will have 2 or 3 positron emission tomography/computed tomography (PET/CT) scans: The first will be about 3 days before they are deliberately infected with malaria for a different study. The second will be about 13 days later, while they have the disease. The third scan is optional; it will be done about 3 and 1/2 weeks after the second scan. For each scan, participants will receive a radioactive tracer called fluorodeoxyglucose (FDG). FDG will be injected through a tube inserted into a vein. They will lie on a table that slides through a doughnut-shaped machine. PET/CT uses x-rays to create images of the inside of the body. All participants will have a follow-up visit about 3 and 1/2 weeks after the second scan. The blood draw and physical exam will be repeated. This visit may be combined with the third scan for those who choose it.

Background: Vision is vital for many of our daily activities. Researchers want to learn more about how we aim our eyes (that is, what images, such as faces, immediately attract our attention) and how we direct our attention (that is, what we see and what we ignore). Objective: To study how healthy adults process and respond to visual images. Eligibility: Healthy people aged 18 years with no vision problems. Design: Participants will have 5 to 10 clinic visits over 2 to 4 months. Some participants may have up to 25 visits. Each visit lasts about 1 hour. Participants will be screened. They will answer questions about their medical and eye history. They will have a standard eye exam; eye drops will be used to dilate the pupils. (They may skip this exam if they have had an eye exam at the NIH within the past year.) Participants will perform eye movement tests. They will sit in front of a computer and view images that appear on the screen. They may be asked to respond to what they see by speaking, moving their hands, looking in a certain direction, or pushing a button. Their eye movements will be tracked. For some tests, participants heads may be held steady using a chinrest and head strap. For some tests, they may wear a cap fitted with cameras that use invisible lights in front of their eyes.

Background: Many people in the United States are overweight or obese. Researchers want to learn why some people can overeat and not gain weight, whereas others who do not overeat still gain weight. Objective: To study factors related to food intake that can lead to weight gain over time. Eligibility: Healthy adults aged 18 to 60 years. Design: Participants will have 6 to 8 clinic visits over 2 years. The first 3 or 4 study visits will be 1 week apart. Procedures during visits may include the following: Collection of blood, hair, urine, and stool samples. Measurement of the waist, neck, thighs, and other parts of the body. Dual energy x-ray absorption (DXA) scan: Participants will lie still on a padded table while they are scanned to measure body fat. Physical activity monitor: Participants will wear a monitor on the wrist for 2 weeks. Cognitive tests: Participants will perform tasks to measure attention, memory, and brain function. Continuous glucose monitor. Participants will wear a device that measures their blood glucose for 1 week. Mixed meal test and stomach emptying test. Participants will drink a breakfast shake and swallow a dose of acetaminophen. Blood will be drawn over the next 4 hours. Resting metabolic rate: Participants will wear a clear hood over their head while they rest for 20 minutes. The hood will measure the gases they breathe. Breakfast and lunch test. Participants will eat a standard breakfast. They will be allowed to select from foods and eat as much as they like at lunch. They will be asked how hungry or full they are. Questionnaires. Participants will answer questions about their health, sleep, physical activity, and eating.

Background: Abnormal fats in the blood can lead to many problems, including heart disease. Researchers want to learn more about how eating meals with different levels of nutrients affects fats in the blood. Specifically, they want to study people with too much body fat, too little body fat, and a kidney problem called nephrotic syndrome. Objective: To learn more about how different types of foods affect fat levels in the blood. Eligibility: People aged 18 years or older with a health condition that affects how their body handles fats. Healthy volunteers are also needed. Design: Participants will have 2 overnight stays in the clinic within 6 months. At each visit, after staying overnight, they will eat a breakfast casserole. At 1 visit, breakfast will be a high-fat, low carbohydrate meal. At the other, it will be a high-carbohydrate, low-fat meal. Participants will have a tube inserted into a vein in their arm. They will have blood drawn via the tube 12 times in 8 hours: 2 times before they eat the breakfast and 10 times after. Participants will have other tests during their stays: * A resting metabolic test captures the air they exhale and measures how much energy they use at rest. * A dual energy X-ray absorptiometry (DXA) scan measures how much fat and muscle they have. * A Fibroscan is a special type of ultrasound of the liver. * A body surface scan uses lasers to measure the total area of the body. * A bioelectric impedance (BIS) exam measures how fast small electric currents move through their body. Participants may opt to have a third visit. At this visit, the breakfast will be high in protein....

Background: Many people in the United States are overweight or obese. This natural history study will look into how life events during childhood can impact eating behaviors and weight gain as adults. Objective: To explore how childhood experiences affect adult eating behaviors. Eligibility: Healthy people aged 18 to 60 years. Design: Participants will have 3 clinic visits. They will be screened with blood tests. They will answer questions about their alcohol and tobacco use. At the next visit, participants will undergo these activities: Parts of their body (such as waist, neck, and thighs) will be measured with a tape. They will have an imaging scan to find out how much body fat they have. They will start wearing a device like a wristwatch that measures their physical activity. They will wear this device for up to 10 days. They will wear a device on their upper arm or belly that measures blood glucose (sugar) levels. Participants will wear this for 7-10 days. They will answer questions about their education, childhood, and routines. They will receive a kit to collect a stool sample at home. At the last visit, participants will have these tests: Participants will relax and breathe normally while wearing a clear, plastic canopy that fits over their entire head. Blood samples will be taken before and after participants drink a sugary drink. Participants will be offered a large selection of foods for lunch. They will eat as much as they want. Then they will answer questions about how they feel about food and themselves.

Background: As people age, the cells in the pancreas that produce insulin begin to release less of this hormone, and levels of blood glucose (sugar) rise. This can lead to illnesses such as diabetes. Urolithin A (UA) is a natural nutritional supplement that may improve how the body controls blood glucose. Objective: To learn if UA improves levels of insulin and other hormones that help control blood glucose. Eligibility: People aged 55 years and older with a body mass index of 27 or higher. Design: Participants will have 6 clinic visits over 8 weeks. Participants will be screened. They will have a physical exam with blood and urine tests and a test of their heart function. UA gelcaps are taken by mouth every morning at home. Half of participants will take UA. The other half will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which they are taking. Participants will have tests during the study including: Oral glucose tolerance: Participants will drink a sweet liquid. Blood will be drawn at intervals over the next 3 hours. Continuous glucose monitor: A sensor with a needle that goes just under the skin will be placed on the upper arm. Participants will wear this sensor throughout the study. Exercise. Participants will walk on a treadmill while their heart rate, hearth rhythm, and blood pressure are monitored. They will walk in a hallway at normal and fast paces. Imaging scans of the thigh; scans of the brain are optional....

Background: Most medications that treat depression take weeks or months to work. Researchers want to develop fast-acting treatments. One dose of ketamine has a rapid antidepressant effect. For most people, this lasts a week or less. Repeated doses of ketamine may help maintain this effect. Objective: Main Study: To study the effects of ketamine in treating depression. Ketamine Metabolites Substudy: To study how ketamine effects brain chemistry. To study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down. Eligibility: Main Study: People ages 18-65 with major depressive disorder and healthy volunteers Ketamine Metabolites Substudy: Healthy volunteers ages 18-65 Design: Main Study: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 phases totaling 14-20 weeks. Phase I (2-7 weeks): * Gradually stop current medications * MRI: Participants lie and perform tasks in a machine that takes pictures of the body. * Mood and thinking tests * Blood and urine tests * Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep. * Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity. * Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks. Phase I tests are repeated in Phases II and III and in the final visit. Phase II (4-5 weeks): * 4 weekly IV infusions of ketamine or a placebo during an MRI or MEG. For the MEG, a cone over the head records brain activity. Phase III (optional): * 8 infusions of ketamine over 4 weeks Phase IV (optional): * Symptoms monitoring for 4 weeks * Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months. Ketamine Metabolites Substudy: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 days. Study Procedures: Mood and thinking tests Blood and urine tests 1 infusion of ketamine Spinal tap and spinal catheter: Used to get samples of cerebrospinal fluid (CSF). This is a fluid that moves around and within the brain and spinal cord. Studying CSF will help us learn how ketamine effects brain chemistry ...

Background: \- Salivary glands in and around the mouth and throat make saliva. Salivary gland disorders can affect a person s quality of life. Studying people who have a disease that affects their salivary gland(s) may teach researchers about the disorders and their genetics. Objectives: \- To study salivary gland diseases and disorders. To collect data and samples from people with salivary gland problems and their relatives. Eligibility: * People more than 4 years old who have or are suspected to have a disease involving salivary glands. * Their relatives more than 4 years old. * Healthy volunteers 18 years or older. Design: * Participants may be screened with: * Medical history * Physical exam * Blood and urine tests * General oral and dental history and exam * Saliva collection * Eye exam and test for dry eyes * Health questionnaires (adults) * Biopsy of some minor salivary glands. A small incision will be made on the inside of the lower lip and several tiny salivary glands will be removed. * Participants will have 2-3 visits. These may include: * Repeats of some screening tests * Ultrasounds of some glands. Researchers will put some gel on the face, then press on it with a smooth wand. * Adults may have other biopsies * A small catheter inserted into the opening of the parotid gland duct on the inside of the cheek. A saline solution (in a syringe) will fill the duct. * Swishing a saltwater solution in the mouth for 10 seconds and then spitting into a cup * Scrapings collected from teeth, tongue, and cheeks

Background: \- Researchers at the National Institutes of Health give many tests of hearing and balance. These tests can help detect problems that affect hearing or balance. It is important to know exactly how healthy people perform on each of these tests. This information will indicate when a test result is normal and when a test result shows a problem. Researchers also want to determine the best methods for each test. Objectives: \- To test different types of hearing and balance tests, and collect information on normal values for each test. Eligibility: \- Healthy volunteers between 5 and 80 years of age. Design: * This study will require a single visit to the National Institutes of Health Clinical Center. It will include both screening tests and study tests of hearing and balance. Sometimes, a second visit may be required if a test is designed to measure the same thing on 2 different days. Each visit will last between 2 and 5 hours, depending on the number of tests scheduled per visit. * Participants will have a physical exam and medical history. They will also have basic tests to check for normal hearing and balance. * Participants may have different hearing tests, including the following: * Auditory Evoked Potentials to study how the ears and brain handle sound information. * Auditory Processing Tests to study how a person processes complex sounds like speech in background noise. * Tests of middle ear and inner ear function. * Participants may have different balance and inner ear tests, including the following: * Balance test on a tilting platform. * Different tests to measure how well the eyes, ears, and brain work together to help maintain balance. * Treatment will not be needed as part of this study.

Background: \- Magnetic resonance imaging (MRI) is a widely used scanning technique to obtain images of the human body and evaluate activity in the brain. A particular MRI method called magnetic resonance spectroscopy (MRS) can be used to study brain chemistry as well, which may help researchers who are studying new treatments for psychiatric illnesses. Researchers are interested in improving current MRI and MRS techniques, as well as developing new MRI and MRS techniques to view and measure brain chemicals and brain activity. Objectives: \- To implement, develop, and optimize brain chemistry imaging techniques using magnetic resonance imaging and magnetic resonance spectroscopy. Eligibility: \- Healthy individuals between 18 and 65 years of age. Design: * This study will involve a screening visit and a scanning visit at the National Institutes of Health Clinical Center. * Participants will be screened with a full medical and physical examination, blood and urine tests, and neurological testing. * During the second visit, participants will have an MRI scan of the brain. (Participants who have received an MRI within the past year will not need to have a second one; the images of the previous scan will be used for this study.) All participants will then have an MRS scan using the same scanning equipment.

The purpose of this investigation is to develop improved magnetic resonance imaging (MRI) techniques and hardware for studying brain function. MRI is a diagnostic tool that provides information about brain chemistry and physiology. This study will evaluate new MRI methods for monitoring blood flow to regions of the brain in response to simple tasks. The MRI machine used in this study is more powerful than those in most hospitals, permitting a higher visual resolution. Normal healthy volunteers over 18 years old may be eligible for this study. Candidates will be screened with a medical history and questionnaire, and a neurological examination. Study participants will have a yearly MRI scan. For this procedure, the subject lies on a stretcher that is moved into a donut-shaped machine with a strong magnetic field. A lightweight circular or rectangular coil-a device that improves the quality of the images-may be placed on the head. The scan time varies from 20 minutes to 3 hours; most scans last between 45 and 90 minutes. During the scan, the subject may perform simple tasks, such as listening to tapes, tapping a finger, moving a hand, watching a screen, or smelling a fragrance. More complex tasks may require thinking about tones or pictures and responding to them by pressing buttons. Information from this study will be used to develop better imaging methods that will, in turn, permit a greater understanding of normal and abnormal brain behaviors. ...

The purpose of this study is to use brain imaging technology to measure changes in blood flow to areas in the brain as individuals perform intellectual tasks. This study will use functional magnetic resonance imaging (fMRI) to examine blood flow to areas of the brain as participants engage in tasks associated with visual perception, visual recognition, and memory.

Setidegrasib (ASP3082) is being developed for certain cancers. In this study, the researchers want to understand how it is processed by the body in healthy male volunteers. To do this, \[14C\] which is a certain chemical (called a tracer, or radionuclide) has been added to setidegrasib. \[14C\] gives off radiation, but the dose is very low (about the same as the dose from an x-ray) and will leave the body within a few days. \[14C\] will be picked up by a scanner and will be used to follow setidegrasib through the body. \[14C\]setidegrasib will be given as 1 single injection slowly through a vein (infusion). The men will stay overnight in the clinic for at least 2 weeks. They will give regular blood, urine and stool samples during their stay and will be closely monitored. The men will return to the clinic about 1 week later for a final safety check.

This study will test a study medicine called REGN20423 to see how effective it is in healthy participants (in Part A) and participants with atopic dermatitis (eczema) (in Part B). REGN20423 is a study medicine that is only used in clinical studies. REGN20423 has not previously been studied in humans. The study is looking at: * What side effects REGN20423 might cause * How much REGN20423 is in the blood at different times * How well REGN20423 works in adults with atopic dermatitis * Whether the body makes antibodies against REGN20423 * How the body changes after having REGN20423, which can help researchers understand why REGN20423 works better in some people than others * What the best dose of REGN20423 is

The goal of this clinical trial is to describe the cardiac and systemic inflammatory adaptations specific to women practicing ultra-endurance sports. The objectives are to: * Improve the understanding of cardiac and systemic inflammatory adaptations specific to women participating in ultra-endurance sports. * Assess the relationship between observed cardiac and systemic inflammatory alterations and the relative levels of estrogen, testosterone, and progesterone. * Describe the vascular adaptations specific to women participating in ultra-endurance sports. * Examine the influence of defense mechanisms on the emotional dynamics observed during and after an ultra-endurance race.

Deciding what to do when for how long - self-organizing one's behaviour - is an important feature of daily life. Emotions arise providing short-cuts for the computational complexities. Yet, one still knows relatively little about the underlying cognitive and neural mechanisms. EMOBB will establish the computational, cognitive and neural underpinnings of the rich interplay between emotions and self-organized behaviour in naturalistic environments. Previous work has almost exclusively relied on tasks structured into experimenter determined trials - thus how people self-organized behaviour could not be measured. To overcome this, EMOBB will combine novel naturalistic tasks in which people have freedom what to do when for how long with subjective and objective measurements of emotions. This will be made possible through a computational modelling approach that allows dissecting and quantifying even complex behaviour-emotion interactions. Specifically, EMOBB will use three cognitive tasks of emotion-behaviour interplay that participants will do while undergoing functional magnetic resonance brain imaging and monitoring of their facial expressions with an MRI-compatible camera. The primary hypothesis of EMOBB is that both unique and shared neural networks will underpin the interplay between emotions and behaviour across our cognitive tasks.

Background: Attention deficit hyperactivity disorder (ADHD) is common in children. It can cause problems with attention and the ability to control actions and impulses. Obsessive compulsive disorder (OCD) is less common in children but not rare. It involves ongoing thoughts, urges, impulses, and repeated behaviors. Researchers want to study differences in brain activity between healthy children, those with ADHD, and those with OCD. Objective: To learn more about how the brain controls thinking and behavior. Eligibility: People aged 10 to 17 years with ADHD, OCD, or neither. Design: Participants will have 3 to 10 clinic visits in up to 1 year. Each visit will last 2 to 3 hours. Three visits are required: Behavioral. Participants will complete a computer task. Their mood, memory, attention, and thinking skills will be tested. EEG. Participants will undergo electroencephalography (EEG) to measure signals in their brain. Small electrodes will be placed on the scalp. A cap will be stretched over the head. Signals will be recorded while participants rest or do tasks on a computer. MRI. Participants will have a magnetic resonance imaging scan (MRI). They will lie on a table that rolls into a tube. The MRI will take pictures of their brain while they do tasks on a computer. Seven more visits are optional. These include 2 more EEG visits and 2 more MRI visits. Three will be magnetoencephalography (MEG) visits: MEG measures small magnetic field changes in the brain. A helmet with sensors will be placed on the head. Brain changes will be recorded while participants rest or do tasks on a computer.

Background: \- Gum disease is a condition in which the tissue around the tooth root becomes swollen and infected. This condition can cause tooth loss if it is not treated. Who gets gum disease and how bad it will be depends on (1) the different bacteria in the mouth and (2) how the immune system of an individual handles these bacteria. Researchers want to look at the oral bacteria and genetic immune problems of different people to learn how these affect gum disease and other conditions of the mouth. Objectives: \- To study how immune system problems may lead to problems in the mouth, including gum disease. Eligibility: * Children and adults at least 7 years of age who have genetic problems with their immune system. * Healthy adults that have periodontal disease * Health adults that do not have periodontal disease Design: * This study will involve a screening visit and a study visit. * Participants will be screened with a medical history, blood work and a full oral and dental exam, including dental x-rays and photos. * The study visit will involve collection of blood, urine, and other samples, including saliva, plaque, and gum swabs. Any abnormal tissue will sampled for a biopsy. Additional oral and dental exams will be performed. Participants will also answer questions about any current medical or dental problems.

Alzheimer's disease is a devastating neurodegenerative disease characterized by accumulation of clumps (also called plaques) and bundles of fibers (also called tangles) in the brain, for which there is currently no cure. Sirolimus (Rapamycin) is an FDA-approved medication which may improve the blood flow to the brain. The purpose of the clinical trial is to find out whether sirolimus can help improve blood flow and energy use in the brain in women ages 45 to 65 who have the ApoE4 gene, a gene which increases the risk of developing Alzheimer's disease later in life. There will be two arms in this trail, a sirolimus arm and a placebo arm. A placebo is a pill that looks like the study drug, but it does not have any real medicine in it. Participants will be randomized to one arm or the other, but not to both arms. Three study visits over a 12-week period are required. Participants will: (i) Complete some questionnaires about how well you think; (ii) Complete genetic testing for the ApoE4 gene; (iii) Have blood work, blood pressure and height and weight collected; (iv) Take either Sirolimus or a placebo daily, by mouth, for approximately 4 weeks; (v) Keep a diary of when the sirolimus or placebo is taken; (vi) Complete 2 Magnetic Resonance Imaging (MRI) exams

The study is a single-center, Phase-1, open-label, one-sequence, two-treatment period, cross-over, DDI study designed to investigate the effects of rilzabrutinib on the PK of digoxin (as P-gp substrate) and of rosuvastatin (as substrate of BCRP, OATP1B1, and OATP1B3) in healthy male and female participants. For this study a cocktail of digoxin and rosuvastatin will be used.

Background: People with HIV take drugs to keep the amount of virus in their body low. One type of these drugs, called integrase strand transfer inhibitors (INSTIs), can cause weight gain over time. Weight gain can cause diabetes, heart disease, and other serious issues. Researchers want to understand how INSTIs cause weight changes. Objective: To characterize the change in plasma metabolite profile that 4 weeks of each treatment may induce in the absence of HIV infection Eligibility: Healthy people aged 18 to 55. Design: Participants will be screened in the outpatient clinic. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function. Participants will be randomized to one of four oral treatments: Tenofovir Disoproxil Fumarate TDF, Tenovovir Alafenamide TAF/Vemlidy, Dolutegravir DTG/Tivicay, or both TAF and DTG taken together for 4 weeks. Participants will have a Day 0 visit for the Lead-In Baseline visit for an exam and blood tests and continuous glucose monitor placement. Participants will return in 2wks or Day 14/Wk 2 for a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density. Optional adiopse (fat) tissue biopsy in the abdomen, and optional microbiome specimen collections. Continuous glucose monitor changed. Oral once a day dose medication will be started with education. Participants will return in 2wks or Day 28/Wk 4 for exam, labs, and continuous glucose monitor changed. Participants will return in 2wks or Day 42/Wk 6 for final exam, labs, repeat DEXA scan, repeat adipose tissue biopsy, and microbiome specimen collections.

Objective: To screen and create a list of adult volunteers in good health for participation in research studies conducted at the National Institutes of Health (NIH) in Bethesda, Maryland. Develop a normative set of structural and functional brain MRI scans that are linked to healthy research volunteer characteristics. Maximize scientific impact of data from volunteers by broadly sharing with other researchers. Study Population: Adult males and females in general good health who are 18 years of age and older. Design: Adult individuals who are interested in participating in NIMH IRP clinical studies as a healthy research volunteer can directly visit or be directed to visit the study website where they will first consent electronically and then complete a set of online self-report measures. Items may include: demographic information, mental health symptoms, disability status, substance use patterns, handedness and clinical/family history. Individuals who are flagged based on predetermined responses to survey items will be further screened by a member of the study clinical team. If found to be ineligible for the study because of a clinically significant or unstable medical or mental health condition, these individuals will be referred back to the community and/or given information about NIMH clinical studies for which they may be eligible. Respondents with no flags or who pass through additional screening will be scheduled for an in-person assessment. During the outpatient appointment and after in-person informed consent, participants will receive a brief clinical interview to screen for current medical and mental conditions, and risk for self-harm. They will complete assessments of psychological, emotional, physiologic, biological and cognitive functioning. Participants will undergo a physical exam and be asked to provide blood and urine samples for routine clinical labs. Participants can separately consent for an optional baseline brain magnetic resonance imaging (MRI) scan and an optional magnetoencephalography (MEG) exam. All consent forms will explicitly inform participants that if enrolled in the study, their de-identified data will be broadly and publicly shared through NIH-approved data repositories. Participants in this recruitment and characterization study will then be placed on a list of healthy research volunteers from which other NIMH IRP studies may recruit according to the inclusion and exclusion criteria in their respective IRB-approved protocols. Outcome Measures: Outcome measures may include demographic data, mental and medical history and symptoms, results of psychological, emotional, physiologic, biological, and cognitive testing, physical exam and MRI findings....

Increased numbers of white blood cells called eosinophils can cause disease. To investigate this disease, researchers need blood, urine, sputum, stool, cerebrospinal fluid, skin and/or bone marrow samples to compare to samples from patients with this problem. Some of the samples will be used for genetic testing or future research. This study will last for about 10 years and will include a maximum of 50 paid volunteers ages 18 to 65.

Background: Alcohol use disorder (AUD) can damage people s health, work, and family. Researchers want to know more about why some people are more vulnerable to AUD than others. The ZIP8 gene may be linked to an increased risk of AUD. Researchers want to find out how different forms of the ZIP8 gene affect how healthy people drink alcohol and how alcohol affects their brain. Objective: To study how genes may affect how people drink alcohol and how it affects their brain. Eligibility: Healthy people aged 21 to 60 years. They must not smoke, and they must have no history of AUD. They must have European ancestry and be enrolled in Natural History Protocol (14-AA-0181). Design: Participants will have 2 study visits. At the first visit, participants will be given alcohol; it will be infused through a tube attached to a needle inserted into a vein. They may self-administer each dose by pressing a button. Over time, they will have to press the button an increasing number of times to receive more alcohol. The infusion period will last 2.5 hours. Participants will have blood samples taken and breath measurments, and they will do computer tasks and complete questionnaires during and after the infusion. After the infusion, they will remain in the clinic until their breath alcohol levels drop to a safe level. At the second visit, participants will have an imaging scan of their brain. They will do tasks and play games on a computer screen during the scan. Some participants may have an extra visit for screening. A mid-study visit may also be needed if more than 6 months pass between the 2 study visits.

The purpose of this research is to measure the extent of lung inflammation between different groups of participants using a radioactive tracer called \[18F\]NOS. A radioactive tracer is a type of imaging drug that is labeled with a radioactive tag and injected into the body.