Suvorexant for Alcohol Use Disorder (AUD): Neural Mechanisms

Background: Alcohol use disorder (AUD) is a leading cause of disease and death worldwide. New treatments for AUD are needed. Dopamine, a chemical that carries signals between brain cells, is thought to play a role in alcohol addiction. Researchers want to learn how Suvorexant, a drug used to treat sleep disorders, affects dopamine receptors in the brain. Objective: To see how Suvorexant affects dopamine receptors in people with AUD and in healthy people. Eligibility: People aged 18 to 75 years seeking treatment for AUD. Healthy volunteers are also needed. Design: Participants with AUD will stay in the clinic for at least 10-28 days for alcohol detoxification. They will receive normal treatment for AUD. Suvorexant is a medicine used to treat sleep problem that is taken taken by mouth, once a day. Some participants will take the study drug. Others 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 wear a device that looks like a wristwatch to track their movements during their clinic stay. Participants will have blood tests and 3 brain imaging scans before starting on the study drug: 2 positron emission tomography (PET) and 1 magnetic resonance imaging (MRI) scan. They will be injected with a radioactive tracer during each PET scan. Participants will have tests to assess their thinking, memory, and attention. They will have sleep studies. Imaging scans and other tests will be repeated at the end of the study. Healthy volunteers will have 1 MRI and 2 PET scans. They will have tests to assess of their thinking, memory, and attention. They will wear a wristwatch like movement monitor for 1 week. ...

* INCLUSION CRITERIA: * All Participants To be eligible to participate in this study, an individual must meet all of the following criteria: * Stated willingness to comply with all study procedures and availability for the duration of the study. * Male or female, ages 18-75 years old. * Ability to understand and the willingness to sign a written informed consent document. * AUD Participants To be eligible to participate in this study, an individual with AUD must meet all of the "All Participants" inclusion criteria (listed above) and also meet the following criteria: * DSM 5 diagnosis of moderate or severe AUD. * Participants seeking treatment for their AUD. * Current AUD with minimum 5-year lifetime history of heavy drinking (SAMSHA's criteria for heavy drinking: for men 5 or more drinks/day on at least 5 different days per month; and for women 4 or more drinks/day on at least 5 different days per month). * Last alcohol use within the 7 days prior to enrollment in the Natural History protocol 14AA0181. * Self-reported insomnia/sleep problems: PSQI score \> 4 and/or endorsing "problems falling asleep or staying asleep throughout the night". * Ability to take oral medication and be willing to adhere to the suvorexant/placebo regimen. * Agreement to commit to at least 28 days, and up to 40 days, inpatient stay (starting from Natural History protocol enrollment). * Agreement to adhere to Lifestyle Considerations throughout study duration. EXCLUSION CRITERIA: -All Participants An individual who meets any of the following criteria will be excluded from participation: * Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head, fear of enclosed spaces, or other standard contraindication to MRI. * Cannot lie comfortably flat on his/her back for up to 2 hours in the MRI scanner. * Body weight \> 400 lbs. The PET scanner bed is tested to a weight limit of 400 lbs. * Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits as determined by medical history and physical exam. * Pregnant or breast-feeding: Females of childbearing potential, or with tubal ligation, or are post-menopausal and are age 55 or less will undergo a urine pregnancy test and it must be negative to continue participation. Urine pregnancy tests will be repeated on subsequent days of study (i.e., within 24 hours before study procedures). Females must not be currently breastfeeding. * Severe head trauma with loss of consciousness \> 60 minutes. * Chronic recurrent primary psychotic disorders like schizophrenia and bipolar 1 disorder. * Montgomery-Asberg depression rating scale (MADRS) total score \> 35 or 'suicidal thoughts' item score \> 3, indicating severe depression or moderate suicidality, respectively. * Major medical problems that can permanently impact brain function (e.g., seizures, psychosis, stroke, Alzheimer's disease, Parkinson's disease, traumatic brain injury, clinically significant arrhythmias except bradycardia, and HIV+). * Hepatic enzymes (ALT/GPT, AST/GOT, Total Bilirubin, Direct Bilirubin) that are \>5x the upper limit of normal, indicating severe hepatic impairment. * Non-English speakers (must also be able to read and comprehend English). * The intent of the research has no prospect of direct benefit to the subject. Therefore, we are excluding non-English speakers in this research study since it includes the administration of questionnaires, surveys and assessments that are validated for English; only some are available in Spanish. In addition, our fMRI paradigms require that the subject be able to speak, read and comprehend English. * AUD Participants An individual with AUD who meets any of the "All Participants" exclusion criteria (listed above) or any of the following criteria will be excluded from participation in this study: * Current daily use of stimulant medications, modafinil, wellbutrin, naltrexone, antipsychotics, or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan). * Current benzodiazepine, opioids, or stimulant misuse (must have misused 5+ days/week for \>1 year, and most recent use must have been within 7 days of inpatient admission). * Current severe substance use disorders (other than alcohol, cannabis, nicotine or caffeine). If a subject had a severe SUD (other than alcohol, cannabis, nicotine or caffeine), they must be in remission for at least 6 months prior to enrollment. * Major medical problems that are contraindicated for the use of suvorexant (narcolepsy, severe obstructive sleep apnea or severe chronic obstructive pulmonary disease, REM behavioral disorder) as determined by history and clinical exam. Note that AUD subjects will not be excluded from enrollment onto this study if their urine test or breath alcohol level (BAL) is positive for drugs/alcohol on initial screening. The following guidelines will be followed for positive drug/alcohol screens on study procedure days involving imaging scans and neuropsychological testing: -If a subject's urine drug/breath alcohol (\>=0.08%) screen test is positive on days involving imaging (MRI and/or PET) and NP testing, the procedures will be postponed until BrAC \0.08%) screen test is positive on days involving imaging (MRI and/or PET) and NP testing, the procedures will be postponed and rescheduled. We will allow for up to 3 rescheduled study days resulting from positive urine drug/breath alcohol screens. If urine drug screen is positive for THC-COOH, a saliva drug screen will be performed and subject may proceed with study day testing procedures if saliva results for THC are negative. If the urine/saliva drug test is positive on the third rescheduled visit, the participant will be withdrawn from the study. * If a participants urine drug screen test is positive for marijuana (urine drug screen positive for THC-COOH) on the day of the scan, we will then perform a saliva drug screen to verify if THC is present. If positive, procedures will be postponed until it becomes negative. * If a participants urine drug screen test is positive for cocaine, heroin or methamphetamine they will be excluded.