Suvorexant for Alcohol Use Disorder (AUD): Neural Mechanisms

Eligibility Criteria

• * All participants
• * 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
• * DSM 5 diagnosis of moderate or severe AUD.
• * Participants seeking treatment for their AUD.
• * Minimum 5-year 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 10 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.
• * 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.
• * Current severe mental illness (schizophrenia, bipolar 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.
• * AUD Participants
• 1. 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).
• * Control Participants
• * Current DSM-5 diagnosis of a psychiatric disorder that requires/required daily psychoactive medications (antidepressant, antipsychotics, stimulants, opioids, benzodiazepines or barbiturates) in the past two months and that could impact brain function at the time of the study as determined by history and clinical exam.
• * History of moderate or severe substance use disorders (other than nicotine or caffeine).
• * The following current chronically used (past 2 months) medications are exclusionary: stimulant or stimulant-like drugs and medications (cocaine, methamphetamine, amphetamine, methylphenidate, modafinil); opioid drugs or medications; antianginal agents; antiarrhythmics; systemic corticosteroids; anticholinergics; anticoagulants; anticonvulsants; antidepressants; antihistamines (sedating); beta-blocker antihypertensives; antineoplastics; antiobesity; antipsychotics; anxiolytics (benzodiazepine or barbiturates); lithium; muscle relaxants; psychotropic drugs not otherwise specified (nos); sedatives/hypnotics, systemic steroids. Note that nicotine and/or caffeine is not exclusionary.
• * 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 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.