Overview

This positron emission tomography imaging study uses \[C-11\]NOP-1A and hydrocortisone to image stress-modulating proteins in heavy drinking alcohol use disorder (AUD) subjects and healthy controls (HC). It will also characterize the role of these stress-regulating proteins in a relapse to alcohol.

Eligibility

Heavy drinking alcohol use disorder subjects (AUD)

1. Males or females between 18 and 55 years old
2. fulfill DSM-5 criteria for moderate or severe ( \> or = 4 criteria) alcohol use disorder
3. fulfill both NIAAA heavy drinking91 (consuming for males \> or = 5 drinks on any day; for females \> or = 4 drinks on any day) and WHO high-risk/very high-risk drinking level criteria66 (for males \> or = 30 drinks/week; for females \> or = 20 drinks/week) in the past four weeks prior to enrollment
4. No lifetime DSM-5 psychiatric disorders, including schizophrenia, schizoaffective disorder, bipolar disorder, or developmental disorders.
5. No comorbid current DSM-5 depressive or anxiety disorders
6. No other current DSM-5 substance use disorders, including opioids, cocaine, amphetamines, sedative-hypnotics, hallucinogens, and inhalants. Subjects with current moderate and severe DSM-5 cannabis use disorder will also be excluded
7. Not currently on psychotropic medications that can directly (e.g., buprenorphine) or indirectly influence binding to NOP (e.g., medications that alter dopamine, GABA, glutamate, etc.) or modify alcohol consumption patterns (e.g., naltrexone, acamprosate, disulfiram);
8. No regular use of medical medications that can potentially interact with hydrocortisone (other corticosteroids, mifepristone, etc.) or increase the risks associated with arterial line removal (warfarin, clopidogrel, aspirin, naproxen, ibuprofen, etc.)
9. No clinically significant medical or neurological illnesses, including a history of immune compromise, HPA-axis dysfunction, Cushing's syndrome, glaucoma, morbid obesity, severe hyperglycemia, and hyperlipidemia, all of which are contraindications for hydrocortisone
10. No history of anemia or history of deep vein thrombosis, pulmonary embolism, thrombocytopenia or thrombocytosis
11. Not currently pregnant or breast-feeding
12. No history of complicated alcohol withdrawal symptoms such as seizures, alcoholic hallucinosis, delirium tremens, or required admission to an inpatient detox program to prevent such symptoms
13. Not currently employed as a radiation worker or has participated in a radiation-related research protocol within the previous year such that the total cumulative annual radiation dose (i.e., from participation in previous radioactive drug studies and this study) would exceed the radiation dose limits specified in the FDA regulations (i.e., 21 CFR 361.1) that govern the research use of radiotracers
14. No metallic objects in the body that are contraindicated for MRI.

Healthy Control subjects (HC)

1. Males or females between 18 and 55 years old
2. No DSM-5 psychiatric or substance use disorders other than tobacco use disorder
3. No NIAAA heavy drinking in the past year (\> or = 5 drinks on any day or more than 14 drinks per week for males; \> or = 4 drinks on any day or more than 7 drinks per week for females)
4. 7 to 14 above.