Imaging CRF X NOP Interactions in Alcohol Use Disorder

Hydrocortisone administration leads to a 10 to 15% increase in [11C]NOP-1A VT in brain regions, including the amygdala. Increased NOP measured in response to cortisol, and by extension, corticotrophin-releasing factor (CRF), in this paradigm reflects an individual's ability to enhance N/OFQ transmission during stress. Here, the investigators propose to use this novel imaging paradigm to compare hydrocortisone-induced increases in [11C]NOP-1A binding (DVT) in the amygdala (and secondary reward regions) in heavy drinking AUD subjects Vs. HC. The hypothesis that hydrocortisone-induced increases in [11C]NOP-1A binding (DVT) will be larger in heavy drinking AUD relative to HC (aim 1), and this will predict relapse to alcohol (aim 2). Such a result will support the presence of a hyperactive NOP receptor system in response to increases in cortisol/CRF during conditions such as stress, chronic pain, etc., promoting relapse in heavy drinking AUD subjects.

Heavy drinking alcohol use disorder subjects (AUD)

• Males or females between 18 and 55 years old
• fulfill DSM-5 criteria for moderate or severe ( > or = 4 criteria) alcohol use disorder
• 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
• No lifetime DSM-5 psychiatric disorders, including schizophrenia, schizoaffective disorder, bipolar disorder, or developmental disorders.
• No comorbid current DSM-5 depressive or anxiety disorders
• 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
• 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);
• 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.)
• 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
• No history of anemia or history of deep vein thrombosis, pulmonary embolism, thrombocytopenia or thrombocytosis
• Not currently pregnant or breast-feeding
• 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
• 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
• No metallic objects in the body that are contraindicated for MRI.

Healthy Control subjects (HC)

• Males or females between 18 and 55 years old
• No DSM-5 psychiatric or substance use disorders other than tobacco use disorder
• 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)
• 7 to 14 above.