Alcohol Use Disorder
Conditions
Keywords
[C-11]NOP-1A PET, Nociceptive opioid peptide receptor
Brief summary
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.
Detailed description
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.
Interventions
Sponsors
Rajesh Narendran
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Alcohol use disorder and controls will receive the same intervention
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amygdala DELTA VT | Baseline/pre hydrocortisone, and 3-hours post hydrocortisone | VT is the volume of distribution expressed relative to total plasma radioligand concentration; DELTA VT is the change from baseline to post-hydrocortisone |
| Total number of negative ETG tests | over 8-week follow-up | Represents level of abstinence in contingency management |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Midbrain DELTA VT | Baseline/pre hydrocortisone and 3-hours post hydrocortisone | VT is the volume of distribution expressed relative to total plasma radioligand |
| Ventral striatum DELTA VT | Baseline/pre hydrocortisone and 3-hours post hydrocortisone | VT is the volume of distribution expressed relative to total plasma radioligand |
| Orbitofrontal Cortex DELTA VT | Baseline/pre hydrocortisone and 3-hours post hydrocortisone | VT is the volume of distribution expressed relative to total plasma radioligand |
| Relapse to alcohol | over 8-weeks follow up | Abstained; Relapsed; Drop-out |
| Relapse to alcohol severity (self-reported) | over 8- week follow up | Heavy drinking days/week and Abstinent days/week |
Countries
United States
Contacts
CONTACTRajesh Narendran
PRINCIPAL_INVESTIGATORRajesh Narendran
University of Pittsburgh
Outcome results
None listed