Condition

• Cocaine Use Disorder

Eligibility

Eligible Ages

Between 18 Years and 55 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

1. Males or females between 18 and 55 years old

2. Fulfil DSM-5 criteria for cocaine use disorder

3. No other current DSM-5 psychiatric or addictive disorders (such as major depressive
disorder, bipolar disorders, psychotic disorders, etc.,)

4. No current abuse (six months) of opiates, sedative-hypnotics, amphetamines, and MDMA
as well as moderate to severe alcohol or cannabis use (twice a week). Nicotine use
will be quantified and controlled between groups using the Fagerstrom Test for
Nicotine Dependence (Heatherton et al., 1991);

5. Not currently on prescription medical or psychotropic medications

6. No current or past severe medical, endocrine or neurological illnesses including
glaucoma, seizure disorders, hypertension, hypercholesterolemia as assessed by a
complete medical history and physical

7. Not currently pregnant or breastfeeding

8. No history of significant radioactivity exposure in past year from another research
study or occupation that exceeds RDRC guidelines

9. No metallic objects in the body that are contraindicated for MRI

10. No baseline BP ≥ 140/90 and/or HR ≥ 100.

11. No first-degree relative with an MI or stroke prior to middle age

12. No first-degree relative with psychosis or mania.

13. Completed a baseline [11C]NOP-1A PET scan in Aim 1 (Study Record: Imaging CRF X NOP
interactions in Cocaine Use Disorders)

Recruiting Locations

Study Contact

Detailed Description

Cocaine use disorder (CUD) is a chronic disorder associated with numerous relapses and periods of abstinence. Studies in CUD suggest that ~ 60 to 75% of abstinent addicts relapse over twelve months. Documenting specific neurochemical abnormalities that lead to relapse in individuals with CUD has the potential to accelerate the development of medications to prevent relapse. Basic investigations postulate an imbalance between brain stress and anti-stress/resilience systems as the underlying mechanism that drives negative reinforcement, craving, and relapse in addiction.. Nociceptin (N/OFQ), which binds to the nociceptive opioid peptide receptors (NOP) is a critical component of the brain's anti-stress system. N/OFQ exerts its anti-stress effect by counteracting the functional effects of the primary stress-promoting neuropeptide corticotrophin releasing factor (CRF) in the brain. Studies have also shown that acute increases in CRF and stress are countered by increased NOP receptor expression (~ 10% ) in brain regions that regulate stress such as bed nucleus of the stria terminalis. PET studies with the NOP radiotracer [11C]NOP-1A show increased binding to NOP in CUD compared to HC. PET studies also show NOP receptors to upregulate (~ 15%) in response to an acute intravenous hydrocortisone challenge (1 mg/Kg). NOP upregulation may represent an adaptive mechanism in the brain to counteract stress-induced increases in cortisol and CRF. Here, we postulate a failure in this adaptive mechanism as a reason that leads to relapse in CUD. CUD subjects and HC will be studied with [11C]NOP-1A before and after an intravenous hydrocortisone challenge (aim 1). Hydrocortisone is used as a challenge because it increases cortisol and CRF in brain regions that regulate stress. We hypothesize that hydrocortisone-induced increases in [11C]NOP-1A binding (DELTA VT) will be smaller in CUD relative to HC, and this will be associated with less time to relapse in a 12-week follow up. Mechanistic studies have also shown N/OFQ to act on ventral tegmental area/midbrain NOP receptors to inhibit the firing of dopamine neurons and limit reward to cocaine. Imaging amphetamine-induced dopamine release in a subset of CUD subjects who participate in aim 1 will allow us to link midbrain NOP receptor expression with ventral striatum (VST) dopamine release and examine its role in reinforcement (aim 2). The aims proposed in this study have the potential to clarify the role of N/OFQ and NOP in stress, reward, and relapse in CUD.