Brain Dopaminergic Signaling in Opioid Use Disorders

Background: The chemical messenger dopamine carries signals between brain cells. It may affect addiction. Heavy use of pain medicines called opioids may decrease the amount of dopamine available to the brain. Researchers want to study if decreased dopamine decreases self-control and increases impulsiveness. Objective: To learn more about how opiate use disorder affects dopamine in the brain. Eligibility: Adults 18-80 years old who are moderate or severe opiate users Healthy volunteers the same age Design: Participants will first be screened under another protocol. They will: * Have a physical exam * Answer questions about their medical, psychiatric, and alcohol and drug use history * Take an MRI screening questionnaire * Give blood and urine samples * Have their breath tested for alcohol Participants will have up to 3 study visits. They will have 2-3 positron emission tomography (PET) scans. A radioactive chemical will be injected for the scans. Participants will lie on a bed that slides in and out of the donut-shaped scanner. A cap or plastic mask may be placed on the head. Vital signs will be taken before and after the PET scans. Participants will get capsules of placebo or the study drug. They will rate how they feel before, during and after. Participants will have their breath and urine tested each day. Participants will have magnetic resonance imaging (MRI) scans. They will lie on a table that slides into a cylinder in a strong magnetic field. They may do tasks on a computer screen while inside the scanner. Participants will have tests of memory, attention, and thinking. Participants will wear an activity monitor for one week.

* INCLUSION CRITERIA: Healthy Volunteer Participants 1. Males or females between 18 and 80 years of age. 2. Ability to provide written informed consent. MAT- Opiate Use Disorder (OUD) Participants 1. Males or females between 18 and 80 years of age. 2. Ability to provide written informed consent. 3. DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam). 4. Minimum of 3 months since last regular use of opioids (no more than 1x/week in the past 3 months as assessed by self-report). 5. Minimum 3 year history of past opiate abuse - self-report. 6. Must have consumed opiates at least 5 days per week (past opioid use) as per self-report. 7. Currently not receiving medications for OUD and a minimum of 3 months since last regularly taking medications for OUD (methadone, buprenorphine or naltrexone) as per self-report. MAT+ OUD Participants 1. Males or females between 18 and 80 years of age. 2. Ability to provide written informed consent. 3. DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam). 4. Active or non-active abuse of opiates. 5. Minimum 3 year history of opiate abuse as per self-report. 6. Must have consumed at least 5 days per week (prior opiate use) as per self-report. 7. Receiving opioid agonist therapy for OUD (e.g., methadone or buprenorphine) and must have taken for at least one week before imaging study Naltrexone OUD Participants 1. Males or females between 18 and 80 years of age. 2. Ability to provide written informed consent. 3. DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam). 4. Active or non-active abuse of opiates. 5. Minimum 3 year history of opiate abuse as per self-report. 6. Must have consumed at least 5 days per week (prior opiate use) as per self-report. 7. Receiving naltrexone treatment for their OUD and must have taken at least one week before imaging study. For all groups of subjects regarding inclusions 1 \& 2: * 1: OUD and HV subjects who are age 66-80 may be included in this study except they will not receive the methylphenidate and subsequent PET/\[11C\]raclopride and MRI scans. They will receive the placebo (Phase D) and subsequent PET/\[11C\]raclopride and MRI scans. * 2: Source documentation for the subject s ability to provide written informed consent will be a note in CRIS documenting that the subject is alert and oriented to person, place, and time; and/or an unremarkable neurological examination; dated on or before the date of consent. EXCLUSION CRITERIA: Healthy Volunteer Subjects 1. Current DSM-5 diagnosis of a psychiatric disorder (other than nicotine/caffeine use) that requires/required daily psychoactive medications (antidepressant, antipsychotics, stimulants, 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. 2. The following current chronically used (2 months) medications are exclusionary: stimulant or stimulant-like medications (amphetamine, methylphenidate, modafinil); opioid analgesics; 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. Subjects on stable antihypertensive medications (except for beta blockers) may be included provided they are on a clinically stable dose for at least a month \[BP must be \ 140/90\] and clinically significant EKG results except bradycardia; and HIV+) as determined by history. 5. Clinically significant laboratory findings that could impact brain function or study procedures (e.g., active infections, significant EKG results, hepatic or renal failure) will be exclusionary. 6. 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. 7. Head trauma with loss of consciousness for more than 30 minutes as determined by medical history and physical exam. 8. Pregnant and/or currently breast-feeding. Females of childbearing potential (age 60 or less) will undergo a urine pregnancy test that must be negative to participate. Urine pregnancy tests will be repeated on subsequent days of study. 9. Presence of ferromagnetic objects in the body that are contraindicated for MRI (pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces - self-report checklist. 10. Personal or family history (parents or siblings) for cerebral aneurysm. 11. Past or present history of chest pain and trouble breathing with activity. 12. Glaucoma as assessed by medical history. 13. Cannot lie comfortably flat on their backs for up to 2 hours in the PET and MRI scanners self-report. 14. Weight \> 400 pounds, which is the maximum weight the PET scanner can hold. 15. Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings). 16. \*Non-English speakers (must also be able to read and comprehend English). OUD Subjects 1. DSM-5 diagnosis of a psychiatric disorder that requires daily use of antipsychotic medications (schizophrenia or any other psychotic disorder) at the time of the study as determined by history and clinical exam. 2. Currently on antipsychotic medications. Subjects on stable antihypertensive medications may be included provided they are clinically stable \[BP must be \