Brain Dopaminergic Signaling in Opioid Use Disorders

NCT03190954 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 17011417-AA-0114
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 1

Brief Summary

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....

Conditions

Opioid Use Disorders; Normal Physiology

Keywords

Raclopride; NNC-112; Functional Magnetic Resonance Imaging (fMRI); Dopamine D1 Receptor; D2 Receptors

Outcome Measures

Primary Outcomes (1)

• Differences in D1R to D2R striatal ratio and in DA release between participants with an OUD and controls and between MAT+, naltrexone, and MAT- groups.

  To assess whether the balance between D1R and D2R in striatum and in DA release is disrupted in participants with an opioid use disorder (OUD) who are being treated with an opioid agonist medication (MAT+), those treated with an opioid antagonist medication (naltrexone) and OUD participants who are not being treated with medications (MAT-).

  End of study

Secondary Outcomes (3)

• 1) To assess the impact of disruptions on striatal D1R to D2R availability on: DA release; Function of brain reward and control networks; Behavior.2) To assess if DA increases as achieved with oral MP influence the brain functional m...

  End of study

• 2) To assess if DA increases as achieved with oral MP influence the brain functional measures.

  End of study

• 3) To assess if there is recovery after protracted treatment (comparing treated and non-treated) by repeating fMRI at 6 month follow-up.

  End of study

Study Arms (3)

[11C]NNC-112

PLACEBO COMPARATOR

\[11C\]NNC-112 PET scan obtained without any drug intervention to measure dopamine D1 receptors. Blind N/A

Drug: [11C]NNC-112

[11C]raclopride plus drug

ACTIVE COMPARATOR

Methylphenidate 60 mg. po will be given 60 minutes prior to \[11C\]raclopride scan to measure striatal dopamine release. MRI scan to follow end of PET scan. Subject blind as to drug administration.

Drug: [11C]raclopride plus drug; Drug: [11C]NNC-112

[11C]raclopride plus placebo

PLACEBO COMPARATOR

Placebo (po) will be given 60 minutes prior to \[11C\]raclopride scan to measure baseline dopamine D2 receptors. MRI scan to follow end of PET scan. Subject blind as to drug administration.

Drug: [11C]raclopride plus placebo; Drug: [11C]NNC-112

Interventions

[11C]raclopride plus drug DRUG

Methylphenidate 60 mg. po will be given 60 minutes prior to \[11C\]raclopride scan to measure striatal dopamine release. MRI scan to follow end of PET scan. Subject blind as to drug administration.

[11C]raclopride plus drug

[11C]NNC-112 DRUG

\[11C\]NNC-112 PET scan obtained without any drug intervention to measure dopamine D1 receptors. Blind N/A

[11C]NNC-112; [11C]raclopride plus drug; [11C]raclopride plus placebo

[11C]raclopride plus placebo DRUG

Placebo (po) will be given 60 minutes prior to \[11C\]raclopride scan to measure baseline dopamine D2 receptors. MRI scan to follow end of PET scan. Subject blind as to drug administration.

[11C]raclopride plus placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Volunteer Participants
• Males or females between 18 and 80 years of age.
• Ability to provide written informed consent.
• MAT- Opiate Use Disorder (OUD) Participants
• Males or females between 18 and 80 years of age.
• Ability to provide written informed consent.
• DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam).
• 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).
• Minimum 3 year history of past opiate abuse - self-report.
• Must have consumed opiates at least 5 days per week (past opioid use) as per self-report.
• 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
• Males or females between 18 and 80 years of age.
• Ability to provide written informed consent.
• DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam).

You may not qualify if:

• Healthy Volunteer Subjects
• 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.
• Current continuous treatment (\> 3 weeks) with methadone, buprenorphine or naltrexone.
• Current major medical problems that can permanently impact brain function (e.g., CNS: including seizures, psychosis, stroke, severe depression, Alzheimer s, Parkinson s disease, Traumatic brain injury; Cardiovascular: including uncontrolled hypertension \[BP \> 140/90\] and clinically significant EKG results except bradycardia; and HIV+) as determined by history.
• 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.
• Head trauma with loss of consciousness for more than 30 minutes as determined by medical history and physical exam.
• 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.
• 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.
• Personal or family history (parents or siblings) for cerebral aneurysm.
• Past or present history of chest pain and trouble breathing with activity.
• Glaucoma as assessed by medical history.
• Cannot lie comfortably flat on their backs for up to 2 hours in the PET and MRI scanners self-report.
• Weight \> 400 pounds, which is the maximum weight the PET scanner can hold.
• Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).
• \*Non-English speakers (must also be able to read and comprehend English).

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Zhang R, Manza P, Tomasi D, Kim SW, Shokri-Kojori E, Demiral SB, Kroll DS, Feldman DE, McPherson KL, Biesecker CL, Wang GJ, Volkow ND. Dopamine D1 and D2 receptors are distinctly associated with rest-activity rhythms and drug reward. J Clin Invest. 2021 Sep 15;131(18):e149722. doi: 10.1172/JCI149722.

  PMID: 34264865 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Nora D Volkow Adler, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2017
• First Posted: June 19, 2017
• Study Start: August 17, 2017
• Primary Completion: October 27, 2025
• Study Completion: October 27, 2025
• Last Updated: January 14, 2026

Record last verified: 2026-01-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)