Overview

Brain Dopaminergic Signaling in Opioid Use Disorders

Status:
Recruiting
Trial end date:
2025-12-31
Target enrollment:
0
Participant gender:
All
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....
Phase:
Early Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Treatments:
Dopamine
Dopamine Agents
Dopamine Agonists
Methylphenidate
Raclopride
Criteria
- INCLUSION CRITERIA:

Healthy Volunteer Participants

1. Males or females between 18 and 65 years of age.

2. Ability to provide written informed consent.

MAT- Opiate Use Disorder (OUD) Participants

1. Males or females between 18 and 65 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 abuse of opiates (last use within one week of study as assessed by
self-reports).

5. Minimum 3 year history of opiate abuse - self-report.

6. Must consume opiates at least 5 days per week as per self-report.

7. Currently not receiving medications for OUD (methadone, buprenorphine or naltrexone).

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 65 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 inclusion #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 and MRI scans.

EXCLUSION CRITERIA:

- All Subjects

1. Current DSM-5 diagnosis of a psychiatric disorder (other than OUD or severe
alcohol/substance use disorders in OUD participants and nicotine/caffeine use in
all participants) 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 (for controls only); 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 and that opiate drugs will not
exclude participants with OUD. Subjects on stable antihypertensive medications
(except for beta blockers) may be included provided they are clinically stable
dose for at least a month [BP less than or equal to 140/90]. OUD subjects who
have hypertension may still be included in this study except they will not
receive the methylphenidate and subsequent PET and MRI scans.

3. Current continuous treatment (> 3 weeks) with methadone, buprenorphine or
naltrexone for controls or MAT- OUD participants; or naltrexone for MAT+ OUD
participants; or agonist treatment (methadone or buprenorphine) for OUD
participants treated with Naltrexone.

4. 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 arrhythmias
except bradycardia; and HIV+) as determined by history. However, OUD subjects who
have hypertension and/or certain EKG findings results may still be included in
this study except they will not receive the methylphenidate and subsequent PET
and/or MRI scans.

5. Clinically significant laboratory findings that could impact brain function or
study procedures (e.g., active infections, arrhythmias, 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. However, OUD subjects who are contraindicated for MRI
participation, or the study team cannot access prior surgical records to confirm
that a subject is cleared for MRI, may still participate in all aspects of the
study except MRI. If it is discovered during the clinical brain MRI or after
enrollment onto the study that the subject experiences anxiety or becomes
claustrophobic, we will discontinue the MRI portion of the study and he/she can
continue to participate in all other aspects of the study.

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).

Additional exclusion criteria for MAT+ / MAT- / Naltrexone OUD participants:

16. Participation in a court ordered residential treatment program.

Additional exclusion criteria for MAT- OUD participants only:

17. Currently seeking treatment for OUD, for the MAT- group.

Note that subjects will not be excluded from enrollment onto this study if their urine test
is positive for drugs on initial screening. The following guidelines will be followed for
positive drug screens on study procedure days:

- If a Healthy Volunteer subject s urine drug screen test is positive on days involving
imaging (MRI and/or PET) and NP testing, the procedures will be postponed and
rescheduled. We will allow for up to 3 rescheduled study days resulting from positive
urine drug screens. If urine drug screen is positive for THC-COOH, a saliva drug
screen will be performed and subject may proceed with study day testing procedures if
saliva results for THC are negative. If the urine/saliva drug test is positive on the
third rescheduled visit, the participant will be withdrawn from the study.

- If an OUD subject s urine drug screen test is positive for drugs (other than opiates),
the procedures will not be postponed. If urine drug screen is positive for THC-COOH, a
saliva drug screen will be performed to verify if THC is present. Positive results for
drugs other than opiates will be considered at the time of data analysis as a
co-variate.

Also, note that at any time during participation in this study if any subject expresses
that he/she wants to get treatment for their OUD, we will immediately refer him/her to a
treatment program. The subject will be withdrawn from the study at that time. No
medications will be stopped or held for participation in this protocol.