Brain Dopaminergic Signaling in Opioid Use Disorders


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  • 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 5 year history of opiate abuse – self-report.
  6. Must consume opiates at least once a day as per self-report.
  7. Currently not receiving medications for OUD (methadone, buprenorphine or vivitrol).

MAT+ 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 5 year history of opiate abuse as per self-report.
  6. Must consume at least once a day as per self-report.
  7. Receiving MAT for OUD (methadone or buprenorphine)

EXCLUSION CRITERIA:

All Subjects

  1. Unwilling or unable to refrain from use within 24 hours of scheduled study procedures: psychoactive medications or medication that may affect study results (e.g., antibiotics (must finish course at least 24 hours prior to a scheduled procedure), antidiarrheal preparations, anti-inflammatory drugs [systemic corticosteroids are exclusionary], anti-nausea, cough/cold preparations) (self-report, medical history). The following medications are allowable for entry on this study: analgesics (non-narcotic and narcotic for OUD participants); antacids; antiasthma agents that are not systemic corticosteroids; antifungal agents for topical use; antihistamines (nonsedating); H2-Blockers/PPI (proton pump inhibitors); laxatives. The use of antihyperlipidemics and/or diuretics are permitted if they have been taken for at least 1 month before procedure visits and dose has been stabilized. The episodic use of benzodiazepines such as alprazolam ( Xanax), diazepam ( Valium) and lorazepam ( Ativan), will not exclude participants from this study unless they have been taken within the last 24 hours prior to the study.
  2. Current or past DSM-5 diagnosis of a psychiatric disorder (including OCD and tics, other than OUD in OUD participants and nicotine/caffeine use in all participants) that required hospitalization (any length), or chronic medication management (more than 3 months) and that could impact brain function at the time of the study as determined by history and clinical exam. 3. The following current chronically used medications are exclusionary from the study: stimulant or stimulant-like medications (amphetamine, methylphenidate, modafinil); analgesics containing narcotics (for controls only); anorexics (sibuteramine); antianginal agents; antiarrhythmics; antiasthma agents that are systemic corticosteroids; antibiotics; anticholinergics; anticoagulants; anticonvulsants; antidepressants; antidiarrheal preparations; antifungal agents (systemic); antihistamines (sedating); antihypertensives; anti-inflammatory drugs (systemic); antineoplastics; antiobesity; antipsychotics; antivirals (except for treatment of HSV with agents without CNS activity, e.g. acyclovir, ganciclovir, famciclovir, valacyclovir); anxiolytics (benzodiazepine or barbiturates); hormones (exceptions: thyroid hormone replacement, oral contraceptives, and estrogen replacement therapy); insulin; lithium; muscle relaxants; psychotropic drugs not otherwise specified (nos) including herbal products (no drugs with psychomotor effects or with anxiolytics, stimulant, antipsychotic, or sedative properties); sedatives/hypnotics. Note that

    nicotine and/or caffeine use will not exclude participants and that the use of opiate drugs will not exclude participants with OUD.

4. Current or past month continuous treatment (> 3 weeks) with methadone, buprenorphine or naltrexone for controls or MAT- OUD participants; or naltrexone for MAT+ OUD participants.

5. Major medical problems that can permanently impact brain function (e.g., CNS including seizures and psychosis; cardiovascular including hypertension [BP > 140/90] and clinically significant arrhythmias except bradycardia; metabolic, autoimmune, endocrine; +HIV) as determined by history.

6. Any clinically significant laboratory finding as determined during the screening procedures that could impact brain function or study procedures as evidenced from clinical laboratory results. Only abnormal laboratory findings associated with altered brain function (e.g., arrhythmias or renal failure) will be exclusionary.

7. 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.

8. Head trauma with loss of consciousness for more than 30 minutes as determined by medical history and physical exam.

9. Pregnant or breast-feeding: Females of childbearing potential, or with tubal ligation, or are post-menopausal and are age 60 or less will undergo a urine pregnancy test and it must be negative to continue participation. Urine pregnancy tests will be repeated on subsequent days of study. Females must not be currently breastfeeding.

10. Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (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.

11. Personal or family history for cerebral aneurism.

12. Past or present history of chest pain and trouble breathing with activity.

13. Diabetes as assessed by medical history.

14. Cannot lie comfortably flat on their backs for up to 2 hours in the PET and MRI scanners self-report.

15. Weight > 400 pounds, which is the maximum weight the PET scanner can hold.

16. Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).

17. Consumption of high levels of alcohol. A heavy drinker is one who drinks more than 5 drinks more than three times a week (for men) or more than 4 drinks more than three times a week (for women).

Additional exclusion criteria for MAT+ / MAT- OUD subjects:

18. Participation in a court ordered treatment program.

19. Scores on MADRS 20 or higher.

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 the 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 (except opiates), the procedures will be postponed and rescheduled to another day. We will not place a limit on rescheduling study days in this group.

Also, note that at any time during participation in this study 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.