Overview

This study will enroll up to 60 adults (including 30 females and 30 males) in three cohorts of up to 20 subjects each. In all three groups, [11C]carfentanil whole-body PET imaging will be used to examine the central nervous system (CNS) and broader systemic opioid binding in an initial scan session. In the two groups not receiving standard of care medication assisted treatment (MAT) for opioid use disorder (OUD) the effects on [11C]carfentanil binding potential of the blockade of opioid binding by the non-selective opioid antagonist naloxone administered parenterally in a second scan session will also be examined. If two scans are completed they can be done on the same day or on different days.

Eligibility

Inclusion Criteria

Cohort 1 (OUD+/MAT+):

1. 18-50 years of age
2. Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.
3. Fluent in English and able to provide written informed consent in English.
4. OUD positive (+): Participants will meet DSM-5 criteria for a lifetime diagnosis of OUD and will be on a stable dosage of buprenorphine or methadone treatment for at least four weeks prior to the screening visit.

Cohort 2 (OUD+/MAT-):

1. 18-50 years of age
2. Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.
3. Fluent in English and able to provide written informed consent in English.
4. OUD positive (+): Participants will meet DSM-5 criteria for a lifetime diagnosis of OUD, but cannot meet criteria for OUD in the 2 months prior to screening, has not used an opioid for any reason in the 30 days prior to screening as evidenced by self-report, medical record review, and urine drug testing at screening and and on the day of the PET scan, and has not received MAT for OUD during the 12 months prior to screening.

Cohort 3 (OUD-, Healthy Controls):

1. Healthy males and females, 18-50 years of age
2. Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.
3. Fluent in English and able to provide written informed consent in English.
4. OUD negative (-): Must never have met criteria for OUD (as per DSM-5) and cannot have used an opioid for any reason in the past 30 days prior to screening as evidenced by self-report, medical record review, and urine drug testing at screening.

Exclusion Criteria

Cohort 1 (OUD+/MAT+):

1. Women who are pregnant or breast feeding will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.
2. Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.
3. Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.
4. Current major DSM-5 Axis 1 psychiatric diagnosis that requires treatment with a medication that interferes with opioid receptor binding, as identified during psychiatric interview or mental status examination at screening/baseline.
5. History of epilepsy or seizure disorder, head trauma or brain (CNS) tumor as assessed by medical record review and/or self-report
6. Current severe substance use disorder (SUD) other than OUD and /or current pharmacological treatment for an SUD other than OUD, including nicotine dependence, that would interfere with study procedures and outcome.
7. A breath alcohol concentration (BAC) reading > 0.01 or a urine toxicology test positive for prohibited drugs.
8. Current use or recent discontinuation (within 14 days of screening) of medications that interfere with radiotracer binding. Participants will be instructed to refrain from using any study-prohibited drugs, though participants will be allowed to take prescription medicines that are not exclusionary throughout their participation in the study.
9. Allergic reaction to any opioid or naloxone
10. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
11. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-report that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study or interfere with distribution of the radiotracer.

Cohort 2 (OUD+/MAT-):

1. Women who are pregnant or breast feeding are not eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.
2. Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.
3. Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.
4. Current major DSM-5 Axis 1 psychiatric diagnosis requiring medications that interfere with radiotracer binding, as identified during a psychiatric interview or mental status examination at screening/baseline.
5. History of epilepsy or seizure disorder, head trauma or brain (CNS) tumor as assessed by medical record review and/or self-report
6. Current severe substance use disorder (SUD) other than OUD and /or current treatment for an SUD other than OUD, including nicotine dependence, that would interfere with study procedures and outcome.
7. A breath alcohol concentration (BAC) reading > 0.01, a urine toxicology test positive for prohibited drugs.
8. Current use or use within the past 12 months of any medications containing naltrexone or other MOR ligands (e.g., buprenorphine, methadone)
9. Use within the month prior to screening of any antipsychotic, anticonvulsant, or stimulant medication or any other medication that is deemed by a physician investigator to potentially interfere with carfentanil binding at the MOR.
10. Allergic reaction to any opioid or naloxone
11. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
12. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-report that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study or interfere with distribution of the radiotracer.

Cohort 3 (Healthy Controls):

1. Women who are pregnant or breast feeding will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.
2. Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.
3. Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.
4. History of or current major DSM-5 Axis 1 psychiatric diagnosis, as identified during psychiatric interview or mental status examination at screening/baseline.
5. History of epilepsy or seizure disorder, head trauma or brain (CNS) tumor as assessed by medical record review and/or self-report
6. A history of substance use disorder (SUD) and /or current treatment for a SUD, including nicotine dependence.
7. Self-reported current alcohol consumption that exceeds 14 standard drinks/week for men and 7 standard drinks/week for women.
8. A breath alcohol concentration (BAC) reading > 0.01 or a urine toxicology test positive for prohibited drugs.
9. Current use or use within the past 12 months of any medications containing naltrexone or other MOR ligands (e.g., buprenorphine, methadone)
10. Current use or use within the past 12 months of medications that could interfere with radiotracer binding. (Participants will be instructed to refrain from using any study-prohibited drugs, though participants will be allowed to take prescription medicines that are not exclusionary throughout their participation in the study.)
11. Any form of smoking cessation medication
12. Any medication prescribed to treat alcohol use disorder or heavy drinking
13. Use within the past 12 months of psychotropic medications (antipsychotics, antidepressants, anti-anxiety medications, stimulants or opioid-containing medications for pain for longer than one week).
14. Allergic reaction to any opioid or naloxone
15. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
16. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-report that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study or interfere with distribution of the radiotracer.