Neurobehavioral Mechanisms of Choice in Opioid Use Disorder

Study Overview
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Brief Summary
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The objective of this protocol is to use probabilistic reinforcement learning choice tasks and magnetic resonance neuroimaging to demonstrate the impact of problematic opioid use and opioid withdrawal on dynamic decision-making and reveal the neurobehavioral and neurobiological processes underlying abnormal task performance. A second objective is to identify an appropriate dose of intravenous remifentanil for subsequent studies in physically dependent individuals with opioid use disorder.

Official Title
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Neurobehavioral Mechanisms of Choice in Opioid Use Disorder

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: Oxycodone
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must meet moderate/severe criteria for moderate/severe opioid use disorder, report recent prescription or illicit opioid use, and be opioid dependent, as evidenced by either a urine sample positive for recent opioid use or being in frank withdrawal during screening. Female subjects must be using an effective form of birth control (e.g., birth control pills, surgical sterilization, IUD, cervical cap with a spermicide, or abstinence). Able to speak and read English Subjects who are interested in completing the remifentanil dose-ranging session must report a history of intravenous opioid use and a baseline O2 saturation of 95% or greater. Exclusion Criteria: History of, or current, clinically significant physical disease (e.g., respiratory disease [asthma, COPD, sleep apnea], impaired cardiovascular functioning, seizure disorder or CNS tumors) or current or past history of psychiatric disorder that would limit compliance in the studies, other than substance use disorder. Meet diagnostic criteria for psychoactive substance use disorder for substances other than opioids (OUD subjects only) or nicotine that would require detoxification (i.e., alcohol, benzodiazepines or barbiturates). Contraindications for MRI scanning (e.g., pacemaker, metal implants, claustrophobia, or any other implanted medical device). Vision or hearing problems that would preclude completion of experimental tasks. At risk for respiratory complications and have predictors of difficult bag mask ventilation (e.g., dentures, very full beard), in case emergency respiratory intervention is needed. Seeking treatment for SUD. Poor venous access (only subjects who will participate in the remifentanil dose-ranging session).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Within-subjects design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment followed by placebo treatment<br>Participants complete a gambling task during oxycodone administration and then complete the same gambling task during placebo administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session. | Drug: Oxycodone<br>* Participants receive oxycodone or placebo.<br>Drug: Remifentanil<br>* Participants with a history of IV opioid use can opt to complete a session in which they receive remifentanil.<br>|
| Experimental: Placebo treatment followed by active treatment<br>Participants complete a gambling task during placebo administration and then complete the same gambling task during oxycodone administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session. | Drug: Oxycodone<br>* Participants receive oxycodone or placebo.<br>Drug: Remifentanil<br>* Participants with a history of IV opioid use can opt to complete a session in which they receive remifentanil.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gambling task | The number of monetary rewards earned on a gambling task, in which two options signaled by distinct cues are presented on a computer screen and choosing either could result in the delivery of money, but the reinforcement probabilities of the options differ, and change during the task. | Change in monetary rewards earned on a gambling task as a function of the intervention will be assessed by administering this task once per session across two sessions during a 9-day inpatient enrollment in each subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiration rate | Breaths per minute measured by capnography device | Measured continuously during a single 2.5 hour session in which remifentanil is administered. | 
| End tidal carbon dioxide | End tidal carbon dioxide measured by capnography device | Measured continuously during a single 2.5 hour session in which remifentanil is administered. | 
| Oxygen saturation | Blood oxygen concentration measured by capnography device | Measured continuously during a single 2.5 hour session in which remifentanil is administered. |