Neurobehavioral Mechanisms of Choice in Opioid Use Disorder

Joshua A. Lile, Ph.D.

Status and phase: Completed; Early Phase 1

Conditions: Opioid Use Disorder

Treatments: Drug: Remifentanil; Drug: Oxycodone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03958474

47844

R01DA047368 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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12 participants in 2 patient groups

Active treatment followed by placebo treatment

Experimental group

Description:

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.

Treatment:

Drug: Oxycodone

Drug: Remifentanil

Placebo treatment followed by active treatment

Experimental group

Description:

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.

Treatment:

Drug: Oxycodone

Drug: Remifentanil