Neurobehavioral Mechanisms of Choice in Opioid Use Disorder

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.

Study Overview

• Status: Completed
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Oxycodone

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0086
      • Laboratory of Human Behavioral Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxycodone; Subjects complete a probabilistic money-vs-money choice task during oxycodone maintenance.	Drug: Oxycodone; Participants receive oxycodone or placebo.
Experimental: Withdrawal; Subjects complete a probabilistic money-vs-money choice task during opioid withdrawal induced via double-blind substitution of placebo for active oxycodone in maintenance capsules.	Drug: Oxycodone; Participants receive oxycodone or placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probabilistic Money vs Money Choice Task	Subjects completed a 300-trial probabilistic concurrent monetary choice task, also known as an n-bandit task (here, n=2 choice options, with unsigned probability reversals every 50 trials). In each trial, subjects chose between two options signaled by blue and green envelopes. When a reward was scheduled for the chosen option, subjects were notified they earned $0.25 USD; task earnings were provided upon session completion. Choice of the high probability option was more likely to be reinforced than the low probability option at a 6:1 ratio, with probabilities summing to 0.3, resulting in a low reinforcement density context. Because choosing the higher probability option is associated with a higher likelihood of receiving a monetary reinforcer, making more high probability choices is considered better performance on the task.	Subjects complete the task twice; once under opioid maintained and once under opioid withdrawn conditions during a 16-day inpatient participation. The task takes approximately 20 minutes to complete each time.

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.

Collaborators and Investigators

• Sponsor: Joshua A. Lile, Ph.D.
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: JOSHUA LILE, Ph.D., University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2019
• Primary Completion (Actual): July 10, 2025
• Study Completion (Actual): July 10, 2025

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 18, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Codeine; Oxycodone
• Other Study ID Numbers: 47844; R01DA047368 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No