Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms

NCT05142267 | Recruiting

• 2 other identifiers: 210399R01DA050334
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see how stress influences the effects of opioid pain medications often used to help relieve back pain. The study will help to learn more about how high stress levels could increase risk for pain medication misuse.

Conditions

Opioid Use Disorder; Back Pain; Stress

Outcome Measures

Primary Outcomes (3)

• Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone condition

  Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone condition (across 2 testing days). The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents most intense pain. Positive change values indicate decreased pain responsiveness post intervention.

  Across 2 laboratory assessment days (an expected average of 15 day period)

• Mean DELTA Drug Liking subscale scores in the oxycodone condition

  Mean DELTA Drug Liking subscale scores in the oxycodone condition. The DELTA Drug Liking subscale consists of a single item asking about overall perceived drug liking. The 1-5 scale is anchored with 1 representing dislike a lot and 5 representing like a lot.

  One 1 laboratory assessment day

• Composite measure of changes in MPQ-2 ratings of low back pain from the placebo to naloxone condition (standardized) plus plasma levels of endocannabinoids (standardized)

  Composite measure of changes in MPQ-2 ratings of low back pain from the placebo to naloxone condition (standardized) plus plasma levels of endocannabinoids (standardized). More negative standardized values will indicate low levels of endogenous pain inhibition and more positive levels will indicate high levels of endogenous pain inhibition.

  Across 2 laboratory assessment days (an expected average of 15 day period)

Secondary Outcomes (15)

• Mean changes in MPQ-2 ratings of ischemic task pain from the placebo to oxycodone condition

  Across 2 laboratory assessment days (an expected average of 15 day period)

• Mean changes in Visual Analog Scale (VAS) intensity ratings of ischemic task pain from the placebo to oxycodone condition

  Across 2 laboratory assessment days (an expected average of 15 day period)

• Mean changes in MPQ-2 ratings of heat task pain from the placebo to oxycodone condition

  Across 2 laboratory assessment days (an expected average of 15 day period)

• Mean changes in VAS intensity ratings of heat task pain from the placebo to oxycodone condition

  Across 2 laboratory assessment days (an expected average of 15 day period)

• DELTA Take Again subscale scores in the oxycodone condition

  1 laboratory assessment day (an expected average of 15 day period)

Study Arms (1)

Adults with chronic non-cancer low back pain

OTHER

Drug: Placebo; Drug: Oxycodone; Drug: Naloxone

Interventions

Placebo DRUG

In randomized order (crossover) across 3 laboratory sessions, participants will undergo laboratory evoked thermal pain response testing with: 1) 0.13 mg/kg of oral oxycodone (in 1mg/ml syrup) plus 20ml i.v. saline placebo, 2) 8mg of i.v. naloxone (in 20ml saline vehicle) plus oral placebo syrup (quantity matching oxycodone syrup volume), or 3) 20ml i.v. saline placebo plus oral placebo syrup (quantity matching oxycodone syrup volume). Thermal pain testing utilizes a Medoc TSAII NeuroSensory Analyzer. This equipment is used to assess heat pain threshold and tolerance using an ascending method of limits protocol.

Also known as: normal saline placebo

Adults with chronic non-cancer low back pain

Oxycodone DRUG

In randomized order (crossover) across 3 laboratory sessions, participants will undergo laboratory evoked thermal pain response testing with: 1) 0.13 mg/kg of oral oxycodone (in 1mg/ml syrup) plus 20ml i.v. saline placebo, 2) 8mg of i.v. naloxone (in 20ml saline vehicle) plus oral placebo syrup (quantity matching oxycodone syrup volume), or 3) 20ml i.v. saline placebo plus oral placebo syrup (quantity matching oxycodone syrup volume). Thermal pain testing utilizes a Medoc TSAII NeuroSensory Analyzer. This equipment is used to assess heat pain threshold and tolerance using an ascending method of limits protocol.

Adults with chronic non-cancer low back pain

Naloxone DRUG

In randomized order (crossover) across 3 laboratory sessions, participants will undergo laboratory evoked thermal pain response testing with: 1) 0.13 mg/kg of oral oxycodone (in 1mg/ml syrup) plus 20ml i.v. saline placebo, 2) 8mg of i.v. naloxone (in 20ml saline vehicle) plus oral placebo syrup (quantity matching oxycodone syrup volume), or 3) 20ml i.v. saline placebo plus oral placebo syrup (quantity matching oxycodone syrup volume). Thermal pain testing utilizes a Medoc TSAII NeuroSensory Analyzer. This equipment is used to assess heat pain threshold and tolerance using an ascending method of limits protocol.

Also known as: narcan

Adults with chronic non-cancer low back pain

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Intact cognitive status and ability to provide informed consent
• Ability to read and write in English sufficiently to understand and complete study questionnaires (which are only validated in English)
• Age 18 or older And
• Presence of persistent daily low back pain of at least three months duration and of at least a 3/10 in average intensity

You may not qualify if:

• History of renal or hepatic dysfunction
• Reports of current or past alcohol or substance abuse or treatment for such condition
• A reported history of PTSD, psychotic, or bipolar disorders
• Chronic pain due to malignancy (e.g., cancer) or autoimmune disorders (e.g., rheumatoid arthritis, lupus)
• Reports of recent benzodiazepine use (confirmed via rapid urine screening prior to each lab session)
• Any medical conditions (e.g., significant cardiovascular disease) that the study physician feels would contraindicate participation in the lab stressors
• Reported daily opiate use within the past 6 months, or use of any opioid analgesic medications within 3 days of study participation (confirmed through rapid urine screening prior to each lab session)
• Pregnancy (females only, to avoid fetal drug exposure - pregnancy tests conducted prior to each lab session to confirm eligibility)
• Prior allergic reaction/intolerance to oxycodone or its analogs

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

RECRUITING

Related Publications (42)

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MeSH Terms

Conditions

Opioid-Related Disorders; Back Pain

Interventions

Oxycodone; Naloxone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Stephen Bruehl, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen Bruehl, PhD

CONTACT

615-936-1821; stephen.bruehl@vumc.org

Gail Mayo

CONTACT

615-936-1705; gail.mayo@vumc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: The participant and investigator will be blinded to the drug order across the 3 laboratory drug administration sessions.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Model Details: The study will be a mixed between/within-subjects design with double-blind counterbalanced placebo-controlled administration of both an opioid antagonist and an opioid agonist. Both drugs are being administered solely to probe mechanisms linking stress with individual differences in opioid analgesic responses (this is not an efficacy trial).

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 2, 2021
• Study Start: March 2, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)