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

Not Applicable
Recruiting
Conditions
Back Pain
Opioid Use Disorder
Stress
Interventions
Registration Number
NCT05142267
Lead Sponsor
Vanderbilt University Medical Center
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.

Detailed Description

The purpose of this project is to advance mechanistic knowledge of how stress impacts differential opioid analgesic responses that enhance risk for opioid use disorder (OUD), potentially informing development of data-driven precision pain medicine algorithms to mitigate opioid related risks.

The study aims to determine whether subjective and physiological stress-related measures are associated with analgesic and misuse-relevant subjective responses to placebo-controlled oxycodone administration. The study also aims to evaluate associations between stress-related measures and both endogenous opioid (EO) function and endocannabinoid (EC) levels and to test whether EO and EC mechanisms contribute to associations between stress-related measures and oxycodone responses

Using a mixed between/within-subject design, the study will obtain baseline assessment of stress related markers followed by 3 laboratory sessions with assessment of endocannabinoids, back pain assessment, and exposure to standardized evoked pain stimuli after administration of placebo, naloxone, and oxycodone.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
Inclusion Criteria
  • 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
Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Adults with chronic non-cancer low back painPlacebo-
Adults with chronic non-cancer low back painOxycodone-
Adults with chronic non-cancer low back painNaloxone-
Primary Outcome Measures
NameTimeMethod
Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

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.

Mean DELTA Drug Liking subscale scores in the oxycodone conditionOne 1 laboratory assessment day

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.

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

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.

Secondary Outcome Measures
NameTimeMethod
Mean changes in MPQ-2 ratings of ischemic task pain from the placebo to oxycodone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

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

Mean changes in Visual Analog Scale (VAS) intensity ratings of ischemic task pain from the placebo to oxycodone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

Mean within participant changes in VAS intensity ratings of ischemic task pain from the placebo to oxycodone condition. The score is a rating of current acute pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain")

Mean changes in MPQ-2 ratings of heat task pain from the placebo to oxycodone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

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

Mean changes in VAS intensity ratings of heat task pain from the placebo to oxycodone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

Mean within participant changes in VAS intensity ratings of heat task pain from the placebo to oxycodone condition. The score is a rating of current acute pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain")

DELTA Take Again subscale scores in the oxycodone condition1 laboratory assessment day (an expected average of 15 day period)

Mean oxycodone condition Take Again (DELTA subscale) score. The score ranges from 1-5 where 1 represents definitely would not and 5 represents definitely would. Positive values indicate decreased overall drug effects post intervention.

Mean Delta Effects subscale in the oxycodone condition1 laboratory assessment day (an expected average of 15 day period)

Mean oxycodone condition Effects (DELTA) -Drug Effect subscale ratings. The score ranges from 1-5 where 1 represents no effect and 5 represents very strong effect. Positive values indicate decreased overall drug effects post intervention.

Mean VAS Opioid Euphoria subscale in the oxycodone condition1 laboratory assessment day (an expected average of 15 day period)

Mean oxycodone condition VAS Opioid Effects-Euphoria subscale ratings. The score ranges from 0-300 where 0 means no euphoria and 300 means most euphoria possible. Positive values indicate greater euphoria.

Mean VAS Opioid Unpleasantness subscale in the oxycodone condition1 laboratory assessment day (an expected average of 15 day period)

Mean oxycodone condition VAS Opioid Effects-Unpleasantness subscale ratings. The score ranges from 0-300 where 0 means no unpleasantness and 300 means the most unpleasantness possible. Positive values indicate greater perceived unpleasantness.

Mean VAS Opioid Sedation subscale in the oxycodone condition1 laboratory assessment day (an expected average of 15 day period)

Mean oxycodone condition VAS Opioid Effects-Sedation subscale ratings. The score ranges from 0-300 where 0 means no sedation and 300 means the most sedation possible. Positive values indicate greater sedation.

Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to naloxone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to naloxone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents the most intense pain. Positive change values indicate greater endogenous opioid pain inhibition .

Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of ischemic task pain from the placebo to naloxone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of ischemic task pain from the placebo to naloxone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents the most intense pain. Positive change values indicate greater endogenous opioid pain inhibition.

Mean changes in VAS intensity ratings of ischemic task pain from the placebo to naloxone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

Mean within participant changes in VAS intensity ratings of ischemic task pain from the placebo to naloxone condition. The VAS score is a rating of ischemic task pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain"). Positive change values indicate greater endogenous opioid pain inhibition.

Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of heat task pain from the placebo to naloxone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

Mean within participant changes in McGill Pain Questionnaire-2 (MPQ-2) ratings of heat task pain from the placebo to naloxone condition. The MPQ-2 score ranges from 0-10 where 0 represents no pain and 10 represents the most intense pain. Positive change values indicate greater endogenous opioid pain inhibition

Mean changes in VAS intensity ratings of heat task pain from the placebo to naloxone conditionAcross 2 laboratory assessment days (an expected average of 15 day period)

Mean within participant changes in VAS intensity ratings of thermal task pain from the placebo to naloxone condition. The VAS score is a rating of ischemic task pain using a 0-100 visual analog scale (VAS) (0 = "no pain" and 100 = "worst possible pain"). Positive change values indicate greater endogenous opioid pain inhibition.

Mean plasma levels of endocannabinoidsAcross 3 laboratory assessment days (an expected average of 15 day period)

Mean plasma levels of endocannabinoids

Trial Locations

Locations (1)

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

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