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

Stress Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05142267
• Other study ID #: 210399
• Secondary ID: R01DA050334
• Status: Recruiting
• Phase: N/A
• Start date: March 2, 2022
• Est. completion date: March 24, 2026

Study information

• Verified date: October 2023
• Source: Vanderbilt University Medical Center
• Contact: Stephen Bruehl, PhD
• Phone: 615-936-1821
• Email: stephen.bruehl[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 24, 2026
• Est. primary completion date: March 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Back Pain
• Opioid Use Disorder
• Opioid-Related Disorders
• Stress

Intervention

Drug:
• Placebo
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.
• Oxycodone
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.
• Naloxone
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.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

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* Note: There are 42 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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	Mean changes in MPQ-2 ratings of ischemic task pain from the placebo to oxycodone condition	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.	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean changes in Visual Analog Scale (VAS) intensity ratings of ischemic task pain from the placebo to oxycodone condition	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")	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean changes in MPQ-2 ratings of heat task pain from the placebo to oxycodone condition	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.	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean changes in VAS intensity ratings of heat task pain from the placebo to oxycodone condition	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")	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	DELTA Take Again subscale scores in the oxycodone condition	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.	1 laboratory assessment day (an expected average of 15 day period)
Secondary	Mean Delta Effects subscale in the oxycodone condition	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.	1 laboratory assessment day (an expected average of 15 day period)
Secondary	Mean VAS Opioid Euphoria subscale in the oxycodone condition	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.	1 laboratory assessment day (an expected average of 15 day period)
Secondary	Mean VAS Opioid Unpleasantness subscale in the oxycodone condition	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.	1 laboratory assessment day (an expected average of 15 day period)
Secondary	Mean VAS Opioid Sedation subscale in the oxycodone condition	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.	1 laboratory assessment day (an expected average of 15 day period)
Secondary	Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to naloxone condition	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 .	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of ischemic task pain from the placebo to naloxone condition	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.	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean changes in VAS intensity ratings of ischemic task pain from the placebo to naloxone condition	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.	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of heat task pain from the placebo to naloxone condition	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	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean changes in VAS intensity ratings of heat task pain from the placebo to naloxone condition	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.	Across 2 laboratory assessment days (an expected average of 15 day period)
Secondary	Mean plasma levels of endocannabinoids	Mean plasma levels of endocannabinoids	Across 3 laboratory assessment days (an expected average of 15 day period)