Opioid Use DisorderPhase 4NCT05142267

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

A Phase 4 study testing Oxycodone and Naloxone in people with Opioid Use Disorder and Back Pain, run by Vanderbilt University Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Opioid Use Disorder, Back Pain, Stress
What is being tested?: Oxycodone and Naloxone
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 101 participants
Where: 1 siteUnited States
Study dates: 2 Mar 2022to 7 Apr 2026
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 9Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University Medical Center
Nashville, Tennessee, 37212

Other trials in United States

About this study

Read the 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.

Conditions: Opioid Use Disorder, Back Pain, Stress
Being tested: Placebo, Oxycodone, Naloxone
Medical subject headings: Opioid-Related Disorders, Back Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Also called normal saline 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.
OxycodoneDrug
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.
NaloxoneDrug
Also called narcan
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.

Study groups in NCT05142267
Study group	Role	What they receive
Adults with chronic non-cancer low back pain	Other	Not described Receives: Drug: Placebo; Drug: Oxycodone; Drug: Naloxone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: 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
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")
Measured: 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
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.
Measured: 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
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")
Measured: Across 2 laboratory assessment days (an expected average of 15 day period)
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.
Measured: 1 laboratory assessment day (an expected average of 15 day period)
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.
Measured: 1 laboratory assessment day (an expected average of 15 day period)
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.
Measured: 1 laboratory assessment day (an expected average of 15 day period)
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.
Measured: 1 laboratory assessment day (an expected average of 15 day period)
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.
Measured: 1 laboratory assessment day (an expected average of 15 day period)
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 .
Measured: Across 2 laboratory assessment days (an expected average of 15 day period)
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.
Measured: Across 2 laboratory assessment days (an expected average of 15 day period)
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.
Measured: Across 2 laboratory assessment days (an expected average of 15 day period)
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
Measured: 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 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.
Measured: Across 2 laboratory assessment days (an expected average of 15 day period)
Mean plasma levels of endocannabinoids
Mean plasma levels of endocannabinoids
Measured: Across 3 laboratory assessment days (an expected average of 15 day period)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Mar 20227 Apr 2026

First posted2 Dec 2021
Study start2 Mar 2022
Primary completion16 Feb 2026
Study completion7 Apr 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (42)Papers the sponsor has linked to this study.
Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Model description: 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).
Masking: None (open label)
Enrolment: 101 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05142267
Sponsor's protocol ID: 210399
Other IDs: R01DA050334
Status last verified: Sep 2026
First submitted: 19 Nov 2021
Last updated: 4 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: No plan to make individual participant data (IPD) available to other researchers.

Publications

al'Absi M, France C, Harju A, France J, Wittmers L. Adrenocortical and nociceptive responses to opioid blockade in hypertension-prone men and women. Psychosom Med. 2006 Mar-Apr;68(2):292-8. doi: 10.1097/01.psy.0000203240.64965.bd.
PubMed 16554396
Altun A, Ozdemir E, Yildirim K, Gursoy S, Durmus N, Bagcivan I. The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats. Gen Physiol Biophys. 2015 Oct;34(4):433-40. doi: 10.4149/gpb_2015017.
PubMed 26374993
Altun A, Yildirim K, Ozdemir E, Bagcivan I, Gursoy S, Durmus N. Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists. J Physiol Sci. 2015 Sep;65(5):407-15. doi: 10.1007/s12576-015-0379-2. Epub 2015 Apr 18.
PubMed 25894754
Baker TB, Piper ME, McCarthy DE, Majeskie MR, Fiore MC. Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev. 2004 Jan;111(1):33-51. doi: 10.1037/0033-295X.111.1.33.
PubMed 14756584
Bedse G, Hartley ND, Neale E, Gaulden AD, Patrick TA, Kingsley PJ, Uddin MJ, Plath N, Marnett LJ, Patel S. Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety. Biol Psychiatry. 2017 Oct 1;82(7):488-499. doi: 10.1016/j.biopsych.2017.03.002. Epub 2017 Mar 15.
PubMed 28438413
Bluett RJ, Baldi R, Haymer A, Gaulden AD, Hartley ND, Parrish WP, Baechle J, Marcus DJ, Mardam-Bey R, Shonesy BC, Uddin MJ, Marnett LJ, Mackie K, Colbran RJ, Winder DG, Patel S. Endocannabinoid signalling modulates susceptibility to traumatic stress exposure. Nat Commun. 2017 Mar 28;8:14782. doi: 10.1038/ncomms14782.
PubMed 28348378
Brat GA, Agniel D, Beam A, Yorkgitis B, Bicket M, Homer M, Fox KP, Knecht DB, McMahill-Walraven CN, Palmer N, Kohane I. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study. BMJ. 2018 Jan 17;360:j5790. doi: 10.1136/bmj.j5790.
PubMed 29343479
Bruehl S, Burns JW, Chung OY, Quartana P. Anger management style and emotional reactivity to noxious stimuli among chronic pain patients and healthy controls: the role of endogenous opioids. Health Psychol. 2008 Mar;27(2):204-14. doi: 10.1037/0278-6133.27.2.204.
PubMed 18377139
Bruehl S, Burns JW, Gupta R, Buvanendran A, Chont M, Kinner E, Schuster E, Passik S, France CR. Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses. Pain. 2013 Sep;154(9):1856-1864. doi: 10.1016/j.pain.2013.06.002. Epub 2013 Jun 6.
PubMed 23748117
Bruehl S, Burns JW, Gupta R, Buvanendran A, Chont M, Schuster E, France CR. Endogenous opioid inhibition of chronic low-back pain influences degree of back pain relief after morphine administration. Reg Anesth Pain Med. 2014 Mar-Apr;39(2):120-5. doi: 10.1097/AAP.0000000000000058.
PubMed 24553304
Bruehl S, Burns JW, Morgan A, Koltyn K, Gupta R, Buvanendran A, Edwards D, Chont M, Kingsley PJ, Marnett L, Stone A, Patel S. The association between endogenous opioid function and morphine responsiveness: a moderating role for endocannabinoids. Pain. 2019 Mar;160(3):676-687. doi: 10.1097/j.pain.0000000000001447.
PubMed 30562268
Bruehl S, Burns JW, Passik SD, Gupta R, Buvanendran A, Chont M, Schuster E, Orlowska D, France CR. The Contribution of Differential Opioid Responsiveness to Identification of Opioid Risk in Chronic Pain Patients. J Pain. 2015 Jul;16(7):666-75. doi: 10.1016/j.jpain.2015.04.001. Epub 2015 Apr 16.
PubMed 25892658
Burns JW, Bruehl S, France CR, Schuster E, Orlowska D, Buvanendran A, Chont M, Gupta RK. Psychosocial factors predict opioid analgesia through endogenous opioid function. Pain. 2017 Mar;158(3):391-399. doi: 10.1097/j.pain.0000000000000768.
PubMed 27898491
Carpenter RW, Lane SP, Bruehl S, Trull TJ. Concurrent and lagged associations of prescription opioid use with pain and negative affect in the daily lives of chronic pain patients. J Consult Clin Psychol. 2019 Oct;87(10):872-886. doi: 10.1037/ccp0000402.
PubMed 31556664
Comer SD, Sullivan MA, Vosburg SK, Kowalczyk WJ, Houser J. Abuse liability of oxycodone as a function of pain and drug use history. Drug Alcohol Depend. 2010 Jun 1;109(1-3):130-8. doi: 10.1016/j.drugalcdep.2009.12.018. Epub 2010 Jan 15.
PubMed 20079977

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms
ClinicalTrials.gov ID: NCT05142267
Acronym / sponsor ID: 210399
Conditions: Opioid Use Disorder, Back Pain, Stress
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 101 participants (actual)
Lead sponsor: Vanderbilt University Medical CenterUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 2 Mar 2022 (actual)
Primary completion: 16 Feb 2026 (actual)
Study completion: 7 Apr 2026 (actual)
First posted: 2 Dec 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: 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).

Arm	Type	Receives
Adults with chronic non-cancer low back pain	Other	Drug: Placebo, Drug: Oxycodone, Drug: Naloxone

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (9 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboAlso: normal saline placeboIn 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.	Drug	Adults with chronic non-cancer low back pain
OxycodoneIn 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.	Drug	Adults with chronic non-cancer low back pain
NaloxoneAlso: narcanIn 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.	Drug	Adults with chronic non-cancer low back pain

Primary outcome

Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone condition
Time frame: Across 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 condition
Time frame: One 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)
Time frame: 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.

15 secondary outcomes

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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
Background: PubMed 16554396al'Absi M, France C, Harju A, France J, Wittmers L. Adrenocortical and nociceptive responses to opioid blockade in hypertension-prone men and women. Psychosom Med. 2006 Mar-Apr;68(2):292-8. doi: 10.1097/01.psy.0000203240.64965.bd.
Background: PubMed 26374993Altun A, Ozdemir E, Yildirim K, Gursoy S, Durmus N, Bagcivan I. The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats. Gen Physiol Biophys. 2015 Oct;34(4):433-40. doi: 10.4149/gpb_2015017.
Background: PubMed 25894754Altun A, Yildirim K, Ozdemir E, Bagcivan I, Gursoy S, Durmus N. Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists. J Physiol Sci. 2015 Sep;65(5):407-15. doi: 10.1007/s12576-015-0379-2. Epub 2015 Apr 18.
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Individual participant dataSharing planned: No. No plan to make individual participant data (IPD) available to other researchers.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephen Bruehl, PhD principal investigator

Vanderbilt University Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Oxycodone and Naloxone in people with Opioid Use Disorder and Back Pain, run by Vanderbilt University Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean change in McGill Pain Questionnaire-2 (MPQ-2) ratings of low back pain from the placebo to oxycodone condition (time frame: Across 2 laboratory assessment days (an expected average of 15 day period)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05142267, which also lists 42 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.