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

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.

Timeline

Start

2022-03-02

Primary completion

2026-07-31

Completion

2026-07-31

Publications

• Background 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.
• Background 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.
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• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background Crombie KM, Brellenthin AG, Hillard CJ, Koltyn KF. Endocannabinoid and Opioid System Interactions in Exercise-Induced Hypoalgesia. Pain Med. 2018 Jan 1;19(1):118-123. doi: 10.1093/pm/pnx058.
• Background Dunne EM, Striley CW, Mannes ZL, Asken BM, Ennis N, Cottler LB. Reasons for Prescription Opioid Use While Playing in the National Football League as Risk Factors for Current Use and Misuse Among Former Players. Clin J Sport Med. 2020 Nov;30(6):544-549. doi: 10.1097/JSM.0000000000000628.
• Background Griffiths RR, Bigelow GE, Ator NA. Principles of initial experimental drug abuse liability assessment in humans. Drug Alcohol Depend. 2003 Jun 5;70(3 Suppl):S41-54. doi: 10.1016/s0376-8716(03)00098-x.
• Background Haller VL, Stevens DL, Welch SP. Modulation of opioids via protection of anandamide degradation by fatty acid amide hydrolase. Eur J Pharmacol. 2008 Dec 14;600(1-3):50-8. doi: 10.1016/j.ejphar.2008.08.005. Epub 2008 Aug 20.
• Background Hassan AN, Le Foll B, Imtiaz S, Rehm J. The effect of post-traumatic stress disorder on the risk of developing prescription opioid use disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III. Drug Alcohol Depend. 2017 Oct 1;179:260-266. doi: 10.1016/j.drugalcdep.2017.07.012. Epub 2017 Aug 8.
• Background Kavushansky A, Kritman M, Maroun M, Klein E, Richter-Levin G, Hui KS, Ben-Shachar D. beta-endorphin degradation and the individual reactivity to traumatic stress. Eur Neuropsychopharmacol. 2013 Dec;23(12):1779-88. doi: 10.1016/j.euroneuro.2012.12.003. Epub 2013 Jan 23.
• Background Koob GF, Le Moal M. Addiction and the brain antireward system. Annu Rev Psychol. 2008;59:29-53. doi: 10.1146/annurev.psych.59.103006.093548.
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• Background Lovallo WR, Acheson A, Vincent AS, Sorocco KH, Cohoon AJ. Early life adversity diminishes the cortisol response to opioid blockade in women: Studies from the Family Health Patterns project. PLoS One. 2018 Oct 12;13(10):e0205723. doi: 10.1371/journal.pone.0205723. eCollection 2018.
• Background Lovallo WR, Enoch MA, Acheson A, Cohoon AJ, Sorocco KH, Hodgkinson CA, Vincent AS, Glahn DC, Goldman D. Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G. Neuropsychopharmacology. 2015 Oct;40(11):2546-54. doi: 10.1038/npp.2015.101. Epub 2015 Apr 16.
• Background Mayo LM, Asratian A, Linde J, Holm L, Natt D, Augier G, Stensson N, Vecchiarelli HA, Balsevich G, Aukema RJ, Ghafouri B, Spagnolo PA, Lee FS, Hill MN, Heilig M. Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice. Mol Psychiatry. 2020 May;25(5):993-1005. doi: 10.1038/s41380-018-0215-1. Epub 2018 Aug 17.
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• Background McCubbin JA, Wilson JF, Bruehl S, Ibarra P, Carlson CR, Norton JA, Colclough GW. Relaxation training and opioid inhibition of blood pressure response to stress. J Consult Clin Psychol. 1996 Jun;64(3):593-601. doi: 10.1037//0022-006x.64.3.593.
• Background Morena M, Patel S, Bains JS, Hill MN. Neurobiological Interactions Between Stress and the Endocannabinoid System. Neuropsychopharmacology. 2016 Jan;41(1):80-102. doi: 10.1038/npp.2015.166. Epub 2015 Jun 12.
• Background da Fonseca Pacheco D, Klein A, de Castro Perez A, da Fonseca Pacheco CM, de Francischi JN, Duarte ID. The mu-opioid receptor agonist morphine, but not agonists at delta- or kappa-opioid receptors, induces peripheral antinociception mediated by cannabinoid receptors. Br J Pharmacol. 2008 Jul;154(5):1143-9. doi: 10.1038/bjp.2008.175. Epub 2008 May 12.
• Background Pacheco Dda F, Klein A, Perez AC, Pacheco CM, de Francischi JN, Reis GM, Duarte ID. Central antinociception induced by mu-opioid receptor agonist morphine, but not delta- or kappa-, is mediated by cannabinoid CB1 receptor. Br J Pharmacol. 2009 Sep;158(1):225-31. doi: 10.1111/j.1476-5381.2009.00310.x. Epub 2009 Jul 7.
• Background Rougemont-Bucking A, Grazioli VS, Marmet S, Daeppen JB, Lemoine M, Gmel G, Studer J. Non-medical use of prescription drugs by young men: impact of potentially traumatic events and of social-environmental stressors. Eur J Psychotraumatol. 2018 May 9;9(1):1468706. doi: 10.1080/20008198.2018.1468706. eCollection 2018.
• Background Sagar DR, Gaw AG, Okine BN, Woodhams SG, Wong A, Kendall DA, Chapman V. Dynamic regulation of the endocannabinoid system: implications for analgesia. Mol Pain. 2009 Oct 8;5:59. doi: 10.1186/1744-8069-5-59.
• Background Salio C, Fischer J, Franzoni MF, Mackie K, Kaneko T, Conrath M. CB1-cannabinoid and mu-opioid receptor co-localization on postsynaptic target in the rat dorsal horn. Neuroreport. 2001 Dec 4;12(17):3689-92. doi: 10.1097/00001756-200112040-00017.
• Background Shonesy BC, Bluett RJ, Ramikie TS, Baldi R, Hermanson DJ, Kingsley PJ, Marnett LJ, Winder DG, Colbran RJ, Patel S. Genetic disruption of 2-arachidonoylglycerol synthesis reveals a key role for endocannabinoid signaling in anxiety modulation. Cell Rep. 2014 Dec 11;9(5):1644-1653. doi: 10.1016/j.celrep.2014.11.001. Epub 2014 Nov 26.
• Background Walsh SL, Nuzzo PA, Lofwall MR, Holtman JR Jr. The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers. Drug Alcohol Depend. 2008 Dec 1;98(3):191-202. doi: 10.1016/j.drugalcdep.2008.05.007. Epub 2008 Jul 7.
• Background Welch SP. Interaction of the cannabinoid and opioid systems in the modulation of nociception. Int Rev Psychiatry. 2009 Apr;21(2):143-51. doi: 10.1080/09540260902782794.
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• Background Wightman R, Perrone J, Portelli I, Nelson L. Likeability and abuse liability of commonly prescribed opioids. J Med Toxicol. 2012 Dec;8(4):335-40. doi: 10.1007/s13181-012-0263-x.
• Background Younger JW, Lawler-Row KA, Moe KA, Kratz AL, Keenum AJ. Effects of naltrexone on repressive coping and disclosure of emotional material: a test of the opioid-peptide hypothesis of repression and hypertension. Psychosom Med. 2006 Sep-Oct;68(5):734-41. doi: 10.1097/01.psy.0000234029.38245.c9.

Drugs

Indications