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Targeting Hedonic Dysregulation to Address Chronic Pain and Opioid Misuse in Primary Care

Principal Investigator (PI) / Project Lead:


Funding Organization:

National Institute of Health, National Institute on Drug Abuse

RFP / FOA Number:


Award Number:


Funding Period:

9/30/2016 – 7/31/2022

Total Funding:


Project Status:



Project Description:

A significant number of individuals with chronic pain receiving long-term opioid therapy are at risk of prescription opioid misuse – a problem for which there is no established, evidence-based treatment. Because of their effects on brain function and behavior, mindfulness interventions may be an effective means of addressing chronic pain, stress, and addiction. The objective of the proposed project is to conduct a full-scale trial of an innovative mindfulness-oriented intervention to decrease pain and opioid misuse behaviors among chronic pain patients in primary care.



Prescription opioid misuse is a public health threat that is being addressed with heightened urgency at both clinical and policy levels. In primary care settings, where chronic pain is commonly treated with long-term opioid therapy, as many as one-in-three chronic pain patients misuse opioids, evidenced by aberrant drug- related behaviors such as dose escalation or use of opioids to self-medicate negative emotions. According to a 2015 NIH-AHRQ systematic review of long-term opioid therapy for chronic pain (Chou et al., 2015), research on risk mitigation strategies for opioid misuse among chronic pain patients is virtually nonexistent. Extant therapies for opioid misuse and chronic pain may have limited efficacy because they fail to directly target the maladaptive emotion-cognition interactions and hedonic dysregulation inherent in these co-occurring problems. To meet this need, the PI developed a novel behavioral intervention, Mindfulness-Oriented Recovery Enhancement (MORE). MORE is innovative in that it aims to modify associative learning mechanisms hijacked during the allostatic process of opioid misuse by strengthening top-down cognitive control to restructure bottom-up reward learning from valuation of drug reward to natural reward – something that no other behavioral intervention for opioid misuse has been designed to do. The goal of the proposed study is to conduct a full-scale RCT of MORE to reduce aberrant drug-related behaviors and chronic pain among opioid misusing patients in primary care. Participants will be randomized to 8 weeks of MORE or a conventional support group control. Patient-reported outcomes will be assessed pre- to post-treatment and through a 9- month follow-up; this data will be triangulated through physician evaluation, urine toxicology, and medical records. Design features of this hybrid study draw upon complementary strengths of Stage II and Stage III research as defined by the NIH Stage Model (Onken et al., 2014) maximizing internal validity, intervention potency, and fidelity assurance with research therapists while maximizing external validity by administering the intervention in community clinics – the setting where the majority of chronic pain patients seek health care. The proposed project will elucidate cognitive, affective, and autonomic mechanisms mediating the therapeutic effect of MORE on aberrant drug-related behavior and pain, and will examine psychiatric and psychophysiological moderators and predictors of treatment response – including an innovative biomarker representing the relative salience of drug and natural reward. Ecological momentary assessments of pain, craving, and affective states will be correlated with opioid dosing data and therapeutic skill practice to reveal how MORE modulates symptoms and opioid misuse in everyday life. This translational research proposal from a New Investigator could significantly reshape the treatment of prescription opioid misuse among chronic pain patients by targeting top-down and bottom-up mechanisms underlying these intersecting issues and advancing evidence-based integration of behavioral health into primary care.


Publications (41, sorted by newest to oldest):

  1. Garland EL, Howard MO. Prescription opioid misusers exhibit blunted parasympathetic regulation during inhibitory control challenge. Psychopharmacology (Berl). 2021 Mar;238(3):765-774. doi: 1007/s00213-020-05729-z. Epub 2021 Jan 7. PMID: 33410988; PMCID: PMC7914222.


  1. Garland EL. Psychosocial intervention and the reward system in pain and opioid misuse: new opportunities and directions. Pain. 2020 Dec;161(12):2659-2666. doi: 1097/j.pain.0000000000001988. PMID: 33197164; PMCID: PMC7678811.


  1. Hanley AW, Garland EL. Salivary measurement and mindfulness-based modulation of prescription opioid cue-reactivity. Drug Alcohol Depend. 2020 Dec 1;217:108351. doi: 1016/j.drugalcdep.2020.108351. Epub 2020 Oct 12. PMID: 33070057; PMCID: PMC7736195.


  1. Hudak J, Hanley AW, Marchand WR, Nakamura Y, Yabko B, Garland EL. Endogenous theta stimulation during meditation predicts reduced opioid dosing following treatment with Mindfulness-Oriented Recovery Enhancement. Neuropsychopharmacology. 2021 Mar;46(4):836-843. doi: 10.1038/s41386-020-00831-4. Epub 2020 Sep 12. Erratum in: Neuropsychopharmacology. 2020 Dec 16; 46(4):836–843. doi: 1038/s41386-020-00831-4. PMID: 32919401.


  1. Garland EL, Hudak J, Hanley AW, Nakamura Y. Mindfulness-oriented recovery enhancement reduces opioid dose in primary care by strengthening autonomic regulation during meditation. Am Psychol. 2020 Sep;75(6):840-852. doi: 1037/amp0000638. PMID: 32915027; PMCID: PMC7490853.


  1. Hudak J, Prince KC, Marchand WR, Nakamura Y, Hanley AW, Bryan CJ, Froeliger B, Garland EL. The temporal dynamics of emotion dysregulation in prescription opioid misuse. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jan 10;104:110024. doi: 1016/j.pnpbp.2020.110024. Epub 2020 Jun 24. PMID: 32589895; PMCID: PMC7484236.


  1. Goldberg SB, Hanley AW, Baldwin SA, Bernstein A, Garland EL. Does mindfulness practice promote psychological functioning or is it the other way around? A daily diary study. Psychotherapy (Chic). 2020 Sep;57(3):310-322. doi: 1037/pst0000286. Epub 2020 Apr 30. PMID: 32352811; PMCID: PMC7484416.


  1. Garland EL, Atchley RM, Hanley AW, Zubieta JK, Froeliger B. Mindfulness-Oriented Recovery Enhancement remediates hedonic dysregulation in opioid users: Neural and affective evidence of target engagement. Sci Adv. 2019 Oct 16;5(10):eaax1569. doi: 1126/sciadv.aax1569. PMID: 31663023; PMCID: PMC6795512.


  1. Garland EL, Hanley AW, Riquino MR, Reese SE, Baker AK, Salas K, Yack BP, Bedford CE, Bryan MA, Atchley R, Nakamura Y, Froeliger B, Howard MO. Mindfulness-oriented recovery enhancement reduces opioid misuse risk via analgesic and positive psychological mechanisms: A randomized controlled trial. J Consult Clin Psychol. 2019 Oct;87(10):927-940. doi: 1037/ccp0000390. PMID: 31556669; PMCID: PMC6764586.


  1. Garland EL, Trøstheim M, Eikemo M, Ernst G, Leknes S. Anhedonia in chronic pain and prescription opioid misuse. Psychol Med. 2020 Sep;50(12):1977-1988. doi: 1017/S0033291719002010. Epub 2019 Aug 19. PMID: 31422776.


  1. Garland EL, Hanley AW, Kline A, Cooperman NA. Mindfulness-Oriented Recovery Enhancement reduces opioid craving among individuals with opioid use disorder and chronic pain in medication assisted treatment: Ecological momentary assessments from a stage 1 randomized controlled trial. Drug Alcohol Depend. 2019 Oct 1;203:61-65. doi: 1016/j.drugalcdep.2019.07.007. Epub 2019 Aug 5. PMID: 31404850; PMCID: PMC6939880.


  1. Hanley AW, Garland EL. Mapping the Affective Dimension of Embodiment With the Sensation Manikin: Validation Among Chronic Pain Patients and Modification by Mindfulness-Oriented Recovery Enhancement. Psychosom Med. 2019 Sep;81(7):612-621. doi: 1097/PSY.0000000000000725. PMID: 31246748.


  1. Thomas EA, Mijangos JL, Hansen PA, White S, Walker D, Reimers C, Beck AC, Garland EL. Mindfulness-Oriented Recovery Enhancement Restructures Reward Processing and Promotes Interoceptive Awareness in Overweight Cancer Survivors: Mechanistic Results From a Stage 1 Randomized Controlled Trial. Integr Cancer Ther. 2019 Jan-Dec;18:1534735419855138. doi: 1177/1534735419855138. PMID: 31165653; PMCID: PMC6552347.


  1. Garland EL, Reese SE, Bedford CE, Baker AK. Adverse childhood experiences predict autonomic indices of emotion dysregulation and negative emotional cue-elicited craving among female opioid-treated chronic pain patients. Dev Psychopathol. 2019 Aug;31(3):1101-1110. doi: 1017/S0954579419000622. Epub 2019 May 7. PMID: 31060644.


  1. Moeller SJ, Hanley AW, Garland EL. Behavioral preference for viewing drug v. pleasant images predicts current and future opioid misuse among chronic pain patients. Psychol Med. 2020 Mar;50(4):644-652. doi: 1017/S0033291719000461. Epub 2019 Apr 15. PMID: 30982480; PMCID: PMC7413318.


  1. McConnell PA, Garland EL, Zubieta JK, Newman-Norlund R, Powers S, Froeliger B. Impaired frontostriatal functional connectivity among chronic opioid using pain patients is associated with dysregulated affect. Addict Biol. 2020 Mar;25(2):e12743. doi: 1111/adb.12743. Epub 2019 Apr 4. PMID: 30945801; PMCID: PMC6776713.


  1. Garland EL, Howard MO. Enhancing Natural Reward Responsiveness Among Opioid Users Predicts Chronic Pain Relief: EEG Analyses From a Trial of Mindfulness-Oriented Recovery Enhancement. J Soc Social Work Res. 2018 Summer;9(2):285-303. doi: 1086/697685. Epub 2018 Apr 27. PMID: 30854168; PMCID: PMC6402811.


  1. Hanley AW, Garland EL. Mindfulness training disrupts Pavlovian conditioning. Physiol Behav. 2019 May 15;204:151-154. doi: 1016/j.physbeh.2019.02.028. Epub 2019 Feb 23. PMID: 30807770.


  1. Garland EL, Fredrickson BL. Positive psychological states in the arc from mindfulness to self-transcendence: extensions of the Mindfulness-to-Meaning Theory and applications to addiction and chronic pain treatment. Curr Opin Psychol. 2019 Aug;28:184-191. doi: 1016/j.copsyc.2019.01.004. Epub 2019 Jan 14. PMID: 30763873; PMCID: PMC6626690.


  1. Garland EL, Bryan MA, Priddy SE, Riquino MR, Froeliger B, Howard MO. Effects of Mindfulness-Oriented Recovery Enhancement Versus Social Support on Negative Affective Interference During Inhibitory Control Among Opioid-Treated Chronic Pain Patients: A Pilot Mechanistic Study. Ann Behav Med. 2019 Aug 29;53(10):865-876. doi: 1093/abm/kay096. PMID: 30668631; PMCID: PMC6735955.


  1. Baker AK, Garland EL. Autonomic and affective mediators of the relationship between mindfulness and opioid craving among chronic pain patients. Exp Clin Psychopharmacol. 2019 Feb;27(1):55-63. doi: 1037/pha0000225. Epub 2018 Sep 27. PMID: 30265061; PMCID: PMC6355352.


  1. Hanley AW, Nakamura Y, Garland EL. The Nondual Awareness Dimensional Assessment (NADA): New tools to assess nondual traits and states of consciousness occurring within and beyond the context of meditation. Psychol Assess. 2018 Dec;30(12):1625-1639. doi: 1037/pas0000615. Epub 2018 Jul 30. PMID: 30058824; PMCID: PMC6265073.


  1. Garland EL, Hanley AW, Bedford CE, Zubieta JK, Howard MO, Nakamura Y, Donaldson GW, Froeliger B. Reappraisal deficits promote craving and emotional distress among chronic pain patients at risk for prescription opioid misuse. J Addict Dis. 2018 Jan-Jun;37(1-2):14-22. doi: 1080/10550887.2018.1459148. Epub 2018 Jun 4. PMID: 29863439.


  1. Hanley AW, Baker AK, Garland EL. The Mindful Personality II: Exploring the Metatraits from a Cybernetic Perspective. Mindfulness (N Y). 2018 Jun;9(3):972-979. doi: 1007/s12671-017-0836-5. Epub 2017 Oct 24. PMID: 29861793; PMCID: PMC5979271.


  1. Priddy SE, Hanley AW, Riquino MR, Platt KA, Baker AK, Garland EL. Dispositional mindfulness and prescription opioid misuse among chronic pain patients: Craving and attention to positive information as mediating mechanisms. Drug Alcohol Depend. 2018 Jul 1;188:86-93. doi: 1016/j.drugalcdep.2018.03.040. Epub 2018 May 3. PMID: 29754031.


  1. Garland EL, Howard MO. Mindfulness-based treatment of addiction: current state of the field and envisioning the next wave of research. Addict Sci Clin Pract. 2018 Apr 18;13(1):14. doi: 1186/s13722-018-0115-3. PMID: 29669599; PMCID: PMC5907295.


  1. Garland EL, Bryan CJ, Kreighbaum L, Nakamura Y, Howard MO, Froeliger B. Prescription opioid misusing chronic pain patients exhibit dysregulated context-dependent associations: Investigating associative learning in addiction with the cue-primed reactivity task. Drug Alcohol Depend. 2018 Jun 1;187:13-21. doi: 1016/j.drugalcdep.2018.02.014. Epub 2018 Mar 27. PMID: 29626741.


  1. Li W, Garland EL, Howard MO. Therapeutic mechanisms of Mindfulness-Oriented Recovery Enhancement for internet gaming disorder: Reducing craving and addictive behavior by targeting cognitive processes. J Addict Dis. 2018 Jan-Jun;37(1-2):5-13. doi: 1080/10550887.2018.1442617. Epub 2018 Mar 22. PMID: 29565776.


  1. Hanley AW, Garland EL. The mindful personality: A meta-analysis from a cybernetic perspective. Mindfulness (N Y). 2017 Dec;8(6):1456-1470. doi: 1007/s12671-017-0736-8. Epub 2017 Jun 17. PMID: 29479377; PMCID: PMC5822739.


  1. Garland EL, Hanley AW, Goldin PR, Gross JJ. Testing the mindfulness-to-meaning theory: Evidence for mindful positive emotion regulation from a reanalysis of longitudinal data. PLoS One. 2017 Dec 6;12(12):e0187727. doi: 1371/journal.pone.0187727. PMID: 29211754; PMCID: PMC5718463.


  1. Hanley AW, Baker AK, Garland EL. Self-interest may not be entirely in the interest of the self: Association between selflessness, dispositional mindfulness and psychological well-being. Pers Individ Dif. 2017 Oct 15;117:166-171. doi: 1016/j.paid.2017.05.045. Epub 2017 Jun 8. PMID: 29200545; PMCID: PMC5703599.


  1. Garland EL, Hanley AW, Baker AK, Howard MO. Biobehavioral Mechanisms of Mindfulness as a Treatment for Chronic Stress: An RDoC Perspective. Chronic Stress (Thousand Oaks). 2017 Feb;1:2470547017711912. doi: 1177/2470547017711912. Epub 2017 Jun 22. PMID: 28840198; PMCID: PMC5565157.


  1. Hanley AW, Mehling WE, Garland EL. Holding the body in mind: Interoceptive awareness, dispositional mindfulness and psychological well-being. J Psychosom Res. 2017 Aug;99:13-20. doi: 1016/j.jpsychores.2017.05.014. Epub 2017 May 18. PMID: 28712417; PMCID: PMC5522814.


  1. Garland EL, Baker AK, Larsen P, Riquino MR, Priddy SE, Thomas E, Hanley AW, Galbraith P, Wanner N, Nakamura Y. Randomized Controlled Trial of Brief Mindfulness Training and Hypnotic Suggestion for Acute Pain Relief in the Hospital Setting. J Gen Intern Med. 2017 Oct;32(10):1106-1113. doi: 1007/s11606-017-4116-9. Epub 2017 Jul 12. PMID: 28702870; PMCID: PMC5602767.


  1. Hanley AW, Garland EL. Clarity of mind: Structural equation modeling of associations between dispositional mindfulness, self-concept clarity and psychological well-being. Pers Individ Dif. 2017 Feb 1;106:334-339. doi: 1016/j.paid.2016.10.028. Epub 2016 Nov 9. PMID: 28584390; PMCID: PMC5455779.


  1. Li W, Garland EL, McGovern P, O'Brien JE, Tronnier C, Howard MO. Mindfulness-oriented recovery enhancement for internet gaming disorder in U.S. adults: A stage I randomized controlled trial. Psychol Addict Behav. 2017 Jun;31(4):393-402. doi: 1037/adb0000269. Epub 2017 Apr 24. PMID: 28437120; PMCID: PMC5468481.


  1. Garland EL, Howard MO, Zubieta JK, Froeliger B. Restructuring Hedonic Dysregulation in Chronic Pain and Prescription Opioid Misuse: Effects of Mindfulness-Oriented Recovery Enhancement on Responsiveness to Drug Cues and Natural Rewards. Psychother Psychosom. 2017;86(2):111-112. doi: 1159/000453400. Epub 2017 Feb 10. PMID: 28183077; PMCID: PMC5331925.


  1. Li W, Howard MO, Garland EL, McGovern P, Lazar M. Mindfulness treatment for substance misuse: A systematic review and meta-analysis. J Subst Abuse Treat. 2017 Apr;75:62-96. doi: 1016/j.jsat.2017.01.008. Epub 2017 Jan 31. PMID: 28153483.


  1. Garland EL, Bryan CJ, Nakamura Y, Froeliger B, Howard MO. Deficits in autonomic indices of emotion regulation and reward processing associated with prescription opioid use and misuse. Psychopharmacology (Berl). 2017 Feb;234(4):621-629. doi: 1007/s00213-016-4494-4. Epub 2016 Dec 8. PMID: 27933366; PMCID: PMC5266620.


  1. Garland EL. Restructuring reward processing with Mindfulness-Oriented Recovery Enhancement: novel therapeutic mechanisms to remediate hedonic dysregulation in addiction, stress, and pain. Ann N Y Acad Sci. 2016 Jun;1373(1):25-37. doi: 1111/nyas.13034. Epub 2016 Apr 1. PMID: 27037786; PMCID: PMC4940274.


  1. Garland EL, Froeliger B, Howard MO. Neurophysiological evidence for remediation of reward processing deficits in chronic pain and opioid misuse following treatment with Mindfulness-Oriented Recovery Enhancement: exploratory ERP findings from a pilot RCT. J Behav Med. 2015 Apr;38(2):327-36. doi: 1007/s10865-014-9607-0. Epub 2014 Nov 11. PMID: 25385024; PMCID: PMC4355224.


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Last Updated: 8/3/22