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.

Project Narrative 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.