PROJECT SUMMARY Patients with chronic pain on opioids frequently experience loneliness, which is associated with poorer health outcomes and higher risks for opioid misuse and opioid use disorder. Given that almost half of opioids are prescribed in primary care, a critical need exists for the development and testing of interventions to reduce loneliness in primary care patients at risk for opioid misuse. The long-term goal of our study is to reduce opioid misuse and opioid use disorder by addressing loneliness in primary care patients on chronic opioids. Interventions addressing maladaptive social cognition through cognitive behavioral therapy and improving social support through social navigation have been shown to be effective in reducing loneliness and improving outcomes in other fields but have not been tested in patients at risk for substance use disorder. In our study, which responds to RFA-DA-23-010 (Enhancing Social Connectedness and Ameliorating Loneliness to Prevent and Treat SUD and Support Recovery), we propose a pilot 3-arm randomized clinical effectiveness trial that will adapt and test the feasibility of implementing two efficacious interventions: (1) a psychological intervention using cognitive behavioral therapy to address maladaptive thought patterns around social connection and (2) a social navigation intervention to connect participants with social opportunities and develop supportive social networks. Our proposed study would take place in primary care practices from the Washington, Wyoming, Alaska, Montana and Idaho region Practice and Research Network, a practice-based research network of over 100 practices. Our specific aims are: (1) to refine and adapt both the social navigation and psychological loneliness interventions for primary care patients on chronic opioids by engaging patients and clinicians in a series of stakeholder group meetings, (2) to assess the feasibility of implementing a 3-arm randomized clinical effectiveness trial with 102 patients using the RE-AIM framework, and (3) to determine the distribution and variability in the mediating outcome (loneliness), the primary outcome (opioid misuse) and secondary outcomes including opioid dose, functional status and patient-reported pain at three time points -- baseline, post-intervention and 3 months post-intervention. Our study is innovative because we are testing evidence-based interventions for loneliness in patients at high risk for opioid misuse where they are already receiving care and where most patients with chronic pain receive their pain related care. We expect that, consistent with the purpose of the R34 mechanism, this project will prepare us for larger scale pragmatic trial, where we can leverage embedded or remote behavioral health professionals within a diverse set of primary care practices, that tests patient outcomes, clinic-level feasibility, and sustainability. The project is expected to have a positive impact in reducing opioid misuse and pote...