This study will elucidate the cognitive mechanisms of response to opioid agonists and antagonists used to prevent relapse in OUD through investigation of the underlying neural circuits. The study will use previously validated cognitive probes, functional Magnetic Resonance Imaging (fMRI), and extended-release injectable preparations of opioid partial agonist buprenorphine (XRBUP, Brixadi) and opioid antagonist naltrexone (XRNTX, Vivitrol), in OUD patients. Using two medications with opposing mu opioid receptor action, the study will allow a comprehensive evaluation of the mechanisms of response to relapse prevention pharmacotherapy in OUD. The study will determine the presence of treatment effects in the domains of executive function, incentive salience, and resting functional connectivity and the interaction that will indicate a difference between the two medications. The study will evaluate the ability of the brain fMRI signal to explain relapse defined by % of opioid-positive urine tests and adherence to the study interventions. The study will screen recently detoxified treatment-seeking participants with OUD who will receive 2 monthly injections of XR-NTX or XR-BUP and have weekly urine toxicology monitoring. The project will enroll 200 participants over 6 years. The proposal would be the first neural systems' level investigation of the cognitive effects of the next generation extended release preparation of buprenorphine and naltrexone to explain the individual heterogeneity of OUD treatment response and failure. This project has the potential to advance the theory and personalized treatment of OUD by elucidating the brain mechanisms of vulnerability to relapse in OUD and in SUD in general.
This project aims to elucidate the brain effects of opioid use disorder (OUD) treatments. The study will investigate the cognitive effects of extended-release preparations of a partial opioid agonist and an antagonist. To this end, the study will use up to three monthly injections of buprenorphine (XRBUP, Brixadi®) and naltrexone (XRNTX, Vivitrol®). Domain-specific brain activity will be induced by cognitive tasks and recorded with Magnetic Resonance Imaging. Participants will be imaged at baseline and in the interval between the 1st and 2nd injection and followed for up to three months.