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Description: Background: Opiate use disorder (OUD) is associated with many deaths from overdoses each year. The dysphoria that OUD individuals experience during withdrawal explains why many individuals relapse to drug use to feel “normal”. This is particularly relevant as OUD has been hypothesized to result from a weakened reward system in which more opioids are required to stimulate dopamine release due to desensitization at µ and δ opioid receptors. At the same time, there is a strengthening of “anti-reward” systems, partially mediated by the dynorphin/κ opioid system, which is associated with dysphoria during withdrawal from opiates. Methods: A systematic scoping review will be conducted following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. A comprehensive search of the following databases will be done: Ovid MEDLINE, Embase (Ovid), PsycInfo (Ovid), Cochrane, Scopus, and Web of Science. We will include preclinical and clinical studies that measured dynorphin/prodynorphin levels or KOR expression and opiate consumption, opiate withdrawal symptoms, or outcomes in animal models of opiate addiction/reward. Only in vivo studies published in the English language will be included. In vitro studies, case reports, abstracts, studies available as ‘gray literature’, reviews/meta-analyses, or non-randomized studies conducted in one group of participants will be excluded. The protocol will be submitted to The Open Science Framework (OSF). Outcomes and dissemination: We will submit the findings of the review for publication in a peer-reviewed journal. We expect that the findings will contribute to development of translational research projects that elucidate mechanisms surrounding opiate use and addiction as well as potential future interventions.