ABSTRACT The standard treatment for opioid use disorder (OUD) involves the use of medications (MOUD), primarily sublingual (SL) buprenorphine due to its accessibility, efficacy, and tolerability. However, recently the Food and Drug Administration (FDA) published an advisory suggesting SL buprenorphine use is linked to oral disease. While compelling, this advisory is based on adverse event reports and case reports that did control for important confounders such as behavioral and lifestyle factors that may increase the risk in individuals with OUD. More so, these reports were cross-sectional providing limited evidence of rate of progression and incidence of new disease. Additionally, the mechanism by which SL buprenorphine may adversely impact oral health remains unclear. The long-term goal of this project is to quantify adverse oral events associated with SL buprenorphine, facilitating implementation of interventions and practice recommendations to mitigate the burden of oral complications in adults taking SL buprenorphine. The objective of this proposal is to understand if and how SL buprenorphine increases the extent, onset, and progression of oral disease in adults with OUD. Our central hypothesis is that SL buprenorphine causes alterations in the oral environment (e.g., reduction in salivary flow/pH/buffer capacity and microbiome and inflammatory host response changes) that facilitate the incidence and progression of oral disease. We will test this hypothesis with three aims: 1) characterize baseline extent of oral complication and identify risk factors in adults receiving MOUD, 2) test whether SL buprenorphine is a risk factor for oral disease onset and progression in adults taking MOUD, and 3) assess whether SL buprenorphine changes saliva quantity, composition, microbial profile, or inflammatory host response in adults taking MOUD. To accomplish these aims, we propose a prospective, multisite, cohort study across Kentucky and North Carolina, leveraging a multidisciplinary team of researchers and clinicians to overcome the limitations identified in the literature and expand our understanding of the link between SL buprenorphine and oral disease. We will enroll 372 participants across two states that have been highly impacted by the opioid epidemic and evaluate clinical, radiographic, physiologic, and behavioral information over an 8-month follow-up period. This study is innovative as it is the first one to: conduct longitudinal follow-up, utilize a comparison MOUD group, and analyze salivary characteristics to clarify the mechanisms of sublingual buprenorphine-induced disease and will quantify the bacterial composition and inflammatory response and correlate to clinical findings. The proposed research is significant because it will generate data-driven conclusions about the risks associated with oral disease extent, onset, and progression in adults taking SL buprenorphine. These findings can be used to develop preventive interventions to reduce the burden of oral disease and improve health in this population.

NARRATIVE Sublingual (SL) buprenorphine is the most common medication used to treat opioid use disorder but FDA data suggests it may be linked to serious oral complications. While the available evidence is compelling, there is a need to develop large, controlled, longitudinal studies to assess if SL buprenorphine is a risk factor for oral disease while accounting for previous history of oral disease and other risk factors. This multidisciplinary prospective cohort study will examine if and how SL buprenorphine influences the extent, onset, and progression of oral disease in patients with opioid use disorder, and will produce data-driven conclusions that in will improve our understanding and the implementation of potential treatments to reduce the burden or oral disease in those taking SL buprenorphine.