Project summary/abstract A critically important intervention to combat the opioid overdose crisis is buprenorphine, a partial-mu opioid agonist that reduces overdose mortality by up to 70%. Buprenorphine undergoes extensive first-pass effect when taken orally, necessitating the sublingual (SL) route of administration which significantly increases bioavailability. To further maximize the absorption, patients with opioid use disorder (OUD) are instructed to wait for the medication to fully dissolve and be absorbed, which can take 5 to 10 minutes or even longer, often taken multiple times a day. Patients also remain on buprenorphine treatment for a prolonged period, often for many years. As such, the oral cavity of OUD patients may experience substantial cumulative exposure to SL buprenorphine during treatment. In 2022, the FDA warned clinicians and patients of the possibility that oral complications may arise from the use of SL buprenorphine, including tooth decay, cavities, oral infections, and tooth loss. While acknowledging the importance of buprenorphine in mitigating the risk for opioid-related adverse outcomes, the notice recommended the inclusion of such dental complications in the prescribing information, and to include strategies to maintain oral health during buprenorphine treatment. Unfortunately, the evidence-base in support of this warning is largely based on case reports/series. In addition, since individuals with OUD infrequently receive dental treatment, to what extent such dental issues arose from the direct effects of SL buprenorphine, or from factors unrelated to buprenorphine, remains unknown. To fill this need, we propose to conduct a prospective cohort study of individuals with OUD receiving either SL buprenorphine or methadone for maintenance treatment. The prevalence of oral diseases and other oral health outcomes will be assessed at enrollment, then prospectively re-assessed at 6- and 12- months. Specifically, we will assess self-reported oral health status as well as tooth enamel loss and dental caries using a portable intra-oral 3D scanner that also utilizes near infra- red imaging technology. As a secondary aim, we will conduct a qualitative study of individuals with OUD to better understand the facilitators and barriers to receiving oral health care. We will also interview OUD treatment providers and dentists to inquire about how to improve oral health care among individuals with OUD. The results from this trial will help inform the design of a clinical trial targeting modifiable risk factors in preventing and treating oral diseases among OUD patients. This innovative R21 proposal is responsive to NIDA and NIDCR programmatic goals and RFA-DE-23-015 by studying the development of oral complications among patients with OUD receiving SL buprenorphine.

Project narrative The FDA recently warned of the possibility of oral complications stemming from the use of sublingual (SL) buprenorphine, one of the most important tools in combating the opioid crisis. To rigorously evaluate the risk of oral complications among those receiving SL buprenorphine, we propose to conduct a prospective cohort study by evaluating oral health outcomes at baseline and at follow-up time points. To inform the design of a future clinical trial, we will also conduct a qualitative study of both patients and providers to better understand the facilitators and barriers to preventing and treating oral complications among individuals with OUD.