Title: Pharmacologically-based Strategies for Buprenorphine Treatment During Pregnancy Abstract This proposal will challenge several current clinical approaches to managing the pregnant woman with an opioid use disorder. Dosing of buprenorphine (BUP) in pregnant women is based on studies in non-pregnant subjects which suggests that symptoms of withdrawal occur when plasma BUP concentrations are < 1ng/ml. No such data exist for pregnant women but this is a prerequisite for defining an appropriate dosing regimen of BUP in pregnant women. We will define his threshold by monitoring women undergoing mild, medically directed withdrawal. The Clinical Opioid Withdrawal Scale score and the Finnegan score for NAS are key to defining when withdrawal occurs and thus dictate treatment in mother and baby. Neither scoring system is based on plasma BUP concentrations and thus, may not reflect true opioid withdrawal. This proposal aims to develop physiologic based scoring systems that refine the accuracy of diagnosis and optimizes treatment. The risk of NAS is assumed to be unrelated to maternal or fetal exposure to opioids leading to a generous use of opioid medications in medication-assisted treatment (MAT) programs. This assumption is based on a few small studies with conflicting results. This relationship will be explored using a maternal and baby hair, placenta , cord and meconium as predictors of chronic maternal and fetal exposure as these are unaffected by maternal truthfulness or acute dosing at the time of delivery. Contemporary thinking views medication-assisted treatment (MAT) as the best strategy for pregnant women with an opioid use disorder. This strategy is based on fetal concerns and the historically high risk of relapse with detoxification approaches. Recent data indicate that fetal risk from detoxification to be minimal if any. Guidelines for detoxification do not currently exist. In this proposal we aim to evaluate 3 components of detoxification that may impact the risk of cravings and relapse. We will assess dose reduction quantity, dose reduction frequency and dosing frequency as each may impact the success rate of detoxification. These 3 elements impact the magnitude of perturbations in plasma BUP concentrations (a measure of BUP exposure) that occur with each dose reduction and the rate of accommodation of opioid induced brain changes.