NIH Backs $3.7 Million Study of Higher Buprenorphine Doses in Pregnancy

Accidental drug overdose has become the leading cause of maternal death during pregnancy and in the year after childbirth in many US states, a grim statistic that underscores how urgently effective treatment for opioid use disorder is needed among expectant mothers. Now, two health services researchers are launching a major five-year investigation to determine whether pregnant women are being systematically underdosed with one of the most effective medications available for the condition, and what that shortfall costs in both human and economic terms. Dr. Jake R. Morgan of Boston University School of Public Health and Dr. Ashley A. Leech of Vanderbilt University School of Medicine have received a $3.7 million award from the National Institute on Drug Abuse to evaluate the health and economic consequences of suboptimal buprenorphine dosing among Medicaid-covered pregnant women, with the goal of guiding evidence-based dosing strategies that improve outcomes for both mothers and infants.

Buprenorphine is one of three drugs approved by the US Food and Drug Administration for long-term treatment of opioid use disorder, and it is widely regarded as among the most effective and accessible options. The medication works by reducing cravings and easing withdrawal symptoms, which in turn lowers the risk of overdose. It occupies opioid receptors in the brain in a way that blunts the euphoric effects of other opioids while preventing the physical agony of withdrawal, allowing patients to stabilize their lives and remain engaged in care. Unlike some other treatments, buprenorphine can now be prescribed in doctor’s offices and pharmacies, following a December 2025 law intended to expand access, a shift that matters enormously as fentanyl, which is up to 50 times stronger than heroin, continues to drive the opioid overdose epidemic across the United States.

Pregnancy, however, fundamentally changes how the body handles this medication. Physical and hormonal changes accelerate the metabolization of buprenorphine in pregnant patients, meaning that higher doses are often required for them to avoid withdrawal. This is not a marginal effect: data suggest that up to 90 percent of pregnant women with opioid use disorder require higher doses of the drug. The problem is compounded by the fentanyl era, since increased doses are often necessary even for people who are not pregnant to adequately counteract the potency of illicit synthetic opioids. A typical daily dose of buprenorphine administered under the tongue begins at 2 to 4 milligrams, with the standard target dosage reaching 16 to 24 milligrams, though some patients can benefit from doses up to 32 milligrams.

Despite a growing body of research supporting increased dosages as clinically needed, buprenorphine treatment during pregnancy remains inconsistent, and patients frequently receive inadequate amounts of the medication. Clinical guidelines on dosing for pregnant and postpartum patients are vague and offer little direction on dose adjustment. State Medicaid policies often go further still, capping doses in ways that are not grounded in the evidence. In some states, pregnancy guidance around buprenorphine includes language that implies dose minimization should be the goal, an approach that contradicts decades of evidence about the clinical needs of pregnant patients with opioid use disorder.

Dr. Morgan, a research assistant professor of health law, policy and management at Boston University School of Public Health, has built his career around the opioid overdose epidemic and the question of how to improve access to and retention on medications for opioid use disorder. He argues that the gap between what the evidence shows and what policy allows is both wide and consequential. Pregnant women generally metabolize drugs differently than non-pregnant individuals due to the profound physiological changes of gestation, and the failure to adjust dosing accordingly can push patients into withdrawal, a condition that carries serious risks for both mother and fetus and that frequently drives people back to illicit opioid use.

Dr. Leech, an assistant professor of health policy at Vanderbilt University School of Medicine, points to a phenomenon known as therapeutic inertia as a key driver of dangerous underdosing. In pregnancy, clinical uncertainty and concerns about fetal safety can make clinicians reluctant to increase medication doses even when the evidence supports doing so. The result is a system in which pregnant patients may be left under-treated at precisely the moment when stable, sustained treatment matters most, both for their own health and for the health of their babies. Her work focuses on how coverage decisions and policy design shape real-world treatment patterns and outcomes.

The new study will concentrate on pregnant women covered by Medicaid, a population that is central to this public health challenge. State Medicaid programs cover more than 80 percent of pregnant women with opioid use disorder in the United States, which makes Medicaid dosing policies a decisive lever in whether these patients receive adequate care. Yet many Medicaid programs cap daily dosages of buprenorphine, and some states actively discourage physicians from increasing the dosage during a patient’s pregnancy. The researchers will collaborate with investigators from Boston Medical Center to assess national and state-level differences in buprenorphine dosing between pregnant and non-pregnant women with opioid use disorder, examining how dosing patterns have evolved over time and in response to the spread of fentanyl.

Beyond documenting these patterns, the team will examine the effectiveness of different buprenorphine dosage thresholds and how those dosages advance or inhibit sustained treatment. Retention in treatment is one of the most important predictors of outcomes in opioid use disorder, since patients who discontinue medication face sharply elevated risks of relapse and overdose. Understanding whether higher doses keep pregnant patients engaged in care longer, and whether inadequate doses push them toward treatment discontinuation, could reshape clinical practice and coverage policy alike. The researchers will also estimate the long-term health and economic consequences of suboptimal dosing by applying a decision analytic model capable of projecting multiple outcomes among pregnant and postpartum women with opioid use disorder, including treatment discontinuation, postpartum treatment continuation, overdose, infant outcomes, life expectancy, and healthcare utilization, as well as the cost-effectiveness of restricting or increasing Medicaid dosing limits.

Decision analytic modeling occupies a distinctive niche in health services research because it allows investigators to quantify outcomes that would be infeasible or unethical to assess in clinical trials. As Dr. Leech explains, the approach can leverage existing evidence on dosing effects to project outcomes such as maternal and infant lives lost and the long-term costs of untreated opioid use disorder or suboptimal care, providing a rigorous method for comparing the tradeoffs of different coverage decisions. Rather than waiting years for observational data to accumulate, policymakers could use these projections to weigh the consequences of dose caps against the benefits of more generous dosing thresholds, with estimates spanning both health effects and budget impacts.

For the research team, the ultimate ambition is to translate a technical dosing question into a policy and ethical imperative. By demonstrating that higher buprenorphine dosing during pregnancy improves maternal and infant outcomes and is cost-effective, Dr. Morgan and Dr. Leech hope to give state Medicaid programs and clinical guideline writers the evidence they need to abandon dose minimization policies and embrace dosing strategies grounded in the realities of pregnancy metabolism and the fentanyl-dominated drug supply. If successful, the five-year project could help ensure that one of the most effective tools against the opioid epidemic finally works as well for pregnant women as it does for everyone else, turning a preventable source of maternal and infant harm into an opportunity for meaningful public health gains.

Subject of Research: Effectiveness and health-economic consequences of higher-dosage buprenorphine treatment for pregnant women with opioid use disorder

Article Title: Professors receive $3.7 million NIH grant to study effectiveness of higher-dosage buprenorphine among pregnant women with opioid use disorder

Article References: Professors receive $3.7 million NIH grant to study effectiveness of higher-dosage buprenorphine among pregnant women with opioid use disorder. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: buprenorphine, opioid use disorder, pregnancy, Medicaid, NIH grant, maternal health, fentanyl, health policy, decision analytic modeling, overdose prevention, Boston University, Vanderbilt University