NCCIH Research Blog

Many people who take herbal supplements also take prescription or over-the-counter medicines. Is it safe to do this? Or might the supplements and medicines interact in harmful ways? In most instances, unfortunately, the answer to these questions is “We’re not sure.”

There’s good reason for concern about possible interactions between drugs and naturally occurring substances found in dietary supplements or foods. Since the 1990s, we’ve known that two natural substances, the herb St. John’s wort and grapefruit juice, can change concentrations of many drugs in the body, leading to a clinically meaningful—sometimes even life-threatening—increase or decrease in a drug’s effects. Interactions like these are particularly important when they involve drugs with a narrow therapeutic index, such as cancer chemotherapeutic agents, the anticoagulant warfarin, and the cardiac glycoside digoxin.

Fortunately, most herbal supplements don’t seem to have St. John’s wort’s or grapefruit juice’s extreme propensity for interacting with drugs. However, we don’t have enough data to reach conclusions about interactions involving most herbs used for health purposes. Individual case reports of possible interactions have been published, but they’re difficult to interpret. Hypothetical reasons why certain drugs and herbs might interact have been proposed, based on animal experiments, cellular assays, or other indirect means, but it’s unclear whether meaningful effects are occurring in people. Good clinical evidence to distinguish the (probably few) instances when drugs and herbs interact in harmful ways from the (probably many) instances when there’s no risk of significant harm is not yet available.

An NCCIH-Supported Center for the Study of Interactions

To help fill this gap in scientific knowledge, the National Center for Complementary and Integrative Health (NCCIH) is supporting research to provide rigorous data to help consumers and health care providers make informed decisions about using drugs and herbs together. Our largest project in this area is the Center for Excellence for Natural Product–Drug Interaction Research (NaPDI), led by researchers from Washington State University, the University of Pittsburgh, and the University of North Carolina, Greensboro.

NaPDI is developing recommended approaches for assessing the clinical relevance of pharmacokinetic natural product–drug interactions, testing those approaches on selected high-priority natural products, and creating a repository for natural product–drug interaction data. You may be interested in NaPDI’s recent publications on mathematical modeling of natural product–drug interactions and on interactions involving the herb goldenseal.

Additional Research Proposals Are Welcome

Although its scope is broad, NaPDI doesn’t address all aspects of drug-herb interactions. If you have an idea for additional research in this area, NCCIH might be interested in funding your work. At the present time, we don’t have any funding opportunity announcements specifically focused on drug-herb interactions, but we can accept applications through the parent R01 (PA-20-183, PA-20-184, and PA-20-185) and parent R21 (PA-20-195 and PA-20-196) funding opportunities.

If you’re considering applying for funding for a study in this area, I strongly recommend that you discuss your proposed research with me or another member of NCCIH’s program staff before submitting your proposal. We can help you determine whether your research aims align with NCCIH’s funding priorities, discuss the most appropriate funding mechanism for your research, and clarify NCCIH’s policies on natural product integrity, human subjects research, and other key topics.

For More Information

View examples of herb-drug interaction studies funded through a recent R21 FOA

Herb-Drug Interactions Clinical Digest (July 2021)