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NCCIH Research Blog

New Funding Opportunities for Natural Product Drug Interaction Research: Preapplication Webinars on October 3

September 25, 2019

D. Craig Hopp, Ph.D.

D. Craig Hopp, Ph.D.

Deputy Director

Division of Extramural Research

National Center for Complementary and Integrative Health

View biographical sketch

Americans consume natural products every day either through their diet or via dietary supplements. The 2012 National Health Interview Survey estimates that 18 percent of adults in the United States use non-vitamin, non-mineral natural products as supplements. An estimated 20 to 30 percent of patients on prescription medication indicate they are also taking dietary supplements concomitantly.

In the late 1990s, reports emerged regarding severe and life-threatening interactions involving both St. John’s wort and grapefruit juice and a variety of medications. This led to widespread concerns about potential interactions with other natural products. Subsequently, numerous reports emerged describing possible interactions between large numbers of natural product–prescription medication (NP/Rx) pairings. However, the evidence for many of these purported interactions came from preclinical models and case studies or was based on purely theoretical arguments, leading to questions about their clinical relevance. While studies in human subjects are the only way to establish definitive evidence of a clinically relevant drug interaction, the justification for the investment in such a trial is often built on in vitro data.

The FDA has published guidance for industry regarding metabolism-mediated drug interaction studies that recommends using carefully designed in vitro studies to determine the mechanisms and magnitude of pharmacokinetic interactions. If those studies indicate a strong interaction, the guidance recommends additional studies in humans. Yet, much of the existing published preclinical research does not follow that guidance and therefore does not provide much meaningful data to predict NP/Rx interactions in humans.

To address this knowledge gap, in July the National Center for Complementary and Integrative Health (NCCIH) published two new requests for applications (RFAs) related to natural products research. We are excited about the potential of these initiatives—both RFAs are focused on research into the identity and mechanisms of action of natural products that can interfere with pharmacokinetics of commonly consumed medications.

One RFA is titled Preclinical Screening for Natural Product Drug Interactions (Clinical Trial Not Allowed, R21). Its application due date is November 2, 2019.

The other RFA is titled Center of Excellence for Natural Product Drug Interaction Research (U54 Clinical Trial Required). Its application due date is November 22, 2019.

NCCIH will host two technical assistance webinars to provide an overview of each of the RFAs and to address applicant questions prior to preparing and submitting applications. Participation in the webinars is optional and not required for application submission. The two webinars are listed below. You must register for each webinar separately to attend.

  • Webinar Information for RFA-AT-20-001, “Preclinical Screening for Natural Product Drug Interactions (Clinical Trial Not Allowed, R21)”
    • Date: Thursday, October 3, 2019
    • Time: 1:30 – 2:30 p.m. ET
    • Register
  • Webinar Information for RFA-AT-20-002, “Center of Excellence for Natural Product Drug interaction Research (U54 Clinical Trial Required)”
    • Date: Thursday, October 3, 2019
    • Time: 3:00 – 4:00 p.m. ET
    • Register

The Q&A portion of each webinar will address prospective applicants’ questions. Applicants are encouraged to submit their questions in advance of the webinar to: Please indicate the RFA number in the subject line of your email. If you have questions about either of the RFAs and are unable to participate in the webinar, contact me at Feel free to share this information with any other researchers you think might be interested in applying.


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