Welcome back to the final segment of our three-part series on the Center of Excellence for Natural Product-Drug Interaction Research (NaPDI Center). Interactions between natural products and conventional drugs are a concern because of their potential impact on drug effectiveness or toxicity.

In case you missed Parts 1 and 2: The NaPDI Center is a multidisciplinary effort involving clinical pharmacologists, natural products chemists, and health informaticists to provide leadership in the study of these complex interactions.

This effort is being led by Mary Paine, who is a pharmaceutical sciences researcher and associate professor at the Washington State University College of Pharmacy and Pharmaceutical Sciences.

Read Part 1: expanding scientific knowledge              Read Part 2: the NaPDI Center

Public health impact

Part 3 (of 3)

The NaPDI Center is working on a set of recommended approaches that will detail the steps for studying pharmacokinetic interactions between natural products and drugs. That is, studies on how a natural product can alter the absorption, distribution, metabolism, or excretion of a drug. If a scientist wants to study natural products but needs to know how to select a natural product to study, or how to source and chemically characterize a natural product, or which in vitro assays to use, or how to run a clinical study, “We will have a recommended approach for that,” Paine said.

By providing recommended approaches that researchers can follow when setting up their studies, future studies on natural products will be more reproducible and should provide reliable, high-quality data.

“Collectively, the efforts of the NaPDI Center are expected to lead to improved design of future research and ultimately, improved decisions regarding the optimal management of clinically relevant interactions,” Paine said.

While this project is unique for natural products, it is not entirely novel. These types of recommended approaches exist and have been followed for decades in other areas. For example, the FDA guidances used in the studies of pharmacokinetic interactions between drugs (drug-drug interactions), among others, are what pharmaceutical companies follow to get new drugs approved. Paine would like to have the suite of recommended approaches available to researchers through the center’s online portal, similar to resources currently available for drug-drug interaction studies.

Outputs from the NaPDI Center surrounding interactions between natural products and drugs could contribute on multiple levels when it comes to decision making on policy, regulation, best practices, and the individual adoption and integration of natural products into the medication therapy of patients.

In the future, the NaPDI Center hopes to expand access to its online database to include health care practitioners. The center would then be both a resource for the proliferation of quality science and a functional data repository for the health care community.

The road ahead

The work is just getting started.

Sourcing natural products for clinical studies can be a major challenge for the center. One example of a natural product that is challenging to source for this purpose is kratom. Kratom is a tropical tree from which its leaves are used as an opioid substitute to treat chronic pain, manage opioid withdrawal symptoms, and even treat post-traumatic stress disorder. There is currently no evidence that kratom is effective or safe as an herbal alternative medicine, despite its known use. According to the National Institute on Drug Abuse, commercial forms of kratom are sometimes laced with other compounds that have caused deaths. While currently not an illegal substance, kratom has come under FDA scrutiny for its use as an ingredient in marketed natural products, raising uncertainty in the feasibility of conducting a clinical study.

With the center’s green tea studies concluded and goldenseal studies in progress, the NaPDI Center is setting up for the next natural product on its list, which may prove to be the most challenging yet: cannabis.

Cannabis is listed as a Schedule I controlled substance by the Drug Enforcement Administration (DEA), which in turn leads to significant barriers to studying it. The NaPDI Center is in the process of obtaining the required legal (DEA) and regulatory (FDA) approvals in order to have access to federally provided cannabis. Through existing and new collaborations with the University of Washington and Johns Hopkins University, the NaPDI Center will overcome these barriers, at least for its currently planned studies.

“The legal and regulatory hoops are substantial, but this is when we need the scientific information to be reliable,” Paine said.

In a July 2016 letter to the governors of Washington and Rhode Island regarding the regulation of cannabis, the DEA sited lack scientific knowledge that was well-controlled, reproducible and “widely available.” A short time later the DEA announced changes to its rules with the aim to expand access to cannabis for scientific study.

Reliable, high-quality data on clinical interactions between cannabis and drugs remains scarce, which makes the NaPDI Center’s recommended approaches to studying natural products an important project to complete as more and more attention gets turned toward the rigorous study of the plant. The NaPDI Center will be focused on evaluating its potential impact on the pharmacokinetics of select drugs.

This NaPDI Center project aligns with the Washington State University’s land-grant research mission to untangle complex problems to enrich quality of life for us all, specifically surrounding sustaining health. The center also contributes to the College of Pharmacy and Pharmaceutical Sciences mission to advance human health through excellence in collaborative research, and its vision to be a leader in advancing, promoting and protecting human health. Expanding scientific knowledge of the potential risks associated with natural products increases safety, which is important for people across the nation who are just trying to do what they can to live their best, healthy life.