Cytochrome P450 2D6 (CYP2D6) is a liver enzyme responsible for the metabolism of approximately 30% of all drugs.

Researchers at the University of Arkansas for Medical Sciences in Little Rock studied the effect of CYP2D6 on the metabolism of several herbal supplements and the risk of drug interactions.

First, the details.

  • 6 botanical extracts were evaluated in 3 separate studies.
  • Each study included 16 healthy volunteers who were randomly assigned to receive a standardized botanical extract for 14 days on separate occasions.
  • The following herbals were studied.
    • Milk thistle (Silybum marianum)
    • Black cohosh (Cimicifuga racemosa)
    • Kava kava (Piper methysticum)
    • Goldenseal (Hydrastis canadensis)
    • St. John’s wort (Hypericum perforatum)
    • Echinacea (Echinacea purpurea)
  • The drug debrisoquine was given before and at the end of each treatment to measure changes in CYP2D6 enzyme activity.

And, the results.

  • Milk thistle, kava kava, black cohosh, echinacea, and St. John’s wort had little effect on CYP2D6.
    • They are unlikely to result in significant herb-drug-CYP2D6 interactions.
  • Goldenseal significantly inhibited CYP2D6 and may lead to significant herb-drug-CYP2D6 interactions when given with drugs metabolized by the CYP2D6 enzyme.

The bottom line?
The authors concluded, “Patients should be strongly discouraged from taking goldenseal-containing supplements concomitantly with prescription medications, especially those extensively metabolized by CYP2D6.”

Predicting who will experience a serious adverse reaction from the effects of a goldenseal-drug-CYP2D6 interaction is problematic. Some drugs are metabolized by CYP2D6, while others might be inhibitors or enhancers of the enzyme.

The outcome and severity of an interaction depend on these and other variables such as the fact that 7% of Caucasians lack CYP2D6 (as do 1% to 2% of non-Caucasians) and can’t metabolize drugs that require this enzyme. For example, if they take codeine they get none of the benefits because they can’t metabolize it to morphine, but are at risk for all of the side effects.

For anyone interested in learning more, a review of CYP2D6 in Pharmacy Times lists drugs that might be associated with an interaction. And summaries of goldenseal interactions on this blog are here.

If you’re taking one of these drugs, you might ask your pharmacist or doctor for advice. However, my experience is that the permutations are so confusing you’ll simply be told that considering the minor reasons that people take goldenseal, you’re best option is to avoid it if there’s a risk of an interaction.

To make things even more confusing, remember that CYP2D6 is just one of several enzymes that metabolizes drugs. Lack of an interaction with CYP2D6 doesn’t mean there’s no risk of an interaction that involves another liver enzyme system.

10/11/08 10:34 JR

Hi, I’m JR

John Russo, Jr., PharmD, is president of The MedCom Resource, Inc. Previously, he was senior vice president of medical communications at, a complementary and alternative medicine website.