St. John's wort -- drug interaction  

St. John's wort (Hypericum perforatum) has been widely shown to be effective as an antidepressant. Studies of extracts standardized for hypericin (one of the herb's constituents) have found it to be about twice as effective as a placebo, and in some cases, more effective than a standard antidepressant. February 2000, British journal Lancet carried reports that research-grade (HBC Protocols) St. John's wort could potentially interfere with the effectiveness of certain life preserving medications (like the AIDS remedy Indinavir) or the immunosuppressive drug (cyclosporin) which is used to protect patients from organ rejection after heart transplantation as well as the anticoagulant (warfarin) Based on this study and other reports in the medical literature, the FDA issued a Public Health Advisory stating:

St. John's wort appears to be an inducer of an important metabolic pathway, cytochrome P450. As many prescription drugs used to treat conditions such as heart disease, depression, seizures, certain cancers or to prevent conditions such as transplant rejection or pregnancy (oral contraceptives) are metabolized via this pathway, health care providers should alert patients about these potential drug interactions to prevent loss of therapeutic effect of any drug metabolized via the cytochrome P450 pathway.

The most widely documented St. John’s wort–drug interaction has been with cyclosporine (Neoral®, Sandimmune®), a drug taken by transplant patients to fend off the immune system’s tendency to reject a transplanted organ. As blood levels of the drug decrease, the risk of organ rejection rises. The tendency for blood levels of the drug to decrease when people start taking St. John’s wort has been cited in several case reports in the medical literature, including a report totaling 45 transplant patients.

Other reports in the medical literature of St. John’s wort–drug interactions include the protease inhibitor indinavir (Crivaxin®), used to treat persons with HIV infection, as well as digoxin (Lanoxin®), warfarin (Coumadin®), theophylline (e.g., Slo-Bid®, Theo-Dur®), and birth control pills.


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While there is no consensus as to why these interactions occur, evidence appears to suggest that St. John’s wort interacts with enzymes in the liver responsible for metabolizing drugs. Known as the cytochrome P450 system, these enzymes are the body’s way of ensuring normal clearance of drugs once they’ve done their job. St. John’s wort appears to induce some of these enzymes to act a bit more quickly than normal, leading to a drop in therapeutic blood levels of some medications.

In addition to the medications previously listed, persons should discuss the use of St. John’s wort with their doctor or pharmacist if they are taking anti-anxiety drugs such as alprazolam (Xanax®), sleep medications, heart medications such as nifedipine (Procardia®, Adalat®), cortisone (internally), nonsedating antihistamines, estrogens, carbamazepine (Tegretol®), and ketoconazole (Nizoral®; internally). While there is no data to prove that St. John’s wort has interacted with these medications, each is metabolized by the part of the cytochrome P450 system with which St. John’s wort has previously been reported to interact. Thus, the potential exists for a St. John’s wort supplement to decrease blood levels of these drugs.

As is the case with drug-drug interactions, knowledge of potential herb-drug interactions is important for persons choosing to use herbal supplements. Armed with this knowledge, consumers should be able to make a more informed choice about whether to use St. John’s wort.


  1. Linde K and others. St. John's wort for depression -- an overview and meta-analysis of randomised clinical trials. British Medical Journal 313:253-258, 1996.
  2. De Smet PAGM, Nolen WA. St. John's wort as an antidepressant: Longer term studies are needed before it can be recommended in major depression British Medical Journal 313:241-242, 1996.
  3. Gaster B, Holroyd J. St. John's wort in depression Archives of Internal Medicine 160:152-156, 2000.
  4. Piscitelli SC and others. Indinavir concentrations and St John's wort. Lancet 355:547, 2000.
  5. Ruschitzka F and others. Acute heart transplant rejection due to Saint John's wort Lancet 355:548, 2000.
  6. Jobst KA and others. Safety of St John's wort. Lancet 355:576, 2000.
  7. Lumpkin MM, Alpert S. Risk of drug interactions with St. John's wort and indinavir and other drugs FDA Health Advisory, Feb 10, 2000.
  8. St. John's wort study launched. Complementary and Alternative Medicine at the NIH 4(4):5, October 1997.
  9. Good Housekeeping Institute. New Good Housekeeping Institute study finds drastic discrepancy in potencies of popular herbal supplement. News release, Consumer Safety Symposium on Dietary Supplements and Herbs, New York City, March 3, 1998.
  10. Monmaney T. Labels' potency claims often inaccurate, analysis finds. Spot check of products finds widely varying levels of key ingredient. But some firms object to testing method and defend their brands' quality. Los Angeles Times, Aug 31, 1998.

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