Hypericum, drug interactions, and liver effects

by Paul Bergner

Medical Herbalism 11(2):16-20

Two articles published in the February 14 issue of The Lancet have identified potentially serious interactions between concentrated extracts of St Johnswort (Hypericum perforatum) and several drugs used in AIDS and organ transplant patients. Hypericum apparently increases the activity of the liver enzymes that metabolize and inactivate the drugs, lowering effective blood levels. In the case of the AIDS drug indinavir, hypericum standardized extracts at a dose of 300 mg three times a day lowered blood levels by 57-82%, rendering it therapeutically ineffective. In two patient with heart transplants, hypericum extracts in the same dosage reduced circulating levels of the anti-rejection drug cyclosporin to the point that both patients began to reject the transplanted heart. Hypericum had reduced circulating cyclosporin levels to approximately 50-70% of their pre-hypericum levels within two weeks.

The specific enzyme system whose activity was increased in the test subjects is the CYP3A, part of the p450 microsomal enzyme system, responsible for Phase I detoxification in the liver and also present in intestinal and kidney cells. The CYP3A subfamily is the most abundant group of p450 enzymes in the liver. Many drugs are mainly metabolized by the CYP3A enzymes, as are many fat soluble hormones, including estrogens and cortisol. Thus hypericum could have similar actions to those reported with many drugs. Depending on whether the drugs are metabolized to their active form or inactive forms by the enzymes, simultaneous consumption of hypericum extracts may either increase or decrease blood levels. Consequences could range from innocuous to fatal depending on the nature of the drug and how critical the drug dose is to the patient’s health. For the two drugs reported in Lancet present a strong hazard for patient injury because of the critical nature of the drugs, the widespread promotion of concentrated extracts of hypericum for depression, and because depression frequently accompanies AIDS and organ transplantation. The reports should prompt modern herbalist to use caution in prescribing hypericum for depression in patient receiving simultaneous pharmaceutical drug prescriptions.

The reports may also explain some traditional uses of hypericum. Older texts in European herbalism describe hypericum as a liver herb. Sebastian Kneipp; My Water Cure, for instance, states: “This medicinal herb has a particular influence on the liver; its tea is an excellent remedy for it.” Andrew Chevallier’s contemporary Encyclopedia of Medicinal Plants states that hypericum is a cholagogue and tonic for the liver and gallbladder. The liver effects of hypericum are hardly taught today, with the herbs antidepressant effects taking the spotlight after clinical trials and intensive marketing of the herb for that reason. Liver effect and antidepressant effects may in fact be related. In traditional Greek/Arabic medicine, as well as in traditional Chinese medicine, some forms of depression are considered as arising from impaired function of the liver, and the same CPY3A system that hypericum stimulates is responsible for clearing cortisol from the system. Elevated cortisol, the adrenal stress hormone, is associated with depression.

The CPY3A system is also responsible for clearing estrogen from the system, and the recent findings may explain the traditional use of hypericum for female complaints associated with hyperestrogenism. Finley Ellingwood, MD classified hypericum as a “sedative especially useful in the diseases of women” in the 1919 version of his materia medica. More recently, Malcolm Stuart said of hypericum in his Encyclopedia of Herbs and Herbalism that “Certainly when taken internally, the herb stimulates both gastric and bile secretions, and is effective for irregular menstruation.”

Some drugs metabolized by the CYP3A enzyme system

aldrin, carbamazepine, corticosteroids cyclosporine, erythromycin, indinavir, lidocaine, lovastatin, methadone, midazolam, nefedipine, quinidine,

Endogenous hormones metabolized by the CYP3A enzyme system

estradiol, estriol, testosterone, cortisol


Chevallier, Andrew. The Encyclopedia of Medicinal Plants. New York: DK Publishing, 1996

Ellingwood, Finley. American materia Medica, Therapeutics and Pharmacognosy. Portland, Oregon: Eclectic Medical Publications, 1983 [Reprint of 1919 original]

Kneipp, Sebastian. My Water Cure. 62nd Edition [translation reprint]. Pomeroy Washington: Health Research, 1972

Piscitelli, SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John’s wort. Lancet 355(9203)

Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Acute heart transplant rejection due to Saint John’s wort. Lancet 355(9203)

Stuart, Malcolm [editor]. The Encyclopedia of Herbs and Herbalism. New York: Grosset and Dunlap, 1976
  Copyright 2001 Paul Bergner          

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