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St. John's wort
Hypericum perforatum

by Evelyn Leigh, HRF Editorial Director

St. John's wort achieved instant fame in the US when clinical studies confirmed its effectiveness in the treatment of mild-to-moderate depression. The news came as no surprise to herbalists, who have long used St. John's wort not only for depression, but also for the treatment of wounds, burns, injured nerves, inflammations, ulcers, anxiety, and other ailments. Today, St. John's wort is one of the most frequently used treatments for mild-to-moderate depression in Germany, and it seems destined to become just as popular in the US. The plant has also generated intense scientific interest because of its potential as an antiviral agent.

Primary uses of St. John's wort

Internal: External: Experimental:


St. John's wort has been esteemed as medicine for centuries, and ancient Europeans believed it had magical protective powers against disease and evil. Native to Europe, Asia and northern Africa, the yellow flowers are now a common midsummer sight throughout North America. St. John's wort grows particularly well in northern California and southern Oregon, where ranchers considered it a pest because it can be toxic to livestock (see Safety). Beetles released as a biological control have vastly reduced plant populations in areas of former abundance.

Health Benefits of St. John's Wort

More than twenty-eight clinical studies involving over 1,500 people have confirmed the benefits of St. John's wort in the treatment of mild-to-moderate depression. Standardized St. John's wort extract proved to be not only more effective than placebo, but just as effective as the antidepressant drugs to which it was compared - including Prozac® -without the troubling side effects. The herb has also been shown to help people with seasonal affective disorder (SAD), a common form of depression believed to be caused by lack of light during fall and winter. Recent research suggests that St. John's wort has potential in the treatment of premenstrual syndrome (PMS), obsessive compulsive disorder, and menopause symptoms.

In laboratory experiments, compounds from St. John's wort showed potent activity against a variety of viruses, including influenza, herpes, Epstein-Barr, and retroviruses such as HIV. Encouraged by these results, many people with AIDS began taking St. John's wort, reporting benefits such as a more positive outlook, more energy, and less fatigue. However, it is likely that the benefits were related to antidepressant rather than antiviral effects. More study is needed in this area.

State of Knowledge

Clinical (human) research
Laboratory research
History of use / Traditional use
Safety record
International acceptance

Stars indicate level of knowledge on a scale from 0 - 5

Research Findings

Currently, much research is devoted to identifying the compounds and actions responsible for the antidepressant effects of St. John's wort. Results of some laboratory studies suggest that the antidepressant effects are similar to those of a certain class of antidepressant drugs called MAO inhibitors, but this remains controversial. More recent research has suggested that St. John's wort may work by interfering with the way the brain utilizes a neurotransmitter (brain chemical) called serotonin. For now, researchers have concluded that the effectiveness of St. John's wort is probably due to a combination of factors.

Specific Studies:

Meta-Analysis: An analysis of 23 clinical studies involving a total of 1757 patients concluded that St. John's wort is significantly more effective than placebo and as effective as standard antidepressant medications in the treatment of mild or moderate depression. (Linde, et al. 1996).

Clinical Study: St. John's wort was as effective as fluoxetine (Prozac®) in improving symptoms of mild to moderate depression in 240 people taking part in a randomized, double-blind study. Seventy two percent of people in the fluoxetine group reported side effects, compared with 28 percent of those taking St. John's wort (Schrader, 2000).

Clinical Study: A double-blind study involving 135 patients proved St. John's wort extract to be more effective than the drug imipramine in relieving symptoms of mild-to-moderate depression (Vorbach, et al. 1994).

Clinical Study: In a double-blind study in 105 patients with mild-to-moderate depression, 67% responded favorably to treatment with St. John's wort extract, compared to only 28% of those on placebo. Significant improvements were noted in depressed mood, difficulty falling asleep, and feelings of fear (Harrer & Sommer, 1994).

Clinical Study: A trial in 20 patients with seasonal affective disorder (SAD) showed St. John's wort to be as effective as phototherapy (light therapy) in improving symptoms of depression (Martinez, et al. 1994).


St. John's wort is well tolerated by most people, and there are no reports of major side effects with recommended doses. In the clinical trials, only a few people experienced minor side effects such as mild stomach upset. However, animals grazing on large amounts of St. John's wort may develop photosensitization, an allergic reaction that occurs with exposure to sunlight. Therefore, it is recommended that people taking St. John's wort try to minimize sun exposure, especially those with fair skin. Although there have been no reports of drug interactions, taking St. John's wort in combination with antidepressant drugs is not recommended.

Recent research has suggested that St. John's wort may interact with certain drugs metabolized by the same liver enzyme system as the herb. According to the studies, St. John's wort may lower blood levels of indinavir (used to treat HIV infection), cyclosporine (used to prevent organ transplant rejection), digoxin (a heart medication) and theophylline (an asthma medication). On the other hand, another recent study showed that St. John's wort had no effect on blood levels of carbamazepine (an epilepsy drug marketed under the trade name Tegretol), and there is no evidence that St. John's wort interferes with the effectiveness of birth control pills.

Using St. John's Wort

St. John's wort extracts and oil infusions are both made from the fresh flowering tops of the herb. Hypericin is the compound in St. John's wort that gives good quality extracts and oils their characteristic vivid red color, and fresh flower buds have the highest hypericin content.

St. John's wort extracts are taken internally (for example, for depression), and the oil is for external use. Extracts are available in the form of tinctures, tablets and capsules. Most of the clinical trials on depression utilized St. John's wort extract standardized to 0.3% hypericin. (Standardization ensures that an extract contains a consistent level of a constituent, such as hypericin.) Unstandardized St. John's wort extracts have been used traditionally, but there has been little or no clinical research to assess their effectiveness.

The officially recommended usage levels, and those used in research studies are:

Important Note:

St. John's wort is considered suitable for the treatment of mild-to-moderate depression, not severe depression that interferes with the ability to function in daily life. Two to three weeks of regular use may be needed before antidepressant effects are seen.

The use of St. John's wort or other herbs is not a substitute for other medical treatment in cases of serious illness. Many conditions are not appropriate for self-diagnosis or self-medication and require the supervision of qualified health care providers. Be sure to tell your doctor about any herbs you are taking. Educate yourself and use caution when practicing self-care.

Recommended Reading

Hypericum and Depression by Harold H. Bloomfield, MD, et al. Prelude Press, 1996.

This page and all contents © 2001 by The Herb Research Foundation, Boulder, CO, USA.

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