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St. John's wort was been considered to be a medicinally valuable plant for over 2000 years. The first-century Greek physicians Galen, Dioscorides, and Hippocrates recommended it as a diuretic, wound-healing herb, as a treatment for menstrual disorders, and as a cure for intestinal worms (3,5). In the sixteenth century, the Swiss herbalist Paracelsus used St. John's wort externally to treat wounds and alleviate pain (3).

The species gained a reputation during the Middle Ages as having mystical properties, and plants were collected for use as a talisman to protect one from demons and to drive away evil spirits. According to legend, the greatest effect was obtained when the plant was harvested on St. John's day (June 24th), which is often the time of peak blooming (3). The generic name Hypericum originated from the Greek name for the plant ''hyperikon.'' Literally translated, the name is an amalgamation of the root words'' hyper'' (meaning ''over'') and ''eikon'' (meaning ''image'') (3), though its meaning is less clear.

St. John's wort's use as a medicinal herb continued in Europe throughout the nineteenth and twentieth centuries. It was commonly made into teas and tinctures for treatment of anxiety, depression, insomnia, water retention, and gastritis. Externally, vegetable oil preparations have been used for treatment of hemorrhoids and inflammation. Others have used St. John's wort extracts to treat sores, cuts, minor burns, and abrasions, especially those involving nerve damage (3,6,7).

St. John's wort enjoys a worldwide reputation as having therapeutic value for treating depression and other mood disorders. Products containing St. John's wort in the form of tablets, capsules, teas, and tinctures accounted for $400 million in sales in 1998 in the United States (8) and an estimated $6 billion in Europe (8,9).

As noted by Barnes et al. (10), St. John's wort has been the subject of several pharmacopoeias and monographs, including the British Herbal Pharmacopoeia (11); European Scientific Cooperative on Phytotherapy

(ESCOP) (12); American HerbalPharmacopoea (13); Parfitt (14); Barnes et al. (15); and the European Pharmacopoeia (16).

Pharmaceutical-grade preparations of St. John's wort are typically comprised of dried aerial parts. One widely available extract that is commonly used in clinical trials, LI 160, is produced by Lichtwer Pharma. It is standardized to contain 0.3% hypericin derivatives, and normally comes in 300-mg capsules (17). A second preparation, Ze 117 (Zeller AG, Switzerland), is a 50% ethanolic extract with an herb to extract ratio of 4-7:1. The hyperforin content of Ze 117 is 0.2%, lower than that of LI 160, whose hyperforin content ranges between 1 and 4%. The dosage of Ze 117 is 500 mg/ day (18). The German Commission E and ESCOP monographs recommend 900 mg of standardized extract per day (7,12). Clinical trials using various H. perforatum preparations have typical dosages in the range of 300-1800 mg/ day (10).

In the United States, St. John's wort (like all herbal remedies) is listed as a dietary supplement by the U.S. Food and Drug Administration (FDA). Therefore, it is not subject to strict scrutiny for safety and efficacy that standard pharmaceutical drugs must pass. The FDA mandates that all herbal remedies must contain a disclaimer informing the consumer that any claims about therapeutic value have not been evaluated by that agency.

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