* Treatment of mild depression with St. John's wort may be effective and is generally well tolerated.
* Data do not support its use in more severe depression.
History of Use
Medicinal properties have been ascribed to the small, woody perennial Hypericum perforatum since the time of the ancient Greek physicians Dioscorides and Galen. The medieval herbalists greatly favored it. Gerard's Herbal, a standard text first published in 1597, says, "S. John's wort with his floures and seed boyled and drunken, provoketh urine, and is right good against the stone in the bladder. The leaves stamped are good to be layd upon burnings, scaldings, and all wounds; and also for rotten and filthy ulcers."
"Wort" derives from the Old English wyrt (plant, root); some traditions hold that it was named for Sr. John because it blooms on or near St. John's Day, June 24. Others claim that reddish spots appear on the leaves on the anniversary of St. John's beheading. Still others say the plant was used as a wound treatment by the medieval crusading Knights of St. John.
St. John's wort was used as late as the mid-19th century in the United States as a diuretic, mild sedative, and as an aid in wound healing.
It remained popular in some areas of Europe as a tea for treating depression and anxiety, and in an oil preparation for external inflammation and wound healing.
Mechanisms of Action
Most St. John's wort preparations are standardized to the hypericin component. This compound has been shown to reduce 5-hydroxytryptamine (5-HT)] receptor density; weakly inhibits reuptake of 5-HT, norepinephrine, and dopamine; and binds to yaminobutyric acid (GABA) receptors.
It also has MAO inhibitor activity, but not to a clinically significant degree.
European researchers have suggested that another phytocompound, hyperforin, may be the more significant active component.
In biochemical and animal studies, the researchers wrote, hyperforin also inhibits the synaptosomal uptake of 5-HT, noradrenaline, dopamine, glutamate, and GABA (Trends Pharmacol. Sci. 22:292-97, 2001).
St. John's wort is one of the most widely studied of all herbal products. A 1996 metaanalysis identified 23 randomized trials, 20 of which were double blind, that included a total of 1,757 patients. In the 15 that were placebo controlled, St. John's wort was significantly more effective than placebo; in the 8 treatment-controlled trials, effects of the herbal extract did not differ from results seen with conventional antidepressants. These studies were heterogenous, however, using various diagnostic criteria and dosages.
Since then, large controlled clinical trials have been published. Advocates and detractors continue to disagree, but the U. …