St. John's Wort

Common names: St. John's wort also is known as klamath weed, John's wort, amber touch-and-heal, goatweed, rosin rose, and millepertuis.

Efficacy rating:

●●●...Positive clinical trials

Safety rating:

What is St. John's Wort?

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St. John's wort is a perennial native to Europe, but now is found throughout the US and parts of Canada. The plant is an aggressive weed found in the dry ground of roadsides, meadows, woods, and hedges. The plant has oval-shaped leaves and yields golden-yellow flowers. The petals contain black or yellow glandular dots and lines. Some say that the blooms are at their brightest coincidental with the birthday of John the Baptist (June 24). There are about 370 species in the genus Hypericum, which is derived from the Greek words, hyper and eikon meaning “over an apparition,” alluding to the plant's ancient use to ward off evil spirits. Perforatum refers to the leaf's appearance. When held up to light, the translucent leaf glands resemble perforations. Harvest of the plant for medicinal purposes must occur in July and August; the plant must be dried immediately to avoid loss of potency. The dried herb consists of the plant's flowering tops.

What is St. John's Wort used for?

This plant has been used as an herbal remedy for its anti-inflammatory and healing properties since the Middle Ages. Many noteworthy ancient herbalists, including Hippocrates and Pliny, recorded the medicinal properties of St. John's wort. It was noted for its wound-healing and diuretic properties as well as for the treatment of neuralgic conditions such as back pain. In 1633, Gerard recorded the plant's use as a balm for burns. The oil of the plant also was popular during this time. An olive oil extract of the fresh flowers that acquires a reddish color after standing in the sunlight for several weeks has been taken internally for the treatment of anxiety, but also has been applied externally to relieve inflammation and promote healing. Its topical application is believed to be particularly useful in the management of hemorrhoids. Although it often is listed as a folk treatment for cancer, there is no scientific evidence to document an antitumor effect.

Although it fell into disuse, a renewed interest in St. John's wort occurred during the past decade, and it now is a component of numerous herbal preparations for the treatment of anxiety and depression. The plant has been used in traditional medicine as an antidepressant and diuretic and for the treatment of gastritis and insomnia. Since 1995, St. John's wort has become the most prescribed antidepressant in Germany. Sales have increased from $10 million to more than $200 million in the past 8 years in the US. Since 1997, St. John's wort has been one of the leading herbal products. Estimated sales of St. John's wort worldwide total $570 million.

St. John's wort has been studied primarily for its potential antidepressant effects. There is information to show that St. John's wort is more effective than placebo. But evidence is still lacking regarding its efficacy compared to the standard antidepressants, partially because of ineffective dosing. Mechanisms of action similar to SSRIs or MAO inhibitors are seen in H. perforatum, but its clinical efficacy may be attributable to the combined contribution of several mechanisms. Hyperforin is confirmed to be a major neuroactive component of H. perforatum extracts. Hyperforin inhibits serotonin uptake by elevating free intracellular sodium, not seen with conventional SSRIs. In a clinical trial involving patients with mild-to-moderate depression, subjects given H. perforatum extract containing greater concentrations of hyperforin exhibited the largest Hamilton Rating Scale for Depression (HAMD) reduction compared with those given lower concentrations or placebo. This study confirmed that the therapeutic effects of St. John's wort depend on its hyperforin content. A meta-analysis evaluating 23 randomized clinical trials, including 1,757 mildly or moderately depressed patients, was conducted to investigate St. John's wort vs placebo and other conventional antidepressants. St. John's wort was found to be superior to placebo, with fewer side effects than with antidepressant medication. Another meta-analysis of 20 clinical trials including 1,787 patients found St. John's wort effective in treating mild to moderate depression. While some results are promising, more clinical studies need to be performed using St. John's wort for the many kinds of depression of different causes in a wide variety of populations.

St. John's wort is still in the early stages of clinical trials investigating its effects against certain viruses, including influenza virus, herpes simplex viruses, and HIV. The FDA sanctioned hypericin as an investigational new antiretroviral drug, making it eligible to be tested on humans. It is in phase1 and 2 clinical trial testing and is being developed under the name VIMRxyn.

Other suggested uses of St. John's wort include the following: wound-healing effects, anti-inflammatory and anti-ulcerogenic properties, effects on the immune system, fibromyalgia, menopausal symptoms of psychological origins, and headaches.

What is the dosage of St. John's Wort?

Traditional use of St. John's wort herb indicated 2 to 4 g/day doses. However, most clinical studies have been conducted on extracts, with hypericin content of 0.3% the earliest form of standardization. With the discovery of hyperforin's bioactivity, a content of 3% to 5% hyperforin has been used as a new standard. Some of the many products include LI 160 (Lichtwer, 0.3% hypericin), Kira (Lichtwer, 300 mcg hypericin in 125 to 225 mg extract tablets), Hyperiforce (Bioforce, 0.33 mg hypericin in 60 mg extract/tablet), Ze 117, WS 5573 (300 mg extract, 0.5% hyperforin), WS 5572 (300 mg, 5% hyperforin), STEI 300 (Steiner, 0.2% to 0.3% hypericin and 2% to 3% hyperforin), Psychotonin, Esbericum, Neuroplant, Sedariston, and Hyperforat. Doses of the extracts have ranged from 500 to 1,800 mg/day.

Is St. John's Wort safe?

See Interactions.

Documented emmenagogue (to stimulate menstrual flow) and abortive effects, uterine stimulant action. Avoid use.

St. John's wort increases the hepatic metabolism of alprazolam, indinavir, midazolam, nevirapine, nifedipine, oral contraceptives, simvastatin, tacrolimus, theophylline, and warfarin decreasing plasma concentrations of these drugs. Because St. John's wort induces intestinal P-glycoprotein, as well as intestinal (CYP3A4) and hepatic (CYP 1A2, 2C9, and 3A4) metabolism, plasma concentrations of amitriptyline, cyclosporine, digoxin, fexofenadine, methadone, nortriptyline, and sirolimus may be decreased. St. John's wort also has been implicated in resulting in additive serotonin reuptake inhibition of nefazodone and sertraline, altering the metabolism of irinotecan and increasing the sedative-hypnotic effects of paroxetine. Emergence from anesthesia may be delayed in patients who receive propofol or sevoflurane while taking St. John's wort. Patients should be cautioned that St. John's wort may interact with numerous medications and to consult their health care provider before taking St. John's wort with prescription or nonprescription drugs.

Side effects are usually mild. Potential side effects include the following: Dry mouth, dizziness, constipation, other GI symptoms, and confusion. Photosensitization also may occur. In clinical trials, side effects and medication discontinuation with St. John's wort were usually less than those observed with standard antidepressants. Other possible rare side effects include induction of mania and effects on male and female reproductive capabilities.

Due to lack of toxicity data in this area, St. John's wort is best avoided during pregnancy.

References

Copyright © 2006 Wolters Kluwer Health

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