Overview

St. John’s wort (Hypericum perforatum) has long been used in Europe for treating mood disorders and has become very popular in the United States. The plant itself is a perennial native to Europe, but it has adapted well to North America and grows as a weed in many places. (Indeed, it is sometimes called klamath weed or goatweed.)
In the Middle Ages, people noticed that the attractive bright yellow flowers of this herb appeared most profusely (or perhaps made their first appearance) around the feast of John the Baptist at the end of June.
The flowers were gathered and soaked in olive oil. The oil turned bright red after a few weeks’ time and was considered a powerful treatment for cuts and scrapes.
Many Crusaders carried “red oil” with them to use to heal the wounds of battle. The plant itself had a reputation going back to Greek and Roman times of being able to protect people against evil spells.

Active Ingredients

The parts of the plant used are the leaves and the flowering tips (flowers and buds) collected when the plant is blooming and dried quickly to preserve their potency.
Hypericin and related compounds, such as pseudohypericin, are characteristic components making up from 0.05 to 0.3 percent of the herb. Concentrations of hypericins differ with the variety of the plant and with how much of the lower leaves and stem are gathered.
St. John’s wort also contains the flavonoids kaempferol, quercitin, amentoflavone, and luteolin, and quercitin glycosides hyperoside and rutin. Together these constituents make up from 2 to 4 percent of the plant material.
Nearly 10 percent of St. John’s wort is composed of tannins, and approximately 1 percent is a volatile oil. Up to 3 percent of the herb is hyperforin, a chemical structurally similar to an active ingredient of hops. In addition, St. John’s wort contains bioflavones and small amounts of procyanidins.
Hypericin was once considered the most relevant of the active ingredients of St. John’s wort, but it now seems possible that it is little more than a marker substance. The amounts of hypericin in a product correlate well with the quantities of hyperforin, flavonoids, and procyanidins. One or more of these is probably essential to the action of the herb on the nervous system. Hyperforin also has antibiotic properties.

Uses

In Germany, where doctors often recommend herbs, St. John’s wort is prescribed more frequently than Prozac for mild to moderate depression. Many herbal authorities consider this plant especially appropriate for minimizing mood swings associated with menopause.
The antidepressant effect is well established. An overview (meta-analysis) in 1996 examined 23 studies including 1,757 patients and showed that Hypericum is more effective than placebo, with 55 percent of patients improving while taking St. John’s wort, compared to 22 percent of the control patients. The herb performed about as well as prescription antidepressants such as amitriptyline or imipramine but resulted in fewer reports of side effects. Most of this research was conducted in Europe.
To assess these results and learn more about optimal dosing and safety of long-term use, the Office of Complementary and Alternative Medicine undertook a major study in the United States.
The multicenter trial compares St. John’s wort both to placebo and to Prozac. It is not clear exactly how St. John’s wort relieves depression.
Laboratory research has shown that different components have effects on GABA receptors, serotonin, dopamine, and monoamine oxidase. No single mechanism has been isolated, and it may be that more than one pathway is important.
Hypericum extract has been reported to improve sleep, perhaps in part because it increases the brain’s output of melatonin at night. One study suggested that treatment with the herb might improve mental concentration and cognitive function in healthy people, but this claim is somewhat speculative.
St. John’s wort has both antiviral and broad-spectrum antibacterial activity in the test tube. The component hypericin is being tested to see if it can fight HIV, delaying the onset of AIDS and prolonging survival.
When applied topically, St. John’s wort has anti-inflammatory properties. This may explain why red oil was so highly prized as a treatment for wounds, burns, and hemorrhoids.
Topical application is also supposed to help treat vitiligo, a condition in which skin loses its melanin and becomes discolored in patches.
Unlike many anti-inflammatory drugs, Hypericum is reported to combat ulcers.
In folk medicine, St. John’s wort has been used to treat diarrhea. The relatively high tannin content may contribute to such an effect. It was also used for rheumatic pains, especially gout, and to deter bed-wetting.
Older antidepressants, such as imipramine, have also been used to treat bed-wetting. St. John’s wort has been reported to have immune-modulating effects, stimulating the immune response when it is low, and suppressing it in some conditions when it is overactive. Further research is needed to confirm and explore this unusual property.
Other studies are being planned to test its potential against cancer. One report suggests it may hold promise against glioblastoma, a type of brain tumor.

Dose

The accepted dose is 300 mg of extract (standardized to 0.3 percent hypericin) three times daily.
A tea may also be prepared by pouring one cup of boiling water over 1 or 2 teaspoons of dried herb and steeping five or ten minutes. One or two cups per day might be expected to supply a therapeutic level of St. John’s wort.
At least ten days to two weeks should be allowed to determine if there is any benefit from the herbal product. If it does not result in improvement of depression after four to six weeks, St. John’s wort should be stopped.
For those who find it helpful, however, there is no limitation on the amount of time it can be taken.
Three standardized products that have been tested in Germany are available here. The brand names are Kira, Movana, and Perika.

Special Precautions

As a general rule, St. John’s wort is not recommended for pregnant women. No studies evaluate its safety for the fetus, and it has been reported to increase uterine tone in animals.
Fair-skinned people and those who have reacted badly to sunlight while taking other medications may need to avoid sunshine, tanning lamps, and other sources of ultraviolet light while taking St. John’s wort. People using this herb should protect their eyes by avoiding all bright light.

Adverse Effects

Veterinary sources classify Hypericum as a toxic plant because it can induce photosensitivity reactions in livestock. Although this type of reaction is not common in humans, it can occur.
After four weeks of self-treatment, one thirty-five-year-old woman developed stinging pain in the parts of her skin exposed to sunlight. After stopping the St. John’s wort, it took two months for her to recover normal sensation in her skin. The physicians reporting this unusual response in a letter to The Lancet hypothesize that the photoactive compound hypericin released free radicals that attacked the myelin protecting the nerves of her skin.
Other people have experienced rash or unexpected sunburn while taking St. John’s wort, presumably an expression of phototoxicity. Eyes should be protected from the sun just as skin should be, since hypericin activated by visible light may damage the lens or the retina.
Side effects are generally mild and not common. Some patients have reported digestive upset.
Occasionally people develop allergic reactions to St. John’s wort and must stop using it. Very rarely, people experience fatigue or restlessness while being treated with this herb.
One side effect that has not been reported in the literature is urinary retention. We spoke with one young woman who landed in the hospital with this problem after consuming many cups of Hypericum tea. She had been told the herb would help alleviate anxiety, and she figured a flower couldn’t do her any harm.
When we spoke with her several weeks after her hospitalization, she was still recovering from the treatment that was necessary for her bladder problem. This is a single anecdote, but it does point up the need to pay attention to dosing recommendations.

Possible Interactions

St. John’s wort can reduce the effectiveness of certain birth control pills, perhaps especially the “low-dose” birth control pills that are so popular, which do not have much “margin for error.
The high tannin content of Hypericum suggests that it should not be taken at the same time as iron supplements, as it may interfere with absorption.
Because so little is known about the mechanism of action of St. John’s wort, possible interactions with prescription antidepressants can’t be ruled out. Switching between antidepressants and herbal treatment calls for medical guidance.
Physicians can find a suggested protocol for gradual substitution of St. John’s wort in Hyla Cass’s book, St. John’s Wort: Nature’s Blues Buster.
Most herbal authorities don’t think dietary restriction of high-tyramine foods is necessary.
Interactions with aged cheese similar to those seen with MAO inhibitor antidepressants such as Nardil or Parnate have not been reported.
The herbal authority Norman Farnsworth told us one anecdote that suggests that such a reaction may be possible, however. His wife, who was taking St. John’s wort, developed a headache and elevated blood pressure after eating some aged cheese.
We suggest that anyone taking St. John’s wort pay attention to symptoms that may occur after consuming high tyramine foods, such as aged cheese, pickled herring, and liver pat├ę. If blood pressure rises, he or she should probably avoid these foods in the future.
St. John’s wort can speed elimination of certain drugs from the body, which could reduce their effectiveness. This interaction has been reported with the following:

  • Digoxin (Lanoxin) for heart problems
  • Birth control pills
  • cyclosporine (a drug to suppress the immune system for organ transplant patients)
  • Indinavil (drug for HIV and AIDS)
  • Theophylline (for asthma)

Other drugs that might be expected to interact with St. John’s wort in a similar way include:

  • amiodorone (Cordorone)
  • Buspirone (BuSpar)
  • Calcium channel blockers such as Cardizem (diltiazem), Plendil (felodipine), Procardia (nifedipine) and Sular (nisoldipine)
  • carbamazipinel (Tegretol)
  • sildenafil (Viagra)
  • “statin” cholesterol-lowering drugs such as Lipitor (atorvastatin), Mevacor (lovastatin) and Zocor (simvastatin)

Doubtless, other medications will be shown to interact with St. John’s wort as more research is undertaken.
Certain medications can make a person more susceptible to sun damage. Since hypericin is a photoactive chemical, and St. John’s wort can cause phototoxicity in animals (and occasionally in people), it is unwise to take this herb in combination with other medicines or herbs that increase sensitivity to sunburn.
Along the same lines, presumably any treatment for psoriasis that requires timed exposure to UV light should not be undertaken while a person is using St. John’s wort.
One reader of “The People’s Pharmacy┬«” column related an experience suggesting that in some circumstances Hypericum may interact adversely with the cough suppressant dextromethorphan:

“Last fall I was taking St. John’s wort for fibromyalgia. I had a bad cough and started taking cough medicine. After about a day, I experienced something I never had before. I was so weak that I could not sit up. I felt dizzy, nauseated, and clammy. It took me a whole day to get over this feeling.”

We have seen no confirmed reports of this interaction, but dextromethorphan interacts dangerously with prescription antidepressants, including MAO inhibitors such as Nardil or Parnate and serotonin-based drugs such as Effexor, Paxil, Prozac, or Zoloft. St. John’s wort can prolong the time that laboratory animals sleep when given a narcotic. The significance for humans is unknown.

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