St. John's Wort

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Definition

Hypericum perforatum is the most medicinally important species of the Hypericum genus, commonly known as St. John's wort. There are as many as 400 species in the genus, which is part of the Guttiferae family. Native to Europe, St. John's wort is found throughout the world. It thrives in sunny fields, open woods, and gravelly roadsides. Early colonists brought this valuable medicinal to North America, and the plant has become naturalized in the eastern United States and California, as well as in Australia, New Zealand, eastern Asia, and South America.

The entire plant, particularly the round, black seed, exudes a slight, turpentine-like odor. The woody, branched root spreads from the base with runners that produce numerous stalks. The simple, dark green leaves are veined and grow in opposite, oblong-obvate pairs on round, branching stalks that reach 3 ft (91.4 cm) high. Tiny holes, visible when the leaf is held to the light, are actually transparent oil glands containing the chemical photo sensitizer known as hypericin. These characteristic holes inspired the species name, perforatum, Latin for perforated. The bright yellow, star-shaped flowers, often clustered in a trio, have five petals. Each blossom has many showy stamens. Black dots along the margins of the blossom contain more of the red-pigmented chemical hypericin. The herb is also useful as a dye. The flowers bloom in branching, flat-topped clusters atop the stalks in mid-summer, around the time of the summer solstice. St. John's wort, sometimes called devil's flight or grace of God, was believed to have magical properties to ward off evil spirits. It's generic name hypericum is derived from a Greek word meaning "over an apparition." The herb was traditionally gathered on mid-summer's eve, June 23. This date was later christianized as the eve of the feast day of St. John the Baptist. This folk custom gave the plant its popular name. The Anglo-Saxon word wort means medicinal herb.

— Clare Hanrahan

Dictionary: Saint John's wort  (jŏnz'wûrt', -wôrt')

Any of various herbs or shrubs of the genus Hypericum, having yellow flowers with five petals and numerous stamens that are united at the base into three to five fascicles.

[From its being gathered on Saint John's Eve to ward off evil.]

Brand names: Centrum® Herbals St. Johns Wort, Herbal Plus® Fingerprinted™ St. John's Wort, Kira™, Movana™, Oleomed™ Mood, Quanterra™ Emotional Balance

Chemical formula:

Español:
• Formas de dosificación oral de hipericina, Hypericum perforatum

St. John's Wort, Hypericum perforatum oral dosage forms

What is St. John's wort?

St. John's wort (Centrum® Herbals St. John's Wort, Hypericalm™, Kira®, Movana™, Quanterra™ Emotional Balance) is an herb or dietary supplement that is being promoted for its ability to improve mildly depressed moods. The herb does not appear to be very effective for persons with severe depression. Its yellow flowers are especially bright on June 24, the traditional birthday of St. John the Baptist, hence the name 'St. John's wort'. Other names include 'goat weed' or 'klamath weed'. This herb is not FDA approved at this time. Many different products containing St. John's wort in combination with other herbs are available.

What should I tell my health care provider before I take this medicine?

It is important for you to tell your prescriber or health care professional or other health care professional that you are using St. John's wort. Some herbs exert potent effects and may interact with other drugs you are taking.

You should discuss St. John's wort with your health care professional BEFORE taking it if you have any of these conditions:
• heart disease or high blood pressure
• heart, liver, kidney or other organ transplant
• history of emotional illness, such as anxiety, mania, or depression
• infection with the human immunodeficiency virus (HIV or AIDS)
• kidney disease
• liver disease
• stroke
• thoughts of suicide
• an unusual or allergic reaction to St. John's wort, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

This herb should be taken orally (i.e., swallowed). Follow the directions on the package labeling, or talk to your health care professional for advice. The effects of St. John's wort take several weeks to appear so it should be taken as directed for several weeks for best results.

Contact your pediatrician or health care professional regarding the use of this herb in children. Special care may be needed.

What drug(s) may interact with St. John's wort?

St. John's wort may interact with many prescription and non-prescription medications. Some of these interactions may be very important, including some that could reduce the effectiveness of your prescribed medications. You should check with your health care professional prior to taking St. John's wort if you are taking other medications. Some of the important interactions are listed:

• amiodarone
• birth control pills, injections, implants, or other female hormones
• bosentan
• caffeine
• carbamazepine
• cough syrups
• cyclosporine
• digoxin
• doxcercalciferol
• excessive intake of tyramine-containing foods (see below)
• fexofenadine
• medications for high blood pressure or heart-related health problems
• medications for depression, anxiety, difficulty sleeping, or other emotional or psychiatric problems
• medications for the treatment of cancer (chemotherapy)
• medications for the treatment of HIV infection
• paricalcitol
• red yeast rice
• sirolimus
• some medicines for high cholesterol (atorvastatin, lovastatin, simvastatin)
• some medications for pain
• tacrolimus
• temsirolimus
• theophylline
• warfarin

For many herbs, interactions with other medications are unknown. That is why you should always be careful when mixing herbal remedies with traditional medications. If you take any other medications, consult with your health care professional prior to taking St. John's wort.

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking St. John's wort?

Since St. John's wort is derived from a plant, allergic reactions are possible. Stop using this herb if you develop a rash.

Do not use St. John's wort if you are currently being treated for a mental or emotional problem such as depression or anxiety, except on the advice of your health care professional. St. John's wort may interfere with your treatments. Also do not stop your prescribed treatments without talking to your prescriber or health care professional. If you are treating yourself with St. John's wort, seek medical advice if your mood does not improve in 6—8 weeks or if you have suicidal thoughts.

You should check your blood pressure closely while taking St. John's wort if you have high blood pressure.

Until more is known about the actions of this herb, it may be advisable to limit intake of certain foods and beverages that contain tyramine. Foods that contain tyramine might produce severe headaches, a rise in blood pressure, or irregular heart beat if taken in excess with St. John's wort. Fortunately these problems have not been noted to occur frequently with St. John's wort. Examples of foods that contain significant amounts of tyramine include aged cheeses; aged, smoked, pickled, or processed meats or fish (such as bologna, pepperoni, salami, herring); beers and ales; red wines; sherry; liqueurs; figs; raisins; soy sauce; yeast/protein extracts; bean curd; fava bean pods; or any over-ripe fruit. Ask your prescriber or health care professional, pharmacist, or nutritionist for a complete listing of tyramine-containing foods and whether you should avoid them. Also, limit drinks containing caffeine, such as tea, coffee, chocolate, or cola.

Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help.

St. John's wort can increase your sensitivity to the sun and you may burn more easily, or develop stinging pain in sun-exposed areas. Always use sunscreen and protective clothing during long periods outdoors. Do not use tanning booths or sun lamps while on this herb.

Different brands of St. John's wort might contain different amounts of active ingredient so be careful to use the same brand. A standardized product is more likely to contain the same amount of herb from dose to dose. Your health care professional or pharmacist can assist you in finding a standardized product.

Inform your prescriber you are taking this herb prior to scheduling surgery. St. John's wort might interact with medications given during surgery or anesthesia. Usually the herb should be discontinued at least 2 to 3 weeks prior to any surgery. Consult your health care professional for advice.

What side effects may I notice from using St. John's wort?

Side effects that you should report to your prescriber or health care professional as soon as possible:
• confusion, forgetfulness
• difficulty staying awake or alert
• anxiety, nervousness, racing thoughts, or other mood changes
• rapid heartbeat or "palpitations"
• rash
• shortness of breath or difficulty breathing
• sunburns after being in sunlight or ultraviolet light, or "stinging pains" of sun-exposed areas

Minor side effects (report to your prescriber or health care professional if they continue or are bothersome):
Rare or less common:
• sexual difficulties
• difficulty sleeping or restlessness
More common:
• upset stomach
• drowsiness
• dry mouth

Where can I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 8 and 25 degrees C (46 and 77 degrees F); do not freeze. Throw away any unused herb after the expiration date.

GENERAL INFORMATION REGARDING DIETARY SUPPLEMENTS:
Dietary supplements include amino acids, vitamins, minerals, herbs, botanicals, and other plant-derived substances, and extracts of these substances. These products are easy to identify as they must state "Dietary Supplement" on the label. A "Supplement Facts" panel is provided on the label for most products. Supplements are not drugs and are not regulated like drugs. You should note that rigid quality control standards are not required for dietary supplements. Big differences in potency and purity of these products can occur. Scientific data to support the use of a dietary supplement for a certain disease or ailment may not be available. This product is not intended to diagnose, treat, cure or prevent any disease.

The Food and Drug Administration suggests the following to help consumers protect themselves:
• Always read product labels and follow directions.
• "Natural" doesn't mean a product is safe for humans to take.
• Look for products containing ingredients with the "USP" notation. This indicates the manufacturer followed the standards of the US Pharmacopoeia.
• Supplements produced or distributed by a nationally known food or drug company are more likely to be made under tight controls as these companies have standards in place for their other products. You can write to the company for more information about how the product was made.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Description

Hypericum perforatum is the most medicinally important species of the Hypericum genus, commonly known as St. John's wort or Klamath weed. There are as many as 400 species in the genus, which belongs to the Clusiaceae family. Native to Europe, St. John's wort is found throughout the world. It thrives in sunny fields, open woods, and gravelly roadsides. Early colonists brought this plant to North America, and it has become naturalized in the eastern United States and California, as well as in Australia, New Zealand, eastern Asia, and South America. As of 2004, St. John's wort is one of the most commonly used herbs in the United States, especially among women.

The entire plant, particularly its round black seeds, exudes a slight turpentine-like odor. The woody-branched root spreads from the base with runners that produce numerous stalks. The simple dark green leaves are veined and grow in opposite, oblong, or oval pairs on round branching stalks that reach as high as 3 ft (91.4 cm). Tiny holes, visible when the leaf is held to the light, are actually transparent oil glands containing a chemical known as hypericin. These characteristic holes inspired the species name, Perforatum, which is the Latin word for "perforated." The bright yellow star-shaped flowers, often clustered in groups of three, have five petals. Black dots along the margins of the blossom contain more hypericin. The flowers bloom in branching flat-topped clusters atop the stalks, around the time of the summer solstice. St. John's wort, sometimes called devil's flight or grace of God, was believed to contain magical properties that ward off evil spirits. Its generic name, Hypericum, is derived from a Greek word meaning "over an apparition." The herb was traditionally gathered on midsummer's eve, June 23. This date was later celebrated in the Christian Church as the eve of the feast day of St. John the Baptist. This folk custom gave the plant its popular name. The Anglo-Saxon word "wort" means "medicinal herb."

General Use

St. John's wort has been known for its medicinal properties as far back as Roman times. On the battlefield, it was a valued remedy that promoted healing from trauma and inflammation. The herb is regarded as a vulnerary, and can speed the healing of wounds, bruises, ulcers, and burns. It is also popularly used as a nervine for its calming effect, easing tension and anxiety, relieving mild depression, and soothing women's mood swings during menopause. The bittersweet herb is licensed in Germany for use in mild depression, anxiety, and sleeplessness. It is said to be helpful in nerve injury and trauma, and was used in the past to speed healing after brain surgery. Its antispasmodic properties have been thought to ease uterine cramping and menstrual difficulties. St. John's wort may also be used as an expectorant.

The hypericin in St. John's wort possesses antiviral properties that are said to be effective against certain cancers. An infusion of the plant taken as a tea has been helpful in treating bedwetting in children. The oil has been used internally to treat colic, intestinal worms, and abdominal pain. The plant's medicinal parts are its fresh leaves and flowers. This herbal remedy has been extensively tested in West Germany, and is dispensed throughout Germany as a popular medicine called Johanniskraut. Commercially prepared extracts are commonly standardized to contain 0.3% hypericin.

Clinical Studies

In contrast to early European reports made in the 1980s, more recent clinical studies tend to undermine the claims made for St. John's wort as a possible treatment for HIV infection and depression. As of 2002, health care professionals and regulatory agencies in Europe were advised to warn AIDS patients that St. John's wort decreases the effectiveness of drugs known as HIV protease inhibitors. In addition, the National Center for Complementary and Alternative Medicine (NCCAM) in the United States released the results of a large-scale multi-site study in April 2002, which reported that St. John's wort is no more effective than a placebo for treating major depression of moderate severity. The study was also published in the Journal of the American Medical Association. Additional studies being conducted in several countries are researching the interactions between St. John's wort and various types of prescription medications.

Preparations

An oil extract can be purchased commercially or prepared by combining fresh St. John's wort flowers and leaves in a glass jar with sunflower or olive oil. The container should be sealed with an airtight lid, and placed on a sunny windowsill for four to six weeks. It should be shaken daily. When the oil absorbs the red pigment, the mixture is strained through muslin or cheesecloth, and stored in a dark container. The medicinal oil maintains its potency for two years or more. The oil of St. John's wort has been known in folk culture as "Oil of Jesus." This oil forms a rub used for painful joints, varicose veins, muscle strain, arthritis, and rheumatism. Placed in a compress, it can help to heal wounds and inflammation, and relieve the pain of deep bruising.

An infusion is made by pouring one pint of boiling water over 1 oz (28 g) of dried herb, or 2 oz (57 g) of fresh, minced flower and leaf. It is steeped in a glass or enamel pot for five to 10 minutes, then strained and covered. The tea should be consumed while it is warm. A general dose is one cup, up to three times daily.

To prepare a capsule, the leaves and flowers are dried, and ground with a mortar and pestle into a fine powder. The mixture is then placed in gelatin capsules. The potency of the herb varies with the soil, climate, and harvesting conditions of the plant. A standardized extract of 0.3% hypericin extract, commercially prepared from a reputable source, is more likely to yield reliable results. Standard dosage is up to three 300 mg capsules of 0.3% standardized extract daily.

A tincture is prepared by combining one part fresh herb to three parts alcohol (50% alcohol/water solution) in a glass container. The mixture is placed in a dark place, and shaken daily for two weeks. Then it is strained through muslin or cheesecloth, and stored in a dark bottle. The tincture should maintain potency for two years. Standard dosage, unless otherwise prescribed, is 0.24–1 tsp added to 8 oz (227 g) of water, up to three times daily.

A salve can be made by warming 2 oz (57 g) of prepared oil extract in a double boiler. Once warmed, 1 oz (28 g) of grated beeswax is added and mixed until melted. The mixture is poured into a glass jar and allowed to cool. The salve can be stored for up to one year. The remedy keeps best if refrigerated after preparation. The salve is useful in treating burns, wounds, and soothing painful muscles. It is also a good skin softener. St. John's wort salve may be prepared in combination with calendula extract (Calendula officinalis) for application on bruises.

Precautions

There are a number of important precautions to observe in using St. John's wort. Pregnant or lactating women should not use the herb at all. Persons taking prescription antidepressants of any kind should not use St. John's wort at the same time, as the herb may precipitate a health crisis known as serotonin syndrome. Serotonin syndrome is potentially life-threatening, and is characterized by changes in level of consciousness, behavior, and neuromotor functioning as a result of increased levels of the neurotransmitter serotonin in the central nervous system. Drug interactions are the most common cause of serotonin syndrome. Several cases of serotonin syndrome have been reported in patients who were taking St. John's wort by itself or in combination with SSRIs, fenfluramine (Pondimin), or nefazodone (Serzone). Persons using the herb should discontinue it a minimum of two weeks prior to any surgery requiring general anesthesia, as it interacts with a number of intravenous and inhaled anesthetics.

It is also important for persons using St. John's wort to purchase the herb from a reputable source, as the quality of herbal products sold in the United States and Canada varies widely. One study of 10 popular herb samples, including St. John's wort, reported in 2003 that each herb had "a large range in label ingredients and recommended daily dose (RDD) across available products." The researchers recommended that physicians and consumers pay very close attention to labels on over the counter (OTC) herbal products.

In addition to the herb's potential risks to humans, it can be toxic to livestock. Toxic effects in cattle include reports of edema of the ears, eyelids, and the face due to photosensitization after the animal eats the herb. Exposure to sunlight activates the hypericin in the plant. Adverse effects have been reported in horses, sheep, and swine, including a staggering gait and blistering or peeling of the skin. Smaller animals, such as rabbits, suffer severe side effects from accidental ingestion of St. John's wort. The Veterinary Botanical Medicine Association (VBMA), which was founded in 2002 as an offshoot of the American Veterinary Medical Association (AVMA), offers a page on its website for reporting adverse effects of St. John's wort or any other herb in cats, dogs, or other animals.

Side Effects

When used either internally or externally, the herb may cause photodermatitis in humans with fair or sensitive skin, following exposure to sunlight or other sources of ultraviolet light. There have also been some case reports of side effects in breast-feeding women taking hypericum extract. Changes in the nutritional quality and flavor of the milk, as well as reduction or cessation of lactation, have been reported. In addition, St. John's wort has been known to cause headaches, stiff neck, nausea or vomiting, and high blood pressure in susceptible individuals.

Interactions

St. John's wort has a number of problematic interactions with many drugs. It has been reported to interact with amphetamines, asthma inhalants, decongestants, diet pills, narcotics, tryptophan and tyrosine (amino acids), as well as antidepressant medications and certain foods. It has also been reported to interfere with the effectiveness of birth control pills as well as with indinavir (Crixivan) and other AIDS medications. Moreover, anesthesiologists have reported that the herb increases bleeding time in patients under general anesthesia. Patients should always consult a mainstream health practitioner before using St. John's wort, and should discontinue taking it at least two weeks prior to major surgery.

Resources

Books

Blumenthal, Mark. The Complete German Commission E Monographs, Therapeutic Guide to Herbal Medicines. American Botanical Council, Boston: Integrative Medicine Communications, 1998.

Bown, Deni. The Herb Society of America, Encyclopedia of Herbs & Their Uses. New York: DK Publishing, Inc., 1995.

Foster, Steven, and James A. Duke. A Field Guide to Medicinal Plants. New York: Peterson Field Guides, Houghton Mifflin Company, 1990.

Hoffmann, David. The New Holistic Herbal. Massachusetts: Element Books, 1992.

McIntyre, Anne. The Medicinal Garden. New York: Henry Holt and Company Inc., 1997.

Periodicals

Deshmukh, R., and K. Franco. "Talking to Patients About St. John's Wort." Cleveland Clinic Journal of Medicine 70 (November 2003): 990.

Finfgeld, D. L. "Serotonin Syndrome and the Use of SSRIs." Journal of Psychosocial Nursing and Mental Health Services 42 (February 2004): 16–20.

Garrard, J., S. Harms, L. E. Eberly, and A. Matiak. "Variations in Product Choices of Frequently Purchased Herbs: Caveat Emptor." Archives of Internal Medicine 163 (October 27, 2003): 2290–95.

Henderson, L., Q. Y. Yue, C. Bergquist, et al. "St. John's Wort (Hypericum perforatum): Drug Interactions and Clinical Outcomes." British Journal of Clinical Pharmacology 54 (October 2002): 349–56.

Hodges, P. J., and P. C. Kam. "The Peri-Operative Implications of Herbal Medicines." Anaesthesia 57 (September 2002): 889–99.

Hypericum Depression Trial Study Group. "Effect of Hypericum perforatum (St. John's Wort) in Major Depressive Disorder: A Randomized, Controlled Trial." Journal of the American Medical Association (JAMA) 287 (April 10, 2002): 1807–14.

Pfrunder, A., M. Schiesser, S. Gerber, et al. "Interaction of St. John's Wort with Low-Dose Oral Contraceptive Therapy: A Randomized Controlled Trial." British Journal of Clinical Pharmacology 56 (December 2003): 683–90.

Steinbach, Harvey, M.D. "Serotonin Syndrome: How to Avoid, Identify, and Treat Dangerous Drug Interactions." CurrentPsychiatry Online 2 (May 2003). .

Yu, S. M., R. M. Ghandour, and Z. J. Huang. "Herbal Supplement Use Among US Women, 2000." Journal of the American Medical Women's Association 59 (Winter 2004): 17–24.

Organizations

American Botanical Council. P.O. Box 201660, Austin, TX 78720-1660.

Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857. (888) 463-6332. .

Herb Research Foundation. 1007 Pearl St., Suite 200, Boulder, CO 80302. (303) 449-2265. .

National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P. O. Box 7923, Gaithersburg, MD 20898-7923. (888) 644-6226. Fax: (866) 464-3615. .

Veterinary Botanical Medicine Association (VBMA). c/o Susan G. Wynn, DVM, 334 Knollwood lane, Woodstock, GA 30188. E-mail: s.wynn@vbma.org. .

Other

National Center for Complementary and Alternative Medicine (NCCAM) Fact Sheet. St. John's Wort and the Treatment of Depression. Bethesda, MD: NCCAM, 2002. .

National Center for Complementary and Alternative Medicine (NCCAM) press release, 9 April 2002. "Study Shows St. John's Wort Ineffective for Major Depression of Moderate Severity." .

[Article by: Clare Hanrahan; Rebecca J. Frey, PhD]

For more information on Saint-John's-wort, visit Britannica.com.

General term for the plant species Hypericum. In classical mythology, the summer solstice was a day dedicated to the sun, and was believed to be a day on which witches held their festivities. St. John's Wort was its symbolic plant. People used to judge from it whether their future would be lucky or unlucky, as it grew they read in its progressive character their future lot. This traditional lore carried over into the Christianera, when this festival period was dedicated to St. John's Wort or root. It became a talisman against evil.

In one of the old Scottish romantic ballads, a young lady falls in love with a demon, who tells her:

Gin you wish to be leman mine [my lover]
Lay aside the St. John's Wort and the vervain.

When hung up on St. John's Day, together with a cross over the door, this plant was supposed to keep out the devil and other evil spirits. To gather the root at sunrise on St. John's Day and to retain it in the house, gave luck to the family in their undertakings, especially in those begun on that day.

hypericum aethiopicum, H. perforatum.

St. John's Wort
Scientific classification
Kingdom: Plantae Division: Magnoliophyta Class: Magnoliopsida Order: Malpighiales Family: Clusiaceae Genus: Hypericum Species: H. perforatum
Binomial name
Hypericum perforatum L.

St John's wort (IPA pronunciation: General American [-wɝt], Received Pronunciation [wɜːt], rhyming with fort) used alone refers to the species Hypericum perforatum, also known as Tipton's Weed or Klamath weed, but, with qualifiers, is used to refer to any species of the genus Hypericum. Therefore, H. perforatum is sometimes called Common St. John's wort to differentiate it. The species of Hypericum have been placed by some in the family Hypericaceae, but more recently have been included in the Clusiaceae.^{[citation needed]} Approximately 370 species of the genus Hypericum exist worldwide with a native geographical distribution including temperate and subtropical regions of North America, Europe, Asia Minor, Russia, India and China.

The plant

Hypericum perforatum is a yellow-flowering, rhizomatous, perennial herb indigenous to Europe, which has been introduced to the Americas and grows wild in many meadows. The common name comes from its traditional flowering and harvesting on St John's day, 24 June. The genus name Hypericum is derived from the Greek words hyper (above) and eikon (picture), in reference to the traditional use of the plant to ward off evil, by hanging plants over a picture in the house during St John's day. The species name perforatum refers to the presence of small oil glands in the leaves that look like windows, which can be seen when they are held against the light.

Although Hypericum perforatum is grown commercially in some regions of south east Europe, it is listed as a noxious weed in more than twenty countries. In pastures, St. John’s Wort acts as both a toxic and invasive weed.^[1] It replaces useful vegetation to the extent of making productive land unviable or acts as an alien species in natural ecosystems. Ingestion by livestock can cause photosensitization, central nervous system depression, spontaneous abortion, and can lead to death. Effective herbicides for control of Hypericum include 2,4-D, picloram, and glyphosate. In western North America three beetles Chrysolina quadrigemina, Chrysolina hyperici and Agrilus hyperici have been introduced as biocontrol agents.

Identification

St. John’s Wort can be visually recognized by leaf and flower type. Yellow, five petaled flowers approximately 20 mm across occur between late Spring and early to mid Summer. Leaves exhibit obvious translucent dots when held up to the light, giving them a ‘perforated’ appearance, hence the plant's Latin name. When flowers or seed pods are crushed, a reddish/purple liquid is produced.

The translucent dots on the St. John's Wort leaves

Botanical description

St. John's wort is a perennial plant with extensive, creeping rhizomes. Its stems are erect, branched in the upper section, and can grow to 1 m high. It has opposing, stalkless, narrow, oblong leaves which are 12 mm long or slightly larger. The leaves are yellow-green in color, with transparent dots throughout the tissue and occasionally with a few black dots on the lower surface. Its flowers measure up to 2.5 cm across, have five petals, and are colored bright yellow with conspicuous black dots. The flowers appear in broad cymes at the ends of the upper branches. The sepals are pointed, with glandular dots in the tissue. There are many stamens, which are united at the base into three bundles.

Ecology

St. John’s Wort has a complex life cycle that includes a mature plant cycle with vegetative and sexual reproduction. It thrives in areas with either a winter- or summer-dominant rainfall pattern; however, distribution is restricted by temperatures too low for seed germination or seedling survival. Altitudes greater than 1500 m, rainfall less than 500 mm, and a daily mean January temperature greater than 24 degrees are considered limiting thresholds. Depending on environmental and climatic conditions, and rosette age, St. John’s Wort will alter growth form and habit to promote survival. Summer rains are particularly effective in allowing the plant to grow vegetatively, following defoliation by insects or grazing.

Hypericum poisoning (livestock)

Clinical signs

At large doses, St. John's wort is poisonous to grazing livestock (cattle, sheep, goats, horses).^[2] Behavioural signs of poisoning are general restlessness and skin irritation. Restlessness is often indicated by pawing of the ground, head shaking, head rubbing, and occasional hindlimb weakness with knuckling over, panting, confusion and depression. Mania and hyperactivity may also result including running in circles until exhausted. Observations of thick wort infestations by Australian graziers include the appearance of circular patches giving hillsides a ‘crop circle’ appearance, possibly from this phenomenon. Animals typically seek shade and have reduced appetite. Hypersensitivity to water has been noted, and convulsions may occur following a knock to the head. Although general aversion to water is noted, some may seek water for relief.

Severe skin irritation is physically apparent, with reddening of non-pigmented and unprotected areas. This subsequently leads to itch and rubbing, followed by further inflammation, exudation and scab formation. Lesions and inflammation that occur are said to resemble the conditions seen in foot and mouth disease. Sheep have been observed to have face swelling, dermatitis, and wool falling off due to rubbing. Lactating animals may cease or have reduced milk production, pregnant animals may abort. Lesions on udders are often apparent. Horses may show signs of anorexia, depression (with a comatose state), dilated pupils, and injected conjunctiva.

Early diagnosis

Increased respiration and heart rate is typically observed while one of the early signs of St. John’s wort poisoning is an abnormal increase in body temperature. Affected animals will lose weight, or fail to gain weight; young animals more affected than old animals. In severe cases death may occur, as a direct result of starvation, or because of secondary disease or septicaemia of lesions. Some affected animals may accidentally drown. Poor performance of suckling lambs (pigmented and non-pigmented) has been noted, suggesting a reduction in the milk production, or the transmission of a toxin in the milk.

Photosensitisation

Most clinical signs are caused by photosensitisation.^[3] Plants may induce either primary or secondary photosensitisation: primary photosensitisation directly from chemicals contained in ingested plants, or secondary photosensitisation from plant-associated damage to the liver. Araya and Ford (1981) explored changes in liver function and concluded there was no evidence of Hypericum-related effect on the excretory capacity of the liver, or any interference was minimal and temporary. However, at high and continuous dose rates changes in blood plasma indicative of some liver damage have been observed.

Photosensitisation causes skin inflammation by a mechanism involving a pigment or photodynamic compound, which when activated by a certain wavelength of light leads to oxidation reactions in vivo. This leads to lesions of tissue, particularly noticeable on and around parts of skin exposed to light. Lightly covered or poorly pigmented areas are most conspicuous. Removal of affected animals from sunlight results in reduced symptoms of poisoning.

Medicinal uses of the herb

The first recorded use of Hypericum for medicinal purposes dates back to ancient Greece, and it has been used ever since. Hypericum was also used by Native Americans internally as an abortifacient and externally as an anti-inflammatory, astringent, and antiseptic. The aerial parts of the plant can be cut and dried for later use in the form of herbal tea, which has long been enjoyed both for its pleasant, though somewhat bitter, taste and for its medicinal properties.

In modern medicine, standardized Hypericum extract (obtained from H. perforatum) is commonly used as a treatment for depression and anxiety disorders. In homeopathy, Hypericum is used in the treatment of numerous medical problems, yet the rate of success has not been adequately documented. Historically, the flowers and stems of St John's wort have also been used to produce red and yellow dyes.

St John's wort is today most widely known as a herbal treatment for depression. In some countries, such as Germany, Hypericum is prescribed for mild depression far more commonly than synthetic antidepressant medication.^[4] In most countries, standardized extracts are available over the counter – usually in tablet or capsule form, and also in teabags and tinctures.

St. John's wort may also decrease alcohol intake. Researchers at the UK Bradford School of Pharmacy discovered that hyperforin, (found in the plant), appears to be the reason why.^[5]

Clinical evidence

Seedlings of St. John's wort

Clinical studies of St John's wort preparations have mainly focused on the efficacy of the herb in clinical depression. Several studies and meta-analyses have found it to be effective in the treatment of mild to moderate depression, with fewer side effects than many conventional antidepressants. Other studies, including a major NIH study that focused on moderate to severe depression, have shown no improvements.^[6]

Evidence for efficacy

An early meta-study indicated that extracts of Hypericum may be more efficacious than placebo for the treatment of mild to moderately severe depressive disorders.^[7] This study, which covered the results from 23 smaller, earlier studies, is perhaps the most often cited by manufacturers and other supporters of St. John's wort.

This study was later updated to include further studies, for a total of 27, to form a Cochrane Review. The updated review found that Hypericum preparations were significantly superior to placebo (rate ratio 2.47; 95% confidence interval 1.69 to 3.61) and similarly effective as standard antidepressants (single preparations 1.01; 0.87 to 1.16, combinations 1.52; 0.78 to 2.94).^[8]

Another meta-analysis, with stricter inclusion criteria, found that Hypericum was more efficacious than placebo; and as efficacious as tricyclic antidepressants, with fewer adverse drug reactions.^[9] This meta-analysis showed that the response rate for St. John’s wort was significantly greater than that for placebo (73.2 versus 37.9%, respectively, relative risk 1.48 and 95% CI 1.03–1.92) and similar to that observed with tricyclic antidepressants (64 versus 66.4% for St. John’s wort and tricyclic antidepressants, respectively, relative risk 1.11 and 95% CI 0.92–1.29).

Other, more recent trials have also shown greater efficacy than placebo, and comparable efficacy to standard antidepressants with a superior adverse effect profile.^{[10][11][12][13][14][15][16]}

Additionally, a 2006 study involving 150 patients with minor depressive symptoms or dysthymia found that St. John's Wort has a clinically significant effect in patients with minor depression, but not those suffering from dysthymia. It was concluded that St. John's Wort can be effective in the treatment of people with minor depression with a Hamilton Depression Scale for Depression (HAM-D) score of up to 17.^[17]

Evidence against efficacy for Major Depressive Disorder

A major study funded by the NIH in the United States failed to find any evidence that Hypericum extract of St John's wort was effective in treating moderate to severe cases of major depression (Hypericum Depression Trial Study Group, 2002). This study involved 340 patients, diagnosed with Major Depressive Disorder based on DSM-IV criteria and assessed using Hamilton Depression Rating Scale (HAM-D) and Clinical Global Impression (CGI) scores. The trial was a multi-centre randomised double-blind placebo-controlled trial, comparing one preparation of St John's wort (Li 160) to the antidepressant sertraline, and to placebo. No statisticallly significant effect was garnered from Li 160. Sertraline was also no better than placebo in this study, based on the primary outcome measure (the HAM-D).^[18] hsbn

Pharmacology

The exact mechanism by which St. John's wort — and even conventional antidepressants — functions is unclear and subject to conjecture.

The St. John's wort mechanism is believed to involve inhibition of serotonin (5-HT) reuptake, much like the conventional selective serotonin reuptake inhibitor (SSRI) antidepressants. It may thus be useful to review that information before using, particularly the complications. The link to the Prozac Product/Prescribing Information is provided below.

The major active constituents in St John's wort are thought to be hyperforin and hypericin, although other biologically active constituents present, for example, flavonoids and tannins, may also be involved.^[19]

Hyperforin has also been found to have excellent antibacterial properties; in ultrapurified form a concentration of 0.1 mg/ml kills methicillin-resistant forms of Staphylococcus aureus (MRSA).^[20]

Some believe that hyperforin is the major constituent responsible for antidepressant activity, and it has been shown to inhibit the uptake of 5-HT, dopamine, noradrenaline, GABA and glutamate.^[21] Also, a hyperforin free extract of St John's wort (Ze 117 - Remotiv) has been shown to have significant antidepressive effects.^[10][11] Therefore current thinking is that the whole extract should be considered the "active ingredient" and that one or two constituents cannot explain the activity of the product.^{[citation needed]}

Dosage and formulations

The dosage and content of St John's wort preparations vary greatly between formulations, because of variability in the plant source and preparation processes. The doses of St. John’s wort extract used in clinical trials generally range from 350 to 1800 mg daily (equivalent to 0.4 to 2.7 mg hypericin depending on the preparation).^[8] Because of the variable nature of herbal medicines, the clinical trial results using one product cannot be extrapolated to other products containing the same herb (just as a prize winning wine is not the same as everything else made from grapes). Only a handful of products made from St John's wort have been used in clinical studies (for example, Li 160 and Ze 117).

The recommended dosage for various forms of St John's wort as recommended by the British Herbal Medicine Association Scientific Committee (1983)^{[citation needed]} are as follows:

• dried herb: 2-4 g or by infusion three times daily
• liquid extract 2-4 mL (1:1 in 25% alcohol) three times daily
• tincture 2-4mL (1:10 in 45% alcohol) three times daily

In markets where standardised extracts are not available, the content of marketed products can vary widely. Some brands of over-the-counter St. John's wort can have a totally different chemical profile than others. The same can even be true of two dosage units from different batches of the same brand. Even where extracts are standardised it is debatable whether using hypericin as the standard is useful, since other constituents including hyperforin are biologically active.

As with other antidepressants, Hypericum should be taken for at least four weeks before its effectiveness can be properly assessed.

Adverse effects

St John's wort is generally well tolerated, with an adverse effect profile similar to placebo.^[22] The most common adverse effects reported are gastrointestinal symptoms, dizziness, confusion, tiredness and sedation.^[23]

Since the St. John's wort mechanism is probably inhibition of Serotonin (5-HT) reuptake, much like the conventional SSRI antidepressants, it may be useful to review that information before using, particularly the complications. The link to the PROZAC Product Information is provided below.

St John's wort may rarely cause photosensitivity. This can lead to visual sensitivity to light and to sunburns in situations that would not normally cause them.^[22]

Some research shows that St John's wort may adversely affect fertility in both men and women.^[24]

St. John's wort may interact with birth control pills and may reduce the effectiveness of oral contraceptives. However, while breakthrough bleeding was observed to occur in the Swedish MPA study (the sample size of 8 women was small enough that the effect could not be differentiated from common breakthrough bleeding) no cases of pregnancy due to St. John's wort have been found in the literature despite over 20 years of widespread prescription in Germany,^[25][26][27]

St. John's Wort has been known to instigate mania in bipolar patients and for these people it should be used with caution, just as with any anti-depressant.^[28][29]

Use caution when discontinuing use.

Drug interactions

Pharmacokinetic interactions

St John's wort has been shown to cause multiple drug interactions mainly through induction of the cytochrome P450 enzyme CYP3A4, but also CYP2C9. This results in the increased metabolism of those drugs, resulting in decreased concentration and clinical effect. The principal constituent thought to be responsible is hyperforin. For further updating on interactions and appropriate management, see http://www.herbological.com/images/SJW_table.pdf

Examples of drugs causing clinically-significant interactions with St John's Wort

Class	Drugs
antiepileptics	carbamazepine, phenytoin
antiretrovirals	non-nucleoside reverse transcriptase inhibitors, protease inhibitors
benzodiazepines	alprazolam, midazolam
hormonal contraception	combined oral contraceptives
immunosuppressants	calcineurin inhibitors, ciclosporin, tacrolimus
others	digoxin, methadone, omeprazole, phenobarbitone, theophylline, warfarin, levodopa
Reference: Rossi, 2005

Pharmacodynamic interactions

St John's Wort may also contribute to serotonin syndrome in combination with other drugs which may elevate 5-HT (serotonin) levels in the central nervous system (CNS).^[30]

Drugs which may contribute to serotonin syndrome with St John's Wort

Class	Drugs
antidepressants	MAOIs, TCAs, SSRIs, mirtazapine, venlafaxine
opioids	tramadol, pethidine
CNS stimulants	phentermine, diethylpropion, amphetamines, sibutramine
5-HT1 agonists	triptans
illicit drugs	methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), cocaine
others	selegiline, tryptophan, buspirone, lithium, linezolid, dextromethorphan, 5-HTP
Reference: Rossi, 2005

References

1. ^ http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm
2. ^ http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm
3. ^ http://www.northwestweeds.nsw.gov.au/st_johns_wort.htm#effect_on_animals
4. ^ Fegert J, Kölch M, Zito J, Gaeske G, Janhsen K (2006). Antidepressant Use in Children and Adolescents in Germany. Journal of Child and Adolescent Psychopharmacology 16, 197-206.
5. ^ http://altmedicine.about.com/od/herbsupplementguide/a/herbs_alcohol.htm
6. ^ Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. Journal of the American Medical Association. 2002;287(14):1807–1814.
7. ^ Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D (1996). St John’s wort for depression – an overview and meta-analysis of randomised clinical trials. Br Med J 313, 253–258.
8. ^ ^{a b} Linde K, Mulrow CD (2003). St John's wort for depression (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.
9. ^ Kim HL, Streltzer J, Goebert D (1999). St. John's Wort for Depression: A Meta-Analysis of Well-Defined Clinical Trials. J Ment Nerv Dis 187 (9), 532-538.
10. ^ ^{a b} Woelk H, et al. (2000). Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. Br Med J 321, 536-9.
11. ^ ^{a b} Schrader E, et al. (2000). Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomised, controlled study in mild-moderate depression. Int Clin Psychopharmacology 15, 61-68.
12. ^ Laakmann G, Schule C, Baghai T, Kieser M (1998). St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 31 (Suppl 1), 54-9.
13. ^ Harrer G, Schmidt U, Kuhn U, Biller A (1999). Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. Arzneimittelforschung 49 (4), 289-96.
14. ^ Philipp M, Kohnen R, Hiller KO (1999). Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. Br Med J 319 (7224), 1534-8.
15. ^ Szegedi A, Kohnen R, Dienel A, Kieser M (2005). "Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine". BMJ 330 (7490): 503–506. 
16. ^ Lecrubier et al. "Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial." Am J Psychiatry. 2002 Aug;159(8):1361-6. PMID 12153829
17. ^ C. Randløv, J. Mehlsen, C.F. Thomsen, C. Hedman, H. von Fircks and K. Winther. "The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia - a double-blind placebo-controlled study" Phytomedicine. 2006 March; 13(4): 215–221. PMID 16423519.
18. ^ Hypericum Depression Trial Study Group (2002). Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder. JAMA 287 (14), 1807-1814. PMID 11939866
19. ^ Nahrstedt A, Butterweck V (1997). Biologically active and other chemical constituents of the herb of Hypericum perforatum L. Pharmacopsychiatry 30 (Suppl 2), 129-34.
20. ^ wissenschaft-online.de (in German)
21. ^ Chatterjee SS, Bhattacharya SK, Wonnemann M, Erdelmeier C (1998b). Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility. Pharmacopsychiatry 31 (Suppl 1), 7-15.
22. ^ ^{a b} Ernst E, Rand JI, Barnes J, Stevinson C (1998). Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 54 (8), 589-94.
23. ^ Barnes J, Anderson LA, Phillipson JD (2002). Herbal Medicines: A guide for healthcare professionals (2 ed.) London: Pharmaceutical Press. ISBN 0-85369-474-5.
24. ^ Stahl, SM (2000). Essential psychopharmacology: neuroscientific basis and practical applications, Cambridge: Cambridge University Press, 2nd ed, page 266.
25. ^ http://www.herbological.com/images/downloads/SJW.pdf
26. ^ Pfrunder, Arabelle; Monika Schiesser, Simone Gerber, Manuel Haschke, Johannes Bitzer, Juergen Drewe (December 2003). "Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial". British Journal of Clinical Pharmacology 56 (6): 683-690. DOI:10.1046/j.1365-2125.2003.02005.x. Retrieved on February 3, 2007. 
27. ^ Schwarz, Ute I.; Barbara Büschel, W. Kirch (January 2003). "Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception". British Journal of Clinical Pharmacology 55 (1): 112-113. DOI:10.1046/j.1365-2125.2003.01716.x. Retrieved on February 3, 2007. 
28. ^ http://bipolar.about.com/cs/menu_nutrition/a/0011_stjohns.htm
29. ^ http://www.pendulum.org/treatments.htm
30. ^ Rossi S (Ed.) (2005). Australian Medicines Handbook 2005. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-9-3.

Further reading

• British Herbal Medicine Association Scientific Committee (1983). British Herbal Pharmacopoeia. West Yorkshire: British Herbal Medicine Association. ISBN 0-903032-07-4

See also

• Dietary supplement
• EU Food supplements directive

External links

• QuackWatch article on St. John's wort Criticism of the use of St. John's wort to treat depression. Includes Food and Drug Administration (FDA) warnings about interference with treatments for heart disease, some cancers, AIDS and others.

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Hypericum

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Hypericum perforatum

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