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St. John's Wort

Scientific Name(S): Hypericum perforatum L. Family: Hypericaceae

Common Name(S): St. John's wort, klamath weed, John's wort, amber touch-and-heal, goatweed, rosin rose, and millepertuis

St. John's wort (Hypericum perforatum), once thought to rid the body of evil spirits, has a history of medicinal use dating back to ancient Greece, where it was used to treat a range of illnesses, including various 'nervous conditions.

Extracts of St John's wort are made into capsules and other types of preparations which are used to treat depression. It recently became a popular treatment for depression.

St John's wort contains many different chemicals. Some are thought to be the active ingredients. How these chemicals actually work in the body is not clear. It is thought that they may alter the balance of some of the chemicals in the brain (neurotransmitters) such as serotonin, dopamine, gamma aminobutyric acid (GABA), and noradrenaline.


St. John's wort has been primarily studied for its potential antidepressant and antiviral effects.

An early study suggests that St. John's wort may be useful in relieving both physical and emotional symptoms of PMS including cramps, irritability, food cravings, and breast tenderness.

Drug Interactions

St. John's wort has been reported to decrease the efficacy of theophylline, warfarin, and digoxin and reduce AUC of indinavir (and potentially other protease inhibitors). Known interactions to cyclosporine have occurred. Likely interactions include (but are not limited to):

Warfarin/coumarins/anti-coagulants (for thinning the blood).

Digoxin (for the heart).

Cyclosporin (for transplants and some diseases such as psoriasis and arthritis).

Theophylline (for asthma).

Side Effects

Side effects are usually mild. Potential side effects include the following: Dry mouth, dizziness, constipation, other GI symptoms, and confusion.

Increased skin sensitivity to the sun is extremely rare.

St John's Wort generally does not seem to cause drowsiness and affect the ability to drive, however a very small percentage of people taking it may feel tired.


The majority of clinical trials for the treatment of depression administered St. John's wort 300 mg tid standardized to 0.3% hypericin, but research has shown that products should contain ≥ 2% to 4% hyperforin.


Several reports regarding the chemical components in St. John's wort are available. The most commonly described constituents are naphthodian­thrones, flavonoids, phloroglucinols, and essential oils.

Naphthodianthrones occur in St. John's wort in concentrations of < 0.1 to 0.15%. The anthraquinone derivatives hypericin and pseudohypericin (also emodin-anthranol and cyclo-pseudohypericin) are the best known components of the plant. Isohypericin and protohypericin are also present. The reddish dianthrone pigment hypericin (hypericum red) is found in a concentration ranging from 0.02% to 2.5%, depending on harvesting period, drying process, and storage. Hypericin content also varies widely among growing regions. Hypericin concentration varies among plant parts: Flowers, buds, top leaves, and secondary stems yielding the highest amount. Microscopic evaluation finds hypericin to accumulate in secretory cell globules within these plant structures. Several reports concerning determination and analysis (ie, HPLC) of hypericin in St. John's wort exist. Liposoluble pigments from the plant, including hypericin, carotenoids, and chlorophylls, have also been reported.

Flavonoid concentrations in St. John's wort occur at < 12% in flowers and ≈ 7% in leaves/stalks. Flavonoids include kaempferol, quercetin, quercitrin, isoquercitrin, amentoflavone, luteolin, myricetin, hyperin, hyperoside. and rutin. The proanthocyanidins (≈ 12% of aerial parts) are certain forms of catechin and epicatechin. Other flavonoids found are miquelianin and astilbin.

Hyperforin and adhyperforin are in the phloroglucinol class of compounds. Hyperforin appears in St John's wort in concentrations of 2% to 4%. Isolation, purity, and stability of this compound have been reported. Recovery of hyperforin in plasma has been measured. Related structure furohyperforin, an oxygenated analog of hyperforin has been isolated from the plant, as have other hyperforin analogs.

The essential oil component of St. John's wort is reported to be between 0.05% and 0.9%. It consists of mono­and sesquiterpines, mainly 2-methyl-octane (16 to > 30%), n-nonane, alpha- and beta-pinene, alpha-terpineol, geraniol, and traces of myrecene, limonene, caryophyllene, and others.

Other compounds present in St. John's wort include xanthones (1.28 mg/100 g) and tannins (3% to 16%). One study reports that tannin content (in extracts) is influenced by parameters such as temperature of maceration. Phenol constituents include caffeic, chlorogenic, and pcoumaric acids, and hyperfolin. Other plant constituents include acids (eg, nicotinic, myristic, palmitic, stearic), carotenoids, choline, pectin, hydrocarbons, and long­chain alcohols. Amino acids include cysteine, GABA, glutamine, leucine, lysine, and others.

Because St. John's wort products are classified as dietary supplements, they are not regulated by the FDA. Several reports evaluating commercial preparations of St. John's wort have found inconsistencies in active ingredients such as variations from 47% to 165% of labeled hypericin concentrations, different concentrations of major components between brands, and marked deviations in hyperforin (and adhyperforin) amounts in certain St. John's wort preparations. Several reports are available addressing these issues, with various proposed standardization methods. One such method has been developed by Paracelsian Inc., a private biotechnology company ( Their Biofit (bio functional integrity tested) quality assurance method has tested several St. John's wort products for structure and function claims of mood support on otc labeling. This testing process evaluated the product's ability to inhibit reuptake of serotonin and dopamine.


St. John's wort has been used traditionally as an herbal treatment in the management of anxiety and depression. Several constituents acting by different mechanisms may contribute to its potent antidepressant activity. Clinical trials concerning use of St. John's wort to treat AIDS and certain cancers are ongoing. H. perforatum possesses antiviral and antibacterial actions, making it potentially useful in treating skin diseases and in wound healing. Side effects from St. John's wort are rare in standard dosing. With higher dosing, photosensitivity is observed. Drug-drug interactions have been documented with theophylline, digoxin, indinavir, cyclosporine, and SSRls. Hyperforin appears to be a major active antidepressive agent.

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