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Clinical use of St. John's wort

Robert B Saper, MD, MPH
Section Editor
Joann G Elmore, MD, MPH
Deputy Editor
H Nancy Sokol, MD


St. John's wort (Hypericum perforatum) is a five petal yellow flower (picture 1) that has been used medicinally since antiquity [1]. It was commonly referred to as "Fuga Demonum" (the devil's scourge) since it was used to protect against demonic possession and "evil spirits" [2]. One of the earliest references to the name St. John's wort is noted in a Gaelic legend from the sixth century where the missionary St. Columba carried a piece of St. John's wort because of his high regard for St. John [1]. It is believed that the name may have been derived from the fact that the flowers bloom around June 24th, the birthday of St. John the Baptist. Wort represents the old English term for plant.

St. John's wort has been utilized mainly for its antidepressant activity, but also for its purported antiinflammatory and wound healing properties [3]. The 2007 National Health Interview Survey found a large decrease in St. John's wort use by adults in the United States [4]. In 2002, St. John's wort was the sixth most popular natural product in the United States, used by 2.2 percent of American adults [5]. In 2007, St. John's wort was not among the 20 most commonly used dietary supplements [4]. This decrease may reflect the public's response to interim news reports of negative clinical trials [6-8] and potentially harmful interactions with prescription drugs [9-22].


A number of compounds isolated from St. John's wort possess pharmacologic activity. Naphthodianthrones (hypericin, pseudohypericin, protohypericin, protopseudohypericin, and cyclopseudohypericin), flavonoids (quercetin, rutin, and luteolin), hyperforin, several amino acids, and tannins have been isolated [23].

Neuropsychiatric activity — The majority of in vitro studies of St. John's wort have attempted to define its neuropharmacology. Hyperforin and hypericin have been studied most extensively. Hypericin was originally thought to be the major active component for St. John's wort in depression; however, it is now believed that hyperforin and related compounds are mostly responsible for St. John's wort's effect on mood.

Hyperforin extracts have been shown to modulate neurotransmitter levels including serotonin, norepinephrine, and dopamine [24,25]. This may be in part from inhibition of neurotransmitter uptake. Other studies have found that hypericum extract possesses a weak catechol-O-methyl transferase activity [26], and the hypericum extract LI 160 causes 50 percent inhibition of serotonin uptake by rat synaptosomes [27]. The latter occurred only at relatively high concentrations.


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Literature review current through: Sep 2016. | This topic last updated: Nov 6, 2015.
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