FWD 2 Expanded Commission E: St. John's wort

Herbal Medicine: Expanded Commission E

St. John's wort

Latin Name: Hypericum perforatum
Pharmacopeial Name: Hyperici herba
Other Names: Hypericum, Klamathweed


St. John's wort (SJW) is a perennial herb native to Europe, North Africa, and western Asia. It has been introduced and naturalized in parts of Africa, Asia, Australia, and the Americas, and is found growing wild in neglected fields, dry pastures, rangelands, and along country roads(Bombardelli and Morazzoni, 1995; Leung and Foster, 1996; Snow, 1996; Upton, 1997; Wichtl and Bisset, 1994).In European medicine, SJW was traditionally obtained from Eastern European countries, where it is still wild collected (BHP, 1996; Braun et al., 1997; Wichtl and Bisset, 1994). It is cultivated in at least four provinces in Germany (Lange and Schippmann, 1997).The SJW used in Indian Ayurvedic medicine is distributed in the temperate western Himalayas, Kashmir, and Simla (Karnick, 1994; Nadkarni, 1976). SJW was initially brought to the northeastern United States by European colonists (Pickering, 1879; Upton, 1997). It is harvested from naturalized plants in the Pacific Northwest and eastern states (Upton, 1997). Since the mid-1990s, in order to meet new demands on supply, it has been quickly brought into large-scale cultivation in Europe, North and South America, Australia, and China.

Many of SJW's therapeutic applications (except antiviral use), including its uses as a vulnerary, diuretic, and treatment for neuralgic conditions, stem from traditional Greek medicine, originally documented by ancient Greek medical herbalists Hippocrates (ca. 460–377 B.C.E.), Theophrastus (ca. 372–287 B.C.E.), Dioscorides (first century C.E.),and Galen (ca. 130–200 C.E.) (Bombardelli and Morazzoni, 1995; Hobbs, 1990; Leung and Foster, 1996; Upton, 1997).Since the time of Swiss physician Paracelsus (ca. 1493–1541 C.E.) it has been used to treat psychiatric disorders. At that time it was described as "arnica for the nerves" (Reuter, 1998). The aerial flowering parts of SJW have been used in traditional European medicine for centuries to treat neuralgia, anxiety, neurosis, and depression (Rasmussen, 1998). The traditional way to take SJW was as herbal tea, an aqueous extract whose single dose corresponded to 2–3 g of dried crude drug (Schulz et al., 1997). In the nineteenth and twentieth centuries, American Eclectic physicians prescribed SJW to treat hysteria and nervous affections with depression. It was prescribed externally to treat wounds, bruises, sprains, and much more (Ellingwood, 1983; Felter and Lloyd, 1983; Felter, 1985; King, 1866; Snow, 1996; Upton, 1997). Today, St. John's wort is official in the national pharmacopeias ofCzechoslovakia, France, Poland, Romania, and Russia (Bruneton, 1995; Hobbs, 1989; Newall et al., 1996;Ph.Fr.X, 1990; Reynolds, 1993; Upton, 1997; USSR X, 1973).

In Germany, SJW is listed in the GermanDrug Codex, approved as a medicine in the Commission E monographs, and licensed as a standard medicinal tea infusion(BAnz, 1998; Braun et al., 1997; DAC, 1991; Meyer-Buchtela, 1999; Schilcher, 1997; Wichtl and Bisset, 1994).It is used in psychiatric drugs in forms including dampoule (Hyperforat®), coated tablet (LI 160, Jarsin®, Lichtwer Pharma, Berlin), juice (Kneipp® Johanniskraut Pflanzensaft N), tea (Kneipp® Johanniskraut-Tee), and tincture (Psychotonin®M). It is used in some urological preparations affecting micturition (e.g., Inconturina®) (Kneipp®, 1996;Schilcher, 1997;Wichtl and Bisset, 1994).In German pediatric medicine,SJW aqueous infusions, alcoholic fluidextracts, and some proprietary products (such as Sedariston®, a combination of SJW and valerian (Valeriana officinalis) extracts) are used to treat depressive states in young people. For example, SJW is acomponentof a sedative tea for children, composed of 30% lemon balm leaf (Mellissa officinalis), 30% lavender flower (Lavandula officinalis), 30% passion flower herb (Passiflora spp.), and 10% SJW herb(Schilcher, 1997).

In the United Statesit is used in a wide range of dietary supplements in forms including alcoholic tincture, aqueous infusion (oral), oil infusion (topical), and dry standardized extract in capsules and tablets (Leung and Foster, 1996; Upton, 1997). In 1998, the United States Pharmacopeia Drug Information division issued a therapeutic monograph and consumer information bulletin stating that the USP Advisory Panels do not recommend or support the use of SJW because they believe that there have not been enough quality studies to prove that it is effective. However, USP noted that research indicated the safety of SJW (USP-DI, 1998). The USP also published an identification monograph that included guidelines for assessing the identity and purity of raw material in bulk or powder form (USP, 1999a).

Since 1979, there have been about 30 controlled trials with Hypericum extracts, involving thousands of patients with mild to moderate depressive disorders. Most studies lasted 28 to 42 days with daily dosages of 900 mg of an extract standardized to 0.3% hypericin (Jarsin®, LI 160, Lichtwer Pharma, Berlin). Up to 1997, there have been at least 15 controlled studies on a methanolic extract of SJW (LI 160) and 12 controlled studies on four additional preparations made from ethanolic extracts of SJW (Schulz et al., 1998). They have confirmed the antidepressant action of SJW extracts in humans (Bombardelli and Morazzoni, 1995; Linde et al., 1996; Reuter, 1998; Upton, 1997).

These studies on SJW do not meet the criteria for conventional antidepressant drugs according to the regulatory guidelines of the European Union, thereby keeping SJW from being accepted for treatment for major depression (De Smet and Nolen, 1996). However, some of these same deficiencies relate to studies on conventional antidepressants when they are first marketed (Cott, 1999). Studies that compare treatment with SJW to treatment with a synthetic antidepressant have not lasted longer than six weeks and have been compared using about one-half the usual dose of the antidepressant (75 mg imipramine instead of 150 mg). In addition, they have not been conducted with severely depressed patients. Yet SJW has been shown to be safe, with very few side effects, compared with synthetic antidepressants: out of 3,250 patients, only allergic reactions (0.5%), gastrointestinal upset (0.6%), and fatigue (0.4%) were observed (De Smet and Nolen, 1996). Evidence of the antidepressant activity of SJW extracts can be found in reviews by Bombardelli and Morazzoni (1995), Linde et al. (1996), and Upton (1997). No significant modern human studies investigating SJW's other therapeutic uses have been found (e.g., orally for dyspeptic complaints and topically for burns, lesions, wounds, and myalgia).

The constituents and mechanism of action responsible for the antidepressant properties of SJW have been investigated, with various authors citing different mechanisms (Bombardelli and Morazzoni, 1995; Rasmussen, 1998; Reuter, 1995, 1998). However, a recent randomized, double-blind, placebo-controlled, multicenter study on 147 male and female patients with mild to moderate depression indicated that hyperforin may be the primary active ingredient, or at least it plays a key role in the antidepressant activity. Patients received 300 mg of either a placebo, a SJW extract standardized to 0.5% hyperforin (WS 5573, W. Schwabe, Germany), or a SJW extract standardized to 5% hyperforin (WS 5572, Schwabe), three times daily for 42 days. While there was a reduction in depression scores in both the 0.5% hyperforin group and the placebo group, results were statistically significant for improvement of depressive symptoms only in the patients receiving the extract with 5% hyperforin (Laakmann et al., 1998a, 1998b). Of particular interest is the finding that patients with severe depression (n=56) experienced greater reduction of symptoms than mild to moderately depressed patients receiving the same dosage (although there is more room for improvement in severely depressed patients). The authors of this study concluded that the antidepressant activity of SJW is due to its hyperforin content. Other experimental studies have also shown the relevance of hyperforin (Chatterjee et al., 1998; Bhattacharya et al., 1998). However, additional animal and human research is being conducted to clarify the importance of hyperforin, since most of the studies on St. John's wort were conducted on preparations standardized to hypericin, not hyperforin, content. Nevertheless, a representative of the leading manufacturer of the most clinically tested hypericin-based SJW extract (i.e., LI 160 from Lichtwer Pharma) has written that this product showed hyperforin levels of 1% to 6% upon analysis; new studies by Lichtwer on LI 160 will be carried out on an extract standardized to hyperforin values of approximately 4% (Schulz, 1998).

Although additional research is warranted, the modern therapeutic application of SJW for mild to moderate depression is supported by its history of use in traditionalmedicine, in vitro studies (Cott, 1997; Wonnemann et al., 1999), in vivo experiments in animals (Butterweck et al., 1999; Okpanyi and Weischer, 1987), pharmacodynamic studies in humans (Kugler et al., 1990; Schulz and Jobert, 1993), pharmacokinetic studies in humans (Staffeldt et al., 1993; Weiser, 1991), human clinical studies (Hnsgen et al., 1994; H bner et al., 1994; Cott, 1997; Fugh-Berman and Cott, 1999), meta-analyses (Linde et al., 1996) and extensive phytochemical investigations (Bombardelli and Morazzoni, 1995; Brantner et al., 1994).

A major three-year, multicenter clinical study on the antidepressant effect of SJW is being carried out in the United States under the auspices of the National Institutes of Health. This is the first clinical study to test SJW directly against a modern selective serotonin reuptake inhibitor (SSRI) (sertraline, Zoloft®) and placebo. The trial consists of 330 patients (110 in each arm—SJW, sertraline, placebo) and the duration of treatment will last six months, the longest trial on SJW to date. Patients are required to test a minimum of 20 points on the Hamilton Depression Scale, thus being classed as moderately to severely depressed.

A small study has investigated the possible use of SJW for seasonal affective disorder (SAD), a condition of depressive mood associated with winter months and lack of sunlight (Kasper, 1997). In an open study, 22 patients diagnosed with SAD were given SJW extract (300 mg three times daily) with additional bright light or the same dose of SJW in dim light conditions. As determined by a standard method for measuring depression symptoms (Hamilton Depression Scale), subjects in both groups experienced a significant reduction in depression score, there being no difference in the bright and dim light groups. Therefore, no conclusion for the effectiveness of SJW in SAD can be drawn from the results of this study.

Pharmacopeial grade SJW consists of the dried flowering tops or aerial parts of Hypericum perforatum L., harvested shortly before or during the flowering period.It must contain not less than 12% water soluble extractive. Botanical identity must be confirmed by thin-layer chromatography (TLC), macrocopic and microscopic examinations, and organoleptic (sensory) evaluation(BHP, 1996).The German Drug Codex additionally required not less than 0.4% dianthrones of the hypericin group, calculated as hypericin (DAC, 1986; Wichtl and Bisset, 1994). The German Standard License monograph requires the material to conform with the German Drug Codex requirements (Braun et al., 1997). However, the German Federal Institute for Drugs and Medical Devices (BfArM) declared that hypericin would no longer be used as a required marker compound for the chemical standardization of St. John's wort (B hler, 1995). The United States Pharmacopeia requires not less than 0.2% of hypericin and pseudohypericin combined and not less than 3.0% of hyperforin (USP, 1999b). The ESCOP monograph requires the material to conform with either the French Pharmacopoeia or the German Drug Codex (ESCOP, 1997).


St. John's wort consists of the dried, aboveground parts of H. perforatum L. [Fam. Hypericaceae], gathered during flowering season, and their preparations in effective dosage.

Chemistry and Pharmacology

St. John's wort herb contains 6.5–15% catechin-type tannins and condensed-type proanthocyanidins (catechin, epicatechin, leucocyanidin); 2–5% flavonoids, mostly hyperoside (0.5–2%), rutin (0.3–1.6%), quercitrin (0.3%), isoquercitrin (0.3%), quercetin, and kaempferol; biflavonoids (approximately 0.26% biapigenin); phloroglucinol derivatives (up to 4% hyperforin); phenolic acids (caffeic, chlorogenic, ferulic); 0.05–1.0% volatile oils, mainly higher n-alkanes; 0.05–0.15% naphthodianthrones (hypericin and pseudohypericin); sterols (b-sitosterol); vitamins C and A; xanthones (up to 10 ppm); and choline (Bruneton, 1995; ESCOP, 1997; Leung and Foster, 1996; Newall et al., 1996; Wichtl and Bisset, 1994).

The Commission E reported that a mild antidepressant action of the herb and its preparations has been observed and reported by many physicians. Although the Commission E categorized St. John's wort as an MAO inhibitor, this was based on in vitro research and not conducted in animal systems. Subsequent research has indicated either no or very slight MAO activity in St. John's wort or its preparations. The Commission E recognized the anti-inflammatory action of topical oily Hypericum preparations.

The British Herbal Pharmacopoeia reported antidepressant action (BHP, 1996). In numerous controlled double-blind and open studies using hydroalcoholic SJW preparations, a significant improvement of mood, and loss of interest and activity and other depressive syndrome symptoms, such as sleep, concentration, and somatic complaints, has been reported (ESCOP, 1997).


In December 1984, the Commission E approved the internal use of St. John's wort for psychovegetative (psychoautonomic) disturbances, depressive moods, anxiety, and nervous unrest. Oily Hypericum preparations are approved for dyspeptic complaints. External use of oily preparations of St. John's wort is approved for treatment and post-therapy of acute and contused injuries, myalgia, and first-degree burns.

ESCOP indicates its use for mild to moderate depressive states, restlessness, anxiety, and irritability (ESCOP, 1997). The German Standard License for St. John's wort tea lists it for nervous excitement and sleep disturbances (Wichtl and Bisset, 1994). With the exception of its antiviral use, other modern applications date back two thousand years (Hobbs, 1990).

Since the 1984 monograph was based on general clinical use and only one clinical study (out of more than 27 that had been published up to 1997) had been published at that time, the Commission was relatively accurate in its evaluation of the therapeutic effects of SJW. However, given that most the recent research has focused on antidepressant activity of SJW, it is reasonable to conclude that this use should be the only primary use, when administered in proper form and dosage (Schulz et al., 1998). SJW may benefit the other uses (psychovegetative disturbances, anxiety, and nervous unrest) only within the framework of its general antidepressant activity (Schulz et al., 1998).


None known.

Side Effects

Commission E noted that photosensitization is possible, especially in fair-skinned individuals. However, animal and human research has indicated that photosensitization is not likely to occur at the recommended dosage levels. Based on experimental studies (animal and human), it would take approximately 30 to 50 times the recommended daily dose of 900 mg of the standardized extract to produce severe phototoxic effects in humans (Schulz et al., 1998).

Use During Pregnancy and Lactation

No restrictions known (McGuffin et al., 1997).

Interactions with Other Drugs

Commission E reported that none were known (in 1984). ESCOP also noted that none were reported (ESCOP, 1997).

Dosage and Administration

The original Commission E monograph (1984) noted the following dosage: "Unless otherwise prescribed: 2–4 g per day of chopped or powdered herb for internal use, or 0.2–1 mg of total hypericin in other forms of preparation application. Liquid and semi-solid preparations for external use. Preparations made with fatty oils for external and internal use." Although the original Commission E monograph specified minimum levels of hypericin, this is no longer required on the label of German products (Ahuis, 1998). In Germany, the current required dosage is 300 mg, three times daily of a hydroalcoholic St. John's wort extract. The registration for infusions (tea) of St. John's wort has recently been withdrawn due to a lack of evidence of efficacy (BfArM, 1998).

Based on the available research, the approved effective equivalent preparations are as follows:


Fluidextract 1:1 (g/ml): 2 ml, twice daily.

Native dry extract 5–7:1: 300 mg, three times daily.


Oily macerate (Oleum hyperici): macerate fresh flowering tops in olive oil or wheat-germ oil for several weeks, stirring often; strain through a cloth and press pulp; for direct application to affected areas.


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This material was adapted from The Complete German Commission E MonographsTherapeutic Guide to Herbal Medicines. M. Blumenthal, W.R. Busse, A. Goldberg, J. Gruenwald, T. Hall, C.W. Riggins, R.S. Rister (eds.) S. Klein and R.S. Rister (trans.). 1998. Austin: American Botanical Council; Boston: Integrative Medicine Communications.

1) The Overview section is new information.

2) Description, Chemistry and Pharmacology, Uses, Contraindications, Side Effects, Interactions with Other Drugs, and Dosage sections have been drawn from the original work. Additional information has been added in some or all of these sections, as noted with references.

3) The dosage for equivalent preparations (tea infusion, fluidextract, and tincture) have been provided based on the following example:

  • Unless otherwise prescribed: 2 g per day of [powdered, crushed, cut or whole] [plant part]
  • Infusion: 2 g in 150 ml of water
  • Fluidextract 1:1 (g/ml): 2 ml
  • Tincture 1:5 (g/ml): 10 ml

4) The References and Additional Resources sections are new sections. Additional Resources are not cited in the monograph but are included for research purposes.

This monograph, published by the Commission E in 1994, was modified based on new scientific research. It contains more extensive pharmacological and therapeutic information taken directly from the Commission E.

Excerpt from Herbal Medicine: Expanded Commission E Monographs
Copyright 2000 American Botanical Council
Published by Integrative Medicine Communications
Available from the American Botanical Council.