Scientific Description of Hypericum Perforatum
Edited version of the ESCOP (European Scientific Corporation of
Phototherapy) Proposal of Product Characteristics
The drug St. John's wort consists of the dried above-ground part
of Hypericum perforatum L collected shortly before or during
the flowering period. It contains not less than 0.04% naphthodianthrones
of the hypericin group (so-called total hypericin). Lower parts
of the stem contain few active ingredients (2,3,4).
- Hypericum extracts contain at least ten components or groups
of components that may contribute to the pharmacological effects.
It is not yet possible to correlate the antidepressive mode of
action with specific components; therefore, the pharmaceutical
quality of the extracts was characterized on the basis of typical
leading substances, especially the hypericins. The substances
most involved in the antidepressant action are thought to be the
hypericins and the flavonoids.
- The red-colored hypericins have been found in very few other
plants while most of hypericum's other ingredients are common
in the plant kingdom.
- The hypericins also have a photodynamic effect; sometimes
they do not occur until the crude drug has been processed and
exposed to light. The amount of total hypericin should be measured
after light exposition, which transforms the biological precursors,
protohypericin and protopseudo-hypericin, into hypericin and pseudohypericin
- The concentration of hypericins (mainly hypericin and pseudohypericin)
in buds and flowers can vary between 0.06% and 0.75%. The usual
concentration is 0.1-0.15%, but lower concentrations (less than
0.1%) might result from harvesting of lower parts of the herb
(4). A minimum content of 0.04% total hypericin is required for
- Other possible active ingredients are polymerization products
of hypericin, the flavonoids quercetin, hyperoside, quercitrin,
isoquercitrin, rutin, campherol, luteolin, and 13-118-biapigenin,
the total concentration of which can amount to 2% to 4%.
- The 1,3,6,7-tetra-hydroxyxanthone, the aglycone of the mangiferin
found in other species of Hypericum, is only present in
concentrations of 0.0004%.
- The procyanidines, which are related to the flavonoids, account
for about 8%.
- Hyperforin, with a structure related to the hop bitters humulon
and lupulon, contributes to about 2.8%.
Hypericum is available in tablets, capsules, drops and teas. It
is also available as an oil for external use.
The oil cannot be recommended for internal use as an antidepressant.
The official German commission monograph lists mild to moderate
depressive states (22-51), fear, and nervous disturbances, and
somatoform disturbances as clinical indications for hypericum.
Most of the scientific documentation on hypericum has been performed
on mild to moderate depressions. Treatment of severe depressions
(with suicidal, psychotic or severe melancholic features) with
hypericum preparations is not yet recommended.
Clinical effect (22-51,109-110)
Besides numerous case reports and drug monitoring studies (with
more than 5,000 patients) on the efficacy and safety of standardized
St. John's wort preparations, 25 controlled double-blind studies
(with more than 2,000 patients) have been conducted. The major
indication was mild to moderate depressive disorders.
Sixteen of the studies compared hypericum with placebo (sugar-pills)
and 9 with reference treatments (Imipramine-2 (34, 44), Amitryptilin-2
(32, 48), Maprotiline-1 (46), Desipramine-1(30), Diazepam-2 (27,29),
and Light-therapy (47).
In most of the studies, both depressive symptoms (depressed mood,
anxiety, loss of interest, feelings of worthlessness, decreased
activity) and secondary symptoms (sleep disturbance, lack of concentration,
somatic complaints) improved significantly (see Figure 1) (25).
Results are summarized in Table 1. Some facts:
- The response rate has generally been between 50 and 80%, comparable
to that of low- to medium dose treatment with "classic"
- In three of the trials (39,45,109) there was -- were no statistically
significant difference between hypericum and placebo. In a criteria-based
clinical review by Ernst (110) two of these studies also were
judged as questionable because of methodological weaknesses. The
third one is a yet unpublished study. They were all made with
low dose hypericum test medications.
- Hypericum leads to an increase in deep sleep and does not
impair cognitive functions or the ability to work or drive a car
- Hypericum has been shown to have a long-term effect on anxiety
comparable to Bromazepam and Diazepam (29, 35).
- A Russian study (102) showed good results combining hypericum
with psychotherapy to treat alcoholics with peptic ulcers.
- A preliminary study by Martinez et al. also showed an effect
comparable to light therapy in the treatment of seasonal affective
- Anti-inflammatory and antibacterial effects of externally
applied St. John's wort preparations have been reported and attributed
to the presence of hyperforin. (1).
Hypericin has also been proven to possess promising anticancer
properties and has been shown to inhibit growth of gliomas (brain
tumors) (103), lung cancer (104) and skin cancer (68) in vitro
(in the laboratory). Its photodynamic properties might lead to
the use of hypericin in combination with lasers in the photodynamic
treatment of cancer (68).