 |
Monograph : Hypericum perforatum
| |
Hypericum
perforatum |
Common name: st john's wort
Other names: hypericum, amber,
goatweed, johnswort, klamath weed, tipton weed, hardhay,
prikbladet perikon, hartheu, herb de millepertuis,
hyperici herba, iperico, johanniskraut, sonnenwendkraut
Family: Clusiaceae
Parts used: above ground parts
Description
Historical Use
Cautions
Dose Dry Herb
Dose Extract
Indications
Contraindications
Qualities
Actions
Constituents
Toxicology
Pharmacological
Studies
Clinical Studies
Description
St John's wort is a perennial herb that grows up to 1
metre high. Stems are 2-lined, woody at the base, and
die back in autumn. Rhizomes are slender. Leaves are
pale green, opposite, dotted with numerous tiny pellucid
glands. The plant produces golden yellow five-petalled
flowers throughout summer.
St John’s wort is a native of Europe, western Asia
and north Africa. It has now spread to many countries in
the world. It is declared a noxious weed in parts of
Australia as it causes photosensitivity in stock that
eat it.
Historical use
St John's wort has a long history of usage, being used
in antiquity for the treatment of burns, snake bites,
fever and wounds.
The fathers of medicine, Dioscorides and Hippocrates
were herbalists who recommended and used this ancient
herb. Kim Fletcher in ‘The Penguin Modern Australasian
Herbal’, explains how St. John’s Wort was named.
“During the medieval period, St. John’s Wort was
ascribed almost magical powers of protection against
evil spirits because of its association with St. John
the Baptist. The yellow petals when bruised show a
reddish mark that symbolised the blood shed by the
saint. Hung in the house or rubbed over the lintels, the
herb would prevent witches and death from entering
during the year.”
“Wort” is from the old English “wyrt”,
meaning a plant or herb, especially one used in
medicine. Paracelsus, the Swiss physician, chemist and
natural philosopher who lived in the 16th century, wrote
of the superior healing powers of St. John’s Wort as
putting “to shame all recipes and doctors, they may
yell as they wish, they will only break their teeth.”
The BHP lists the specific indication for St John's
wort as menopausal neurosis; other indications listed
are excitability, neuralgia, fibrositis and sciatica.1
_____________
1British Herbal
Medicine Association, 1983, British Herbal
Pharmacopoeia, West Yorks, p 115.
ENVELOPED VIRUS (surrounded by a lipid shell)
Hypericum may be useful:
Type of virus
|
Specific Virus
|
Disease
|
| Herpesviruses |
Simplex |
Oral & genital |
|
Varicella |
Chickenpox |
|
Zoster |
Shingles |
|
Cytomegalovirus |
Salivary gland disease |
|
Epstein-Barr |
Glandular fever |
| Hepatitis B |
|
Jaundice |
| Poxviruses |
Vaccinia |
Mild pox disease |
|
Variola |
Smallpox |
| Togaviruses |
Rubella virus |
German measles |
|
Ross River |
Polyarthritis |
| Othomyxoviruses |
|
Influenza |
| Paramyxoviruses |
Morbilivirus |
Measles |
| Retroviruses |
HIV |
AIDS |
| Coronaviruses |
|
Common cold |
NAKED VIRUSES (NOT surrounded by a shell)
Hypericum will not help:
Type of Virus
|
Specific Virus
|
Disease
|
| Picornaviruses |
Rhinovirus |
Common cold |
|
Enterovirus (coxsackie, echovirus) |
Acute fever |
|
|
Viral meningitis (accounts for 90% of all
cases of viral meningitis) |
|
|
Viral encephalitis (20%) |
|
|
Acute myopericarditis |
|
|
Ophthalmic infection |
| Papovaviruses |
many types |
Warts |
| Hepatitis A |
Hepatitis |
Jaundice |
Note: the common cold can be caused by either
enveloped or naked viruses.
Cautions
Avoid excessive sunlight.
Recent research indicates that Hypericum
perforatum induces the cytochrome P450 enzyme
system. The UK Commitee on Safety of Medicines (UKCSM)
advises that hypericum should not be used with indianvir,
warfarin, cyclosporin, oral contraceptives, digoxin and
theophylline.
The FDA and the UKCSM also state that interaction is
expected to occur with HIV protease inhibitors, HIV
non-nucleoside reverse transcriptase inhibitors and
certain anticonvulsants. There is also concern with
interaction with SSRIs and other psychotropic drugs.
B. Uehleke et al evaluated the drug interaction of
different formulations and dosages of hypericum with
digoxin.1 After
reaching steady levels of digoxin, hypericum was co-mediciated
with digoxin for a further 14 days. A standardized
extract, Jarsin (900 mg) and high-dose encapsulated
hypericum powder (4 g daily) reduced 24h-AUC by 24.6%
and 27.1% respectively. Jarsin is standardized to
hypericin, not hyperforin, yet it clearly interacts with
the prescription medication.
_____________
1Uehleke B, 3rd
International Congress on Phytomedicine, Munich
2000.
Toxicology
To investigate the safety and tolerability of hypericum
extract (Remotiv), H. Woelk et al treated 440
outpatients (18-80 years) with mild to moderate
depression for one year with 250 mg bid Remotiv,
standardised to 0.2% hypericin and <0.2% hyperforin.1
According to the poster, the authors concluded that of
the few patients who reported adverse reactions, only
6.7% were possibly or probably related to the study
drug, only 5.7% of patients dropped out of the study,
the vast majority of adverse reactions were mild to
moderate in intensity and completely resolved in most
patients within the study period.
The authors further claimed that most patients
reported significant improvements in their symptoms and
that there was no convincing evidence of a significant
relapse rate. No clinically relevant interaction with
other drugs could be observed during the study and the
authors suggest that this may be due to the fact that
this particular hypericum extract has a very low level
hyperforin.
_____________
1Woelk H, et al, 3rd
International Congress on Phytomedicine, Munich
2000.
DoseDryHerb
6 to 12 g per day.
DoseExtract
15 to 40 mL per week (Std Ext).
Indications
anxiety,
depression,
depression,
post natal, fibrositis,
irritability,
menopause,
depression, menopause,
symptoms, nervous
exhaustion, neuralgia,
premenstrual
syndrome, sciatica,
wounds
(topically)
Contra Indications
cyclosporin
, HIV
non-nucleoside transcriptase inhibitors & protease
inhibitors
Qualities
cold,
pungent
Actions
antidepressant,
anti-inflammatory,
antiseptic
(topically), antiviral
(topically), anxiolytic,
astringent,
nervine
tonic, relaxant,
vulnerary
Constituents
The debate about the true active constituents of
hypericum continues. The following research findings
were presented at the 3rd International Congress on
Phytomedicine, Munich 2000.
A study by V. Butterweck, B. Korte and H. Winterhoff
suggests that the antidepressive effect of hypericum/hypericin
may be, at least partly, mediated by the dopaminergic
system. In patients with depression, a considerable
number of endocrine abnormalities have been reported,
including changes in the hypothalamic-pituitary-adrenal
(HPA) axis. Hypericum extract and hypericin clearly
inhibited thyroid-releasing-hormone-stimulated prolactin
release in primary pituitary cell cultures in a dose
dependent manner.
As companies endeavor to prove the efficacy of their
botanical products, it is essential that the studies are
well designed and that proper statistical analysis is
applied in order to reach irrefutable conclusions. The
controversy surrounding hypericum is not likely to
disappear in a hurry.
The German pharmaceutical company, Bayer, sponsored a
large randomized controlled study comparing the effects
of their hypericum extract Remotiv (produced by Zeller
in Switzerland) with Imipramine in the treatment of mild
to moderate depression.
The study, recently published in the British Medical
Journal1, generated a
substantial amount of comments on the BMJ website.
Although the study showed that hypericum and imipramine
are therapeutically equivalent, the study design, and
therefore its relevance, has been criticized by other
researchers.
James L. Spira, Ph.D., M.P.H., Head, Division of Health
Psychology Naval Medical Center, San Diego, as well as
Arthur Rifkin, MD, Attending Psychiatrist Hillside
Hospital, New York, questions the choice of imipramine
which is not considered the drug of choice for
depression, with more side effects than the newer drugs
such as the selective serotonin reuptake inhibitors, and
furthermore, that the dosage used in the study is
considered suboptimal. The study is also criticized for
only running for six weeks, too short a time frame when
exploring the efficacy of an anti-depressant drug. The
statistical analysis of the study has even been
criticized by an independent German biostatistician,
Andreas V๖lp.
Conversely, other comments from researchers and medical
doctors from around the world, expressed the view that
there are sufficient data to suggest that hypericum is a
safe, efficacious alternative in the treatment of mild
to moderate depression and the dosage of the tri-cyclic
antidepressant imipramine used in the study actually
reflects the common prescribing practices of GPs, if not
psychiatrists.
Other presentations by E. Schrader et al and M. Friede
et al, compared Hypericum extract Ze 117 with fluoxetine.
Not only was the botanical extract as effective as the
drug in treating depression, it was also effective in
reducing anxiety and agitation, and patients reported
fewer side effects.
In conclusion, it seems that both hypericin and
hyperforin show antidepressive activity and that both
may contribute to hypericum extract's ability to
interact with the intestinal absorption, distribution or
renal excretion of digoxin. This effect seems to be
mediated by the drug transporter P-glycoprotein.
Hypericum extract also interacts with the drugs via its
effect on hepatic cytochrome P450 enzyme systems. Until
further notice, it seems prudent to caution against the
use of hypericum with HIV proteases, immunosuppressants
such as cyclosporin, warfarin, digoxin and SSRIs.
In view of the problems in identifying a single active
constituent in hypericum, it seems essential to
recommend a full-spectrum extract of hypericum.
Full-spectrum extracts contain all the constituents as
found in the raw herb (provided they are well extracted
in the chosen solvent). However, since both hypericin
and hyperforin are important constituents, they are
useful as marker compounds for the purpose of quality
control, and since the clinical trials have been
conducted with extracts standardized to hypericin, it
seems prudent to recommend products which are at least
standardized to hypericin. There is also evidence to
suggests that hyperforin may be unstable in liquid form.
A presentation by A. Nahrstedt et al showing that the
napthadiantrone, procyanidin B2, but not procyanidin C1
or epicatechin, improved the solubility of hypericin.
Nahrstedt also considers hyperoside and isoquercetin to
be active constituents in hypericum. Honegger et al made
the discovery that hypericum extract caused changes in
the phospholipid composition in the membranes leading to
greater fluidity and may therefore reduce symptoms of
depression. Honegger felt that the reported ability of
hypericum to inhibit the reuptake of noradrenalin and
serotonin may account for its short term antidepressant
activity whereas the phospholipid changes may be more
significant in explaining the long term effects.
Until studied further, the importance of hyperforin and
other constituents, such as the flavonoids in hypericum,
and which constituents are mostly responsible for the
drug interaction remains elusive.
_____________
1Woelk H, 'Comparison
of St John's wort and imipramine for treating
depression: randomised controlled trial', BMJ
2000; 321: 536-539.
alpha-pinene,
beta-pinene,
caffeic
acid, caryophyllene,
chlorogenic
acid, coumarin,
essential
oil, flavonoids,
glycosides,
hyperforin,
hypericin,
n-alkanes,
oligomeric
procyanidins (OPCs), pectin,
procyanidins,
pseudohypericin,
quercitin,
resin,
rutin,
sesquiterpenes,
tannin,
xanthones
Pharmacological studies
Alcoholism Treatment
of alcoholism with herbs
Central nervous system response Hypericum
is anxiolytic and affects exploratory behavior in rats
Clinical studies
Depression Comparison
of St John's wort and imipramine Depression
in alcoholics Hypericum:
depression, anxiety and agitation
Herpes infections Reduced
frequency and severity
Interactions Interaction
of Hypericum perforatum with cyclosporin A metabolism
Obsessive-compulsive disorder Treatment
of OCD with hypericin
Author: Michael Thomsen
|
|
