FAQ on St. Johns wort
(Hypericum perforatum and Hypericum Augustifolia)
Copyright August 1997 by Camilla Cracchiolo R.N.
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1. What is St. John's wort?
2. Indications for use.
3. How effective is it in treating depression?
4. Dosage and administration
5. Chemical constituents
6. Adverse reactions and side effects.
7. Precautions and drug interactions.
8. The MAOI controversy.
9. Possible non-MAOI mechanisms of antidepressant action
10. Does St. John's wort have anti-cancer properties?
11. Research on St. John's wort and pregnancy.
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1. WHAT IS ST. JOHN'S WORT?
The name St. John's wort refers to the plants Hypericum perforatum
and Hypericum augustifolia. These plants are native to Europe and
western Asia. The leaves and leaf oils appear to be what is used to
make teas and extracts.
St. John's wort has recently come to popular attention in the U.S.
primarily because of its scientifically documented antidepressant action.
However, it does possess other medicinal properties as well.
2. MEDICAL INDICATIONS:
St. John's wort is approved in Germany for the following conditions:
Psychogenic disturbances, depressive states, anxiety and/or nervous
excitement, particularly those associated with menopause. Oily
hypericum preparations are approved for stomach and gastrointestinal
complaints and has anti-diarrheal activity.
Oily hypericum preparations for the treatment and after-treatment of
incised and contused wounds, muscle aches and 1st degree burns.
The U.S. FDA has not approved St. John's wort for any purpose and does
not allow manufacturers to make medical claims on the bottle. It currently
occupies the regulatory limbo of 'foods', even though it is never eaten,
used in cooking or to flavor foods.
3. HOW EFFECTIVE IS ST. JOHN'S WORT IN TREATING DEPRESSION?
In essence, there are a number of small but double-blind and placebo-
controlled studies in humans and all demonstrate that St.John's wort
has anti-depressant and sedative effects.
Its effects seem to be mild. It has been compared to a standard
antidepressant in at least one study and found to be as effective.
Another study found it to be less effective than amitriptyline, a common
tricyclic antidepressant also known as Elavil.
All the verbal reports I've gotten indicate that it's fairly weak.
A few psychiatrists on the psychopharmacology list are trying St. John's
wort for some of their patients. The one physician who has reported
results to me states that it doesn't seem to real effective for his
patients; however, a person seeking a physician's care for depression
may have a more serious case than most people on the street.
4. DOSAGE AND ADMINISTRATION:
(The information below is from _Herbal Drugs and Phytopharmaceuticals_ by
Unless otherwise prescribed, 2 to 4 grams of the raw herb or 0.2 to 1.0 mg
of extracted hypericin per day.
St. John's wort can be taken orally as chopped or powdered herb, a liquid or
semi-solid preparation or a water/grain alcohol tincture. Tea bags
containing 2 grams of the raw herb are also available.
Brands standardized for hypericin content are to be preferred.
A tea can be made of St. John's wort by pouring about 1 cup
of boiling water over 2 teaspoons (2-4 grams) of chopped raw herb,
waiting for 5-10 minutes, then straining.
1 teaspoon of finely chopped St. John's wort equals about 1.8 g.
The solution should not be simmered because this will boil off the
Two cups of the freshly prepared tea are drunk regularly morning and
evening. (It's unclear in Wichtel, but given that the normal dose is 4
grams per day, I assume this means that the dose is divided into one cup
in the A.M. and one in the P.M.)
Wichtel states that it is necessary to use the compound over a period of
several weeks or months to notice an effect.
5. CHEMICAL COMPOSITION OF ST. JOHN'S WORT:
Like most plant drugs, St. John's wort is a very complex substance with
over a dozen bioactive compounds. It contains agents with antibiotic
and anti-viral effects, at least one anti-inflammatory compound, an
estrogenic agent, coumarins and an MAOI.
According to Wichtel, the bioactive agents in St. John's wort consist
- Hypericin and related compounds: 0.05 to 0.3% hypericin, pseudohypericin,
isohypericin, protohypericin. H. perforatum appears to contain less
hypericin than H. augustifolia.
- Flavonoids: hyperoside (also called hyperin), rutin, and biflavones.
- Hyperforin: up to 3% (Hyperforin possesses antibiotic properties and is
chemically related to the bitter substances found in hops)
- Tannins: up to 10%
- Procyanidins: small amounts.
- The usual essential oils (n-alkanes, alpha-pinene and other mono-
Hypericum also contains beta-sitosterol, an estrogenic agent, but
Wichtel doesn't list the amount.
Finally, Wichtel states that adulteration of St. John's wort is fairly
common, most notably with other Hypericum species. See my general
article on herbal medicine: _Herbal Medicine: Sometimes Helpful but Use
With Care_ for information on testing for adulterants and consumer
rights re: adulterated herbs. (See top of document for how to get a
5. DOES ST. JOHN'S WORT CAUSE BAD REACTIONS OR SIDE EFFECTS?
No adverse effects in humans have ever been reported in the scientific
literature, although herb side effects are probably underreported for a
variety of reasons. St. John's wort can cause photosensitivity in certain
animals. I have two anecdotal reports of people developing a photosensitive
(made worse by sunlight) rash from St.John's wort. Both were in very
fair-skinned, blonde haired, blue eyed persons.
Even though no adverse effects have been reported for St. John's wort,
the following precautions are indicated based on theoretical
information about this plant:
a. Don't take St. John's wort with other antidepressants including
SSRIs, tricyclic antidepressants and MAOIs.
b. Don't take St. John's wort with other drugs, such as stimulants, known
to adversely interact with MAOIs.
For a full list of MAOI precautions see:
c. Stick to the standard dosage or the dose on the bottle and don't keep
increasing the dose if it's not working.
d. Do not stop taking prescription antidepressants without proper
medical care. If stopping an MAOI, wait a minimum of 4 weeks before
taking any other antidepressant including St. John's wort.
e. Do not take St. John's wort for bipolar (manic-depressive) illness.
f. Do not take St. John's wort if you are pregnant or breast feeding.
g. Do not take St. John's wort if you have an estrogen dependent
cancer, such as certain breast and uterine cancers. Even though the
estrogenic agent in St. John's wort does not appear to affect breast
tissue, not enough is known to state that it is safe to use in
people with breast cancer. Beta-sitosterol DOES stimulate uterine
and ovarian tissue.
h. Don't self-treat serious depression.
About the last precaution:
Depression is a very serious illness and the suicide rate in
untreated depression is at least 15% over the long term. An occasional
case of the blues is one thing; a depression that lasts for weeks or
months is a whole different matter. Because depression so strongly
affects a person's view of reality, it's very important for folks with
depression to have someone else to check in with who can tell if things
are to the point where suicide is a real risk. Most cases of depression
ARE treatable and if people need more information, I suggest that they
check in on alt.support.depression.
7. WHAT IS THE CHEMICAL RESPONSIBLE FOR ITS ANTIDEPRESSANT EFFECTS?
Nobody knows what is the antidepressant agent in the plant.
It used to be thought that the antidepressant compound was hypericin,
which is the substance believed to inhibit MAO. However, it's now
known that hyperforin and some of the biflavones (known to be CNS
depressants) are involved in the sedative effects of the plant.
The only thing folks are pretty sure about is that St. John's wort's
antidepressant properties are probably not due to MAO inhibition, so there
may well be some other unidentified agent in the plant.
8. THE MAOI CONTROVERSY:
Until recently, most people believed that St.John's exerted its
antidepressant effects by inhibiting a brain chemical key to the
breakdown of dopamine and norepinephrine called monoamine oxidase (MAO).
Compounds that prevent the action of MAO are called MAO Inhibitors
or MAOI's. MAOIs are antidepressant drugs, with the most commonly
prescribed MAOIs being Parnate (tranylcypromine) and Nardil
(phenylzine). These drugs are highly effective antidepressants but
are used only to treat depression resistant to all other drugs
because of potentially dangerous drug and food interactions.
When something interferes with the action of MAO, certain
compounds that stimulate the sympathetic nervous system have much
stronger effects on the body. In particular, the consumption of
foods containing large amounts of tyramine (a metabolite
of the amino acid tyrosine and a key chemical precursor of
the neurotransmitters dopamine and norepinephrine) and/or
particular drugs, such as stimulants and most antidepressants, can
cause a very dangerous sudden sharp rise in blood pressure when
taken by people using MAOIs. This reaction can cause strokes and many
fatalities are on record from adverse MAOI interactions.
MAOIs come in two forms: reversible (which inactivates but does not
destroy MAO) and irreversible (which does destroy MAO). Irreversible
MAOIs are much more dangerous than reversible ones and have far more
drug and food interactions.
The MAOI in St. John's wort is of the more dangerous, irreversible form.
A recent study on rat brains states that an extremely high dose of this
herb is needed to actively inhibit MAO-A. The researchers suggest
that another compound must therefore be the active agent. This
would certainly be consistent with the fact that MAOI type adverse
reactions have never been reported from this herb.
St. John's *is* in common use in Germany, England and several other
European countries and people are NOT keeling over in the streets from it.
Since doctors in these countries have been paying close attention to the
MAOI effects of this plant, I would think we would have heard reports by
now if people were having MAOI related problems.
St.John's may well be free of MAOI interactions at normally used doses.
However, until a human study on this is done, we won't know for sure. Rat
brains are actually a fairly good model to test this stuff, but rats and
humans do have some significant differences.
9. OTHER POSSIBLE MECHANISMS OF ANTIDEPRESSANT ACTION:
Today, the most popular hypothesis is that hypericum works like other
non-MAOI antidepressants such as SSRIs (Prozac, Zoloft) and tricyclics,
through serotonin and norepinephrine reuptake inhibition. (In other words,
preventing the brain from reabsorbing the neurotransmitters in question
and so keeping serotonin and norepinephrine levels in the brain at a
A 1984 study on 6 women found that St. John's Wort increased the levels
of norepinephrine metabolic byproducts. (This study also found St.
John's Wort to have anti-depressive effects). This would be consistent
with increased norepinephrine levels in the body. This could occur
either from a mechanism of action similar to Prozac or it could indicate
MAOI action. It could also be the result of stimulant action, although
no stimulant activity or side effects have ever been reported for St.
Another theory is that hypericum acts on many levels simultaneously,
creating an accumulating effect via serotonin, norepinephrine, and
dopamine-reuptake inhibition, and by action on the hypothalamus inhibiting
St.John's wort has been used a lot in the treatment of depression
associated with menopause. The estrogenic effects of beta-sitosterol
might account for some of its effectiveness in women during and after
menopause. The estrogenic action of St. John's wort does not appear
to cause any problems in men who take it.
St. John's wort also contains coumarins; some coumarins inhibit blood
clotting. I have not been able to find out if the coumarins in
St.John's wort affect blood clotting or not.
10. DOES ST. JOHN'S WORT HAVE ANTI-CANCER EFFECTS?
A couple of years ago, Neurosurgery (a highly respected medical journal)
published *one* case report on the use of an hypericin extract on a person
who had an inoperable brain tumor. The tumor this person had was a glioma,
which is almost always fatal. I have not read the article in question and
so do not have all the details. The authors apparently did not claim a
cure or even a full remission, but the extract may have slowed or temporarily
stopped the progression of the tumor. Given the grim prognosis for glioma,
even slowing its course is an improvement and so people on the BRAIN TUMOR-L
have been very interested in this substance.
The idea that it might have anti-cancer effects is not entirely off the
wall: many cancer chemotherapy agents were originally derived from plant
sources. The most recent example is Taxol, made from the Pacific Yew.
Vincristine is another common cancer chemo agent originally derived from
However much more research is needed. At this point in time, it should
NOT be promoted as a cancer cure. I personally would *not* use it in place
of standard glioma treatments. However, it appears to be pretty safe,
and I might take it as an adjunct to standard therapy. Certainly, a person
whose tumor does not respond to standard treatments has nothing to lose by
NOTE: If you want to try hypericin for this purpose, please let your
doctor know about it. Seriously ill people should never take herbs or
any over the counter drugs without their physician knowing about it.
Plant derived drugs can and do have interactions with standard
pharmaceuticals, foods and other herbs.
11. RESEARCH ON ST. JOHN'S WORT AND PREGNANCY:
I recommend that St. John's wort NOT be used while pregnant or if breast
First, hypericum extract has been shown to cause contraction of uterine
muscles of rats and mice in vitro. Not a great indicator of what it does
in the human body, but why take any agent that could cause uterine
and so risk miscarriage?
Second, we don't know if hypericum can cause birth defects.
A water/ethanol extract has been tested for mutagenicity (the ability
to change or alter DNA) against salmonella bacteria and has been
found to have anti-mutagenic effects. This is called the Ames test
and is the standard method used to determine if an agent can
cause cancer or birth defects. It's also been tested in test tubes
(in vitro) against rat embryo cells with negative results. Therefore
it's highly unlikely that water/alcohol extracts of St. John's wort
cause chromosomal damage.
However, it's never been tested for teratogenicity (the ability to cause
birth defects) in living organisms (in vivo) in either animals or humans.
There has not been enough human use to know if birth defects are associated
with hypericum or not.
This result also doesn't tell us whether any of the oily substances
in St. John's wort can cause birth defects, since oily compounds are not
very soluble in water or alcohol and so aren't necessarily picked up
by the solution.
There are many mechanisms other than chromosomal damage by which birth
defects can occur. Thalidomide, for example, probably causes birth defects
by blocking the formation of new blood vessels between the 6th and
9th week of pregnancy. Thus, it's conceivable that an agent that passes the
Ames test could still be teratogenic.
Of particular concern to me is the effect of an anti-depressant agent on the
developing nervous system and brain of a fetus or newborn. This might
actually be MORE of a risk in the last trimester of pregnancy or shortly
after birth (when the infant brain is undergoing subtle but critical
formation) so just avoiding the first 12 week 'window of vulnerability'
A note of caution is also due regarding the estrogenic agents in St.
John's wort. To my knowledge, beta-sitosterol has never been tested for
teratogenic effects. We do know that certain estrogens, notably D.E.S.
(diethylstilbesterol) cause deformities and cancers of the reproductive
system and reduce fertility in people exposed to them in utero (while
still in the womb). It can take many years for such problems to become
evident: DES daughters did not develop vaginal cancers until well into
I think we would do well to remember the effects of DES on both males and
females, as well as the possible role of estrogenic organohalides in
breast cancers and reduced male fertility. In other words, I personally
wouldn't take any estrogenic agent during pregnancy if I could avoid it.
If an anti-depressant is still needed during pregnancy, I'd use a standard
prescription antidepressant that's had a long history of use and that
we've got some data about in pregnant women. I'd use such a drug only if
I couldn't get by without it (i.e. suicide or psychosis is an immediate
danger) and for as short a period of time as possible.
"The trick is to keep an open mind, without it being so open that
your brain falls out"
Camilla Cracchiolo, R.N.