St. John's wort (Hypericum perforatum) is a long-living, wild-growing herb with
yellow flowers that has been used for centuries to treat mental disorders as well as nerve
pain. In ancient times, doctors and herbalists (herb specialists) wrote about its use as a
sedative and antimalarial agent as well as a balm for wounds, burns, and insect bites.
Today, the herb is a popular treatment for mild to moderate depression; it also is used to
treat anxiety, seasonal affective disorder, and sleep disorders.1
St. John's wort is most widely used in Germany, where doctors prescribed almost 66
million daily doses in 1994 for psychological complaints.2
In fact, German doctors prescribe St. John's wort about 20 times more often than Prozac,
one of the most widely prescribed antidepressants in the United States.3
The use of St. John's wort is growing in the United States, and several brands now are
available. Extracts of the plant are sold as a nutritional supplement after being prepared
with a powder or an oil; the herb is available in capsule, tea, or tincture forms. St.
John's wort was among the top-selling botanical products in the United States in 1997,
with industry-estimated sales of $400 million in 1998.4
St. John's wort is 1 of 200 plant products approved by the U.S. Food and Drug
Administration (FDA) for sale to the public as a dietary supplement. The FDA does not
subject dietary supplements to an extensive premarket approval process, however, as it
does new drugs.5 On the other hand, the Dietary Supplement
Health and Education Act of 1994 permits the FDA to remove a supplement from the market if
it determines the supplement is unsafe. Herbal products such as St. John's wort can be
marketed without stating standards for dosage or evidence of safety. Often, information on
specific products may be misleading or even inaccurate. For instance, when the Los
Angeles Times, a newspaper in California, commissioned laboratory tests on 10 St.
John's wort products, researchers found that the potency of the products varied
dramatically from what their labels claimed.6
At the same time, a St. John's wort product stating the words "standardized
extract" in its label may be more likely to contain the exact amount of the specific
active ingredient needed to be effective. Standardized products generally are considered
the highest-quality herbal products that a consumer can buy.7
Depression is a common illness that strikes perhaps 1 in 15 Americans each year. A
person's mood, thoughts, physical health, and behavior all may be affected. Symptoms can
include a persistent sad, anxious, or "empty" feeling; loss of energy, appetite,
or sexual drive; and lack of interest in socializing, work, or hobbies.
Depression can be mild, moderate, or severe. Mild depression is characterized by
difficulty in functioning normally, while moderate depression may involve impaired
functioning at work or in social activities. Severe depression, which may involve
delusions or hallucinations, markedly interferes with a person's ability to work or
otherwise function and may lead to suicide. Genetic factors may put a person at risk for
developing depression, and alcohol or drug use can make the problem worse.8 While the public misperception persists that depression is
voluntary or a "character flaw," depression is a real condition that can be
treated effectively by qualified professionals.9
Specific psychotherapies (such as interpersonal and cognitive-behavioral therapy) and
antidepressant medications both have been found to be effective for patients with major
depression. Major depression includes mild, moderate, or severe depression that is not
characterized by manic-depressive mood swings or induced by a substance such as alcohol.
Several antidepressant drugs have become more widely used in the past several years and
been found to be effective. However, patients sometimes report unpleasant side effects
such as a dry mouth, nausea, headache, diarrhea, or impaired sexual function or sleep.10
In part because of these types of drug side effects, many patients with depression are
turning to herbal treatments such as St. John's wort. Researchers are studying it for
possibly having fewer and less severe side effects than antidepressant drugs. St. John's
wort also costs far less than antidepressant medication. In addition, St. John's wort does
not require a prescription.11
St. John's wort is not completely free of side effects, however. Some users have
complained of a dry mouth, dizziness, gastrointestinal symptoms, increased sensitivity to
sunlight, and fatigue.12 In addition, herbal treatments
often are not as potent or as quick to act as conventional treatments. Furthermore, herbal
treatments may not produce the desired results and may not be as effective as conventional
medicine. Still, some people turn to herbs because they prefer to use "natural"
Clinical depression is a serious medical disorder that, in many cases, can be treated.
However, St. John's wort is not a proven therapy for clinical depression. Therefore, there
is some risk in taking it to treat clinical depression.5
In any case, St. John's wort should not be mixed with other standard antidepressants
because side effects may result. This is one reason why it is important to tell your
doctor about all medications you are taking. Check with your doctor before taking St.
John's wort or any other herb or medication. Your doctor can help you weigh the risks and
benefits of a particular treatment so you can make informed health care decisions.
How St. John's Wort Works
The major components in extracts of St. John's wort include flavonoids, kaempferol,
luteolin, biapigenin, hyperforin, polycyclic phenols, hypericin, and pseudohypericin.
Researchers believe the last three substances are the active ingredients.5 New research suggests that hyperforin also may play a large role
in the herb's antidepressant effects. Some German manufacturers of St. John's wort have
begun standardizing, not only to hypericin as most U.S. manufacturers do, but to
hyperforin as well.13 Standardizing means that the
manufacturer ensures that each individual supplement contains a uniform amount of a
certain compound, in this case hypericin and hyperforin.
Recent research suggests a possible application of St. John's wort for alcoholism.
Researchers from the University of North Carolina at Chapel Hill found that St. John's
wort reduced alcohol intake in laboratory animals.14
Several mechanisms of action of St. John's wort have been proposed, including the
- Inhibition of monoamine (serotonin, dopamine, and norepinephrine) re-uptake: St.
John's wort appears to reduce the rate at which brain cells reabsorb serotonin (an
important neurotransmitter or chemical that aids communication between nerve cells). Low
levels of serotonin in the body are associated with depression.15,16
- Modulation of interleukin-6 (IL-6) activity: Raised levels of IL-6, a protein
involved in the communication between cells in the body's immune (disease-fighting)
system, may lead to increases in adrenal regulatory hormones, a hallmark of depression.
St. John's wort may reduce levels of IL-6, and thus help treat depression.17
More research is needed to determine precisely the active ingredients in St. John's
wort and to learn how the herb works.
Clinical trials (studies of a treatment's safety and effectiveness in humans) have
found a similar rate of response with St. John's wort as with standard, conventional
antidepressants in treating mild to moderate depression.18,19 However, it is hard to interpret these studies as definite
proof of the efficacy of St. John's wort because low doses of standard antidepressants
were used and there was no placebo (a pharmacologically inactive substance) control. An
analysis of 23 European clinical studies of St. John's wort that was published in the British
Medical Journal in 1996 concluded that the herb has antidepressive effects in cases of
mild to moderate depression (the dosage varied considerably among the studies).2 However, no studies of its long-term use have been conducted. More
research is needed to explore the long-term effects and optimum safe dosage of the
A new study
funded by the National Institutes of Health's National Center for Complementary and
Alternative Medicine (NCCAM), Office of Dietary Supplements, and the National Institute of
Mental Health will provide more information about St. John's wort. This study, which is in
progress, is the first large-scale controlled clinical trial in the United States to
assess whether the herb has a significant therapeutic effect in patients with clinical
The $4.3 million study will involve 336 patients with major depression. The Duke
University Medical Center in Durham, North Carolina, is coordinating the 3-year study,
which has 13 clinical sites around the country.
There are three different treatment groups in the trial. One group will receive an
initial dose of 900 mg per day of St. John's wort; a second will receive a placebo; and
the third will receive Zoloft (a commonly used antidepressant). Patients who respond
positively to their randomly assigned treatment will be continued on it for another 4
For more information about depression, contact the National Institute of Mental Health
toll-free at 1-800-421-4211. For more information about St. John's wort, contact the
American Botanical Council at 512-926-4900 or the Herb Research Foundation at
303-449-2265. For more information about complementary and alternative medicine, contact
the NCCAM Clearinghouse at 1-888-644-6226.
- American Herbal Pharmacopoeia and Therapeutic Compendium. "St. John's Wort (Hypericum
perforatum) Monograph." Herbalgram. The Journal of the American Botanical
Council and the Herb Research Foundation. 1997. (40):1-16.
- Linde, K., Ramirez, G., Mulrow, C.D., Weidenhammer, W., and Melchart, D. "St.
John's Wort for DepressionAn Overview and Metaanalysis of Randomized Clinical
Trials." British Medical Journal. 1996. 313(7052):253-8.
- Murray, M. "Common Questions About St. John's Wort Extract." American
Journal of Natural Medicine. 1997. 4(7):14-9.
- Nutrition Business Journal. San Diego, CA: Nutrition Business International,
- National Institute of Mental Health. Questions and Answers About St. John's Wort.
Bethesda, MD: National Institute of Mental Health, 1997.
- Monmaney, T. "Remedy's U.S. Sales Zoom, but Quality Control Lags. St. John's Wort:
Regulatory Vacuum Leaves Doubt About Potency, Effects of Herb Used for Depression."
Los Angeles, CA: Los Angeles Times, August 31, 1998.
- Duke, J. The Green Pharmacy. Emmaus, PA: Rodale Press, 1997.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders. 4th ed. Washington, DC: American Psychiatric Association, 1995.
- National Institute of Mental Health. General Facts About Depression. Bethesda,
MD: National Institute of Mental Health, 1997.
- Medical Economics Company. Physician's Desk Reference 1998. 52nd ed. Montvale,
NJ: Medical Economics Company, 1997.
- Kincheloe, L. "Herbal Medicines Can Reduce Costs in HMO." Herbalgram. The
Journal of the American Botanical Council and the Herb Research Foundation. 1997.
- Woelk, H., Burkard, G., and Grunwald, J. "Benefits and Risks of the Hypericum
Extract LI 160: Drug Monitoring Study With 3,250 Patients." Journal of Geriatric
Psychiatry and Neurology. 1994. 7(Supplement 1):S34-8.
- Laakmann, G., Schule, C., Baghai, T., and Kieser, M. "St. John's Wort in Mild to
Moderate Depression: The Relevance of Hyperforin for the Clinical Efficacy." Pharmacopsychiatry.
June 1998. 31(Supplement):54-9.
- Rezvani, A.H. 1998 Annual Meeting of the Research Society on Alcoholism. Hilton
Head, SC: Research Society on Alcoholism, June 23, 1998.
- Andrews, E. "In Germany, Humble Herb Is Rival to Prozac." New York, NY: New
York Times, September 9, 1997.
- Perovic, S. and Muller, W.E.G. "Pharmacological Profile of Hypericum Extract.
Effect of Serotonin Uptake by Postsynaptic Receptors." Arzneimittel-Forschuns.
- Thiele, B., Brink, I., and Ploch, M. "Modulation of Cytokine Expression by
Hypericum Extract." Journal of Geriatric Psychiatry and Neurology. 1994.
- Harrer, G., Hubner, W.D., and Podzuweit, H. "Effectiveness and Tolerance of the
Hypericum Extract LI 160 Compared to Maprotiline: A Multicenter Double-Blind Study." Journal
of Geriatric Psychiatry and Neurology. 1994. 7(Supplement 1):S24-8.
- Harrer, G. and Sommer, H. "Treatment of Mild/Moderate Depressions With
Hypericum." Phytomedicine. 1994. 1:3-8.