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St. John's Wort and Depression

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St. John's wort is a plant with yellow flowers that has been used for centuries for health purposes, such as for depression and anxiety. This fact sheet answers some frequently asked questions about St. John's wort and depression, and summarizes what the science says about its effectiveness and the research being done.


Key Points


About St. John's Wort

St. John's wort (Hypericum perforatum) is a long-living plant with yellow flowers whose medicinal uses were first recorded in ancient Greece. It contains many chemical compounds. Some are believed to be the active ingredients that produce the herb's effects, including the compounds hypericin and hyperforin.

How these compounds actually work is not yet fully understood, but several theories have been suggested. Preliminary studies suggest that St. John's wort might work by preventing nerve cells in the brain from reabsorbing the chemical messenger serotonin, or by reducing levels of a protein involved in the body's immune system functioning. St. John's wort has been used over the centuries for mental conditions, nerve pain, and a wide variety of other health conditions. Today, St. John's wort is used for anxiety, mild to moderate depression, and sleep disorders.

In Europe, St. John's wort is widely prescribed for depression. In the United States, there is public interest in St. John's wort as a treatment for depression, but it is not a prescription medicine; it is, however, one of the most commonly used herbal supplements.

In the United States, St. John's wort products are sold as:


About Depression

Depression is a medical condition that affects nearly 21 million American adults each year, according to the National Institute of Mental Health. Mood, thoughts, physical health, and behavior all may be affected. Symptoms of depression commonly include:

Depression comes in several forms and its symptoms and severity can vary from person to person. For example:

In addition, milder forms of depression exist that fall into the category of minor depression. In minor depression, people experience the same symptoms as major depression, but they are fewer in number and are less disabling. Symptoms last at least 6 months but less than 2 years continuously.

Depression can be treated effectively with conventional medicineMedicine as practiced by holders of M.D. (medical doctor) or D.O. (doctor of osteopathy) degrees and by their allied health professionals such as physical therapists, psychologists, and registered nurses., including antidepressants and certain types of psychotherapy.


What the Science Says About St. John's Wort for Depression

Scientific evidence regarding the effectiveness of St. John's wort for depression is inconsistent. An analysis of the results of 37 clinical trials concluded that St. John's wort may have only minimal beneficial effects on major depression. However, the analysis also found that St. John's wort may benefit people with minor depression; these benefits may be similar to those from standard antidepressants. Overall, St. John's wort appeared to produce fewer side effects than some standard antidepressants.

One of the studies included in the analysis was cofunded by NCCAM and two other components of the National Institutes of Health (NIH)—the National Institute of Mental Health and the Office of Dietary Supplements. This study found that St. John's wort was no more effective than placebo in treating major depression of moderate severity. However, the antidepressant sertraline, used in one arm of the study, also showed little difference from placebo.


Side Effects and Risks

The most common side effects of St. John's wort include dry mouth, dizziness, diarrhea, nausea, increased sensitivity to sunlight, and fatigue.

Research has shown that taking St. John's wort can limit the effectiveness of some prescription medicines, including:

When combined with certain antidepressants, St. John's wort also may increase side effects such as nausea, anxiety, headache, and confusion.


Herbal Products: Issues To Consider

Herbal products such as St. John's wort are classified as dietary supplements by the U.S. Food and Drug Administration (FDA). The FDA's requirements for testing and obtaining approval to sell dietary supplements are different from its requirements for drugs. Unlike drugs, herbal products can be sold without requiring studies on dosage, safety, or effectiveness.

The strength and quality of herbal products are often unpredictable. Products can differ in content not only from brand to brand, but from batch to batch. Information on labels may be misleading or inaccurate.

In addition, "natural" does not necessarily mean "safe." Many natural substances can have harmful effects–especially if they are taken in large quantities or if they interact with other supplements or with prescription medicines.

Tell your health care providers about any complementary and alternative practices you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care.


NCCAM Research on St. John's Wort

Recent projects supported by NCCAM include studies of the:


For More Information

NCCAM Clearinghouse

The NCCAM Clearinghouse provides information on CAM and NCCAM, including publications and searches of Federal databases of scientific and medical literature. The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.

Toll-free in the U.S.: 1-888-644-6226
TTY (for deaf and hard-of-hearing callers): 1-866-464-3615
Web site:

National Institute of Mental Health (NIMH)

NIMH is committed to reducing the burden of mental illness through research on mental disorders and the underlying basic science of brain and behavior. NIMH provides publications on depression and other illnesses.

Toll-free in the U.S.: 1-866-615-6464
Web site:

Office of Dietary Supplements (ODS), NIH

ODS seeks to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, supporting research, sharing research results, and educating the public. Its resources include publications and the International Bibliographic Information on Dietary Supplements database.

Web site:


A service of the National Library of Medicine (NLM), PubMed contains publication information and (in most cases) brief summaries of articles from scientific and medical journals. CAMA group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine. Complementary medicine is used together with conventional medicine, and alternative medicine is used in place of conventional medicine. on PubMed, developed jointly by NCCAM and NLM, is a subset of the PubMed system and focuses on the topic of CAM.

Web site:
CAM on PubMed: is a database of information on federally and privately supported clinical trials (research studies in people) for a wide range of diseases and conditions. It is sponsored by the National Institutes of Health and the U.S. Food and Drug Administration.

Web site:


Selected Sources

American Herbal Pharmacopoeia and Therapeutic Compendium. St. John's Wort (Hypericum perforatum). Monograph. American Herbal Pharmacopoeia; 1997.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM–IV). Washington, DC: American Psychiatric Association, 1994.

Barnes PM, Powell-Griner E, McFann K, Nahin RL. Complementary and alternative medicine use among adults: United States, 2002. CDC Advance Data Report #343. 2004.

De Smet PA. Herbal remedies. New England Journal of Medicine. 2002;347(25):2046–2056.

Greenblatt DJ, von Moltke LL. Interaction of warfarin with drugs, natural substances, and foods. Journal of Clinical Pharmacology. 2005;45(2):127–132.

Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. Journal of the American Medical Association. 2002;287(14):1807–1814.

Kasper S, Anghelescu IG, Szegedi A, et al. Superior efficacy of St. John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial. BMC Medicine [online journal]. 2006; 4(1):14. Accessed at on November 26, 2007.

Lee LS, Andrade AS, Flexner C. Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects. Clinical Infectious Diseases. 2006;43(8):1052–1059.

Linde K, Mulrow CD, Berner M, et al. St. John's wort for depression. Cochrane Database of Systematic Reviews. 2005;(2):CD000448. Accessed at on February 9, 2007.

Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John's wort on irinotecan metabolism. Journal of the National Cancer Institute. 2002;94(16):1247–1249.

Murphy PA, Kern SE, Stanczyk FZ, et al. Interaction of St. John's wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception. 2005;71(6):402–408.

National Institute of Mental Health. Depression. National Institute of Mental Health Web site. Accessed at health/publications/depression/ complete-publication.shtml on December 14, 2007.

National Institute of Mental Health. The Numbers Count: Mental Disorders in America. National Institute of Mental Health Web site. Accessed at /health/publications/ the-numbers-count-mental- disorders-in-america.shtml on December 14, 2007.

St. John's Wort. In: Blumenthal M, Goldberg A, Brinckman J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Lippincott Williams & Wilkins; 2000:359–366.


This publication is not copyrighted and is in the public domain. Duplication is encouraged.

NCCAM has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your primary health care provider. We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy is not an endorsement by NCCAM.

NCCAM Publication No. D005
Updated December 2007


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