St. John’s wort (Hypericum perforatum) is a popular herbal therapy for depression. It is also known as hypericum, Klamath weed, and goat weed. For centuries, St. John’s wort has been used worldwide to treat mental disorders and nerve pain. It has been referred to in ancient texts as a sedative, as well as a balm for wounds, burns, and bites. Paracelsus called the herb an “arnica of the nerves,” and Hippocrates discussed its use in the treatment of nervous conditions. It is also used for anxiety and sleep disorders.1 Today, sales of the herb total more than $400 million annually.2


Native to Europe and Asia, St. John’s wort grows worldwide. In the United States, the plant thrives especially in northern California and southern Oregon. A perennial hedgerow plant, St. John’s wort resembles a small, bushy flowering weed. It blooms with numerous small yellow flowers, which comprise the medicinal part of the plant. The flowers are made into teas, tablets, and concentrated extracts.3

Wort is an Old English word, literally meaning “plant.” The St. John moniker is believed to be related to the appearance of small red spots resembling blood that form on the leaves at the time of year when John the Baptist was beheaded.

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Mechanism of action

Like so many other herbs, the mechanism of action is poorly understood. The plant’s active ingredient, hypericin, is thought to exert a mild serotonin reuptake inhibitory effect, thereby maintaining higher levels of intrasynaptic serotonin and improving mood. Full efficacy usually requires at least two to four weeks of use, but studies have shown that plasma levels begin to rise two to three hours after consumption; a rapid cumulative increase occurs within the first three days.3


Two large NIH-funded studies (N = 200) found that St. John’s wort did not surpass placebo in treating major depression.4 All participants in these trials had scores >20 on the Hamilton Rating Scale for Depression. This scale rates the severity of depression in patients already diagnosed (a complete copy of the questionnaire can be found at [accessed June 8, 2006]). However, a review of 23 European clinical trials demonstrated the herb’s effectiveness in treating more moderate cases of depression. For a complete list of depression symptoms, see Table 1. These placebo-controlled studies (N = 1,757) found St. John’s wort to be safe and tolerable in patients with mild to moderate depression, as indicated by a Hamilton Rating Scale score <10.5 A recent Cochrane meta-analysis of 27 studies (N = 2,291) found St. John’s wort to be superior to placebo in treating mild-to-moderate depression.1 No studies, however, support use of the herb for severe depression, suicidal ideations, or other potentially harmful conditions.


Women who are lactating, pregnant, or may become pregnant should not take St. John’s wort. Effects in children are unknown because no studies have been conducted in pediatric patients. Persons with severe depression, suicidal ideations or plans, should not use St. John’s wort but should immediately be referred for professional care. As with any botanical product, there is a potential for allergy. Anyone with a history of allergic reactions to plants and pollen should use the herb with extreme caution.


Preparations of St. John’s wort are standardized to contain 0.3% hypericin, the active chemical in the flowers. The recommended daily dose is 300 mg taken with food three times a day. This dosage yields 2.7 mg of pure hypericin in capsules, tablets, teas, or concentrated extracts.2

Side effects

Part of St. John’s wort’s appeal is that it causes milder side effects than most prescription antidepressants. However, a number of studies have found that the plant can interfere with other medications. Of particular concern is a warning in 2000 by the FDA that hypericin appears to inhibit many of the antiretrovirals used in HIV therapy.3

The effects of other prescription drugs may be weakened when taken in conjunction with St. John’s wort, including digoxin, warfarin, oral contraceptives, and some antidepressants. For the most part, concomitant use of St. John’s wort with these drugs serves to decrease the level of the prescription drug in the blood.2

Generally, side effects are mild but can include nausea, vomiting, diarrhea, dizziness, anxiety, dry mouth, and confusion. Headache is common.A few cases of sexual side effects have also been reported with use of St. John’s wort; however, it is important to note that selective serotonin reuptake inhibitors, the leading class of prescription pharmaceuticals for depression, are also well known for interfering with sexual function.2


Depending on the market, St. John’s wort costs approximately $15-$30 per month.


St. John’s wort is a safe, inexpensive alternative to prescription medication for mild-to-moderate depression. Due to inconsistency of clinical trial evidence, no efficacy claim can be made for major or severe depression. As is the case with all depression, however, the need for psychotherapy or other forms of intervention may still exist even if the patient is not on a prescription drug. Comprehensive therapy for depression is still the most effective approach and should be pursued.


1. Lawvere S, Mahoney MC. St. John’s wort. Am Fam Physician. 2005;72:2249-2254.

2. National Center for Complementary and Alternative Medicine. St. John’s wort. Available at /stjohnswort. Accessed June 8, 2006.

3. Benjamin SD. St. John’s wort and depression. Patient Care for the Nurse Practitioner. 1999;2:50-52.

4. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St. John’s wort in major depression: a randomized controlled trial. JAMA. 2001;285:1978-1986.

5. Linde K, Ramirez G, Mulrow CD, et al. St. John’s wort for depression — an overview and meta-analysis of randomised clinical trials. BMJ. 1996;313:253-258.