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St. John's wort

What is St. John's wort?

St. John’s wort is found in Europe and the United States. It is especially abundant in northern California and southern Oregon. The above-ground (aerial) parts of the plant are gathered during the flowering season.

What are the historical uses of St. John's wort?

In ancient Greece, St. John’s wort was used to treat many ailments,including sciatica and poisonous reptile bites. In Europe, St. John’s wort was used by herbalists for the topical treatment of wounds and burns. It is also a folk remedy for kidney and lung ailments as well as for depression.

What are the active constituents of St. John's wort?

The major constituents in St. John’s wort include hypericin and other dianthrones, flavonoids, xanthones, and hyperforin.1 While it was previously thought the antidepressant actions of St. John’s wort were due to hypericin and the inhibition of the enzyme monoamine oxidase,2 current research has challenged this belief, focusing on other constituents, such as hyperforin, and flavonoids.3 4 5

Test tube studies suggest that St. John’s wort extracts may exert their antidepressant actions by inhibiting the reuptake of the neurotransmitters serotonin, norepinephrine, and dopamine.6 This action is possibly due to the constituent hyperforin.7 St. John’s wort is able to act as an antidepressant, by making more of these neurotransmitters available to the brain.

How much St. John's wort is usually taken?

The standard recommendation for mild to moderate depression is 500–1,050 mg of St. John’s wort extract per day.8 9 10 Results may be noted as early as two weeks. Length of use should be discussed with a healthcare professional. For more severe depression, higher intakes may be used, under the supervision of a healthcare professional.

Are there any side effects of St. John's wort?

St. John’s wort has a low incidence of side effects compared to prescription antidepressants. An adverse events profile of St. John’s wort found that, of 14 controlled clinical trials, seven reported no adverse reactions, two had no information, and five reported a total of seven mild reactions.11 Adverse effects reported included stomach upset, fatigue, itching, sleep disturbance, and skin rash. The rate of adverse reactions was always similar to that of the placebo. Additionally, in seven trials comparing St. John’s wort with other antidepressants, the adverse reaction rate for St. John’s wort was consistently lower than that of the antidepressant drugs with which it was compared.

St. John’s wort can make the skin more sensitive to sunlight.12 Therefore, fair-skinned people should be alert for any rashes or burns following exposure to the sun. Three cases of severe blistering and burns were reported in people taking St. John’s wort internally or applying it topically and then being exposed to sunlight.13 There is a case report of a woman experiencing neuropathy (nerve injury and pain) in sun-exposed skin areas after taking 500 mg of whole St. John’s wort for four weeks.14 Although St. John’s wort has photosensitizing properties, the severity of this reaction is not typical for people taking the herb.

People with a history of manic-depressive illness (bipolar disorder) or a less severe condition known as hypomania, should avoid use of St. John’s wort as it may trigger a manic episode.15 16 17 18

There is a single case report in which ingestion of St. John's wort appeared to cause high blood pressure in a 56-year-old man. The blood pressure returned to normal when the herb was discontinued.19

Are there any drug interactions is St. John's wort?

Certain medicines may interact with St. John’s wort. Refer to drug interactions for a list of those medicines.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.20Consequently, St. John's wort could potentially interfere with a large number of medications. Individuals taking any medication should, therefore, consult with a physician before taking St. John's wort.


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1. Gruenwald J. Standardized St. John’s wort clinical monograph. Quart Rev Nat Med 1997;Winter:289–99.
2. Suzuki O, Katsumata Y, Oya M. Inhibition of monoamine oxidase by hypericin. Planta Med 1984;50:272–4.
3. Holzl J, Demisch L, Gollnik B. Investigations about antidepressive and mood changing effects of Hypericum perforatum. Planta Med 1989;55:643.
4. Chatterjee SS, Koch E, Noldner M, et al. Hyperforin with hypericum extract: Interactions with some neurotransmitter systems. Quart Rev Nat Med 1997;Summer:110.
5. Calapai G, Crupi A, Firenzuoli F, et al. Effects of Hypericum perforatum on levels of 5-hydroxytryptamine, noradrenaline and dopamine in the cortex, diencephalon and brainstem of the rat. J Pharm Pharmacol 1999;51:723–8.
6. Müller WE, Rolli M, Schäfer C, Hafner U. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 1997;30(suppl):102–7.
7. Müller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998;31(suppl):16–21.
8. Brown DJ. Herbal Prescriptions for Better Health. Rocklin, CA: Prima Publishing, 1996, 159–65.
9. Woelk H. Comparison of St. John’s wort and imipramine for treating depression: Randomized controlled trial. BMJ 2000;321:536–9.
10. Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomized multicenter study of treatment for eight weeks. BMJ 1999;319:1534–9.
11. Ernst E, Rand JI, Barnes J, et al. Adverse effects profile of the herbal antidepressant St. John’s wort (Hypericum perforatum L.) Eur J Clin Pharmacol 1998;54:589–94.
12. Brockmöller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: Pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30(suppl):94–101.
13. Lane-Brown MM. Photosensitivity associated with herbal preparations of St. John’s wort (Hypericum perforatum). MJA 2000;172:302[Letter].
14. Bove GM. Acute neuropathy after exposure to sun in a patient treated with St John’s Wort. Lancet 1998;352:1121–2 [letter].
15. Nierenberg AA, Burt T, Matthews J, Weiss AP. Mania associated with St. John’s wort. Biol Psychiatry 1999;46:1707–8.
16. Moses EL, Mallinger AG. St. John’s wort: Three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115–7.
17. O’Breasail AM, Argouarch S. Hypomania and St John’s wort. Can J Psychiatry 1998;43:746–7 [letter].
18. Schneck C. St. John’s wort and hypomania. J Clin Psychiatry 1998;59:689 [letter].
19. Zullino D, Borgeat F. Hypertension induced by St. John's Wort: a case report. Pharmacopsychiatry. 2003;36:32.

20. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003;290:1500–4.

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