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St. John's Wort (Hypericum perforatum)

Be aware that the U.S. Food and Drug Administration does not strictly regulate herbs and dietary supplements. There is no guarantee of strength, purity or safety of products containing or claiming to contain shark cartilage. Decisions to use herbs or supplements should be carefully considered. Individuals using prescription drugs should discuss taking herbs or supplements with their pharmacists or health care providers before starting.


Scientists have studied St. John's wort for the following health problems:

Many small studies over the past 20 years report that St. John's wort is more effective than placebo (sugar pill) and equally effective as tricyclic antidepressant drugs in the short-term treatment of mild-to-moderate depression (one to three months). It is not clear if St. John's wort has the same benefits as selective serotonin reuptake inhibitors (SSRIs), which are commonly used for depression in the United States. Two recent well-designed studies have found no benefit of St. John's wort, although the results of these studies raise questions about whether they are reliable. Other data suggest that St. John’s wort may be just as effective as SSRIs with fewer side effects. The use of St. John's wort remains controversial, but most natural medicine experts and textbooks continue to believe that this product is effective. Safety concerns exist, as they do with most conventional and complementary therapies.
Studies of St. John's wort for depression have also reported reductions in anxiety. However, there is currently not enough evidence to recommend St. John's wort for the primary treatment of anxiety disorders.
Obsessive-compulsive disorder
Because of a lack of well-designed studies, there is not enough evidence to recommend St. John's wort for the management of obsessive-compulsive disorder. Better studies are needed before a recommendation can be made.
Antiviral effects noted in laboratory tests have not been noted in humans. There are multiple reports of significant adverse effects and interactions with prescription HIV and AIDS drugs (protease inhibitors and non-nucleoside reverse transcriptase inhibitors). Therefore, there are reasons to recommend against the use of St. John's wort in patients with HIV or AIDS.
Atopic dermatitis
Early study of hypericum cream in the topical treatment of mild to moderate atopic dermatitis shows positive results. The therapeutic efficacy of the hypericum cream, however, has to be evaluated in further studies with larger patient populations and in comparison with therapeutic standards (such as glucocorticoids) before a firm recommendation can be made.
Social phobia
Results of early study fail to provide evidence for the efficacy of St. John’s wort in social phobia.
Early scientific evidence on St. John's wort for treating perimenopausal symptoms, including depressed mood, premenstrual syndrome, seasonal depressive disorder, or somatoform disorders, remains controversial.

Unproven Uses     

St. John's wort has been suggested for many other uses, based on tradition or on scientific theories. However, these uses have not been thoroughly studied in humans, and there is limited scientific evidence about safety or effectiveness. Some of these suggested uses are for conditions that are potentially serious and even life-threatening. You should consult a health care provider before using St. John's wort for any unproven use.

Abrasions — used topically
Athletic performance
Bacterial skin infections — used topically
Benzodiazepine withdrawal
Bruises — used topically
Burns — used topically
Chronic colitis
Chronic ear infections
Dental pain
Epstein-Barr virus
Herpes virus infection
Liver protection
Pain relief
Painful menstrual periods
Nerve pain
Wound healing — used topically

Potential Dangers     


Side Effects

Pregnancy And Breast-Feeding


Interactions with drugs, supplements and other herbs have not been thoroughly studied. The interactions listed below have been reported in scientific publications. If you are taking prescription drugs, speak with your health care provider or pharmacist before using herbs or dietary supplements.

Interactions With Drugs

St. John's wort may alter the blood levels of drugs that are broken down by certain liver enzymes. This affects many different drugs, with potentially serious effects. If you are considering taking St. Johns wort with other drugs, herbs, supplements or vitamins, it is important for you to speak with your health care provider and pharmacist first.

The U.S. Food and Drug Administration suggests that you avoid St. John's wort if you are taking HIV and AIDS drugs called protease inhibitors, such as indinavir (Crixivan), or non-nucleoside reverse transcriptase inhibitors, such as nevirapine (Viramune). There is a risk of lowering the levels of these drugs in your body if you take them with St. John's wort. St. John's wort may also decrease the effects of tricyclic antidepressants, such as amitriptyline (Elavil); cholesterol-lowering drugs, such as lovastatin (Mevacor); nifedipine (Procardia); midazolam (Versed); digoxin; and theophylline. Avoid St. John's wort if you are taking an immunosuppressant drug such as cyclosporine, tacrolimus, or myophenic acid, especially if you have received an organ transplant; there have been multiple reports of significant reductions in drug levels and possible organ rejection.

St. John's wort may increase the risk of sun sensitivity when used with drugs such as tetracycline or tretinoin (Retin-A). St. John's wort may decrease the effects of the blood-thinning drug warfarin. Be careful if you take monoamine oxidase inhibitors, such as phenelzine (Nardil), or selective serotonin reuptake inhibitors, such as fluoxetine (Prozac), because of the potential for increased side effects when taken with St. John's wort.

Use St. John's wort cautiously if you are taking birth control pills, because of reports of altered menstrual flow, bleeding and unwanted pregnancies. St. John's wort may reduce the thyroid activity of drugs such as levothyroxine (Synthroid). St. John's wort may increase the anti-inflammatory effects of cyclooxygenase (COX-2) inhibitors, such as celecoxib (Celebrex), or nonsteroidal anti-inflammatory drugs, such as ibuprofen (Motrin).

Interactions With Herbs And Dietary Supplements


The doses listed below are based on scientific research, publications or traditional use. Because most herbs and supplements have not been thoroughly studied or monitored, safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients even within the same brand. Combination products often contain small amounts of each ingredient and may not be effective. Appropriate dosing should be discussed with a health care provider before starting therapy; always read the recommendations on a product's label. The dosing for unproven uses should be approached cautiously, because scientific information is limited in these areas.

For Depression  Adults (Aged 18 Or Older)

For Social Phobia  Adults (Aged 18 Or Older)

For Somatoform Disorders  Adults (Aged 18 Or Older)

For Cardiovascular Regulation  Adults (Aged 18 Or Older)

For Atopic Dermatitis  Adults (Aged 18 Or Older)

Children (Younger Than 18): There is insufficient available evidence to recommend St. John's wort in children.


Although St. John's wort has been suggested for many conditions, it has been most studied as a treatment for mild to moderate depression. St. John's wort has not been proven for any other health condition. It has been studied for up to three months, but it has not been proven safe for longer use. Although research does not report many serious side effects, there are potentially dangerous interactions if St. John's wort is used with other drugs. For example, people taking certain drugs for HIV or AIDS, organ transplants, birth control, high cholesterol, high blood pressure and thyroid conditions should not use St. John's wort. These individuals should speak with a health care provider or pharmacist if considering its use. St. John's wort may interact with other drugs used for depression. Many other serious interactions are possible. St. John's wort should be avoided in pregnant or breast-feeding women and in children, because there is not enough information about safety. Consult your health care provider immediately if you experience side effects.

The information in this monograph was prepared by the professional staff at Natural Standard, based on thorough systematic review of scientific evidence. The material was reviewed by the Faculty of the Harvard Medical School with final editing approved by Natural Standard.


  1. Natural Standard: An organization that produces scientifically based reviews of complementary and alternative medicine topics.
  2. National Center for Complementary and Alternative Medicine (NCCAM): A division of the U.S. Department of Health & Human Services dedicated to research.
Selected Scientific Studies: St. John's Wort

Some of the more recent studies are listed below:

  1. Bauer S, Stormer E, Johne A, et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol 2003;Feb, 55(2):203-211.
  2. Behnke K, Jensen GS, Graubaum HJ, Gruenwald J. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Adv Ther 2002;Jan-Feb, 19(1):43-52.
  3. Findling RL, McNamara NK, O'Riordan MA, et al. An open-label pilot study of St. John's wort in juvenile depression. J Am Acad Child Adolesc Psychiatry 2003;42(8):908-914.
  4. Frye RF, Fitzgerald SM, Lagattuta TF, et al. Effect of St John's wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004;76(4):323-329.
  5. Gelenberg AJ, Shelton RC, Crits-Christoph P, et al. The effectiveness of St. John's wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication. J Clin Psychiatry 2004;65(8):1114-1119.
  6. Hall SD, Wang Z, Huang SM, et al. The interaction between St John's wort and an oral contraceptive. Clin Pharmacol Ther 2003;74(6):525-535.
  7. Hammerness P, Basch E, Ulbricht C, et al. St. John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003;44:271-282.
  8. Hebert MF, Park JM, Chen YL, et al. Effects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 2004;44(1):89-94.
  9. Hicks SM, Walker AF, Gallagher J, et al. The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's wort (Hypericum perforatum L.) for premenstrual symptoms. J Altern Complement Med 2004;10(6):925-932.
  10. Jiang X, Williams KM, Liauw WS, et al. Effect of St. John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57(5):592-599.
  11. Johne A, Schmider J, Brockmoller J, et al. Decreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St. John's wort (Hypericum perforatum). J Clin Psychopharmacol 2002;22(1):46-54.
  12. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66(4):338-345.
  13. Kalb R, Trautmann-Sponsel RD, Kieser M. Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients: a randomized double-blind multicenter clinical trial. Pharmacopsych 2001;34(3):96-103.
  14. Kawaguchi A, Ohmori M, Tsuruoka S, et al. Drug interaction between St John's Wort and quazepam. Br J Clin Pharmacol 2004;58(4):403-410.
  15. Kim HL, Streltzer J, Goebert D. St. John's wort for depression: a meta-analysis of well-defined clinical trials. J Nerv Ment Dis 1999;187(9):532-539.
  16. Linde K, Mulrow CD. St John's wort for depression. Cochrane Database Syst Rev 2000;(2):CD000448.
  17. 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(7052):253-258.
  18. Mai I, Bauer S, Perloff ES, et al. Hyperforin content determines the magnitude of the St. John's wort-cyclosporine drug interaction. Clin Pharmacol Ther 2004;76(4):330-340.
  19. Mai I, Stormer E, Bauer S, et al. Impact of St. John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003;18(4):819-822.
  20. Mauro VF, Mauro LS, Kleshinski JF, et al. Impact of ginkgo biloba on the pharmacokinetics of digoxin. Am J Ther 2003;10(4):247-251.
  21. Miller LG. Drug interactions known or potentially associated with St. John's wort. J Herbal Pharmacother 2001;1(3):51-64.
  22. Mills E, Montori VM, Wu P, et al. Interaction of St. John's wort with conventional drugs: systematic review of clinical trials. BMJ 2004;329(7456):27-30.
  23. Parker V, Wong AH, Boon HS, et al. Adverse reactions to St John's wort. Can J Psychiatry 2001;46(1):77-79.
  24. Morimoto T, Kotegawa T, Tsutsumi K, et al. Effect of St. John's wort on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 2004;44(1):95-101.
  25. Mueller SC, Uehleke B, Woehling H, et al. Effect of St. John's wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther 2004;75(6):546-557.
  26. Muller D, Pfeil T, von den Driesch V. Treating depression comorbid with anxiety: results of an open, practice-oriented study with St. John's wort WS 5572 and valerian extract in high doses. Phytomedicine 2003;10(Suppl 4):25-30.
  27. Muller T, Mannel M, Murck H, Rahlfs VW. Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial. Psychosom Med 2004;66(4):538-547.
  28. Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St. John's wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003;56(6):683-690.
  29. Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ 1999; 319(7224):1534-1538.
  30. Schempp CM, Windeck T, Hezel S, Simon JC. Topical treatment of atopic dermatitis with St. John's wort cream: a randomized, placebo controlled, double blind half-side comparison. Phytomedicine 2003;10(Suppl 4):31-37.
  31. Schroeder C, Tank J, Goldstein DS, et al. Influence of St. John's wort on catecholamine turnover and cardiovascular regulation in humans. Clin Pharmacol Ther 2004;76(5):480-489.
  32. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA 2001;285(15):1978-1986.
  33. Siepmann M, Kirch W, Krause S, et al. The effects of St. John's wort extract and amitriptyline on autonomic responses of blood vessels and sweat glands in healthy volunteers. J Clin Psychopharmacol 2004;24(1):79-82.
  34. Smith P, Bullock JM, Booker BM, et al. The influence of St. John's wort on the pharmacokinetics and protein binding of imatinib mesylate. Pharmacotherapy 2004;24(11):1508-1514.
  35. Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St. John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 2005;330(7490):503.
  36. Tannergren C, Engman H, Knutson L, et al. St John's wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism. Clin Pharmacol Ther 2004;75(4):298-309.
  37. Wang LS, Zhou G, Zhu B, et al. St. John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004;75(3):191-197.
  38. Wenk M, Todesco L, Krahenbuhl S. Effect of St. John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females. Br J Clin Pharmacol 2004;57(4):495-499.
  39. Wheatley D. Safety of St John's wort (Hypericum perforatum). Lancet 2000; 355(9203):576.

Last updated June 23, 2005