Nutritional Supplement

St. John’s Wort

Also indexed as: Hypericum perforatum, Saint John’s Wort, St. John's Wort

Parts Used & Where Grown

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.

How It Works

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.

References

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. MĂĽller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998;31(suppl):16-21.

8. 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.

9. Harrer G, Sommer H. Treatment of mild/moderate depressions with Hypericum. Phytomedicine 1994;1:3-8.

10. Ernst E. St. John's wort, an antidepressant? A systemic, criteria-based review. Phytomedicine 1995;2:67-71.

11. 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 [ISRCTN77277298]. BMC Med 2006 Jun 23;4:14.

12. Vorbach EU, HĂĽbner WD, Arnoldt KH. Effectiveness and tolerance of the Hypericum extract LI 160 in comparison with imipramine: Randomized double-blind study with 135 outpatients. J Geriatr Psychiatry Neurol 1994;7(suppl):S19-23.

13. 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.

14. Woelk H. Comparison of St. John's wort and imipramine for treating depression: Randomized controlled trial. BMJ 2000;321:536-9.

15. Wheatley D. LI 160, an extract of St. John's wort versus amitriptyline in mildly to moderately depressed outpatients—controlled six week clinical trial. Pharmacopsychiatry 1997;30(suppl):77-80.

16. Volz HP, Laux P. Potential treatment for subthreshold and mild depression: a comparison of St. John's wort extracts and fluoxetine. Compr Psychiatry 2000;41(2 Suppl 1):133-7 [review].

17. Harrer G, HĂĽbner WD, Poduzweit H. Effectiveness and tolerance of the Hypericum extract LI 160 compared to maprotiline: A multicenter double-blind study. J Geriatr Psychiatry Neurol 1994;7(suppl 1);S24-8.

18. Harrer G, Schmidt U, Kuhn U, Biller A. Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. Arzneimittelforschung 1999;49:289-96.

19. Schrader D. Equivalence of St. John's wort extract (ZE 117) and fluoxetine: a randomized, controlled study in mild - moderate depression. International Clin Psychopharmacol 2000;15:61-8.

20. Vorbach EU, Arnoldt KH, HĂĽbner WD. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry 1997;30(suppl):81-5.

21. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA 2001;285:1978-86.

22. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's Wort) in major depressive disorder: a randomized controlled trial. JAMA 2002;287:1807-14.

23. 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.

24. 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;187:532-8 [review].

25. Martinez B, Kasper S, Ruhrmann S, Moller HJ. Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol 1994;7:S29-33.

26. Wheatley D. Hypericum in seasonal affective disorder (SAD). Curr Med Res Opin 1999;15:33-7.

27. 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.

28. Witte B, Harrer G, Kaptan T, et al. Treatment of depressive symptoms with a high concentration Hypericum preparation. A multicenter placebo-controlled double-blind study. Fortschr Med 1995;113:404-8 [in German].

29. 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.

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):31-7.

31. 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.

32. 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.

33. Witte B, Harrer G, Kaptan T, et al. Treatment of depressive symptoms with a high concentration Hypericum preparation. A multicenter placebo-controlled double-blind study. Fortschr Med 1995;113:404-8 [in German].

34. 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.

35. 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.

36. 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.

37. Cooper WC, James J. An observational study of the safety and efficacy of hypericin in HIV+ subjects. Int Conf AIDS 1990;6:369 [abstract no. 2063].

38. Steinbeck-Klose A, Wernet P. Successful long term treatment over 40 months of HIV-patients with intravenous hypericin. Int Conf AIDS 1993;9:470 [abstract no. PO-B26-2012].

39. Gulick RM, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active compound in St. John's wort, as an antiretroviral agent in HIV-infected adults. AIDS clinical trial group protocols 150 and 258. Ann Intern Med 1999;130:510-4.

40. Uebelhack R, Blohmer JU, Graubaum HJ, et al. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107:247-55.

41. 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.

42. Uebelhack R, Blohmer JU, Graubaum HJ, et al. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107:247-55.

43. Grube B, Walper A, Wheatley D. St. John's Wort extract: efficacy for menopausal symptoms of psychological origin. Adv Ther 1999;16:177-86.

44. Al-Akoum M, Maunsell E, Verreault R, et al. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause 2009;16:307-14.

45. Uebelhack R, Blohmer JU, Graubaum HJ, et al. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107:247-55.

46. 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.

47. Uebelhack R, Blohmer JU, Graubaum HJ, et al. Black cohosh and St. John's wort for climacteric complaints: a randomized trial. Obstet Gynecol 2006;107:247-55.

48. Grube B, Walper A, Wheatley D. St. John's Wort extract: efficacy for menopausal symptoms of psychological origin. Adv Ther 1999;16:177-86.

49. Al-Akoum M, Maunsell E, Verreault R, et al. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause 2009;16:307-14.

50. 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.

51. Weiss RF. Herbal Medicine. Beaconsfield, UK: Beaconsfield Publishers Ltd, 1989, 114-5.

52. 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.

53. 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.

54. 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.

55. 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.

56. Brown DJ. Herbal Prescriptions for Better Health. Rocklin, CA: Prima Publishing, 1996, 159-65.

57. Woelk H. Comparison of St. John's wort and imipramine for treating depression: Randomized controlled trial. BMJ 2000;321:536-9.

58. 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.

59. 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.

60. Brockmöller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: Pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30(suppl):94–101.

61. Lane-Brown MM. Photosensitivity associated with herbal preparations of St. John's wort (Hypericum perforatum). MJA 2000;172:302[Letter].

62. Bove GM. Acute neuropathy after exposure to sun in a patient treated with St John's Wort. Lancet 1998;352:1121-2 [letter].

63. Nierenberg AA, Burt T, Matthews J, Weiss AP. Mania associated with St. John's wort. Biol Psychiatry 1999;46:1707-8.

64. Moses EL, Mallinger AG. St. John's wort: Three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115-7.

65. O'Breasail AM, Argouarch S. Hypomania and St John's wort. Can J Psychiatry 1998;43:746-7 [letter].

66. Schneck C. St. John's wort and hypomania. J Clin Psychiatry 1998;59:689 [letter].

67. Zullino D, Borgeat F. Hypertension induced by St. John's Wort: a case report. Pharmacopsychiatry. 2003;36:32.

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The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2025.