Saint Johns Wort Supplement

Updated | 2021-01-26

Written and reviewed by the NatureClaim Team

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Saint Johns Wort

Overview of Saint Johns Wort

Scientific Name: Hypericum perforatum

Order: Malpighiales

Family: Hypericaceae

Saint John's Wort (or St. John's Wort) is commonly used to treat depression. Although, this plant is widely used, it has a relatively large list of major interactions. Saint John's Wort is sometimes misspelled as St. Johns Wort, St John's Wort, or St Johns Wort.



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  • Minor to Mild to Moderate Depression [1-42]
    • Clinical trials have found that Saint John’s wort independently or in combination with valerian may be effective. Some suggest the possibility of a placebo effect or that the effects of Saint John’s wort are dose dependent. It appears that Saint John’s wort may affect the response, remission, recovery, relapse, and recurrence of depression


  • Peri-menopausal and Menopausal Complaints, Saint John’s wort in combination with black cohosh or chaste tree [43-48]
  • Somatic Symptom Disorder [49-51]
  • Winter Depression [52-54]

Conflicting (Unclear):

  • Major Depression (Major Depressive Disorder), an NCCAM funded study [Hypericum Depression Trail Study Group 2002] found that Saint John’s wort might not be effective in relieving major depression [55-71]
    • Many have reported that Saint John’s wort is effective for major depression, while others have found it to be ineffective

Limited Evidence:

  • Anti-platelet Agent [72-73]
  • Atopic Dermatitis (Eczema), a cream containing Saint John’s wort [74]
  • C-Section Wound Healing, an ointment containing Saint John’s wort [75-76]
  • Ear Inflammation in Children, drops containing either Saint John’s wort / calendula flowers / mullein in olive oil or Saint John’s wort / garlic / calendula flowers / mullein / lavender / vitamin E in olive oil [77-78]
  • Herpes, a cream containing Saint John’s wort / copper sulfate pentahydrate [79]
  • Irritable Bowel Syndrome [80-81]
  • Non-melanoma Skin Cancer, an ointment containing Saint John’s wort [82]
  • Obsessive Compulsive Disorder (ODC) [83-84]
  • Osteomyelitis in the feet of Diabetics, local injection of a mixture of phenothiazine (2% in water) and Saint John’s wort extract (10% in propylene glycol) [85]
  • Premenstrual Syndrome (PMS) [86]
  • Schizophrenia [87]
  • Venous Ulcers, an ointment containing Saint John’s wort / garlic / calendula [88]

No Evidence:

  • ADHD (Attention Deficit Hyperactivity Disorder) [89]
  • Autism [90]
  • Burning Mouth Syndrome [91]
  • Chronic Pain [92-93]
  • Cognition and Memory [94-96]
  • Hepatitis C [97]
  • Knee Pain, a blend with Saint John’s wort / Arnica montana / Bryonia alba / Ruta graveolens [98]
  • Social Phobia [99]
  • Quit Smoking (Smoking Cessation) [100-103]

No Clinical Research:

All other conditions.

Side Effects
Side effects may include:
  • Allergic Reactions
  • Constipation
  • Diarrhea
  • Dizziness
  • Dry Mouth
  • Fatigue
  • Feeling of Fullness
  • Frequent Urination
  • Gastrointestinal Upset
  • Headache
  • Indigestion
  • Insomnia
  • Itching
  • Sensitivity to Sunlight
  • Restlessness
  • Trouble Sleeping
Precautions and Adverse Events:
  • Avoid or contact a licensed healthcare practitioner, since some people may have allergic reactions (rashes, itching) to Saint John’s wort, and use caution if you have had a history of mania, photosensitivity, psychiatric disorders.
  • There have been rare adverse events such as photosensitivity, phototoxic reaction to a laser treatment, mania (from high doses of Saint John’s wort), severe nosebleed (after nasal insertion of Saint John’s wort), schizophrenia relapse, neuropathy, severe anxiety, sleep disorders, psychosis, serotonin syndrome, impotence (erectile dysfunction), decreased sex drive, anorexia, and changes in blood pressure and pulse. If you have any of these adverse events, consult a licensed healthcare practitioner.
  • A case of scalp and eyebrow hair loss was reported after a schizophrenia patient on olanzapine began taking Saint John’s wort.
  • A rare serious adverse event (and possibly death) from bone marrow necrosis may have been caused by Saint John’s wort.
  • Saint John’s wort has a long list of interactions (not a complete list below). If you are taking any medications, consult a licensed healthcare practitioner before using Saint John’s wort.

Pregnant or Nursing

There is not enough research on the use of supplements containing Saint John’s wort during pregnancy and breast-feeding, so consult a licensed healthcare practitioner before use or avoid use. A small study of infants born to mothers using Saint John’s wort reported an increase in colic, drowsiness, and lethargy. Saint John’s wort may have uterine stimulant properties. [104-117]



  • Avoid using Saint John’s wort if you are taking selective serotonin reuptake inhibitors, anti-coagulants (for example, cyclosporine), oral contraceptives, protease inhibitors (for example, HIV/AIDS drugs)
  • Saint John’s wort may interact with anesthetics, so do NOT use Saint John’s wort at least 2 weeks before a surgery
  • Drugs changed by Cytochrome P450s (CYPs) in the liver
  • Warfarin
  • Adrenergic Vasopressors
  • Alprazolam
  • Amiodarone
  • Amitriptyline
  • Amprenavir
  • Amsacrine
  • Anesthetics, general
  • Anti-Coagulants
  • Anti-Depressants; Saint John’s wort may enhance their activity
  • Anti-Diabetic Drugs
  • Atazanavir
  • Atorvastatin
  • Barbiturates
  • Benzodiazepines
  • Bupropion
  • Buspirone
  • Calcium Channel Blockers
  • Chlorzoxazone
  • Cyclosporine (Ciclosporin)
  • Darunavir
  • Digoxin
  • Docetaxel
  • Drugs transported by P-glycoproteins
  • Eletriptan
  • Erlotinib
  • Erythromycin
  • Ethinyl Estradiol
  • Etopside
  • Fenfluramine
  • Fexofenadine
  • Finasteride
  • Fluoxetine
  • Gliclazide
  • Heart Beta-Blockers
  • Hormone-Like Drugs (such as drugs containing estrogen)
  • Imatinib
  • Immunosuppressant Drugs
  • Indinavir
  • Irinotecan
  • Ivabradine
  • Ketodesogestrel
  • Lapatinib
  • Linezolid
  • Loperamide; Saint John’s wort interacts with loperamide and has caused delirium
  • Lopinavir
  • Lovastatin
  • Mephenytoin
  • Methadone
  • Methylphenidate
  • Midazolam
  • Nefazodone
  • Nevirapine
  • Nifedipine
  • Norethindrone
  • Nortriptyline
  • Omeprazole
  • Opioid Painkillers
  • Oral Contraceptives; Saint John’s wort may cause failure of contraceptive and inter-menstrual bleeding
  • Paclitaxel
  • Paroxetine
  • Phenprocoumon
  • Phenytoin
  • Propofol, an anesthetic
  • Protease Inhibitors including HIV/AIDS Drugs
  • Quazepam
  • Rasagiline
  • Reserpine
  • Ritonavir
  • Rosuvastatin
  • Saquinavir
  • Selective Serotonin Reuptake Inhibitors (SSRIs); Saint John’s wort has caused serotonin syndrome (particularly in elderly people) and mania
  • Selegiline
  • Sertraline
  • Sevoflurane, an anesthetic
  • Simvastatin
  • Sirolimus
  • Sunitinib
  • Tacrolimus
  • Talinolol
  • Tamoxifen
  • Theophylline
  • Tibolone; Saint John’s wort interacts with tibolone and may cause liver damage
  • Tramadol
  • Trazodone
  • Tricyclic Antidepressants
  • Tryptophan (which is naturally occurring in many foods, including, diary products, poultry, etc.)
  • Verapamil
  • Venlafaxine
  • Voriconazole


  • Herbal Medicines Containing Ginkgo (Ginkgo biloba)
  • Amphetamines
  • Cerivastatin
  • Clozapine
  • Cyclophosphamide
  • Fluvastatin
  • Monoamine Oxidase Inhibitors (MAOIs)
  • Olanzapine
  • Phenelzine
  • Serotonin Agonists
  • Sorafenib
  • Temozolomide, a drug for radio-chemotherapy
  • Tranylcypromine


  • Iron-Containing Products; since Saint John’s wort contains tannins, take iron and Saint John’s wort at least several hours apart to prevent non-absorption of iron
  • Acitretin
  • Carbamazepine
  • Cimetidine
  • Debrisoquine
  • Caffeine Products (for example, coffee, tea, etc.)
  • Food Containing Tyramine (for example, wine, beer, aged cheese, etc.)
  • Saint John’s wort may NOT interact with Dextromethorphan, Ibuprofen, Mycophenolic Acid, Pravastatin, Prednisone, and Tolbutamide (though Saint John’s wort may not interact with Tolbutamide, it may cause an increase in hypoglycemia incidences)


Saint John’s wort is not a "drug", so the best doses have not been thoroughly established. Make sure to follow the specific product instructions and take as directed on the label, or consult a licensed healthcare practitioner before use.


1. Anghelescu IG, Kohnen R, Szegedi A, Klement S, Kieser M. Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study. Pharmacopsychiatry. 2006 Nov;39(6):213-9. 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. Bitran S, Farabaugh AH, Ameral VE, LaRocca RA, Clain AJ, Fava M, Mischoulon D. Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among depressed outpatients? Comparison of two controlled trials of St John's wort (Hypericum perforatum) versus a SSRI. Int Clin Psychopharmacol. 2011 Jul;26(4):206-12. 4. Bjerkenstedt L, Edman GV, Alken RG, Mannel M. Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients. Eur Arch Psychiatry Clin Neurosci. 2005 Feb;255(1):40-7. 5. Brattström A. Long-term effects of St. John's wort (Hypericum perforatum) treatment: a 1-year safety study in mild to moderate depression. Phytomedicine. 2009 Apr;16(4):277-83. 6. Brenner R, Azbel V, Madhusoodanan S, Pawlowska M. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther. 2000 Apr;22(4):411-9. 7. Dimpfel W, Koch K, Weiss G. Early effect of NEURAPAS® balance on current source density (CSD) of human EEG. BMC Psychiatry. 2011 Aug 2;11:123. doi: 10.1186/1471-244X-11-123. 8. Donovan JL, DeVane CL, Lewis JG, Wang JS, Ruan Y, Chavin KD, Markowitz JS. Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study. Phytother Res. 2005 Oct;19(10):901-6. 9. Friede M, Henneicke von Zepelin HH, Freudenstein J. Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort. Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S38-41. 10. Gastpar M, Singer A, Zeller K. Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline. Pharmacopsychiatry. 2005 Mar;38(2):78-86. 11. Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. 2006 Mar;39(2):66-75. 12. Harrer G, Hübner WD, Podzuweit H. Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S24-8. 13. Harrer G, Sommer H. Treatment of mild/moderate depressions with Hypericum. Phytomedicine. 1994 Jun;1(1):3-8. 14. Johnson D, Ksciuk H, Woelk H, Sauerwein-Giese E, Frauendorf A. Effects of hypericum extract LI 160 compared with maprotiline on resting EEG and evoked potentials in 24 volunteers. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S44-6. 15. 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. Pharmacopsychiatry. 2001 May;34(3):96-103. 16. Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. 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. 17. Kasper S, Dienel A. Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from three randomized, placebo-controlled trials. Psychopharmacology (Berl). 2002 Nov;164(3):301-8. 18. Kasper S, Gastpar M, Müller WE, Volz HP, Dienel A, Kieser M, Möller HJ. Efficacy of St. John's wort extract WS 5570 in acute treatment of mild depression: a reanalysis of data from controlled clinical trials. Eur Arch Psychiatry Clin Neurosci. 2008 Feb;258(1):59-63. 19. Laakmann G, Dienel A, Kieser M. Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities. Phytomedicine. 1998 Dec;5(6):435-42. 20. Laakmann G, Schüle C, Baghai T, Kieser M. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. 1998 Jun;31 Suppl 1:54-9. 21. Lecrubier Y, Bech P. The Ham D(6) is more homogenous and as sensitive as the Ham D(17). Eur Psychiatry. 2007 May;22(4):252-5. 22. Lecrubier Y, Clerc G, Didi R, Kieser M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. 2002 Aug;159(8):1361-6. 23. Lenoir S, Degenring FH, Saller R. A double-blind randomised trial to investigate three different concentrations of a standardised fresh plant extract obtained from the shoot tips of Hypericum perforatum L. Phytomedicine. 1999 Jul;6(3):141-6. 24. Linden M, Wurzendorf K, Ploch M, Schaefer M. Self medication with St. John's wort in depressive disorders: an observational study in community pharmacies. J Affect Disord. 2008 Apr;107(1-3):205-10. 25. Mannel M, Kuhn U, Schmidt U, Ploch M, Murck H. St. John's wort extract LI160 for the treatment of depression with atypical features - a double-blind, randomized, and placebo-controlled trial. J Psychiatr Res. 2010 Sep;44(12):760-7. 26. Melzer J, Brignoli R, Keck ME, Saller R. A hypericum extract in the treatment of depressive symptoms in outpatients: an open study. Forsch Komplementmed. 2010 Mar;17(1):7-14. 27. Moreno RA, Teng CT, Almeida KM, Tavares Junior H. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial in a Brazilian sample. Rev Bras Psiquiatr. 2006 Mar;28(1):29-32. 28. Mueller BM. St. John's Wort for depressive disorders: results of an outpatient study with the Hypericum preparation HYP 811. Adv Ther. 1998 Mar-Apr;15(2):109-16. 29. Müller 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. 30. 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 Dec 11;319(7224):1534-8. 31. Randløv C, Mehlsen J, Thomsen CF, Hedman C, von Fircks H, Winther K. The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia--a double-blind placebo-controlled study. Phytomedicine. 2006 Mar;13(4):215-21. 32. Rapaport MH, Nierenberg AA, Howland R, Dording C, Schettler PJ, Mischoulon D. The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo. J Psychiatr Res. 2011 Jul;45(7):931-41. 33. Schrader E. Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol. 2000 Mar;15(2):61-8. 34. Sharpley AL, McGavin CL, Whale R, Cowen PJ. Antidepressant-like effect of Hypericum perforatum (St John's wort) on the sleep polysomnogram. Psychopharmacology (Berl). 1998 Oct;139(3):286-7. 35. Singer A, Schmidt M, Hauke W, Stade K. Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: a reanalysis of data from a controlled clinical trial. Phytomedicine. 2011 Jun 15;18(8-9):739-42. 36. Sommer H, Harrer G. Placebo-controlled double-blind study examining the effectiveness of an hypericum preparation in 105 mildly depressed patients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S9-11. 37. Uebelhack R, Gruenwald J, Graubaum HJ, Busch R. Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial. Adv Ther. 2004 Jul-Aug;21(4):265-75. 38. Vorbach EU, Arnoldt KH, Hübner 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 Sep;30 Suppl 2:81-5. 39. Vorbach EU, Hübner 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 Oct;7 Suppl 1:S19-23. 40. Wheatley D. LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial. Pharmacopsychiatry. 1997 Sep;30 Suppl 2:77-80. 41. Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. BMJ. 2000 Sep 2;321(7260):536-9. 42. Woelk H, Burkard G, Grünwald J. Benefits and risks of the hypericum extract LI 160: drug monitoring study with 3250 patients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S34-8. 43. Abdali K, Khajehei M, Tabatabaee HR. Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause. 2010 Mar;17(2):326-31. 44. Al-Akoum M, Maunsell E, Verreault R, Provencher L, Otis H, Dodin S. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009 Mar-Apr;16(2):307-14. 45. Chung DJ, Kim HY, Park KH, Jeong KA, Lee SK, Lee YI, Hur SE, Cho MS, Lee BS, Bai SW, Kim CM, Cho SH, Hwang JY, Park JH. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J. 2007 Apr 30;48(2):289-94. 46. Grube B, Walper A, Wheatley D. St. John's Wort extract: efficacy for menopausal symptoms of psychological origin. Adv Ther. 1999 Jul-Aug;16(4):177-86. 47. van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. J Altern Complement Med. 2009 Sep;15(9):1045-8. 48. van Die MD, Burger HG, Bone KM, Cohen MM, Teede HJ. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause. 2009 Jan-Feb;16(1):156-63. 49. Hübner WD, Lande S, Podzuweit H. Hypericum treatment of mild depressions with somatic symptoms. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S12-4. 50. Müller 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 Jul-Aug;66(4):538-47. 51. Volz HP, Murck H, Kasper S, Möller HJ. St John's wort extract (LI 160) in somatoform disorders: results of a placebo-controlled trial. Psychopharmacology (Berl). 2002 Nov;164(3):294-300. 52. Kasper S. Treatment of seasonal affective disorder (SAD) with hypericum extract. Pharmacopsychiatry. 1997 Sep;30 Suppl 2:89-93. 53. Martinez B, Kasper S, Ruhrmann S, Möller HJ. Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S29-33. 54. Wheatley D. Hypericum in seasonal affective disorder (SAD). Curr Med Res Opin. 1999;15(1):33-7. 55. Anghelescu IG, Kohnen R, Szegedi A, Klement S, Kieser M. Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study. Pharmacopsychiatry. 2006 Nov;39(6):213-9. 56. Chen JA, Papakostas GI, Youn SJ, Baer L, Clain AJ, Fava M, Mischoulon D. Association between patient beliefs regarding assigned treatment and clinical response: reanalysis of data from the Hypericum Depression Trial Study Group. J Clin Psychiatry. 2011 Dec;72(12):1669-76. 57. Farabaugh A, Mischoulon D, Fava M, Wu SL, Mascarini A, Tossani E, Alpert JE. The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients. Int Clin Psychopharmacol. 2005 Mar;20(2):87-91. 58. Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Murck H, Rosenbaum JF. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 2005 Oct;25(5):441-7. 59. Findling RL, McNamara NK, O'Riordan MA, Reed MD, Demeter CA, Branicky LA, Blumer JL. An open-label pilot study of St. John's wort in juvenile depression. J Am Acad Child Adolesc Psychiatry. 2003 Aug;42(8):908-14. 60. Gelenberg AJ, Shelton RC, Crits-Christoph P, Keller MB, Dunner DL, Hirschfeld RM, Thase ME, Russell JM, Lydiard RB, Gallop RJ, Todd L, Hellerstein DJ, Goodnick PJ, Keitner GI, Stahl SM, Halbreich U, Hopkins HS. 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 Aug;65(8):1114-9. 61. Hänsgen KD, Vesper J, Ploch M. Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S15-8. 62. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002 Apr 10;287(14):1807-14. 63. Kieser M, Szegedi A. Predicting stable treatment response in patients with major depression treated with hypericum extract WS 5570/5572. Pharmacopsychiatry. 2005 Sep;38(5):194-200. 64. Murck H, Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Mannel M, Rosenbaum JF. Hypericum extract in patients with MDD and reversed vegetative signs: re-analysis from data of a double-blind, randomized trial of hypericum extract, fluoxetine, and placebo. Int J Neuropsychopharmacol. 2005 Jun;8(2):215-21. 65. Papakostas GI, Crawford CM, Scalia MJ, Fava M. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hypericum perforatum versus fluoxetine. Neuropsychobiology. 2007;56(2-3):132-7. 66. Sarris J, Fava M, Schweitzer I, Mischoulon D. St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry. 2012 Nov;45(7):275-8. 67. Sarris J, Kavanagh DJ, Deed G, Bone KM. St. John's wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trial. Hum Psychopharmacol. 2009 Jan;24(1):41-8. 68. Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME, Russell J, Lydiard RB, Crits-Cristoph P, Gallop R, Todd L, Hellerstein D, Goodnick P, Keitner G, Stahl SM, Halbreich U. Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA. 2001 Apr 18;285(15):1978-86. 69. Simeon J, Nixon MK, Milin R, Jovanovic R, Walker S. Open-label pilot study of St. John's wort in adolescent depression. J Child Adolesc Psychopharmacol. 2005 Apr;15(2):293-301. 70. 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 Mar 5;330(7490):503. 71. van Gurp G, Meterissian GB, Haiek LN, McCusker J, Bellavance F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician. 2002 May;48:905-12. 72. Lau WC, Welch TD, Shields T, Rubenfire M, Tantry US, Gurbel PA. The effect of St John's Wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity. J Cardiovasc Pharmacol. 2011 Jan;57(1):86-93. 73. Trana C, Toth G, Wijns W, Barbato E. St. John's Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: a single-center randomized open-label trial (St. John's Trial). J Cardiovasc Transl Res. 2013 Jun;6(3):411-4. 74. 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. 75. Lavagna SM, Secci D, Chimenti P, Bonsignore L, Ottaviani A, Bizzarri B. Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section. Farmaco. 2001 May-Jul;56(5-7):451-3. 76. Samadi S, Khadivzadeh T, Emami A, Moosavi NS, Tafaghodi M, Behnam HR. The effect of Hypericum perforatum on the wound healing and scar of cesarean. J Altern Complement Med. 2010 Jan;16(1):113-7. 77. Sarrell EM, Cohen HA, Kahan E. Naturopathic treatment for ear pain in children. Pediatrics. 2003 May;111(5 Pt 1):e574-9. 78. Sarrell EM, Mandelberg A, Cohen HA. Efficacy of naturopathic extracts in the management of ear pain associated with acute otitis media. Arch Pediatr Adolesc Med. 2001 Jul;155(7):796-9. 79. Clewell A, Barnes M, Endres JR, Ahmed M, Ghambeer DK. Efficacy and tolerability assessment of a topical formulation containing copper sulfate and hypericum perforatum on patients with herpes skin lesions: a comparative, randomized controlled trial. J Drugs Dermatol. 2012 Feb;11(2):209-15. 80. Saito YA, Rey E, Almazar-Elder AE, Harmsen WS, Zinsmeister AR, Locke GR, Talley NJ. A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome. Am J Gastroenterol. 2010 Jan;105(1):170-7. 81. Wan H, Chen Y. Effects of antidepressive treatment of Saint John's wort extract related to autonomic nervous function in women with irritable bowel syndrome. Int J Psychiatry Med. 2010;40(1):45-56. 82. Kacerovská D, Pizinger K, Majer F, Smíd F. Photodynamic therapy of nonmelanoma skin cancer with topical hypericum perforatum extract--a pilot study. Photochem Photobiol. 2008 May-Jun;84(3):779-85. 83. Kobak KA, Taylor LV, Bystritsky A, Kohlenberg CJ, Greist JH, Tucker P, Warner G, Futterer R, Vapnik T. St John's wort versus placebo in obsessive-compulsive disorder: results from a double-blind study. Int Clin Psychopharmacol. 2005 Nov;20(6):299-304. 84. Taylor LH, Kobak KA. An open-label trial of St. John's Wort (Hypericum perforatum) in obsessive-compulsive disorder. J Clin Psychiatry. 2000 Aug;61(8):575-8. 85. Tardivo JP, Baptista MS. Treatment of osteomyelitis in the feet of diabetic patients by photodynamic antimicrobial chemotherapy. Photomed Laser Surg. 2009 Feb;27(1):145-50. 86. Canning S, Waterman M, Orsi N, Ayres J, Simpson N, Dye L. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS Drugs. 2010 Mar;24(3):207-25. 87. Murck H, Spitznagel H, Ploch M, Seibel K, Schaffler K. Hypericum extract reverses S-ketamine-induced changes in auditory evoked potentials in humans - possible implications for the treatment of schizophrenia. Biol Psychiatry. 2006 Mar 1;59(5):440-5. 88. Kundaković T, Milenković M, Zlatković S, Nikolić V, Nikolić G, Binić I. Treatment of venous ulcers with the herbal-based ointment Herbadermal®: a prospective non-randomized pilot study. Forsch Komplementmed. 2012;19(1):26-30. 89. Weber W, Vander Stoep A, McCarty RL, Weiss NS, Biederman J, McClellan J. Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA. 2008 Jun 11;299(22):2633-41. 90. Niederhofer H. St John's Wort treating patients with autistic disorder. Phytother Res. 2009 Nov;23(11):1521-3. 91. Sardella A, Lodi G, Demarosi F, Tarozzi M, Canegallo L, Carrassi A. Hypericum perforatum extract in burning mouth syndrome: a randomized placebo-controlled study. J Oral Pathol Med. 2008 Aug;37(7):395-401. 92. Otto M, Bach FW, Jensen TS, Sindrup SH. Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy. Eur J Pain. 2007 Jul;11(5):572-8. 93. Sindrup SH, Madsen C, Bach FW, Gram LF, Jensen TS. St. John's wort has no effect on pain in polyneuropathy. Pain. 2001 Apr;91(3):361-5. 94. Ellis KA, Stough C, Vitetta L, Heinrich K, Nathan PJ. An investigation into the acute nootropic effects of Hypericum perforatum L. (St. John's Wort) in healthy human volunteers. Behav Pharmacol. 2001 Jun;12(3):173-82. 95. Siepmann M, Krause S, Joraschky P, Mück-Weymann M, Kirch W. The effects of St John's wort extract on heart rate variability, cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men. Br J Clin Pharmacol. 2002 Sep;54(3):277-82. 96. Timoshanko A, Stough C, Vitetta L, Nathan PJ. A preliminary investigation on the acute pharmacodynamic effects of hypericum on cognitive and psychomotor performance. Behav Pharmacol. 2001 Dec;12(8):635-40. 97. Jacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, Cabana BE, Lee D, Spritzler J, Prince AM. Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother. 2001 Feb;45(2):517-24. 98. Paris A, Gonnet N, Chaussard C, Belon P, Rocourt F, Saragaglia D, Cracowski JL. Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled study. Br J Clin Pharmacol. 2008 Feb;65(2):180-7. 99. Kobak KA, Taylor LV, Warner G, Futterer R. St. John's wort versus placebo in social phobia: results from a placebo-controlled pilot study. J Clin Psychopharmacol. 2005 Feb;25(1):51-8. 100. Barnes J, Barber N, Wheatley D, Williamson EM. A pilot randomised, open, uncontrolled, clinical study of two dosages of St John's wort (Hypericum perforatum) herb extract (LI-160) as an aid to motivational/behavioural support in smoking cessation. Planta Med. 2006 Mar;72(4):378-82. 101. Lawvere S, Mahoney MC, Cummings KM, Kepner JL, Hyland A, Lawrence DD, Murphy JM. A Phase II study of St. John's Wort for smoking cessation. Complement Ther Med. 2006 Sep;14(3):175-84. 102. Parsons A, Ingram J, Inglis J, Aveyard P, Johnstone E, Brown K, Franklin M, Bermudez I. A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent weight gain on smoking cessation. Drug Alcohol Depend. 2009 Jun 1;102(1-3):116-22. 103. Sood A, Ebbert JO, Prasad K, Croghan IT, Bauer B, Schroeder DR. A randomized clinical trial of St. John's wort for smoking cessation. J Altern Complement Med. 2010 Jul;16(7):761-7. 104. Cotterill JA. Severe phototoxic reaction to laser treatment in a patient taking St John's Wort. J Cosmet Laser Ther. 2001 Sep;3(3):159-60. 105. Crampsey DP, Douglas CM, Cooke LD. Nasal insertion of St John's wort: an unusual cause of epistaxis. J Laryngol Otol. 2007 Mar;121(3):279-80. 106. Demiroglu YZ, Yeter TT, Boga C, Ozdogu H, Kizilkilic E, Bal N, Tuncer I, Arslan H. Bone marrow necrosis: a rare complication of herbal treatment with Hypericum perforatum (St. John's wort). Acta Medica (Hradec Kralove). 2005;48(2):91-4. 107. DerMarderosian A, Beutler JA. The review of natural products: the most complete source of natural product information. 7th ed. St. Louis, MO, USA: Wolters Kluwer Health; 2012. 108. Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of St. John's wort (hypericum) during pregnancy and lactation. Can J Clin Pharmacol. 2006 Fall;13(3):e268-76. 109. Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Ann Intern Med. 2002 Jan 1;136(1):42-53. 110. Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol. 1998 Oct;54(8):589-94. 111. Fahmi M, Huang C, Schweitzer I. A case of mania induced by hypericum. World J Biol Psychiatry. 2002 Jan;3(1):58-9. 112. Fetrow CW, Avila JR. The complete guide to herbal medicines. Spring House, PA, USA: Springhouse Corporation; 2000. 113. Gruenwald J, Brendler T, Jaenicke C, editors. PDR for herbal medicines. 4th ed. Montvale, NJ, USA: Thomson Healthcare; 2007. 114. Hammerness P, Basch E, Ulbricht C, Barrette EP, Foppa I, Basch S, Bent S, Boon H, Ernst E; Natural Standard Research Collaboration. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics. 2003 Jul-Aug;44(4):271-82. 115. Nierenberg AA, Burt T, Matthews J, Weiss AP. Mania associated with St. John's wort. Biol Psychiatry. 1999 Dec 15;46(12):1707-8. 116. Parker V, Wong AH, Boon HS, Seeman MV. Adverse reactions to St John's Wort. Can J Psychiatry. 2001 Feb;46(1):77-9. 117. Schempp CM, Winghofer B, Müller K, Schulte-Mönting J, Mannel M, Schöpf E, Simon JC. Effect of oral administration of Hypericum perforatum extract (St. John's Wort) on skin erythema and pigmentation induced by UVB, UVA, visible light and solar simulated radiation. Phytother Res. 2003 Feb;17(2):141-6. 118. Barbenel DM, Yusufi B, O'Shea D, Bench CJ. Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline. J Psychopharmacol. 2000 Mar;14(1):84-6. 119. Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-Ezz SR. Drug interaction between St. John's wort and cyclosporine. Ann Pharmacother. 2000 Sep;34(9):1013-6. 120. DerMarderosian A, Beutler JA. The review of natural products: the most complete source of natural product information. 7th ed. St. Louis, MO, USA: Wolters Kluwer Health; 2012. 121. Ernst E. St John's Wort supplements endanger the success of organ transplantation. Arch Surg. 2002 Mar;137(3):316-9. 122. Etogo-Asse F, Boemer F, Sempoux C, Geubel A. Acute hepatitis with prolonged cholestasis and disappearance of interlobular bile ducts following tibolone and Hypericum perforatum (St. John's wort). Case of drug interaction? Acta Gastroenterol Belg. 2008 Jan-Mar;71(1):36-8. 123. Fetrow CW, Avila JR. The complete guide to herbal medicines. Spring House, PA, USA: Springhouse Corporation; 2000. 124. Gold JL, Laxer DA, Dergal JM, Lanctôt KL, Rochon PA. Herbal-drug therapy interactions: a focus on dementia. Curr Opin Clin Nutr Metab Care. 2001 Jan;4(1):29-34. 125. Gruenwald J, Brendler T, Jaenicke C, editors. PDR for herbal medicines. 4th ed. Montvale, NJ, USA: Thomson Healthcare; 2007. 126. Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part 2): drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Med. 2012 Sep;78(13):1490-514. 127. Hammerness P, Basch E, Ulbricht C, Barrette EP, Foppa I, Basch S, Bent S, Boon H, Ernst E; Natural Standard Research Collaboration. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics. 2003 Jul-Aug;44(4):271-82. 128. Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol. 2002 Oct;54(4):349-56. 129. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61(15):2163-75. 130. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-98. 131. Karliova M, Treichel U, Malagò M, Frilling A, Gerken G, Broelsch CE. Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol. 2000 Nov;33(5):853-5. 132. Knüppel L, Linde K. Adverse effects of St. John's Wort: a systematic review. J Clin Psychiatry. 2004 Nov;65(11):1470-9. 133. Mai I, Krüger H, Budde K, Johne A, Brockmöller J, Neumayer HH, Roots I. Hazardous pharmacokinetic interaction of Saint John's wort (Hypericum perforatum) with the immunosuppressant cyclosporin. Int J Clin Pharmacol Ther. 2000 Oct;38(10):500-2. 134. Mannel M. Drug interactions with St John's wort: mechanisms and clinical implications. Drug Saf. 2004;27(11):773-97. 135. Markowitz JS, DeVane CL. The emerging recognition of herb-drug interactions with a focus on St. John's wort (Hypericum perforatum). Psychopharmacol Bull. 2001 Winter;35(1):53-64. 136. Moschella C, Jaber BL. Interaction between cyclosporine and Hypericum perforatum (St. John's wort) after organ transplantation. Am J Kidney Dis. 2001 Nov;38(5):1105-7. 137. Nadkarni A, Oldham MA, Howard M, Berenbaum I. Drug-drug interactions between warfarin and psychotropics: updated review of the literature. Pharmacotherapy. 2012 Oct;32(10):932-42. 138. Nowack R. Review article: cytochrome P450 enzyme, and transport protein mediated herb-drug interactions in renal transplant patients: grapefruit juice, St John's Wort - and beyond! Nephrology (Carlton). 2008 Jun;13(4):337-47. 139. Pal D, Mitra AK. MDR- and CYP3A4-mediated drug-herbal interactions. Life Sci. 2006 Mar 27;78(18):2131-45. 140. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John's wort. Lancet. 2000 Feb 12;355(9203):547-8. 141. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Acute heart transplant rejection due to Saint John's wort. Lancet. 2000 Feb 12;355(9203):548-9. 142. Schreiber S, Prox-Vagedes V, Elolf E, Brueggemann I, Gademann G, Galazky I, Bartels C. Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report. BMC Cancer. 2010 Oct 1;10:520. 143. Schulz V. Incidence and clinical relevance of the interactions and side effects of Hypericum preparations. Phytomedicine. 2001 Mar;8(2):152-60. 144. Spinella M, Eaton LA. Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury. Brain Inj. 2002 Apr;16(4):359-67. 145. Tsai HH, Lin HW, Simon Pickard A, Tsai HY, Mahady GB. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. 2012 Nov;66(11):1056-78. 146. Turton-Weeks SM, Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-Ezz SR. St John's wort: a hidden risk for transplant patients. Prog Transplant. 2001 Jun;11(2):116-20. 147. van Strater AC, Bogers JP. Interaction of St John's wort (Hypericum perforatum) with clozapine. Int Clin Psychopharmacol. 2012 Mar;27(2):121-4. 148. Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006 Nov;62(5):512-26. 149. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol. 2004 Jun;18(2):262-76. 150. Zhou SF, Lai X. An update on clinical drug interactions with the herbal antidepressant St. John's wort. Curr Drug Metab. 2008 Jun;9(5):394-409. 151. Afendi FM, Okada T, Yamazaki M, Hirai-Morita A, Nakamura Y, Nakamura K, Ikeda S, Takahashi H, Altaf-Ul-Amin M, Darusman LK, Saito K, Kanaya S. KNApSAcK family databases: integrated metabolite-plant species databases for multifaceted plant research. Plant Cell Physiol. 2012 Feb;53(2):e1.