St. John's Wort

Last Updated: June 20, 2024

St. John’s wort, also known by its Linnean name of Hypericum perforatum (HP), is an anti-depressant herb that is commonly used for its neurological effects. While it appears effective, it is well known to adversely interact with a variety of pharmaceuticals.

dosageDosage
examine-databaseExamine Database
research-feedResearch feed

St. John's Wort is most often used for

What is St. John’s wort?

St. John's wort, or Hypericum perforatum, is a yellow-flowered plant native to Europe that is traditionally associated with St. John's feast day and believed to protect against malevolent spirits. It contains active compounds like hypericin and hyperforin and is commonly used in traditional medicine to treat depression.

What are the main benefits of St. John’s wort?

St. John's wort is effective for treating mild to moderate depression and has show similar clinical responses as selective serotonin reuptake inhibitors (SSRIs), with fewer side effects and lower dropout rates than tricyclic antidepressants. Additionally, it may enhance neuronal plasticity and neurogenesis while exhibiting anti-inflammatory properties and protecting neurons from cytotoxicity.

What are the main drawbacks of St. John’s wort?

The main drawbacks of St. John's wort include its potential to interfere with the metabolism of various medications, which leads to reduced effectiveness or unexpected outcomes, particularly with oral contraceptives, anticoagulants, and certain antidepressants, which may increase the risk of serotonin syndrome. Additionally, commonly reported side effects include gastrointestinal issues, headache, fatigue, and photosensitivity, and further research is needed to assess its safety profile.

Does St. John’s wort interact with any other medication?

Can St. John’s wort interact with other supplements?

Is St. John’s wort safe during pregnancy?

Is St. John’s wort safe during breastfeeding?

How does St. John’s wort work?

St. John's wort, particularly its active compound hyperforin, may enhance mood by inhibiting the reuptake of neurotransmitters like serotonin, norepinephrine, and dopamine through mechanisms that differ from those of traditional selective serotonin reuptake inhibitors (SSRIs). Additionally, hyperforin activates the pregnane-X-receptor, which influences the cytochrome P450 system and potentially affects drug interactions.

Does St. John’s wort have other mechanisms of action?

What are other names for St. John's Wort?
Note that St. John's Wort is also known as:
  • St. John's Wort
  • Hypericum Perforatum
  • Klamath Weed
  • Tipton Weed
  • Johanniskraut
  • 圣约翰草 (Guan Ye Lian Qiao)
Dosage information

The most common dosage of St. John's wort extract found in studies is 300mg, taken up to three times a day (for a total of 900 mg).[1]

Supplements Demystified: Get Our Unbiased, Evidence-Based Guide

Examine Database: St. John's Wort
What works and what doesn't?

Unlock the full potential of Examine

Get started

Don't miss out on the latest research

Update History
2024-06-20 00:30:03

Dosage info clarification

minor

Some of the wording in our dosage section was unclear. St. John's Wort studies generally administer 300 mg of extract up to 3 times daily (300 to 900 mg overall).

Written By

Nick Milazzo
2023-10-07 00:30:04

New meta-analyses added

minor

We added a few meta-analyses to our database and update the clinical effects accordingly.

Written By

Giulia Guerrini

Reviewed By

Nick Milazzo
References
  1. ^Ng QX, Venkatanarayanan N, Ho CYClinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.J Affect Disord.(2017-Mar-01)
  2. ^Peterson B, Nguyen HSt John's WortStatPearls.(2023-05)
  3. ^Zhao X, Zhang H, Wu Y, Yu CThe efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials.Adv Clin Exp Med.(2022-Oct-11)
  4. ^Knüppel L, Linde KAdverse effects of St. John's Wort: a systematic review.J Clin Psychiatry.(2004-Nov)
  5. ^Bonaterra GA, Schwendler A, Hüther J, Schwarzbach H, Schwarz A, Kolb C, Abdel-Aziz H, Kinscherf RNeurotrophic, Cytoprotective, and Anti-inflammatory Effects of St. John's Wort Extract on Differentiated Mouse Hippocampal HT-22 Neurons.Front Pharmacol.(2017)
  6. ^McDonnell AM, Dang CHBasic review of the cytochrome p450 system.J Adv Pract Oncol.(2013-Jul)
  7. ^Bauer S, Störmer E, Johne A, Krüger H, Budde K, Neumayer HH, Roots I, Mai IAlterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients.Br J Clin Pharmacol.(2003 Feb)
  8. ^Hennessy M, Kelleher D, Spiers JP, Barry M, Kavanagh P, Back D, Mulcahy F, Feely JSt Johns wort increases expression of P-glycoprotein: implications for drug interactions.Br J Clin Pharmacol.(2002-Jan)
  9. ^Whiskey E, Werneke U, Taylor DA systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review.Int Clin Psychopharmacol.(2001-Sep)
  10. ^Singer A, Wonnemann M, Müller WEHyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1.J Pharmacol Exp Ther.(1999-Sep)
  11. ^Thiede HM, Walper AInhibition of MAO and COMT by hypericum extracts and hypericin.J Geriatr Psychiatry Neurol.(1994-Oct)
  12. ^Butterweck VMechanism of action of St John's wort in depression : what is known?CNS Drugs.(2003)
  13. ^Mathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom AEffects of St. John's wort on irinotecan metabolism.J Natl Cancer Inst.(2002 Aug 21)
  14. ^Zhou S, Chan E, Pan SQ, Huang M, Lee EJPharmacokinetic interactions of drugs with St John's wort.J Psychopharmacol.(2004 Jun)
  15. ^Russo E, Scicchitano F, Whalley BJ, Mazzitello C, Ciriaco M, Esposito S, Patanè M, Upton R, Pugliese M, Chimirri S, Mammì M, Palleria C, De Sarro GHypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug-drug interactions.Phytother Res.(2014 May)
  16. ^Wang XD, Li JL, Lu Y, Chen X, Huang M, Chowbay B, Zhou SFRapid and simultaneous determination of nifedipine and dehydronifedipine in human plasma by liquid chromatography-tandem mass spectrometry: Application to a clinical herb-drug interaction study.J Chromatogr B Analyt Technol Biomed Life Sci.(2007 Jun 1)
  17. ^Tannergren C, Engman H, Knutson L, Hedeland M, Bondesson U, Lennernäs HSt John's wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism.Clin Pharmacol Ther.(2004 Apr)
  18. ^Chen XW, Serag ES, Sneed KB, Liang J, Chew H, Pan SY, Zhou SFClinical herbal interactions with conventional drugs: from molecules to maladies.Curr Med Chem.(2011)
  19. ^Morimoto T, Kotegawa T, Tsutsumi K, Ohtani Y, Imai H, Nakano SEffect of St. John's wort on the pharmacokinetics of theophylline in healthy volunteers.J Clin Pharmacol.(2004 Jan)
  20. ^Lau WC, Welch TD, Shields T, Rubenfire M, Tantry US, Gurbel PAThe 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)
  21. ^Roby CA, Anderson GD, Kantor E, Dryer DA, Burstein AHSt John's Wort: effect on CYP3A4 activity.Clin Pharmacol Ther.(2000-May)
  22. ^Hammerness et al.St. John’s Wort: A Systematic Review of Adverse Effects and Drug Interactions for the Consultation PsychiatristPsychosomatics.(2003-07-01)
  23. ^Spiess D, Winker M, Dolder Behna A, Gründemann C, Simões-Wüst APAdvanced Safety Assessment of Herbal Medicines for the Treatment of Non-Psychotic Mental Disorders in Pregnancy.Front Pharmacol.(2022)
  24. ^Moretti ME, Maxson A, Hanna F, Koren GEvaluating the safety of St. John's Wort in human pregnancy.Reprod Toxicol.(2009-Jul)
  25. ^St. John's Wort.Drugs and Lactation Database (LactMed®).(2006)
  26. ^Nierenberg AA, Burt T, Matthews J, Weiss APMania associated with St. John's wort.Biol Psychiatry.(1999 Dec 15)
  27. ^Schneck CSt. John's wort and hypomania.J Clin Psychiatry.(1998 Dec)
  28. ^Güzelcan Y, Scholte WF, Assies J, Becker HEMania during the use of a combination preparation with St. John's wort (Hypericum perforatum).Ned Tijdschr Geneeskd.(2001 Oct 6)
  29. ^
  30. ^Ferrara M, Mungai F, Starace FSt John's wort (Hypericum perforatum)-induced psychosis: a case report.J Med Case Rep.(2017 May 15)
  31. ^Andreescu C, Mulsant BH, Emanuel JEComplementary and alternative medicine in the treatment of bipolar disorder--a review of the evidence.J Affect Disord.(2008 Sep)
  32. ^
  33. ^
  34. ^
  35. ^
  36. ^
  37. ^
  38. ^
  39. ^
  40. ^
  41. ^Hypericum Depression Trial Study Group, Davidson JR, Gadde KM, Fairbank JA, Krishnan KRR, Califf RM, Binanay C, Parker CB, Pugh N, Hartwell TD, Vitiello B, Ritz L, Severe J, Cole JO, de Battista C, Doraiswamy PM, Feighner JP, Keck P, Kelsey J, Lin KM, Londborg PD, Nemeroff CB, Schatzberg AF, Sheehan DV, Srivastava RK, Taylor L, Trivedi MH, Weisler RHEffect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.JAMA.(2002 Apr 10)
  42. ^
  43. ^Golsch S, Vocks E, Rakoski J, Brockow K, Ring JReversible increase in photosensitivity to UV-B caused by St. John's wort extract.Hautarzt.(1997 Apr)
  44. ^Schempp CM, Lüdtke R, Winghofer B, Simon JCEffect of topical application of Hypericum perforatum extract (St. John's wort) on skin sensitivity to solar simulated radiation.Photodermatol Photoimmunol Photomed.(2000 Jun)
  45. ^Jacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, Cabana BE, Lee D, Spritzler J, Prince AMPharmacokinetics, 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)
  46. ^Schempp CM, Winghofer B, Müller K, Schulte-Mönting J, Mannel M, Schöpf E, Simon JCEffect of oral administration ofHypericum 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)
  47. ^Hohmann N, Maus A, Carls A, Haefeli WE, Mikus GSt. John's wort treatment in women bears risks beyond pharmacokinetic drug interactions.Arch Toxicol.(2016 Apr)
  48. ^Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KDEffect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme.JAMA.(2003 Sep 17)
  49. ^Wang LS, Zhou G, Zhu B, Wu J, Wang JG, Abd El-Aty AM, Li T, Liu J, Yang TL, Wang D, Zhong XY, Zhou HHSt John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole.Clin Pharmacol Ther.(2004 Mar)
  50. ^Wenk M, Todesco L, Krähenbühl SEffect 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 Apr)
  51. ^Wang LS, Zhu B, Abd El-Aty AM, Zhou G, Li Z, Wu J, Chen GL, Liu J, Tang ZR, An W, Li Q, Wang D, Zhou HHThe influence of St John's Wort on CYP2C19 activity with respect to genotype.J Clin Pharmacol.(2004 Jun)
  52. ^F Ruschitzka, P J Meier, M Turina, T F Lüscher, G NollAcute heart transplant rejection due to Saint John's wortLancet.(2000 Feb 12)
  53. ^Breidenbach T, Hoffmann MW, Becker T, Schlitt H, Klempnauer JDrug interaction of St John's wort with cyclosporin.Lancet.(2000 May 27)
  54. ^Mai I, Störmer E, Bauer S, Krüger H, Budde K, Roots IImpact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients.Nephrol Dial Transplant.(2003 Apr)
  55. ^Hebert MF, Park JM, Chen YL, Akhtar S, Larson AMEffects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers.J Clin Pharmacol.(2004 Jan)
  56. ^Hojo Y, Echizenya M, Ohkubo T, Shimizu TDrug interaction between St John's wort and zolpidem in healthy subjects.J Clin Pharm Ther.(2011 Dec)
  57. ^Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis BD, Duke CC, Day RO, McLachlan AJEffect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.Br J Clin Pharmacol.(2004 May)
  58. ^Van Strater AC, Bogers JPInteraction of St John's wort (Hypericum perforatum) with clozapine.Int Clin Psychopharmacol.(2012 Mar)
  59. ^Eggertsen R, Andreasson A, Andrén LEffects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin.Scand J Prim Health Care.(2007 Sep)
  60. ^
  61. ^
  62. ^Xu H, Williams KM, Liauw WS, Murray M, Day RO, McLachlan AJEffects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide.Br J Pharmacol.(2008 Apr)
  63. ^Eich-Höchli D, Oppliger R, Golay KP, Baumann P, Eap CBMethadone maintenance treatment and St. John's Wort - a case report.Pharmacopsychiatry.(2003 Jan)
  64. ^Ernst ESecond thoughts about safety of St John's wort.Lancet.(1999 Dec 11)
  65. ^Berry-Bibee EN, Kim MJ, Tepper NK, Riley HE, Curtis KMCo-administration of St. John's wort and hormonal contraceptives: a systematic review.Contraception.(2016 Dec)
  66. ^Hall SD, Wang Z, Huang SM, Hamman MA, Vasavada N, Adigun AQ, Hilligoss JK, Miller M, Gorski JCThe interaction between St John's wort and an oral contraceptive.Clin Pharmacol Ther.(2003 Dec)
  67. ^Andreas Johne, Jürgen Schmider, Jürgen Brockmöller, Andreas M Stadelmann, Elke Störmer, Steffen Bauer, Gudrun Scholler, Matthias Langheinrich, Ivar RootsDecreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St. John's wort ( Hypericum perforatum )J Clin Psychopharmacol.(2002 Feb)
  68. ^Lei HP, Yu XY, Xie HT, Li HH, Fan L, Dai LL, Chen Y, Zhou HHEffect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers.Xenobiotica.(2010 Apr)
  69. ^Johne A, Brockmöller J, Bauer S, Maurer A, Langheinrich M, Roots IPharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum).Clin Pharmacol Ther.(1999-Oct)
  70. ^Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow BEffect of St John's wort dose and preparations on the pharmacokinetics of digoxin.Clin Pharmacol Ther.(2004 Jun)
  71. ^Frye RF, Fitzgerald SM, Lagattuta TF, Hruska MW, Egorin MJEffect of St John's wort on imatinib mesylate pharmacokinetics.Clin Pharmacol Ther.(2004 Oct)
  72. ^Smith PF, Bullock JM, Booker BM, Haas CE, Berenson CS, Jusko WJInduction of imatinib metabolism by hypericum perforatum.Blood.(2004 Aug 15)
  73. ^Goey AK, Meijerman I, Rosing H, Marchetti S, Mergui-Roelvink M, Keessen M, Burgers JA, Beijnen JH, Schellens JHThe effect of St John's wort on the pharmacokinetics of docetaxel.Clin Pharmacokinet.(2014 Jan)
  74. ^Lundahl A, Hedeland M, Bondesson U, Knutson L, Lennernäs HThe effect of St. John's wort on the pharmacokinetics, metabolism and biliary excretion of finasteride and its metabolites in healthy men.Eur J Pharm Sci.(2009 Mar 2)
  75. ^Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Laine K, Neuvonen PJ, Olkkola KTSt John's wort greatly reduces the concentrations of oral oxycodone.Eur J Pain.(2010 Sep)
  76. ^S C Piscitelli, A H Burstein, D Chaitt, R M Alfaro, J FalloonIndinavir concentrations and St John's wortLancet.(2000 Feb 12)
  77. ^Rengelshausen J, Banfield M, Riedel KD, Burhenne J, Weiss J, Thomsen T, Walter-Sack I, Haefeli WE, Mikus GOpposite effects of short-term and long-term St John's wort intake on voriconazole pharmacokinetics.Clin Pharmacol Ther.(2005 Jul)
  78. ^Portolés A, Terleira A, Calvo A, Martínez I, Resplandy GEffects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial.J Clin Pharmacol.(2006 Oct)
  79. ^Booker A, Agapouda A, Frommenwiler DA, Scotti F, Reich E, Heinrich MSt John's wort (Hypericum perforatum) products - an assessment of their authenticity and quality.Phytomedicine.(2018 Feb 1)
  80. ^Gafner S, Blumenthal M, Foster S, Cardellina JH 2nd, Khan IA, Upton RBotanical Ingredient Forensics: Detection of Attempts to Deceive Commonly Used Analytical Methods for Authenticating Herbal Dietary and Food Ingredients and Supplements.J Nat Prod.(2023 Feb 24)
  81. ^Shah AK, Avery BA, Wyandt CMContent analysis and stability evaluation of selected commercial preparations of St. John's wort.Drug Dev Ind Pharm.(2005 Oct)
  82. ^Cada AM, Hansen DK, LaBorde JB, Ferguson SAMinimal effects from developmental exposure to St. John's wort (Hypericum perforatum) in Sprague-Dawley rats.Nutr Neurosci.(2001)
  83. ^Rayburn WF, Gonzalez CL, Christensen HD, Stewart JDEffect of prenatally administered hypericum (St John's wort) on growth and physical maturation of mouse offspring.Am J Obstet Gynecol.(2001 Jan)
  84. ^Kolding L, Pedersen LH, Henriksen TB, Olsen J, Grzeskowiak LEHypericum perforatum use during pregnancy and pregnancy outcome.Reprod Toxicol.(2015 Dec)
  85. ^W F Rayburn, H D Christensen, C L GonzalezEffect of antenatal exposure to Saint John's wort (Hypericum) on neurobehavior of developing miceAm J Obstet Gynecol.(2000 Nov)
  86. ^Rayburn WF, Gonzalez CL, Christensen HD, Harkins TL, Kupiec TCImpact of hypericum (St.-John's-wort) given prenatally on cognition of mice offspring.Neurotoxicol Teratol.(2001 Nov-Dec)
  87. ^Pariente G, Leibson T, Carls A, Adams-Webber T, Ito S, Koren GPregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.PLoS Med.(2016 Nov)
  88. ^Costantine MMPhysiologic and pharmacokinetic changes in pregnancy.Front Pharmacol.(2014)
  89. ^Klier CM, Schäfer MR, Schmid-Siegel B, Lenz G, Mannel MSt. John's wort (Hypericum perforatum)--is it safe during breastfeeding?Pharmacopsychiatry.(2002 Jan)
  90. ^Klier CM, Schmid-Siegel B, Schäfer MR, Lenz G, Saria A, Lee A, Zernig GSt. John's wort (Hypericum perforatum) and breastfeeding: plasma and breast milk concentrations of hyperforin for 5 mothers and 2 infants.J Clin Psychiatry.(2006 Feb)
  91. ^
Examine Database References
  1. Depression Symptoms - Linde K, Berner MM, Kriston LSt John's wort for major depression.Cochrane Database Syst Rev.(2008-Oct-08)
  2. Depression Symptoms - Rahimi R, Nikfar S, Abdollahi MEfficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis.Prog Neuropsychopharmacol Biol Psychiatry.(2009-Feb-01)
  3. Depression Symptoms - Linde K, Berner M, Egger M, Mulrow CSt John's wort for depression: meta-analysis of randomised controlled trials.Br J Psychiatry.(2005-Feb)
  4. Depression Symptoms - Cui YH, Zheng YA meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults.Neuropsychiatr Dis Treat.(2016)
  5. Depression Symptoms - Whiskey E, Werneke U, Taylor DA systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review.Int Clin Psychopharmacol.(2001-Sep)
  6. Depression Symptoms - Ng QX, Venkatanarayanan N, Ho CYClinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.J Affect Disord.(2017-Mar-01)
  7. Depression Symptoms - Zhao X, Zhang H, Wu Y, Yu CThe efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials.Adv Clin Exp Med.(2022-Oct-11)