St. John's Wort
•Last Updated: September 28 2022
Hypericum Perforatum (St. John's Wort) 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.
St. John's Wort is most often used for
Last Updated: September 28 2022
St. John's Wort (Hypericum perforatum) is a herb which, through the active component hypericin, works as a dopamine-related anti-depressant and is effective at doing so. This is also the prototypical 'adverse drug-interaction' herb; it interacts with several compounds by affecting the several phase I enzymes as well as other drug elimination pathways.
Note that St. John's Wort is also known as:
- St. John's Wort
- Hypericum Perforatum
Research feed
1.^Tian J1, Zhang F1, Cheng J2, Guo S3, Liu P3, Wang H2Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum LSci Rep.(2014 Jul 9)
2.^Brockmöller J1, Reum T, Bauer S, Kerb R, Hübner WD, Roots IHypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humansPharmacopsychiatry.(1997 Sep)
3.^Kerb R1, Brockmöller J, Staffeldt B, Ploch M, Roots ISingle-dose and steady-state pharmacokinetics of hypericin and pseudohypericinAntimicrob Agents Chemother.(1996 Sep)
4.^Treiber K1, Singer A, Henke B, Müller WEHyperforin activates nonselective cation channels (NSCCs)Br J Pharmacol.(2005 May)
5.^Yang B1, Samson WK, Ferguson AVExcitatory effects of orexin-A on nucleus tractus solitarius neurons are mediated by phospholipase C and protein kinase CJ Neurosci.(2003 Jul 16)
6.^Leuner K1, Kazanski V, Müller M, Essin K, Henke B, Gollasch M, Harteneck C, Müller WEHyperforin--a key constituent of St. John's wort specifically activates TRPC6 channelsFASEB J.(2007 Dec)
7.^Leuner K1, Li W, Amaral MD, Rudolph S, Calfa G, Schuwald AM, Harteneck C, Inoue T, Pozzo-Miller LHyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+) -permeable TRPC6 channelsHippocampus.(2013 Jan)
8.^Gobbi M1, Valle FD, Ciapparelli C, Diomede L, Morazzoni P, Verotta L, Caccia S, Cervo L, Mennini THypericum perforatum L. extract does not inhibit 5-HT transporter in rat brain cortexNaunyn Schmiedebergs Arch Pharmacol.(1999 Sep)
9.^Singer A1, Wonnemann M, Müller WEHyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1J Pharmacol Exp Ther.(1999 Sep)
10.^Chatterjee SS1, Bhattacharya SK, Wonnemann M, Singer A, Müller WEHyperforin as a possible antidepressant component of hypericum extractsLife Sci.(1998)
11.^Yoshitake T1, Iizuka R, Yoshitake S, Weikop P, Müller WE, Ogren SO, Kehr JHypericum perforatum L (St John's wort) preferentially increases extracellular dopamine levels in the rat prefrontal cortexBr J Pharmacol.(2004 Jun)
12.^Russo E1, 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 interactionsPhytother Res.(2014 May)
13.^Staffeldt B1, Kerb R, Brockmöller J, Ploch M, Roots IPharmacokinetics of hypericin and pseudohypericin after oral intake of the hypericum perforatum extract LI 160 in healthy volunteersJ Geriatr Psychiatry Neurol.(1994 Oct)
14.^Biber A1, Fischer H, Römer A, Chatterjee SSOral bioavailability of hyperforin from hypericum extracts in rats and human volunteersPharmacopsychiatry.(1998 Jun)
15.^Kerb R, Brockmöller J, Staffeldt B, Ploch M, Roots ISingle-dose and steady-state pharmacokinetics of hypericin and pseudohypericin.Antimicrob Agents Chemother.(1996 Sep)
16.^Kober M, Pohl K, Efferth TMolecular mechanisms underlying St. John's wort drug interactions.Curr Drug Metab.(2008 Dec)
17.^Goodwin B, Moore LB, Stoltz CM, McKee DD, Kliewer SARegulation of the human CYP2B6 gene by the nuclear pregnane X receptor.Mol Pharmacol.(2001 Sep)
18.^Chen Y, Ferguson SS, Negishi M, Goldstein JAInduction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor.J Pharmacol Exp Ther.(2004 Feb)
19.^Rahimi R, Abdollahi MAn update on the ability of St. John's wort to affect the metabolism of other drugs.Expert Opin Drug Metab Toxicol.(2012 Jun)
20.^Obach RSInhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression.J Pharmacol Exp Ther.(2000 Jul)
21.^Bauer S, Störmer E, Kerb R, Johne A, Brockmöller J, Roots IDifferential effects of Saint John's Wort (hypericum perforatum) on the urinary excretion of D-glucaric acid and 6beta-hydroxycortisol in healthy volunteers.Eur J Clin Pharmacol.(2002 Dec)
22.^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)
23.^Smith P, Bullock JM, Booker BM, Haas CE, Berenson CS, Jusko WJThe influence of St. John's wort on the pharmacokinetics and protein binding of imatinib mesylate.Pharmacotherapy.(2004 Nov)
25.^Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, Hall SDThe effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity.Clin Pharmacol Ther.(2001 Oct)
26.^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)
27.^Imai H, Kotegawa T, Tsutsumi K, Morimoto T, Eshima N, Nakano S, Ohashi KThe recovery time-course of CYP3A after induction by St John's wort administrationBr J Clin Pharmacol.(2008 May)
28.^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)
29.^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)
30.^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)
31.^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)
32.^Schulz VSafety of St. John's Wort extract compared to synthetic antidepressants.Phytomedicine.(2006 Feb)
33.^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)
34.^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)
35.^Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, Kawaguchi A, Harada K, Arakawa M, Sakamoto K, Masada M, Miyamori I, Fujimura ADifferent effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin.Clin Pharmacol Ther.(2001 Dec)
36.^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)
37.^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)
38.^Mannel MDrug interactions with St John's wort : mechanisms and clinical implications.Drug Saf.(2004)
39.^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)
40.^Di YM, Li CG, Xue CC, Zhou SFClinical drugs that interact with St. John's wort and implication in drug development.Curr Pharm Des.(2008)
41.^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)
42.^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)
43.^Zhou S, Chan E, Pan SQ, Huang M, Lee EJPharmacokinetic interactions of drugs with St John's wort.J Psychopharmacol.(2004 Jun)
44.^Jakobs D1, Hage-Hülsmann A, Prenner L, Kolb C, Weiser D, Häberlein HDownregulation of β1 -adrenergic receptors in rat C6 glioblastoma cells by hyperforin and hyperoside from St John's wortJ Pharm Pharmacol.(2013 Jun)
45.^Prenner L1, Sieben A, Zeller K, Weiser D, Häberlein HReduction of high-affinity beta2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopyBiochemistry.(2007 May 1)
46.^Simbrey K1, Winterhoff H, Butterweck VExtracts of St. John's wort and various constituents affect beta-adrenergic binding in rat frontal cortexLife Sci.(2004 Jan 9)
47.^De Marchis GM1, Bürgi S, Kientsch U, Honegger UEVitamin E reduces antidepressant-related beta-adrenoceptor down-regulation in cultured cells. Comparable effects on St. John's wort and tricyclic antidepressant treatmentPlanta Med.(2006 Dec)
48.^Müller WE1, Rolli M, Schäfer C, Hafner UEffects of hypericum extract (LI 160) in biochemical models of antidepressant activityPharmacopsychiatry.(1997 Sep)
49.^Müller WE1, Singer A, Wonnemann M, Hafner U, Rolli M, Schäfer CHyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extractPharmacopsychiatry.(1998 Jun)
50.^Müller WECurrent St John's wort research from mode of action to clinical efficacyPharmacol Res.(2003 Feb)
51.^Carboni E1, Tanda GL, Frau R, Di Chiara GBlockade of the noradrenaline carrier increases extracellular dopamine concentrations in the prefrontal cortex: evidence that dopamine is taken up in vivo by noradrenergic terminalsJ Neurochem.(1990 Sep)
52.^Mollenhauer HH1, Morré DJ, Rowe LDAlteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicityBiochim Biophys Acta.(1990 May 7)
53.^Suzuki O, Katsumata Y, Oya M, Bladt S, Wagner HInhibition of monoamine oxidase by hypericinPlanta Med.(1984 Jun)
54.^Bladt S1, Wagner HInhibition of MAO by fractions and constituents of hypericum extractJ Geriatr Psychiatry Neurol.(1994 Oct)
55.^Thiede HM1, Walper AInhibition of MAO and COMT by hypericum extracts and hypericinJ Geriatr Psychiatry Neurol.(1994 Oct)
56.^Linde K, Berner MM, Kriston LSt John's wort for major depressionCochrane Database Syst Rev.(2008 Oct 8)
57.^Linde K, Berner M, Egger M, Mulrow CSt John's wort for depression: meta-analysis of randomised controlled trialsBr J Psychiatry.(2005 Feb)
58.^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 HSThe effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medicationJ Clin Psychiatry.(2004 Aug)
59.^Brenner R, Madhusoodanan S, Pawlowska MEfficacy of continuation treatment with hypericum perforatum in depressionJ Clin Psychiatry.(2002 May)
60.^Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Murck H, Rosenbaum JFA Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorderJ Clin Psychopharmacol.(2005 Oct)
61.^Hypericum Depression Trial Study GroupEffect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trialJAMA.(2002 Apr 10)
62.^Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser MSuperior 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)
63.^Hypericum treatment of mild–moderate depression in a placebo–controlled study. A prospective, double–blind, randomized, placebo–controlled, multicentre study.()
64.^Laakmann G, Schüle C, Baghai T, Kieser MSt. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacyPharmacopsychiatry.(1998 Jun)
66.^Kalb R, Trautmann-Sponsel RD, Kieser MEfficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trialPharmacopsychiatry.(2001 May)
67.^Hänsgen KD, Vesper J, Ploch MMulticenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160J Geriatr Psychiatry Neurol.(1994 Oct)
69.^Lecrubier Y, Clerc G, Didi R, Kieser MEfficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trialAm J Psychiatry.(2002 Aug)
70.^Uebelhack R, Gruenwald J, Graubaum HJ, Busch REfficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trialAdv Ther.(2004 Jul-Aug)
71.^Schrader EEquivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depressionInt Clin Psychopharmacol.(2000 Mar)
72.^Behnke K, Jensen GS, Graubaum HJ, Gruenwald JHypericum perforatum versus fluoxetine in the treatment of mild to moderate depressionAdv Ther.(2002 Jan-Feb)
73.^Bjerkenstedt L, Edman GV, Alken RG, Mannel MHypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatientsEur Arch Psychiatry Clin Neurosci.(2005 Feb)
74.^Brenner R, Azbel V, Madhusoodanan S, Pawlowska MComparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot studyClin Ther.(2000 Apr)
75.^Gastpar M, Singer A, Zeller KEfficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertralinePharmacopsychiatry.(2005 Mar)
76.^Gastpar M, Singer A, Zeller KComparative 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 studyPharmacopsychiatry.(2006 Mar)
78.^Harrer G, Hübner WD, Podzuweit HEffectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind studyJ Geriatr Psychiatry Neurol.(1994 Oct)
79.^Harrer G, Schmidt U, Kuhn U, Biller AComparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetineArzneimittelforschung.(1999 Apr)
80.^Vitiello B, Shader RI, Parker CB, Ritz L, Harlan W, Greenblatt DJ, Gadde KM, Krishnan KR, Davidson JRHyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression TrialJ Clin Psychopharmacol.(2005 Jun)
81.^Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: A meta-analysis.()
82.^Moreno RA, Teng CT, Almeida KM, Tavares Junior HHypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: a randomized double-blind trial in a Brazilian sampleRev Bras Psiquiatr.(2006 Mar)
83.^Anghelescu IG, Kohnen R, Szegedi A, Klement S, Kieser MComparison 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 studyPharmacopsychiatry.(2006 Nov)
84.^Philipp M, Kohnen R, Hiller KOHypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeksBMJ.(1999 Dec 11)
85.^Comparison of St John's wort and imipramine for treating depression: randomised controlled trial.()
86.^Vorbach EU, Arnoldt KH, Hübner WDEfficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10Pharmacopsychiatry.(1997 Sep)
87.^Wheatley DLI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trialPharmacopsychiatry.(1997 Sep)
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