Hypericum perforatum (St. John's wort)
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Interactions by Drug (Human Studies Only)
Only studies done in human beings are used for this database. Animal and in vitro studies are notoriously inaccurate at predicting such interactions in humans. Also note that many of these studies were conducted in extremely small groups of people, often used only a single dose of the medication at the end of period of taking the herb/constituent, and often only looked at pharmacokinetic effects not pharmacological/clinical effects (all indicated in the database below). Such studies require verification in larger populations, with multiple doses of a drug, and looking at whether the drug's efficacy is actually impacted, not just pharmacokinetic parameters. This information is for use by professional health care providers only and not the lay public. Clinical judgement must be used when making an individual determination of whether to combine and herb and a drug in each patient. Click at the small links at the bottom to see the abbreviations and references.
Note: online commercial interaction checkers have been shown to have no connection to the actual evidence base from humans on interactions (Babos MB, Heinan M, Redmond L, et al. (2021) "Herb-drug interactions: Worlds intersect with the patient at the center" Medicines (Basel) 8(8):44.).
Note: online commercial interaction checkers have been shown to have no connection to the actual evidence base from humans on interactions (Babos MB, Heinan M, Redmond L, et al. (2021) "Herb-drug interactions: Worlds intersect with the patient at the center" Medicines (Basel) 8(8):44.).
Herbs/Herbal Constituents Consistently Documented to Affect CYP450 in Humans
Agent |
CYP450 Induced (location of induction) |
CYP450 Inhibited (location of inhibition) |
Necessary dose |
Artemisinin from Artemisia annua |
CYP3A4 (int), CYP2C19 (int) (Asimus 2007) CYP2B6 (int) (Zang 2014) |
CYP1A2 (int) (Asimus 2007) |
Artemisinin: 125 mg qd (Zang 2014) |
Hyperforin from Hypericum perforatum |
CYP3A4 (int)* (Chrubasik-Hausmann 2019; Soleymani 2017; Zhou 2004; Wang 2001) |
none documented |
Hyperforin: <1 mg qd leads to minimal risk of interactions (Chrubasik-Hausmann 2019) |
Glycyrrhizin from Glycyrrhiza spp |
CYP3A4 (LOIU) (Tu 2010a and 2010b) |
none documented |
Glycyrrhzin: 150 mg bid** (Tu 2010a and 2010b) |
Berberine from Berberis/Mahonia spp, Hydrastis canadensis, Coptis chinensis, etc. |
none documented |
CYP3A4 (int) (Gurley 2008a; Xin 2006 and 2005; Wu 2005); mild with whole Hydrastis root (Gurley 2007) CYP2D6 (int) (Guo 2012b; Gurley 2008b; Gurley 2005) CYP2C9 (Guo 2012b) |
Berberine: 200 mg tid (Wu 2005); 300 mg bid (Xin 2006); 300 mg tid (Guo 2007) Hydrastis: 3.2 g qd (Gurley 2007) |
Grapefruit (Citrus x paradisi), pomelo (Citrus maxima), bitter orange (Citrus x aurantium)*** |
none documented |
CYP3A4 (int) |
Grapefruit: 250 ml juice |
Rhodiola rosea |
none documented |
CYP2C9 (LOIU) (Thu 2016) |
Rhodiola: Dry root 1 g qd |
Salvia miltiorrhiza |
Multiple doses induce CYP3A4 (int) (Qiu 2013; Qiu 2010) |
Single doses inhibit CYP3A4 (int) (Qiu 2013) |
Salvia: 1 g (single dose), 1–4 g tid (multiple dose) |
Schisandra sphaenanthera |
none documented |
CYP3A4 (LOIU) (Jiang 2010; Xin 2009 and 2007) |
Schisandra: 500 mg tid |
Location of induction: hep = hepatic CYP450 affected; int = intestinal CYP450 affected; LOIU = location of induction unknown
* Likely actually acts via activating the pregnane X receptor (PXR), which in turn induces CYP3A4 and P-glycoprotein (Wang 2009).
** This is quite a high dose, and well above the usual 100 mg daily dose of glycyrrhizin that will induce hypokalemia and hypertension after a couple of weeks in most people; this interaction is thus highly unlikely at usual doses of whole Glycyrrhiza, or crude extracts thereof.
*** Bitter orange is much less potent than grapefruit or pomelo
* Likely actually acts via activating the pregnane X receptor (PXR), which in turn induces CYP3A4 and P-glycoprotein (Wang 2009).
** This is quite a high dose, and well above the usual 100 mg daily dose of glycyrrhizin that will induce hypokalemia and hypertension after a couple of weeks in most people; this interaction is thus highly unlikely at usual doses of whole Glycyrrhiza, or crude extracts thereof.
*** Bitter orange is much less potent than grapefruit or pomelo
References for the Table
Asimus S, Elsherbiny D, Hai TN, et al. (2007) “Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in healthy subjects” Fund Clin Pharmacol 21:307–16. PMID 17521300
Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ (2019) "Understanding drug interactions with St John's wort (Hypericum perforatum L): Impact of hyperforin content" J Pharm Pharmacol 71(1):129–138. PMID 29411879
Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH (2012b) "Repeated administration of berberine inhibits cytochromes P450 in humans" Eur J Clin Pharmacol 68(2):213–217. PMID 21870106
Gurley BJ, Gardner SF, Hubbard MA, et al. (2005) "In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes” Clin Pharmacol Ther 77(5):415–426. PMID 15900287
Gurley BJ, Swain A, Barone GW, et al. (2007) “Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans” Drug Metab Dispos 35(2):240–245. PMID 17079360
Gurley BJ, Swain A, Hubbard MA, et al. (2008a) “Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo” Clin Pharmacol Ther 83(1):61–69. PMID 17495878
Gurley BJ, Swain A, Hubbard MA, et al. (2008b) “Clinical assessment of CYP2D6-mediated herb–drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John’s wort, and Echinacea” Mol Nutr Food Res 52:755–763. PMID 18214849
Jiang W, Wang X, Xu X, Kong L (2010) "Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients" Int J Clin Pharmacol Ther 48(3):224–229. PMID 20197017
Qiu F, Wang G, Zhang R, et al. (2010) "Effect of danshen extract on the activity of CYP3A4 in healthy volunteers" Br J Clin Pharmacol 69(6):656–662. PMID 20565457
Qiu F, Jiang J, Ma Y, et al. (2013) "Opposite effects of single-dose and multidose administration of the ethanol extract of danshen on CYP3A in healthy volunteers" Evid Based Complement Alternat Med 2013:730734. PMID 24223062
Soleymani S, Bahramsoltani R, Rahimi R, Abdollahi M (2017) "Clinical risks of St John's wort (Hypericum perforatum) co-administration" Expert Opin Drug Metab Toxicol 13(10):1047–1062. PMID 28885074
Thu OK, Spigset O, Nilsen OG, Hellum B (2016) "Effect of commercial Rhodiola rosea on CYP enzyme activity in humans" Eur J Clin Pharmacol 72(3):295–300. PMID 26613955
Tu JH, He YJ, Chen Y, et al. (2010a) “Effect of glycyrrhizin on the activity of CYP3A enzyme in humans” Eur J Clin Pharmacol 66(8):805–810. PMID: 20393696
Tu JH, Hu DL, Dai LL, et al. (2010b) "Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes" Xenobiotica 40(6):393–399. PMID 20350051
Wang XD, Li JL, Su QB, et al. (2009) "Impact of the haplotypes of the human pregnane X receptor gene on the basal and St John's wort-induced activity of cytochrome P450 3A4 enzyme" Br J Clin Pharmacol 67(2):255–261. PMID 19173680
Wang Z, Gorski JC, Hamman MA, et al. (2001) “The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity” Clin Pharmacol Ther 70(4):317–26. PMID 11673747
Wu X, Li Q, Xin H, Yu A, Zhong M (2005) “Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: Clinical and pharmacokinetic study” Eur J Clin Pharmacol 61(8):567–572. PMID 16133554
Xin HW, Wu XC, Li Q, et al. (2006) “The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers” Methods Find Exp Clin Pharmacol 28(1):25–29. PMID 16541194
Xin H-W, Wu X-C, Li Q, et al. (2007) “Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers” Br J Clin Pharmacol 64(4):469–475. PMID 17506780
Xin H-W, Wu X-C, Li Q, Yu A-R, Xiong L (2009) “Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers” Br J Clin Pharmacol 67(5):541–546. PMID 19552749
Zang M, Zhu F, Li X, Yang A, Xing J (2014) "Auto-induction of phase I and phase II metabolism of artemisinin in healthy Chinese subjects after oral administration of a new artemisinin-piperaquine fixed combination" Malar J 13:214. PMID 24889062
Zhou SF, Chan E, Pan SQ, Huang M, Lee EJ (2004) “Pharmacokinetic interactions of drugs with St John's wort” J Psychopharmacol 18(2):262–276. PMID 15260917
Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ (2019) "Understanding drug interactions with St John's wort (Hypericum perforatum L): Impact of hyperforin content" J Pharm Pharmacol 71(1):129–138. PMID 29411879
Guo Y, Chen Y, Tan ZR, Klaassen CD, Zhou HH (2012b) "Repeated administration of berberine inhibits cytochromes P450 in humans" Eur J Clin Pharmacol 68(2):213–217. PMID 21870106
Gurley BJ, Gardner SF, Hubbard MA, et al. (2005) "In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes” Clin Pharmacol Ther 77(5):415–426. PMID 15900287
Gurley BJ, Swain A, Barone GW, et al. (2007) “Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans” Drug Metab Dispos 35(2):240–245. PMID 17079360
Gurley BJ, Swain A, Hubbard MA, et al. (2008a) “Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo” Clin Pharmacol Ther 83(1):61–69. PMID 17495878
Gurley BJ, Swain A, Hubbard MA, et al. (2008b) “Clinical assessment of CYP2D6-mediated herb–drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John’s wort, and Echinacea” Mol Nutr Food Res 52:755–763. PMID 18214849
Jiang W, Wang X, Xu X, Kong L (2010) "Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients" Int J Clin Pharmacol Ther 48(3):224–229. PMID 20197017
Qiu F, Wang G, Zhang R, et al. (2010) "Effect of danshen extract on the activity of CYP3A4 in healthy volunteers" Br J Clin Pharmacol 69(6):656–662. PMID 20565457
Qiu F, Jiang J, Ma Y, et al. (2013) "Opposite effects of single-dose and multidose administration of the ethanol extract of danshen on CYP3A in healthy volunteers" Evid Based Complement Alternat Med 2013:730734. PMID 24223062
Soleymani S, Bahramsoltani R, Rahimi R, Abdollahi M (2017) "Clinical risks of St John's wort (Hypericum perforatum) co-administration" Expert Opin Drug Metab Toxicol 13(10):1047–1062. PMID 28885074
Thu OK, Spigset O, Nilsen OG, Hellum B (2016) "Effect of commercial Rhodiola rosea on CYP enzyme activity in humans" Eur J Clin Pharmacol 72(3):295–300. PMID 26613955
Tu JH, He YJ, Chen Y, et al. (2010a) “Effect of glycyrrhizin on the activity of CYP3A enzyme in humans” Eur J Clin Pharmacol 66(8):805–810. PMID: 20393696
Tu JH, Hu DL, Dai LL, et al. (2010b) "Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes" Xenobiotica 40(6):393–399. PMID 20350051
Wang XD, Li JL, Su QB, et al. (2009) "Impact of the haplotypes of the human pregnane X receptor gene on the basal and St John's wort-induced activity of cytochrome P450 3A4 enzyme" Br J Clin Pharmacol 67(2):255–261. PMID 19173680
Wang Z, Gorski JC, Hamman MA, et al. (2001) “The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity” Clin Pharmacol Ther 70(4):317–26. PMID 11673747
Wu X, Li Q, Xin H, Yu A, Zhong M (2005) “Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: Clinical and pharmacokinetic study” Eur J Clin Pharmacol 61(8):567–572. PMID 16133554
Xin HW, Wu XC, Li Q, et al. (2006) “The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers” Methods Find Exp Clin Pharmacol 28(1):25–29. PMID 16541194
Xin H-W, Wu X-C, Li Q, et al. (2007) “Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers” Br J Clin Pharmacol 64(4):469–475. PMID 17506780
Xin H-W, Wu X-C, Li Q, Yu A-R, Xiong L (2009) “Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers” Br J Clin Pharmacol 67(5):541–546. PMID 19552749
Zang M, Zhu F, Li X, Yang A, Xing J (2014) "Auto-induction of phase I and phase II metabolism of artemisinin in healthy Chinese subjects after oral administration of a new artemisinin-piperaquine fixed combination" Malar J 13:214. PMID 24889062
Zhou SF, Chan E, Pan SQ, Huang M, Lee EJ (2004) “Pharmacokinetic interactions of drugs with St John's wort” J Psychopharmacol 18(2):262–276. PMID 15260917
Commentary on Hypericum perforatum and Herb-Drug Interactions
There is a wide interindividual variation in response to Hypericum perforatum and its interacting compound, hyperforin. This problem is aggravated by very small sample sizes in most of the studies on Hypericum perforatum and drug interactions. It has plausibly been theorized this could be due to pregnane and xenobiotic receptor (PXR) haplotype variability. In one study of 10 healthy Chinese adults (so, too small a sample size to really be sure), the H1/H1 haplotype of the PXR gene was associated with the greatest inducibility (PMID 19173680). It is important to note the interaction with hyperforin occurs primarily in the intestines, less so in the liver (PMID 18294328, 11180019). Hyperforin mainly reduces the absorption of drugs, secondarily their ability to get past liver metabolism. The upregulation of CYP3A4 and Pgp by hyperforin takes up to 7 days after discontinuation to return to baseline, according to human clinical trials (PMID 18294328, 11673747, 13129991).
Herbs/Herbal Constituents Affecting CYP450 in Humans with Mixed Research
Agent |
CYP450 Induced (location of induction) |
CYP450 Inhibited (location of inhibition) |
Allium sativum |
CYP3A4 (LOIU) Positive study: Piscatelli 2002 Negative study: Markowitz 2003a |
none documented |
Angelica dahurica |
none documented |
CYP1A2 mild (Yi 2009) |
Camellia sinensis |
none documented |
CYP3A4 (int) Positive study: Hegazy 2014 Negative studies: Greenblatt 2006b; Donovan 2004b |
Curcuma longa |
none documented |
CYP2D6, no effect on CYP3A4 or CYP2C9 (Al-Jenobi 2015b; Volak 2013; Ikehata 2008) |
Genistein |
CYP3A, mild (Xiao 2012) |
none documented |
Ginkgo biloba |
CYP2C19 (Yin 2004; negative study Zadoyan 2012), no effect on CYP1A2, 2C9, 2D6, 3A4 (Zadoyan 2012; Guo 2012a; Markowitz 2003b; Greenblatt 2006a) |
none documented |
Isothiocyanates, Brassica vegetables |
CYP1A1/2, 2E1 H (Hakooz 2007; Lampe 2000) |
none documented |
Keishi-bukuryo-gan (gui zi fu ling wan) |
none documented |
CYP1A2 mild (Saruwatari 2012) |
Nigella sativa |
none documented |
CYP2D6, 3A4 (Al-Jenoobi 2010) |
Panax ginseng |
CYP3A4 (hep mild) (Malati 2012; negative trials: Seong 2018; Kim 2016a, b; Calderón 2014) |
none documented |
Panax quinquefolius |
CYP2C9 int |
none documented |
Phenylethyl isothiocyanate |
none documented |
CYP2E1 hep, int? |
Piperine (from Piper longum, P. nigrum) |
none documented |
CYP3A4 (int) (negative study: Volak 2013) |
Quercetin |
CYP3A5 (Nguyen 2015; Duan 2012) |
none documented |
Scutellaria baicalensis |
CYP2E1 (Yi 2009) |
CYP2C9 (Yi 2009) |
Sho-saiko-tō (xiao chai hu tang) |
none documented |
CYP1A2 (Saruwatari 2003) |
Location of induction: hep = hepatic CYP450 affected; int = intestinal CYP450 affected; LOIU = location of induction unknown
References for the Table
Al-Jenoobi FI, Al-Thukair AA, Alam MA, et al. (2015b) "Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects" Eur J Drug Metab Pharmacokinet 40(1):61–66. PMID 24510399
Donovan JL, Chavin KD, Devane CL, et al. (2004b) “Green tea (Camellia sinensis) extract does not alter cytochrome P450 3A4 or 2D6 activity in healthy volunteers” Drug Metab Dispos 32(9):906–908. PMID 15319329
Greenblatt DJ, von Moltke LL, Luo Y, et al. (2006a) "Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate" J Clin Pharmacol 46(2):214–221. PMID 16432273
Greenblatt DJ, von Moltke LL, Perloff ES, et al. (2006b) "Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: In vitro and clinical studies" Clin Pharmacol Ther 79(1):125–133. PMID 16413247
Guo CX, Pei Q, Yin JY, et al. (2012a) "Effects of Ginkgo biloba extracts on pharmacokinetics and efficacy of atorvastatin based on plasma indices" Xenobiotica 42(8):784–790. PMID 22381135
Hegazy SK (2014) "The effect of green tea on sildenafil pharmacokinetics in Egyptian healthy volunteers" Br J Pharmaceut Res 4:289–300.
Ikehata M, Ohnishi N, Egami S, et al. (2008) "Effects of turmeric extract on the pharmacokinetics of nifedipine after a single oral administration in healthy volunteers" J Dietary Suppl 5(4):401–410. PMID 22436099
Markowitz JS, Devane CL, Chavin KD, et al. (2003a) “Effects of garlic (Allium sativum L) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers” Clin Pharmacol Ther 74(2):170–177. PMID 12891227
Markwotiz JS, Donovan JL, Lindsay DeVane C, et al (2003b) “Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers” J Clin Psychopharmacol 23(6):576–581. PMID 14624188
Piscatelli SC, Burstein AH, Welden N, et al. (2002) “The effect of garlic supplements on the pharmacokinetics of saquinavir” Clin Infect Dis 34(2):234–238. PMID 11740713
Volak LP, Hanley MJ, Masse G, et al. (2013) "Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers" Br J Clin Pharmacol 75(2):450–62. PMID 22725836
Xiao CQ, Chen R, Lin J, et al. (2012) "Effect of genistein on the activities of cytochrome P450 3A and P-glycoprotein in Chinese healthy participants" Xenobiotica 42(2):173–178. PMID 21943317
Yi SJ, Cho JY, Lim KS, et al. (2009) “Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers” Basic Clin Pharmacol Toxicol 105:249–256. PMID 19422358
Yin OQ, Tomlinson B, Waye MM, Chow AH, Chow MS (2004) “Pharmacogenetics and herb-drug interactions: Experience with Ginkgo biloba and omeprazole” Pharmacogenetics 14(12):841–850. PMID 15608563
Zadoyan G, Rokitta D, Klement S, et al. (2012) "Effect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: A cocktail interaction study in healthy volunteers" Eur J Clin Pharmacol 68(5):553–560. PMID 22189672
Donovan JL, Chavin KD, Devane CL, et al. (2004b) “Green tea (Camellia sinensis) extract does not alter cytochrome P450 3A4 or 2D6 activity in healthy volunteers” Drug Metab Dispos 32(9):906–908. PMID 15319329
Greenblatt DJ, von Moltke LL, Luo Y, et al. (2006a) "Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate" J Clin Pharmacol 46(2):214–221. PMID 16432273
Greenblatt DJ, von Moltke LL, Perloff ES, et al. (2006b) "Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: In vitro and clinical studies" Clin Pharmacol Ther 79(1):125–133. PMID 16413247
Guo CX, Pei Q, Yin JY, et al. (2012a) "Effects of Ginkgo biloba extracts on pharmacokinetics and efficacy of atorvastatin based on plasma indices" Xenobiotica 42(8):784–790. PMID 22381135
Hegazy SK (2014) "The effect of green tea on sildenafil pharmacokinetics in Egyptian healthy volunteers" Br J Pharmaceut Res 4:289–300.
Ikehata M, Ohnishi N, Egami S, et al. (2008) "Effects of turmeric extract on the pharmacokinetics of nifedipine after a single oral administration in healthy volunteers" J Dietary Suppl 5(4):401–410. PMID 22436099
Markowitz JS, Devane CL, Chavin KD, et al. (2003a) “Effects of garlic (Allium sativum L) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers” Clin Pharmacol Ther 74(2):170–177. PMID 12891227
Markwotiz JS, Donovan JL, Lindsay DeVane C, et al (2003b) “Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers” J Clin Psychopharmacol 23(6):576–581. PMID 14624188
Piscatelli SC, Burstein AH, Welden N, et al. (2002) “The effect of garlic supplements on the pharmacokinetics of saquinavir” Clin Infect Dis 34(2):234–238. PMID 11740713
Volak LP, Hanley MJ, Masse G, et al. (2013) "Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers" Br J Clin Pharmacol 75(2):450–62. PMID 22725836
Xiao CQ, Chen R, Lin J, et al. (2012) "Effect of genistein on the activities of cytochrome P450 3A and P-glycoprotein in Chinese healthy participants" Xenobiotica 42(2):173–178. PMID 21943317
Yi SJ, Cho JY, Lim KS, et al. (2009) “Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers” Basic Clin Pharmacol Toxicol 105:249–256. PMID 19422358
Yin OQ, Tomlinson B, Waye MM, Chow AH, Chow MS (2004) “Pharmacogenetics and herb-drug interactions: Experience with Ginkgo biloba and omeprazole” Pharmacogenetics 14(12):841–850. PMID 15608563
Zadoyan G, Rokitta D, Klement S, et al. (2012) "Effect of Ginkgo biloba special extract EGb 761® on human cytochrome P450 activity: A cocktail interaction study in healthy volunteers" Eur J Clin Pharmacol 68(5):553–560. PMID 22189672
Herbs Not Affecting CYP450 in Humans
This information is for use by professional health care providers only and not the lay public. Clinical judgement must be used when making an individual determination of whether to combine and herb and a drug in each patient.
Actaea racemosa (Gurley 2006 and 2005)
Angelica tenuissima (Yi 2009)
Astragalus propinquus = A. membranaceus (Zhou 2013)
Coffea arabica (Dresser 2017)
Curcuma longa (Volak 2013)
Crataegus laevigata (Tankanow 2003)
Echinacea purpurea (Goey 2013; Moltó 2011 and 2012; Gurley 2008c and 2004)
Dissenting study showing CYP1A2 inhibition and possible CYP3A4 inhibition (Gorski 2004)
Eleutherocococcus senticosus (Donovan 2003)
Glycine max (Wang 2009)
Humulus lupulus (Van Breemen 2020)
Lavandula angustifolia (Heger-Mahn 2014; Doroshyenko 2013)
Liu wei di huang wan formula (Chen 2012)
Paeonia lactiflora (Xie 2002; Chen 2000)
Piper methysticum (Gurley 2008a and 2007)
Dissenting study: CYP2E1 inhibition in one study (Gurley 2005)
Punica granatum (Abdlekawy 2017; Hanley 2012; Farkas 2007)
Serenoa repens standardized extract (Gurley 2004; Markowitz 2003c)
Silybum marianum—silymarin extract (Kawaguchi-Suzuki 2014; Gurley 2006; Mills 2005)
Trigonella foenum-graecum (Al-Jenoobi 2015a)
Vaccinium macrocarpon juice (Greenblatt 2006b; Lilja 2007; Grenier 2006)
One dissenting study possibly not related to CYP interactions (Mohammed Abdul 2008)
Vaccinium corymbosum (Hanley 2013)
Valeriana officinalis (Donovan 2004; Gurley 2005)
Vitis vinifera (Greenblatt 2006b)
Angelica tenuissima (Yi 2009)
Astragalus propinquus = A. membranaceus (Zhou 2013)
Coffea arabica (Dresser 2017)
Curcuma longa (Volak 2013)
Crataegus laevigata (Tankanow 2003)
Echinacea purpurea (Goey 2013; Moltó 2011 and 2012; Gurley 2008c and 2004)
Dissenting study showing CYP1A2 inhibition and possible CYP3A4 inhibition (Gorski 2004)
Eleutherocococcus senticosus (Donovan 2003)
Glycine max (Wang 2009)
Humulus lupulus (Van Breemen 2020)
Lavandula angustifolia (Heger-Mahn 2014; Doroshyenko 2013)
Liu wei di huang wan formula (Chen 2012)
Paeonia lactiflora (Xie 2002; Chen 2000)
Piper methysticum (Gurley 2008a and 2007)
Dissenting study: CYP2E1 inhibition in one study (Gurley 2005)
Punica granatum (Abdlekawy 2017; Hanley 2012; Farkas 2007)
Serenoa repens standardized extract (Gurley 2004; Markowitz 2003c)
Silybum marianum—silymarin extract (Kawaguchi-Suzuki 2014; Gurley 2006; Mills 2005)
Trigonella foenum-graecum (Al-Jenoobi 2015a)
Vaccinium macrocarpon juice (Greenblatt 2006b; Lilja 2007; Grenier 2006)
One dissenting study possibly not related to CYP interactions (Mohammed Abdul 2008)
Vaccinium corymbosum (Hanley 2013)
Valeriana officinalis (Donovan 2004; Gurley 2005)
Vitis vinifera (Greenblatt 2006b)
References for the List
Abdlekawy KS, Donia AM, Elbarbry F (2017) "Effects of grapefruit and pomegranate juices on the pharmacokinetic properties of dapoxetine and midazolam in healthy subjects" Eur J Drug Metab Pharmacokinet 42(3):397–405.
Al-Jenoobi FI, Al-Thukair AA, Alam MA, et al. (2015a) "Effect of Trigonella foenum-graecum L on metabolic activity of CYP2D6 and CYP3A4" Forsch Komplementmed 22(3):180–4.
Chen LC, Chou MH, Lin MF, Yang LL (2000) "Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers" J Clin Pharm Ther 25(6):453–9.
Chen Y, Ouyang DS, Kang Z, et al. (2012) “Effect of a traditional Chinese medicine Liu Wei Di Huang Wan on the activities of CYP2C19, CYP2D6 and CYP3A4 in healthy volunteers” Xenobiotica 42(6):596–602.
Donovan JL, DeVane CL, Chavin KD, et al. (2003) “Siberian ginseng (Eleutherococcus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers” Drug Metab Dispos 31:519–22.
Donovan JL, DeVane CL, Chavin KD, et al. (2004a) “Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers” Drug Metab Dispos 32(12):1333–6.
Doroshyenko O, Rokitta D, Zadoyan G, et al. (2013) "Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome P450 enzymes in healthy volunteers" Drug Metab Dispos 41(5):987–93.
Dresser GK, Urquhart BL, Proniuk J, et al. (2017) "Coffee inhibition of CYP3A4 in vitro was not translated to a grapefruit-like pharmacokinetic interaction clinically" Pharmacol Res Perspect 5(5):e00346.
Farkas D, Oleson LE, Zhao Y, et al. (2007) “Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice” J Clin Pharmacol 47(3):286–94.
Goey AK, Meijerman I, Rosing H, et al. (2013) "The effect of Echinacea purpurea on the pharmacokinetics of docetaxel" Br J Clin Pharmacol 76(3):467–74.
Gorski JC, Huang SM, Pinto A, et al. (2004) “The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo” Clin Pharmacol Ther 75;89–100.
Greenblatt DJ, von Moltke LL, Perloff ES, et al. (2006b) "Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: In vitro and clinical studies" Clin Pharmacol Ther 79(1):125–33.
Grenier J, Fradette C, Morelli G, et al. (2006) “Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans” Clin Pharmacol Ther 79(3):255–62.
Gurley BJ, Gardner SF, Hubbard MA, et al. (2004) “In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto” Clin Pharmacol Ther 76(5):428–40.
Gurley BJ, Gardner SF, Hubbard MA, et al. (2005) "In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes” Clin Pharmacol Ther 77(5):415–26.
Gurley B, Hubbard MA, Williams DK, et al. (2006) “Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin” J Clin Pharmacol 46(2):201–13.
Gurley BJ, Swain A, Barone GW, et al. (2007) “Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans” Drug Metab Dispos 35(2):240–5.
Gurley BJ, Swain A, Hubbard MA, et al. (2008a) “Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo” Clin Pharmacol Ther 83(1):61–9.
Gurley BJ, Swan A, Williams DK, et al. (2008c) “Gauging the clinical significance of P-glycoprotein- mediated herb-drug interactions: Comparative effects of St. John’s wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics” Mol Nutr Food Res 52:772–9.
Hanley MJ, Masse G, Harmatz JS, et al. (2012) "Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: Divergence from in vitro results" Clin Pharmacol Ther 92(5):651–7.
Hanley MJ, Masse G, Harmatz JS, et al. (2013) "Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers" Br J Clin Pharmacol 75(4):1041–52.
Heger-Mahn D, Pabst G, Dienel A, et al. (2014) "No interacting influence of lavender oil preparation Silexan on oral contraception using an ethinyl estradiol/levonorgestrel combination" Drugs in R&D 14(4):265–72.
Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. (2014) "The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity" Drug Metab Dispos 42(10):1611–6.
Lilja JJ, Backman JT, Neuvonen PJ (2007) “Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam-probes of CYP2C9, CYP1A2, and CYP3A4” Clin Pharmacol Ther 81(6):833–9.
Markowtiz JS, Donovan JL, Devane CL, et al. (2003c) “Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers” Clin Pharmacol Ther 74:536–42.
Mills E, Wilson K, Clarke M, et al. (2005) “Milk thistle and indinavir: A randomized controlled pharmacokinetics study and meta-analysis” Eur J Clin Pharmacol 61:1–7.
Mohammed Abdul MI, Jiang X, Williams KM, et al. (2008) “Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects” Br J Pharmacol 154(8):1691–700.
Moltó J, Valle M, Miranda C, et al. (2011) "Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients" Antimicrob Agents Chemother 55(1):326–30.
Moltó J, Valle M, Miranda C, et al. (2012) "Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients" Antimicrob Agents Chemother 56(10):5328–31.
Tankanow R, Tamer HR, Streetman DS, et al. (2003) "Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha)" J Clin Pharm 43(6):637–42.
van Breemen RB, Chen L, Tonsing-Carter A, et al. (2020) "Pharmacokinetic interactions of a hop dietary supplement with drug metabolism in perimenopausal and postmenopausal women" J Agric Food Chem 68(18):51212–20.
Volak LP, Hanley MJ, Masse G, et al. (2013) "Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers" Br J Clin Pharmacol 75(2):450–62. PMID 22725836
Wang G, Xiao CQ, Li Z, et al. (2009) "Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers" Ann Pharmacother 43(6):1045–9.
Xie HJ, Yasar U, Sandberg M, Rane A (2002) "Paeoniae Radix, a traditional Chinese medicine, and CYP2C9 activity" J Clin Pharm Ther 27(3):229–30. PMID 12081638
Yi SJ, Cho JY, Lim KS, et al. (2009) “Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers” Basic Clin Pharmacol Toxicol 105:249–56.
Zhou Q, Ye Z, Ruan Z, Zeng S (2013) "Investigation on modulation of human P-gp by multiple doses of Radix Astragali extract granules using fexofenadine as a phenotyping probe" J Ethnopharmacol 146(3):744–9.
Al-Jenoobi FI, Al-Thukair AA, Alam MA, et al. (2015a) "Effect of Trigonella foenum-graecum L on metabolic activity of CYP2D6 and CYP3A4" Forsch Komplementmed 22(3):180–4.
Chen LC, Chou MH, Lin MF, Yang LL (2000) "Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers" J Clin Pharm Ther 25(6):453–9.
Chen Y, Ouyang DS, Kang Z, et al. (2012) “Effect of a traditional Chinese medicine Liu Wei Di Huang Wan on the activities of CYP2C19, CYP2D6 and CYP3A4 in healthy volunteers” Xenobiotica 42(6):596–602.
Donovan JL, DeVane CL, Chavin KD, et al. (2003) “Siberian ginseng (Eleutherococcus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers” Drug Metab Dispos 31:519–22.
Donovan JL, DeVane CL, Chavin KD, et al. (2004a) “Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers” Drug Metab Dispos 32(12):1333–6.
Doroshyenko O, Rokitta D, Zadoyan G, et al. (2013) "Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome P450 enzymes in healthy volunteers" Drug Metab Dispos 41(5):987–93.
Dresser GK, Urquhart BL, Proniuk J, et al. (2017) "Coffee inhibition of CYP3A4 in vitro was not translated to a grapefruit-like pharmacokinetic interaction clinically" Pharmacol Res Perspect 5(5):e00346.
Farkas D, Oleson LE, Zhao Y, et al. (2007) “Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice” J Clin Pharmacol 47(3):286–94.
Goey AK, Meijerman I, Rosing H, et al. (2013) "The effect of Echinacea purpurea on the pharmacokinetics of docetaxel" Br J Clin Pharmacol 76(3):467–74.
Gorski JC, Huang SM, Pinto A, et al. (2004) “The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo” Clin Pharmacol Ther 75;89–100.
Greenblatt DJ, von Moltke LL, Perloff ES, et al. (2006b) "Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: In vitro and clinical studies" Clin Pharmacol Ther 79(1):125–33.
Grenier J, Fradette C, Morelli G, et al. (2006) “Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans” Clin Pharmacol Ther 79(3):255–62.
Gurley BJ, Gardner SF, Hubbard MA, et al. (2004) “In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto” Clin Pharmacol Ther 76(5):428–40.
Gurley BJ, Gardner SF, Hubbard MA, et al. (2005) "In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes” Clin Pharmacol Ther 77(5):415–26.
Gurley B, Hubbard MA, Williams DK, et al. (2006) “Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin” J Clin Pharmacol 46(2):201–13.
Gurley BJ, Swain A, Barone GW, et al. (2007) “Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans” Drug Metab Dispos 35(2):240–5.
Gurley BJ, Swain A, Hubbard MA, et al. (2008a) “Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo” Clin Pharmacol Ther 83(1):61–9.
Gurley BJ, Swan A, Williams DK, et al. (2008c) “Gauging the clinical significance of P-glycoprotein- mediated herb-drug interactions: Comparative effects of St. John’s wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics” Mol Nutr Food Res 52:772–9.
Hanley MJ, Masse G, Harmatz JS, et al. (2012) "Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: Divergence from in vitro results" Clin Pharmacol Ther 92(5):651–7.
Hanley MJ, Masse G, Harmatz JS, et al. (2013) "Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers" Br J Clin Pharmacol 75(4):1041–52.
Heger-Mahn D, Pabst G, Dienel A, et al. (2014) "No interacting influence of lavender oil preparation Silexan on oral contraception using an ethinyl estradiol/levonorgestrel combination" Drugs in R&D 14(4):265–72.
Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. (2014) "The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity" Drug Metab Dispos 42(10):1611–6.
Lilja JJ, Backman JT, Neuvonen PJ (2007) “Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam-probes of CYP2C9, CYP1A2, and CYP3A4” Clin Pharmacol Ther 81(6):833–9.
Markowtiz JS, Donovan JL, Devane CL, et al. (2003c) “Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers” Clin Pharmacol Ther 74:536–42.
Mills E, Wilson K, Clarke M, et al. (2005) “Milk thistle and indinavir: A randomized controlled pharmacokinetics study and meta-analysis” Eur J Clin Pharmacol 61:1–7.
Mohammed Abdul MI, Jiang X, Williams KM, et al. (2008) “Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects” Br J Pharmacol 154(8):1691–700.
Moltó J, Valle M, Miranda C, et al. (2011) "Herb-drug interaction between Echinacea purpurea and darunavir-ritonavir in HIV-infected patients" Antimicrob Agents Chemother 55(1):326–30.
Moltó J, Valle M, Miranda C, et al. (2012) "Herb-drug interaction between Echinacea purpurea and etravirine in HIV-infected patients" Antimicrob Agents Chemother 56(10):5328–31.
Tankanow R, Tamer HR, Streetman DS, et al. (2003) "Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha)" J Clin Pharm 43(6):637–42.
van Breemen RB, Chen L, Tonsing-Carter A, et al. (2020) "Pharmacokinetic interactions of a hop dietary supplement with drug metabolism in perimenopausal and postmenopausal women" J Agric Food Chem 68(18):51212–20.
Volak LP, Hanley MJ, Masse G, et al. (2013) "Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers" Br J Clin Pharmacol 75(2):450–62. PMID 22725836
Wang G, Xiao CQ, Li Z, et al. (2009) "Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers" Ann Pharmacother 43(6):1045–9.
Xie HJ, Yasar U, Sandberg M, Rane A (2002) "Paeoniae Radix, a traditional Chinese medicine, and CYP2C9 activity" J Clin Pharm Ther 27(3):229–30. PMID 12081638
Yi SJ, Cho JY, Lim KS, et al. (2009) “Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers” Basic Clin Pharmacol Toxicol 105:249–56.
Zhou Q, Ye Z, Ruan Z, Zeng S (2013) "Investigation on modulation of human P-gp by multiple doses of Radix Astragali extract granules using fexofenadine as a phenotyping probe" J Ethnopharmacol 146(3):744–9.