Herb-Drug Interactions

 
 

Herbal medicine has a long history of use and the adverse reactions are well understood.

With the development of pharmaceutical drugs and concentrated nutritional supplements, however, things have changed and it's become important to understand the potential for interactions between herbs, nutrients, and drugs. Some of these interactions can be very dangerous.

 
 
 

Agonistic Interactions:

Agonistic interactions involve herbs, nutrients, or drugs with the same effect profile. This will make the effect profile stronger by compounding the various actions. This can make the results TOO strong, resulting in adverse reactions Over and above what the desired outcome was meant to be.

An example of this is St John's Wort and SSRI medications. Both of these substances have the same effect, which can increase serotonin levels to a point that may result in serotonin syndrome if used carelessly.

 

Antagonistic Interactions:

Antagonistic interactions involve herbs, nutrients, or drugs neutralising eachother. This can be the result of CYP450 enzyme induction (thus speeding up metabolism of active constituents), or having one action cause a directly oposing effect to another.

An example of this interaction is milk thistle dramatically increasing the excretion of drugs metabolised through the CYP3A4 enzyme pathway, thus negating their potency and half life.

 
 
 
 
HerbEnzymesDrug effectReference
Andrographis
(Andrographis paniculata)
CYP2C11
CYP2C
CYP3A4
CYP2C9
Induction - Increase metabolism4
Astragalus
(Astragalus membranaceus)
CYP3A4Inhibition -
Decrease drug effect
5
Bacopa
(Bacopa monnieri)
CYP2C19
CYP3A4
CYP1A2
CYP2D6
Inhibition
Inhibition
Inhibition
Weak Inhibition – minimal interaction
6
Baical Skullcap
(Scutellaria baicalensis)
CYP2C9
CYP2E1
CYP3A4
Induction – Losartan
Inhibition – Chlorzoxazone
Inhibition - Benzodiazepam
7, 8
Barberry
(Berberis vulgaris)
CYP3A4
CYP2C19
CYP2D6
CYP3A11
CYP3A25
CYP2C9
Inhibition – Benzodiazepam
Inhibition – Omeprazole
Inhibition - Dextromethorphan
Minimal activity at low dose
Minimal activity at low dose
Minimal activity at low dose
9, 10
Black Cohosh
(Cimicifuga racemose)
CYP3A4
CYP2D6
P-gp
Weak inhibition
Weak inhibition
Insignificant effect - Digoxin
11, 12
Buchu
Agathosma betulina
CYP2C9
CYP2C8
Inhibition
Weak inhibition
13, 14
Calendula
(Calendula officinalis)
CYP450Induction Increased sedative effects at high doses – No significant drug interaction at recommended dose reported.15
California Poppy
Eschscholzia californica
CYP3A4
CYP2C9
CYP2C19
CYP2D6
CYP1A2
P-gp
Inhibition
Inhibition
Inhibition
Inhibition
Inhibition
Unaffected

Tea form does not affect CYP450’s
16
Celery Seed
Apium graveolens
CYP2A5
CYP2A6
CYP2D6
CYP3A4
Insignificant inhibition
Insignificant inhibition
Insignificant inhibition
Insignificant inhibition
17, 18
Chamomile
(Matricaria recutita)
CYP1A2
CYP3A4
CYP2C9
CYP2D6
Inhibition
Weak inhibition
Weak inhibition
Weak inhibition
19
Chaste Tree
(Vitex agnus-castus)
CYP1A1
CYP2C9
CYP2C19
CYP3A4
Insignificant inhibition
Insignificant inhibition
Inhibition
Inhibition
20
Cinnamon
Cinnamomum verum
CYP3A4Inhibition - Pioglitazone21
Coleus
(Coleus forskohlii)
CYP2CInduction – Warfarin22
Corn Silk
(Zea mays)
------
Damiana
(Turnera diffusa)
CYP450Induction – Possible increased drug effect – Hypoglycaemics23, 55
Dandelion
Taraxacum officinale
CYP2DC
CYP3A4
Induction
Induction – Thiazide diuretics
25, 26
Devil’s claw
Harpagophytum procumbens
P-gp
CYP3A4
Weak Inhibition at low dose – Corticosteroids
Weak Induction – Warfarin
27, 28
Echinacea
Echinacea angustifolia
CYP3A4
CYP1A2
CYP2D6
Weak inhibition
Induction – up-regulated enzyme activity
29, 30
Eleutherococcus
Eleutherococcus senticosus
CYP3A4
CYP2C9
CYP2E1
Insignificant inhibition at standard dose31
Fennel
Foeniculum vulgare
CYP3A4
CYP2D6
Weak inhibition32
Fenugreek
Trigonella foenum-graecum
CYP3A4Weak induction – Warfarin33
Frankincense
Boswellia serrata
CYP3A4
CYP1A2
CYP2C9
Inhibition34, 35
Gentian
Gentiana lutea
CYP2D6
CYP1A2
CYP3A4
Insignificant inhibition36
Ginger
Zingiber officinale
CYP3A4
CYP2C9
Insignificant inhibition at standard dose – Warfarin37
Ginkgo
Ginkgo biloba
CYP2D6
CYP2C9
CYP3A4
Minor induction – Warfarin
Minor induction
Inhibition - Digoxin
38, 67
Globe artichoke
Cynara scolymus
CYP450Globe artichoke is metabolised by CYP450’s, however insufficient data to confirm inhibition or induction on specific enzymes.--
Goldenseal
Hydrastis Canadensis
CYP2D6
CYP2C9
CYP3A4
Inhibition – PPI’s
Induction – ARB’s
Inhibition - Benzodiazepam
9, 41
Gotu Kola
Centella asiatica
CYP3A4
CYP2D6
Inhibition
Inhibition
42
Gymnema
Gymnema sylvestre
CYP3A4
CYP2C9
CYP1A2
CYP2D6
Moderate inhibition
Weak inhibition
Moderate inhibition
Weak inhibition
43
Hawthorn
Crataegus monogyna
Thromboxane A2Inhibition – Aspirin, warfarin44
Hops
Humulus lupulus
CYP1A2
CYP3A4
CYP2D6
CYP2C9
Weak inhibition at low dose
Weak inhibition at low dose
Moderate inhibition
Moderate inhibition
Avoid with warfarin, benzodiazepine, tamoxifen and antidepressants
45
Horsetail
Equisetum arvense
CYP1A2
CYP2C8

CYP3A4
Inhibition potential
Inhibition potential – Statins, loop diuretics
Weak inhibition at low dose
46, 47
Jamaica Dogwood
Piscidia erythrina
--Limited scientific data available, however due to its actions of spasmolytic and anodyne properties, theoretically this herb could interact with pharmaceuticals with similar actions. Barnes J, Anderson L. & Phillipson (1998).Herbal Medicines, Third edition.London; Pharmaceutical Press; p.380.--
Kava kava
Piper methysticum
CYP2E1Weak inhibition at low dose48
Korean ginseng
Panax ginseng
CYP3A4
CYP2D6
P-gp
Inhibition potential at high doses
Insignificant activation at low dose
49
Lavender
Lavendula officinalis
CYP3A4
CYP2D6
CYP2C19
CYP1A2
Clinically insignificant inhibitory or inducing effects50
Lemon balm
Melissa officinalis
CYP2D6

CYP1A2
CYP3A4
Moderate inhibition – tamoxifen
Induction – Barbiturates
Induction – Benzodiazepine
Inhibition – SSRI’s
51, 52
Licorice
Glycyrrhiza glabra
CYP3A4

CYP2D6
P-gp
Moderate interaction - Benzodiazepine
Moderate inhibition
Weak inhibition at low dose
53, 66
Marshmallow
Althaea officinalis
--There is insufficient scientific data on Marshmallow’s metabolism.--
Meadowsweet
Filipendula ulmaria
CYP3A4
CYP2D6
Inhibition – warfarin
Inhibition -
55, 56
Milk Thistle
Silybum marianum
P-gp
CYP3A4
CYP2D6
Insignificant interaction
Inhibition potential at high doses
57, 58
Motherwort
Leonurus cardiaca
CYP3A4
Thromboxane A
Induction – Benzodiazepine
Inhibition – Aspirin, warfarin
59
Nettle Leaf
Urtica dioica
CYP2C9Inhibition – Aspirin56
Oats
Avena sativa
CYP2D6
CYP3A4
Beneficial interaction – Antihypertensives, Statins
Insufficient data on metabolism ofAvena sativa
55
Passion Flower
Passiflora incarnata
CYP1A2
CYP3A4
Moderate inhibition – SSRI’s
Moderate inducer – Benzodiazepine
62. 63
Peppermint
Mentha piperita
CYP3A4
CYP2C9
Weak inhibition at low dose
Weak inhibition at low dose
64
Rehmannia
Rehmannia glutinosa
CYP3A4Induction – Decreased drug effect65
Rosemary
Rosmarinus officinalis
P-gp
CYP1A2
CYP3A4
CYP2C9
Inhibition
Inhibition
Inhibition
Insignificant inhibition
66
Sarsaparilla
Smilax ornata
--Insufficient scientific data on Sarsaparilla and constituents to determine interactions.--
Saw Palmetto
Serenoa repens
CYP3A4
CYP2D6
CYP2C9
Weak inhibition – Warfarin
Weak inhibition
Weak inhibition
67, 68
Schisandra
Schisandra chinensis
CYP1A2
CYP3A1/2
CYP2D6
CYP3A4
No significant effect at standard dose
Inhibition at high dose
Inhibition at high dose
69, 70
Shatavari
Asparagus racemosus
CYP3A4
CYP2E1
No inhibition at standard dose
Inhibitory effects - acetaminophen
71, 72
Skullcap
Scutellaria lateriflora
CYP2C9
CYP2E1
CYP3A4
Induction – Losartan
Inhibition – Chlorzoxazone
Inhibition - Benzodiazepam
7, 74
St. John’s Wort
Hypericum perforatum
CYP3A4
CYP2C
Inhibition – Digoxin
Weak inhibition – Antidiabetic drugs
67, 76
Thyme
Thymus vulgaris
CYP2C9

CYP3A4
Inhibitory effect at high dose, synergistic effect at low dose
Inducing effects at high dose
77, 78
Turmeric
Curcuma longa
P-gp
CYP1A1
CYP1A2
CYP3A4
CYP2B1
Inhibition at high dose
Inhibition at high dose
Inhibition at high dose
66, 80
Uva-ursi / Bearberry
Arctostaphylos uva-ursi
CYP3A4
P-gp
Inhibition
Inhibition
81
Valerian
Valeriana officinalis
CYP1A2
CYP3A4
Weak inhibition
Weak inhibition
48, 67
Vervain
Verbena officinalis
--Limited scientific research on the effect of Vervain on CYP450’s.62, 85
White Peony
Paeonia lactiflora
CYP3A4Inhibition - OCP86
White Willow Bark
Salix alba.
CYP3A4
CYP2E1
Inhibition – Warfarin
Inhibition - Clomethiazone

Moderate interaction with salicylate containing drugs
55, 87
Wild Yam
Dioscorea villosa
CYP3A4
CYP2D6
CYP1A2
CYP2C9
P-gp
Inhibition at high dose
Insignificant interactions at high doses - OCP

Weak mediation
89
Withania
Withania somnifera
CYP3A4
CYP2D6
Inhibition - Antidepressants
Inhibition
90
 
 

References:

  1. Yale, S. H., & Glurich, I. (2005). Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. Journal of Alternative & Complementary Medicine, 11(3), 433-439.
  2. Gurley, B. J., Swain, A., Hubbard, M. A., Williams, D. K., Barone, G., Hartsfield, F., ... & Battu, S. K. (2008). 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. Molecular nutrition & food research, 52(7), 755-763.
  3. Markowitz, J. S., Donovan, J. L., DeVane, C. L., Taylor, R. M., Ruan, Y., Wang, J. S., & Chavin, K. D. (2003). Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. Jama, 290(11), 1500-1504.
  4. Pekthong D, Blanchard N, Abadie C, Bonet A, Heyd B, Mantion G, Berthelot A, Richert L & Martin H. (2009). Effects of Andrographis paniculata extract and Andrographolide on hepatic cytochrome P450 mRNA expression and monooxygenase activities after in vivo administration to rats and in vitro in rat and human hepatocyte cultures.Chemico-Biological Interactions, vol.179(2-3),p.247-255.
  5. Lau C, Mooiman K, Maas-Bakker R, Beijnen J, Schellens J. & Meijerman I. (2013). Effect of Chinese Herbs on CYP3A4 Activity and Expression in vitro.Journal of Ethnopharmacology, vol, 49(2),p.543-549.
  6. Ramasamy S, Kiew L. & Chung L. (2014). Inhibition of Human Cytochrome P450 Enzymes by Bacopa monnieri Standardized Extract and Constituents.Molecules, vol.19(2),p.2588-2601.
  7. Yi S, Cho J, Lim K, Kim K, Kim J, Kim B, Hong J, Jang I, Shin S. & Yu K. (2009). Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers.Basic Clinical Pharmacology Toxicology, vol.105(4),p.249-256.
  8. Pao L, Hu O, Fan H, Lin C, Liu L. & Huang P. (2012). Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo.American Journal of Chinese Medicine, vol.40(1),p.57-73.
  9. Guo Y, Chen Y, Tan Z, Klaassen C. & Zhou H. (2012). Repeated Administration of Berberine Inhibits Cytochromes P450 in Humans.European Journal of Clinical Pharmacology, vol.68(2),p.213-217.
  10. Guo Y, Pope C, Cheng X, Zhou H. & Klaassen C. (2011). Dose-response of berberine on hepatic cytochromes P450 mRNA expression and activities in mice.Journal of Ethnopharmacology, vol.138(1),p.111-118.
  11. Gurley B, Gardner S, Hubbard M, Williams D, Gentry W, Khan I. & Shah A. (2005). In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.Clinical Pharmacology Theories, vol.77(5),p.415-426.
  12. Gurley B, Barone G, Williams D, Carrier J, Breen P, Yates C, Song P, Hubbard M, Tong Y. & Cheboyina S. (2006). Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans.Drug Metabolism Disposition, vol.34(1),p.69-74.
  13. Quintieri L, Bortolozzo S, Stragliotto S, Moro S, Pavanetto M, Nassi A, Palatini P. & Floreani M. (2010). Flavonoids diosmetin and hesperetin are potent inhibitors of cytochrome P450 2C9-mediated drug metabolism in vitro.Drug Metabolism Pharmacokinetics, vol.25(5),p.466-76.
  14. Quintieri L, Palatini P, Moro S. & Floreani M. (2011). Inhibition of cytochrome P450 2C8-mediated drug metabolism by the flavonoid diosmetin.Drug Metabolism Pharmacokinetics, vol.26(6),p.559-568.
  15. Basch E, Bent S, Foppa I, Haskmi S, Kroll D, Mele M, Szapary P, Ulbricht C, Vora M. & Yong S. (2006). Marigold (Calendula officinalis L.): an evidence-based systematic review by the Natural Standard Research Collaboration.Journal of Herbal Pharmacotherapy, vol.6(3-4),p.135-159.
  16. Manda V, Ibrahim M, Dale O, Kumarihamy M, Cutler S, Khan I, Walker L, Muhammad I. & Khan S. (2016). Modulation of CYPs, P-gp, and PXR by Eschscholzia californica (California Poppy) and Its Alkaloids.Planta Medica, vol.82(6),p.551-558.
  17. Deng X, Pu Q, Wang E. & Yu C. (2016). Celery extract inhibits mouse CYP2A5 and human CYP2A6 activities via different mechanisms.Oncology Letters, vol.12(6),p.5309-5314.
  18. Nguyen S, Huang H, Foster B, Tam T, Xing T, Smith M, Arnason J. & Akhtar H. (2014). Antimicrobial and P450 inhibitory properties of common functional foods.Journal of Pharmacy & Pharmaceutical Sciences, vol.17(2),p.254-265.
  19. Ganzera M, Schneider P. & Stuppner H. (2006). Inhibitory effects of the essential oil of chamomile (Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes.Life Science vol.78(8),p.856-861.
  20. Ho S, Singh M, Holloway A. & Crankshaw D. (2011). The effects of commercial preparations of herbal supplements commonly used by women on the biotransformation of fluorogenic substrates by human cytochromes P450.Phytotherapy Research, vol.25(7),p.983-989.
  21. Mamindla S, Koganti V, Ravouru N. & Koganti B. (2017). Effect of Cinnamomum cassia on the Pharmacokinetics and Pharmacodynamics of Pioglitazone.Current Clinical Pharmacology, vol.12(1),p.41-49.
  22. Yokotani K, Chilba T, Sato Taki Y, Yamada S, Shinozuka K, Murata M. & Umegaki K. (2010). Hepatic cytochrome P450 mediates interaction between warfarin and Coleus forskohlii extract in vivo and in vitro.Journal of Pharmacy & Pharmacology, vol.64(12),p.1793-1801.
  23. Hui H, Tang G. Go V. (2008). Hypoglycaemic Herbs and their Action Mechanisms: Review.Chinese Medicine, vol.4(11),p.1-11.
  24. Maliakal, P. P., & Wanwimolruk, S. (2001). Effect of herbal teas on hepatic drug metabolizing enzymes in rats. Journal of Pharmacy and Pharmacology, 53(10), 1323-1329.
  25. Awortwe C, Bouic P, Masimirembwa C. & Rosenkranz B. (2014). Inhibition of Major Drug Metabolizing CYPs by Common Herbal Medicines used by HIV/AIDS Patients in Africa– Implications for Herb-Drug Interactions.Drug Metabolism Letters, vol.7(2),p.83-95.
  26. Clare B, Conroy R. & Spelman K. (2009). The Diuretic Effect in Human Subjects of an Extract of Taraxacum officinale Folium over a Single Day.The Journal of Alternative and Complimentary Medicine, vol.15(8),p.929-934.
  27. Romiti N, Tramonti G, Corti A. & Chieli E. (2009). Effects of Devil's Claw (Harpagophytum procumbens) on the multidrug transporter ABCB1/P-glycoprotein.Phytomedicine, vol.16(12),p.1095-1100.
  28. Ge B, Zhang Z. & Zuo Z. (2014). Updates on the Clinical Evidenced Herb-Warfarin Interactions: Review Article.Evidence-Based Complementary & Alternative Medicine, vol.2014,p.1-18.
  29. Hansen T. & Nilsen O. (2008). In vitro CYP3A4 metabolism: inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition.Basic Clinical Pharmacology Toxicology, vol.103(5),p.445-449.
  30. Awortwe C, Manda V, Avonto C, Khan S, Khan I, Walker L, Bouic P. & Rosenkranz B. (2015). Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway.Xenobiotica, vol.45(3), p.218-229.
  31. Guo S, Liu Y, Lin Z, Tai S, Yin S. & Liu G. (2014). Effects of Eleutheroside B and Eleutheroside E on activity of cytochrome P450 in rat liver microsomes.BMC Complementary and Alternative Medicine, vol.14(1),p.1-7.
  32. Subehan, Usia T, Iwata H, Kadota S. & Tezuka Y. (2006). Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants.Journal of Ethnopharmacology, vol.105(3),p.449-455.
  33. Ge B, Zhang Z. & Zuo Z. (2014). Updates on the Clinical Evidenced Herb-Warfarin Interactions: Review Article.Evidence-Based Complementary & Alternative Medicine, vol.2014,p.1-18.
  34. Samala, S., & Veeresham, C. (2016). Pharmacokinetic and pharmacodynamic interaction of boswellic acids and andrographolide with glyburide in diabetic rats: including its PK/PD modeling. Phytotherapy research, 30(3), 496-502.
  35. Frank, A., & Unger, M. (2006). Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. Journal of Chromatography A, 1112(1-2), 255-262.
  36. Deng Y, Wang L, Yang Y, Sun W, Xie R, Liu X. & Wang Q. (2013). In vitro inhibition and induction of human liver cytochrome P450 enzymes by gentiopicroside: potent effect on CYP2A6.Drug Metabolism Pharmacokinetics, vol.28(4),p.339-344.
  37. Jiang X, Williams K, Liauw W, Ammit A, Roufogalis B, Duke C, Day R. & McLachlan A. (2005). Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.British Journal of Clinical Pharmacology, vol.59(4),p.425-432.
  38. Ge B, Zhang Z. & Zuo Z. (2014). Updates on the Clinical Evidenced Herb-Warfarin Interactions: Review Article.Evidence-Based Complementary & Alternative Medicine, vol.2014,p.1-18.
  39. Suo, M., Ohta, T., Takano, F., & Jin, S. (2013). Bioactive phenylpropanoid glycosides from Tabebuia avellanedae. Molecules, 18(7), 7336-7345.
  40. Zhang, C. Z., Wang, S. X., Zhang, Y., Chen, J. P., & Liang, X. M. (2005). In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. Journal of ethnopharmacology, 98(3), 295-300.
  41. Gurley B, Swain A, Hubbard M, Hartsfield F, Thaden J, Williams D, Gentry W. & Tong Y. (2008). Supplementation with Goldenseal (Hydrastis canadensis), But Not Kava (Piper Methysticum) Inhibits CYP3A Activity in Vitro.Clinical Pharmacology Theories, vol.83(1),p.61-69.
  42. Savai J, Varghese A, Pandita N. & Chintamaneni M. (2015). Investigation of CYP3A4 and CYP2D6 Interactions of Withania somnifera and Centella asiatica in Human Liver Microsomes.Phytotherapy Research, vol.29(5),p.785-790.
  43. Rammohan B, Samit K, Chinmoy D, Arup S, Amit K, Ratul S, Sanmoy K, Dipan A. & Tuhinadri S. (2016). Human Cytochrome P450 Enzyme Modulation by Gymnema sylvestre: A Predictive Safety Evaluation by LC-MS/MS.Pharmacognosy Magazine, vol.12(4),p.S389-394.
  44. Tachjian A, Maria V. & Jahangir A. (2010). Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases.JACC: Journal of the American College of Cardiology, vol.55(6),p.515-525.
  45. Yuan Y, Qiu X, Nikolic D, Chen S, Huang K, Li G, Pauli G. & van Breemen R. (2014). Inhibition of human cytochrome P450 enzymes by hops (Humulus lupulus) and hop prenyl phenols.European Journal of Pharmaceutical Sciences, vol.53,p.55-61.
  46. Langhammer A. & Nilsen O. (2014). In vitro inhibition of human CYP1A2, CYP2D6, and CYP3A4 by six herbs commonly used in pregnancy.Phytotherapy Research, vol.28(4),p.603-610.
  47. Sevior D, Hokkanen J, Tolonen A, Abass K, Turas L, Pelkonen O. & Ahokas J. (2010). Rapid screening of commercially available herbal products for the inhibition of major human hepatic cytochrome P450 enzymes using the N-in-one cocktail.Xenobiotica, vol.40(4),p.245-254.
  48. Gurley B, Gardner S, Hubbard M, Williams D, Gentry W, Khan I. & Shah A. (2005). In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.Clinical Pharmacology Theories, vol.77(5),p.415-426.
  49. Hermann R. & von Richter O. (2012). Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions.Planta Medicine, vol.78(13),p.1458-1477.
  50. Doroshyenko O, Rokitta D, Zadoyan G, Klement S, Schlafke S, Dienel A, Grematte T, Luck H. & Fuhr U. (2013). Drug cocktail interaction study on the effect of the orally administered lavender oil preparation silexan on cytochrome P450 enzymes in healthy volunteers.Drug Metabolism Dispositions, vol.41(5),p.987-993.
  51. Posadzki P, Watson L. & Ernst E. (2012). Herb–drug interactions: an overview of systematic reviews.British Journal of Clinical Pharmacology, vol.75(3),p.603-618.
  52. Taiwo A, Leitre F, Lucena G, Barros M, Silveira D, Silva M. & Ferreira V. (2012). Anxiolytic and antidepressant-like effects of Melissa officinalis (lemon balm) extract in rats: Influence of administration and gender.Indian Journal of Pharmacology, vol.44(2),p.189-192.
  53. Chen H, Zhang X, Feng Y, Rui W, Shi Z. & Wu L. (2014). Bioactive components of Glycyrrhiza uralensis mediate drug functions and properties through regulation of CYP450 enzymes.Molecular Medicine Reports, vol.10(3),p.1355-1362.
  54. Kim, B. R., Kim, D. H., Park, R. K., Kwon, K. B., Ryu, D. G., Kim, Y. C., ... & Kim, K. S. (2001). Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes. Planta medica, 67(05), 396-399.
  55. Braun L. & Cohen M. (2015).Herbs & Supplements: an evidence based-guide Volume 2.Sydney; Churchill Elsevier Livingstone; p.694.
  56. Bojic M, Sedgeman C, Nagy L. & Guengerich F. (2015). Aromatic Hydroxylation of Salicylic Acid and Aspirin by Human Cytochromes P450.European Journal of Pharmaceutical Sciences, vol.73,p.49-56.
  57. Gurley B, Barone G, Williams D, Carrier J, Breen P, Yates C, Song P, Hubbard M, Tong Y. & Cheboyina S. (2006). Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans.Drug Metabolism Disposition, vol.34(1),p.69-74
  58. Hermann R. & von Richter O. (2012). Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions.Planta Medicine, vol.78(13),p.1458-1477.
  59. Tachjian A, Maria V. & Jahangir A. (2010). Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases.JACC: Journal of the American College of Cardiology, vol.55(6),p.515-525.
  60. Or, P. M., Lam, F. F., Kwan, Y. W., Cho, C. H., Lau, C. P., Yu, H., ... & Yeung, J. H. (2012). Effects of Radix Astragali and Radix Rehmanniae, the components of an anti-diabetic foot ulcer herbal formula, on metabolism of model CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 probe substrates in pooled human liver microsomes and specific CYP isoforms. Phytomedicine, 19(6), 535-544.
  61. Campos, M. M., Fernandes, E. S., Ferreira, J., Santos, A. R., & Calixto, J. B. (2005). Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms. Psychopharmacology, 182(1), 45-53.
  62. Shimada H, Eto M, Ohtaguro M, Ohtsubo M, Mizukami Y, Ide T. & Imamura Y. (2010). Differential mechanisms for the inhibition of human cytochrome P450 1A2 by apigenin and genistein.Journal of Biochemistry & Molecular Toxicology, vol.24(4),p.230-234.
  63. Elsas S, Rossi D, Raber J, White G, Seeley C, Gregory W, Mohr C, Pfankuch T. & Soumyanath A. (2010). Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method.Phytomedicine, vol.17(12),p.940-949.
  64. Kimura Y, Ito H, Ohnishi R. & Hatano T. (2010). Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity.Food Chemistry and Toxicology, vol.48(1),p.429-435.
  65. Lau C, Mooiman K, Maas-Bakker R, Beijnen J, Schellens J. & Meijerman I. (2013). Effect of Chinese Herbs on CYP3A4 Activity and Expression in vitro.Journal of Ethnopharmacology, vol, 49(2),p.543-549.
  66. Cho H. & Yoon I. (2015). Pharmacokinetic Interactions of Herbs with cytochrome P450 and P-Glycoprotein.Evidence-Based Complementary & Alternative Medicine, vol.2015,p.1-10.
  67. Hellum B. & Nilsen O. (2008). In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products.Basic Clinical Pharmacology Toxicology, vol.102(5),p.466-475.
  68. Wanwimorlruk S, Phopin K. & Prachayasittkul V. (2014). Cytochrome P450 Enzyme Mediated Herbal Drug Interactions (Part 2): Review Article.EXCLI Journal, vol.13,p.869-896.
  69. Wang B, Hu J, Sheng L. & Li Y. (2011). Effects of Schisandra chinensis (Wuweizi) constituents on the activity of hepatic microsomal CYP450 isozymes in rats detected by using a cocktail probe substrates method.Yao Xue Xue Bao, vol.46(8),p.922-927.
  70. Wang B, Yang S, Hu J. & Li Y. (2014). Multifaceted interaction of the traditional Chinese medicinal herb Schisandra chinensis with cytochrome P450-mediated drug metabolism in rats.Journal of Ethnopharmacology, vol.155(3),p.1473-1482.
  71. Borse S. & Kamble B. (2015). Effects of Ayurvedic Rasayana botanicals on CYP3A4 isoenzyme system.Journal of Integrated Medicine, vol.13(3),p.165-172.
  72. Palanisamy N. & Manian S. (2012). Protective effects of Asparagus racemosus on oxidative damage in isoniazid-induced hepatotoxic rats: an in vivo study.Toxicology & Industrial Health, vol.28(3),p.238-244.
  73. Wuttke, W., Jarry, H., Christoffel, V., Spengler, B., & Seidlova-Wuttke, D. (2003). Chaste tree (Vitex agnus-castus)–pharmacology and clinical indications. Phytomedicine, 10(4), 348-357.
  74. Pao L, Hu O, Fan H, Lin C, Liu L. & Huang P. (2012). Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo.American Journal of Chinese Medicine, vol.40(1),p.57-73.
  75. Mazzio, E., Deiab, S., Park, K., & Soliman, K. F. A. (2013). High throughput screening to identify natural human monoamine oxidase B inhibitors. Phytotherapy Research, 27(6), 818-828.
  76. Gupta R, Chang D, Nammi S, Bensoussan A, Bilinski K. & Roufogalis B. (2017). Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications.Diabetology & Metabolic Syndrome, vol.9,p.1-12.
  77. Posadzki P, Watson L. & Ernst E. (2012). Herb–drug interactions: an overview of systematic reviews.British Journal of Clinical Pharmacology, vol.75(3),p.603-618.
  78. Kaeffer C. & Milner J. (2011). Herbs & Spices in Cancer Prevention and Treatment.Herbal Medicine, Biomolecular & Clinical Aspects vol.2.
  79. Silvestrini, G. I., Marino, F., & Cosentino, M. (2013). Effects of a commercial product containing guaraná on psychological well-being, anxiety and mood: a single-blind, placebo-controlled study in healthy subjects. Journal of negative results in biomedicine, 12(1), 9.
  80. Zhang, W., Tan, T. M. C., & Lim, L. Y. (2007). Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug metabolism and disposition, 35(1), 110-115.
  81. Chauhan B, Yu C, Krantis A, Scott I, Arnason J, Marles R. & Foster B. (2007). In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P-glycoprotein.Canadian Journal of Physiology & Pharmacology, vol.85(11),p.1099-1107.
  82. Rogers, P. J., Heatherley, S. V., Mullings, E. L., & Smith, J. E. (2013). Faster but not smarter: effects of caffeine and caffeine withdrawal on alertness and performance. Psychopharmacology, 226(2), 229-240.
  83. Carney, J. M. (1982). Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. British journal of pharmacology, 75(3), 451-454.
  84. Fisone, G., Borgkvist, A., & Usiello, A. (2004). Caffeine as a psychomotor stimulant: mechanism of action. Cellular and Molecular Life Sciences CMLS, 61(7-8), 857-872.
  85. Khan A, Khan A. & Ahmed T. (2016). Anticonvulsant, Anxiolytic, and Sedative Activities ofVerbena officinalis. Frontiers in Pharmacy, vol.7(400),p.1-8.
  86. Pao L, Hu O, Fan H, Lin C, Liu L. & Huang P. (2012). Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo.American Journal of Chinese Medicine, vol.40(1),p.57-73.
  87. Sutrisna E. (2016). The Impact of CYP1A2 and CYP2E1 Genes Polymorphism on Theophylline Response.Journal of Clinical and Diagnostic Research, vol.10(11),p.FE01-FE03.
  88. Sharangi, A. B. (2009). Medicinal and therapeutic potentialities of tea (Camellia sinensis L.)–A review. Food Research International, 42(5-6), 529-535.
  89. Manda V, Avula B, Ali Z, Wong Y, Smillie T, Khan I. & Khan S. (2013). Characterization of in Vitro ADME Properties of Diosgenin and Dioscin from Dioscorea villosa.Planta Medicine, vol.79(15),p.1421-1428.
  90. Savai J, Varghese A, Pandita N. & Chintamaneni M. (2015). Investigation of CYP3A4 and CYP2D6 Interactions of Withania somnifera and Centella asiatica in Human Liver Microsomes.Phytotherapy Research, vol.29(5),p.785-790.
  91. Zand, R. S. R., Jenkins, D. J., & Diamandis, E. P. (2001). Effects of natural products and nutraceuticals on steroid hormone-regulated gene expression. Clinica chimica acta, 312(1-2), 213-219.
  92. Bryant, B., & Knights, K. (2014). Pharmacology for Health Professionals ebook. Elsevier Health Sciences.
  93. Perovic, S., & Müller, W. E. (1995). Pharmacological profile of hypericum extract. Effect on serotonin uptake by postsynaptic receptors. Arzneimittel-Forschung, 45(11), 1145-1148.
  94. Suthar, A. C., Banavalikar, M. M., & Biyani, M. K. (2003). A review on ginger (Zingiber officinale): Pre-clinical and clinical trials.
  95. De Souza, N. J., Dohadwalla, A. N., & Reden, Ü. (1983). Forskolin: a labdane diterpenoid with antihypertensive, positive inotropic, platelet aggregation inhibitory, and adenylate cyclase activating properties. Medicinal research reviews, 3(2), 201-219.

Selective Serotonin Reuptake Inhibitors (SSRIs):

+ Mechanism of Action

On the other hand, we denounce with righteous indignation and dislike men who are so beguiled and demoralized by the charms of pleasure of the moment, so blinded by desire, that they cannot foresee the pain and trouble that are bound to ensue; and equal blame belongs to those who fail in their duty through weakness of will, which is the same as saying through shrinking from toil and pain. These cases are perfectly simple and easy to distinguish.

+ Pharmacokinetics

On the other hand, we denounce with righteous indignation and dislike men who are so beguiled and demoralized by the charms of pleasure of the moment, so blinded by desire, that they cannot foresee the pain and trouble that are bound to ensue; and equal blame belongs to those who fail in their duty through weakness of will, which is the same as saying through shrinking from toil and pain. These cases are perfectly simple and easy to distinguish.

+ Pharmacodynamics

On the other hand, we denounce with righteous indignation and dislike men who are so beguiled and demoralized by the charms of pleasure of the moment, so blinded by desire, that they cannot foresee the pain and trouble that are bound to ensue; and equal blame belongs to those who fail in their duty through weakness of will, which is the same as saying through shrinking from toil and pain. These cases are perfectly simple and easy to distinguish.

+ Serotonin Syndrome

On the other hand, we denounce with righteous indignation and dislike men who are so beguiled and demoralized by the charms of pleasure of the moment, so blinded by desire, that they cannot foresee the pain and trouble that are bound to ensue; and equal blame belongs to those who fail in their duty through weakness of will, which is the same as saying through shrinking from toil and pain. These cases are perfectly simple and easy to distinguish.

In a free hour, when our power of choice is untrammelled and when nothing prevents our being able to do what we like best, every pleasure is to be welcomed and every pain avoided. But in certain circumstances and owing to the claims of duty or the obligations of business it will frequently occur that pleasures have to be repudiated and annoyances accepted. The wise man therefore always holds in these matters to this principle of selection: he rejects pleasures to secure other greater pleasures, or else he endures pains to avoid worse pains.

 

SSRI Medications:

 

Sertraline

Insert descriptive text here.

It's sold under the brand name Zoloft.

 

Vilazodone

Insert descriptive text here.

It's sold under the brand name Viibryd.

 

Paroxetine

Insert descriptive text here.

It's sold under the brand name Paxil, Pexeva.

 

Citalopram

Insert descriptive text here.

It's sold under the brand name Celexa.

 

Escitalopram

Insert descriptive text here.

It's sold under the brand name Lexapro.

 

Fluoxetine

Fluoxetine is one of the primary SSRI meditations used in the treatment of anxiety, and depression.

It's sold under the brand names Prozac and Sarafem.

 
 

SSRI Herb-Drug Interactions

Drug/Herb Class Herbs Interaction Level Of Caution
CNS Depressants Piper methysticum Increased chances of developing orthostatic hypotension Caution
Anti-Diabetic drugs - Can increase blood glucose levels Caution
Other drugs affecting platelet aggregation Zingiber officinale [94]
Coleus forskholii [95]
Increased risk of bleeding Caution
MAO inhibitors Phellodendron amurense [75]
Glycyrrhiza uralensis [75]
Psoralea corylifolia [75]
Glycyrrhiza glabra [75]
Cyamopsis psoralioides [75]
Piper negrum [75]
Camellia sinensis [75]
Piper methysticum [75]
Alchemilla vulgaris [75]
Curcuma longa [75]
Increased drug effects and risk of serotonin syndrome Caution
Other Serotonergics Hypericum perforatum [93] Increased risk of serotonin syndrome Contraindicated
CYP2D6 Inhibitors
(Fluoxetine)
Berberis vulgaris [9, 10]
Centella asiatica [42]
Eschscholzia californica [16]
Filipendula ulmaria [55, 56]
Glycyrrhiza glabra [53, 66]
Hydrastis Canadensis [9, 41]
Melissa officinalis [51, 52]
Silybum marianum [57, 58]
Withania somnifera [90]
Increased half-life and risk of serotonin syndrome Caution
CYP2D6 Inducers
(Fluoxetine)
- Decreased drug effect Caution
CYP3A4 Inhibitors
(Fluoxetine, Fluvoxamine)
Arctostaphylos uva-ursi [81]
Astragalus membranaceus [5]
Bacopa monieri [6]
Berberis vulgaris [9, 10]
Boswellia serrata [34, 35]
Centella asiatica [42]
Cinnamomum verum [21]
Eschscholzia californica [16]
Filipendula ulmaria [55, 56]
Ginkgo biloba [38, 67]
Gymnema sylvestre [43]
Hydrastis Canadensis [9, 41]
Hypericum perforatum [67, 76]
Melissa officinalis [51, 52]
Paeonia lactiflora [86]
Panax ginseng [49]
Passiflora incarnata [63]
Rosmarinus officinalis [66]
Salix alba [55]
Scutellaria baicalensis [8]
Scutellaria lateriflora [74]
Tabebuia impetiginosa [39]
Vitex agnus-castus [20]
Withania somnifera [90]
Increased half-life and risk of serotonin syndrome Caution
CYP3A4 Inducers
(Fluoxetine, Fluvoxamine)
Andrographis paniculata [4]
Taraxacum officinale [25, 26]
Leonurus cardiaca [59]
Decreased drug effect Caution
CYP1A2 Inhibitors
(Fluvoxamine)
Bacopa monieri [6]
Boswellia serrata [34, 35]
Equisetum arvense [46, 47]
Eschscholzia californica [16]
Gymnema sylvestre [43]
Humulus lupulus [45]
Matricaria recutita [19, 24]
Passiflora incarnata [62, 63]
Rosmarinus officinalis [66]
Scutellaria baicalensis [54]
Increased half-life and risk of serotonin syndrome Caution
CYP1A2 Iducers
(Fluvoxamine)
Echinacea angustifolia [29, 30]
Melissa officinalis [51, 52]
Decreased drug effect Caution
CYP2C19 Inhibitors
(Fluvoxamine)
Bacopa monieri [6]
Berberis vulgaris [9, 10]
Eschscholzia californica [16]
Vitex agnus-castus [20]
Increased half-life and risk of serotonin syndrome Caution
CYP2C19 Inducers
(Fluvoxamine)
- Decreased drug effect Caution