Main Article Content

Jean-Jacques Dugoua
Edward Mills Mills
Daniel Perri
Gideon Koren


St. John’s wort, hypericum perfoliatum, pregnancy, lactation, breastfeeding, systematic review



There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and  safety  of  herbal  medicines  in  pregnancy  and  lactation.  This  is  one  article  in  a  series  that systematically reviews the evidence for commonly used herbs during pregnancy and lactation.


To systematically review the literature for evidence on the use, safety, and pharmacology of St. John’s wort focusing on issues pertaining to pregnancy and lactation.


We searched 7 electronic databases and compiled data according to the grade of evidence found.


There is very weak scientific evidence based on a case report that St Johns wort is of minimal risk when taken during pregnancy. There is in vitro evidence from animal studies that St John’s wort during pregnancy does not affect cognitive development nor cause long-term behavioral defects, but may lower offspring birth weight. There is weak scientific evidence that St. John’s wort use during lactation does not affect maternal milk production nor affect infant weight, but, in a few cases, may cause colic, drowsiness or lethargy. There is weak scientific evidence that St John’s wort induces CYP450 enzymes, which may lower serum medication levels below therapeutic range; this may be of concern when administering medications during pregnancy and lactation.


Caution is warranted with the use of St John’s wort during pregnancy until further high quality human research is conducted to determine its safety. St John’s wort use during lactation appears to be of minimal risk, but may cause side effects. Caution is warranted when using medications along with St John’s wort.

Abstract 5034 | PDF Downloads 689


1. Woelk H. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. BMJ 2000; 321:536-9.
2. Weissman MM, Olfson M. Depression in women:implications for health care research. Science 1995; 269:799-801.
3. Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M, Mintz J. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry 1996; 153:592- 606.
4. OTIS. Organization of Teratology Information Services: ( 2004.
5. Jellin JM, Batz F, Hitchens K. Natural medicines comprehensive database 3rd Edition. Stockton, CA: Therapeutic Research Faculty, 2002:1530.
6. Upton R. St Johns Wort - Hypericum perforatum. American Herbal Pharmacopoeia - American Botanical Council 1996.
7. Brinker F. The toxicology of botanical medicines. Sandy, Oregon: Eclectic Medical Publications, 2000:296.
8. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. St John's wort for depression--an overview and meta-analysis of randomised clinical trials. BMJ 1996; 313:253-8.
9. Linde K, Mulrow CD. St John's wort for depression. Cochrane Database Syst Rev 2000:CD000448.
10. Kim HL, Streltzer J, Goebert D. St. John's wort for depression: a meta- analysis of well-defined clinical trials. 1999.
11. Whiskey E, Werneke U, Taylor D. A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review. Int Clin Psychopharmacol 2001; 16:239-52.
12. Gaster B, Holroyd J. St John's wort for depression: a systematic review. Arch Intern Med. 2000; 160:152-6.
13. Panijel M. [Treatment of moderately severe anxiety states]. Therapiewoche 1985; 35:4659-68.
14. Sarrell EM, Mandelberg A, Cohen HA. Efficacy of naturopathic extracts in the management of ear pain associated with acute otitis media. Archives of Pediatrics & Adolescent Medicine 2001; 155:796-9.
15. Taylor LH, Kobak KA. An open- label trial of St. John's Wort (Hypericum perforatum) in obsessive- compulsive disorder. J Clin Psychiatry 2000; 61:575- 8.
16. Grube B, Walper A, Wheatley D. St. John's Wort extract: efficacy for menopausal symptoms of psychological origin. Adv Ther 1999; 16:177 -86.
17. Stevinson C, Ernst E. A pilot study of Hypericum perforatum for the treatment of premenstrual syndrome. BJOG 2000; 107:870- 6.
18. Chakurski I, Matev M, Koichev A, Angelova I, Stefanov G. [Treatment of chronic colitis with an herbal combination of Taraxacum officinale, Hipericum perforatum, Melissa officinaliss,Calendula officinalis and Foeniculum vulgare]. Vutr Boles 1981; 10:51-4.
19. Martinez B, Kasper S, Ruhrmann S, Moller HJ. Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol 1994; 7:S29-33.
20. Kasper S. Treatment of seasonal affective disorder (SAD) with hypericum extract. Pharmacopsychiatry 1997; 30:89-93.
21. Wheatley D. Hypericum in seasonal affective disorder (SAD). Curr Med Res Opin 1999; 15:33-7.
22. Grush LR, Nierenberg A, Keefe B, Cohen LS. St John's wort during pregnancy. JAMA 1998; 280:1566.
23. Rayburn WF, Gonzalez CL, Christensen HD, Harkins TL, Kupiec TC. Impact of hypericum (St.-John's-wort) given prenatally on cognition of mice offspring. Neurotoxicol Teratol 2001; 23:629-37.
24. Rayburn WF, Christensen HD, Gonzalez CL. Effect of antenatal exposure to Saint John's wort (Hypericum) on neurobehavior of developing mice. Am J Obstet Gynecol 2000; 183:1225-31.
25. Cada AM, Hansen DK, LaBorde JB, Ferguson SA. Minimal effects from developmental exposure to St. John's wort (Hypericum perforatum) in Sprague- Dawley rats. Nutr Neurosci 2001; 4:135-41.
26. Rayburn WF, Gonzalez CL, Christensen HD, Stewart JD. Effect of prenatally administered hypericum (St John's wort) on growth and physical maturation of mouse offspring. Am J Obstet Gynecol 2001; 184:191-5.
27. Okpanyi SN, Lidzba H, Scholl BC, Miltenburger HG. [Genotoxicity of a standardized Hypericum extract]. Arzneimittelforschung. 1990; 40:851-5.
28. Chan LY, Chiu PY, Lau TK. A study of hypericin-induced teratogenicity during organogenesis using a whole rat embryo culture model. Fertil Steril 2001; 76:1073-4.
29. Shipochliev T. [Uterotonic action of extracts from a group of medicinal plants]. Vet Med Nauki. 1981; 18:94-8.
30. Farnsworth NR, Bingel AS, Cordell GA, Crane FA, Fong HH. Potential value of plants as sources of new antifertility agents I. J Pharm Sci 1975; 64:535- 98.
31. Ernst E. A systematic review of systematic reviews of homeopathy. Br J Clin Pharmacol 2002; 54:577-82.
32. Lee A, Minhas R, Matsuda N, Lam M, Ito S. The safety of St. John's wort (Hypericum perforatum) during breastfeeding. J Clin Psychiatry 2003; 64:966- 8.
33. Klier CM, Schafer MR, Schmid-Siegel B, Lenz G, Mannel M. St. John's wort (Hypericum perforatum)--is it safe during breastfeeding? Pharmacopsychiatry 2002; 35:29 -30.
34. Duke JA. Handbook of medicinal herbs. Boca Raton: CRC, 1985.
35. Benner MH, Lee HJ. Toxic reactions to plant products sold in health food stores. Med Lett 1979; 21:29-32.
36. Mitchell J, Rook A. Botanical dermatology - plants and plant products injurious to the skin. Vancouver: Greengrass, 1979.
37. Frohne D, Pfander HJ. A colour atlas of poisonous plants. London: Wolfe, 1984.
38. Newall CA, Anderson LA, Phillipson JD. Herbal medicines : a guide for health-care professionals. London, UK: Pharmaceutical Press, 1996:296.
39. Calapai G, Crupi A, Firenzuoli F, et al. Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum. Pharmacopsychiatry 2001; 34:45-9.
40. Kleber E, Obry T, Hippeli S, et al. Biochemical activities of extracts from Hypericum perforatum. Arzneimittelforschung 1999; 49:106 -9.
41. Muller WE, Singer A, Wonnemann M, Hafner U, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. pharmacopsychiatry 1998; 31:16-21.
42. Chatterjee SS, Noldner M, Koch E, Erdelmeier C.Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility. Pharmacopsychiatry 1998; 31:7 -15.
43. Singer A, Wonnemann M, Muller WE. Hyperforin, a major antidepressant constituent of St. John's wort, inhibits serotonin uptake by elevating free intracellular Na+11. J Pharmacol Exp Ther 1999; 290:1363 -8.
44. Jensen AG, Hansen SH, Nielsen EO. Adhyperforin as a contributor to the effect of Hypericum perforatum L. in biochemical models of antidepressant activity. Life Sci 2001; 68:1593-605.
45. Suzuki O, et al. Inhibition of monoamine oxidase by hypericin. Planta Med 1984; 50:272-4.
46. Schempp CM, Kirkin V, Simon- Haarhaus B, et al Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Oncogene 2002;21:1242-50.
47. Schempp CM, Winghofer B, Ludtke R, Simon- Haarhaus B, Schopf E, Simon JC. Topical application of St John's wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells. Br J Dermatol 2000; 142:979-84.
48. Wang Z, Gorski JC, Hamman MA, et al. The effects of St. John's wort (Hyericum perforatum)on human cytochrome P450 activity. Clin
Pharmacol Ther 2001; 70:317- 26.
49. Schempp CM, Pelz K, Wittmer A, Schopf E, Simon JC. Antibacterial activity of hyperforin from St John's wort, against multiresistant Staphylococcus aureus and gram -positive bacteria. Lancet 1999; 353:2129.
50. Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002; 54:349-56.
51. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002; 58:130-3.
52. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St. John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290:1500- 4.
53. Ladner DP, Klein SD, Steiner RA, Walt H. Synergistic toxicity of delta- aminolaevulinic acid- induced protoporphyrin IX used for photodiagnosis and hypericum extract, a herbal antidepressant. Br J Dermatol 2001; 144.
54. Roots I, Johne A, Schmider B, Brockmoller J, et al. Interaction of a herbal extract from St. John's wort with amitriptyline and its metabolites. Clin Pharmacol Ther 2000; 67:159.
55. Durr D, Stieger B, Kullak-Ublick GA, et al. St. John's Wort induces Intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000; 68:598-604.
56. Schulz V. Incidence and clinical relevance of the interactions and side effects of Hypericum preparations. Phytomedicine 2001; 8:152-60.
57. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200- 11.
58. Gordon JB. SSRIs and St. John's Wort: possible toxicity? Am Fam Physician 1998; 57:950- 3.
59. Beckman SE, Sommi RW, Switzer J. Consumer use of St. John's wort: A survey of effectiveness, safety, and tolerability. Pharmacotherapy 2000; 20:568- 74.
60. Upton R. St. John's wort, Hypericum perforatum: Quality control, analytical and therapeutic monograph. American Herbal Pharmacopoeia. Santa Cruz, CA, 1997:1- 2.
61. Burstein AH, Horton RL, Dunn T, et al. Lack of effect of St John's Wort on carbamazepine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther 2000; 68:605- 12.
62. Abul- Ezz SR, Barone GW, Gurley BJ, et al. Effect of herbal supplements on cyclosporine blood levels and associated acute rejection, Am Soc of Nephrol Ann Mtg, Toronto, CAN, 2000.
63. Mai I, Kruger H, Budde K, et al. Hazardous pharmacokinetic interaction of Saint John's wort (Hypericum perforatum) with the immunosuppressant cyclosporin. Int J Clin Pharmacol Ther 2000; 38:500-2.
64. Gurley BJ, Barone GW. Herb-drug interaction involving St. John's wort and cyclosporine, AAPS Ann Mtg & Expo, Indianapolis, IN, Oct29- Nov2, 2000. Vol. presentation #3443.
65. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John's wort. Lancet 2000; 355:548-9.
66. Barone GW, Gurley BJ, Ketel BL, et al. Drug interaction between St. John's wort and cyclosporin. Ann Pharmacother 2000; 34:1013-6.
67. Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St John's wort with ciclosporin. Lancet 2000; 355:1912.
68. Moschella C, Jaber BL. Interaction between cyclosporine and Hypericum perforatum (St. John's wort) after organ transplantation. Amer J Kidney Dis 2001; 38:1105-7.
69. Karliova M, Treichel U, Malago M, et al. Interaction of Hypericum perforatum (SJW) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 2000; 33:853- 5.
70. Mandelbaum A, Pertzborn F, Martin- Facklam M, Wiesel M. Unexplained decrease of cyclosporin trough levels in a compliant renal transplant patient. Nephrol Dial Transplant 2000; 15:1473-4.
71. Ernst E. St. John's Wort supplements endanger the success of organ transplantation. Arch Surg 2002; 137:316-9.
72. Bauer S, Stormer E, Johne A, et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol 2003; 55:203- 11.
73. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66:338-45.
74. Cheng TO. St. John's wort interaction with digoxin [letter]. Arch Intern Med 2000; 160:2548.
75. H ennessy M, Kelleher D, Spiers JP, et al. St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002; 53:75-82.
76. Wang Z, Hamman MA, Huang SM, et al. Effect of St. John's wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther 2002; 71:414-20.
77. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John's wort on irinotecan metabolism. J Natl Cancer Inst 2002; 94:1247-9.
78. Mathijssen RHJ, Verweij J, De Bruijn P, et al. Modulation of irinotecan (CPT- 11) metabolism by St. John's wort in cancer patients, American Association for Cancer Research Annual Meeting, San Francisco, April, 2002.
79. Mai I, Stormer E, Bauer S, et al. Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003;18:819- 22.
80. Hussain MD, Teixeira MG. Saint John's wort and analgesia: effect of Saint John's wort on morphine induced analgesia, AAPS Ann Mtg & Expo, Indianapolis, IN, Oct 29- Nov 2, 2000. Vol. presentation #3453.
81. Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol 1999; 12:7-10.
82. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St. John's wort. Lancet 2000; 355:547- 8.
83. de Maat M, Hoetelmans R, Mathot R, et al. Drug interaction between St. John's wort and nevirapine. AIDS 2001; 15:420- 1.
84. Yue QY, Bergquist C, Gerden B. Safety of St John's wort (Hypericum perforatum). Lancet 2000; 355:576- 7.
85. Schwarz UI, Buschel B, Kirch W. Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception. Br J Clin Pharmacol 2003; 55:112-3.
86. Gorski JC, Hamman MA, Wang Z, et al. The effect of St. John's wort on the efficacy of oral contraceptives. Clin Pharmacol Ther 2001; 71:P25.
87. Sugimoto K, Ohmori M, Tsuruoka S. Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001; 70:518-24.
88. Mai I, Bauer S, Krueger H, et al. Wechselwirkungen von Johaniskraut mit tacrolismus bei nierentransplantierten patienten, Symposium Phytopharmaka VII, Berlin, GER, October, 2001. Forschung und Klinische Anwendung.
89. Nebel A, Schneider BJ, Baker RA, et al. Potential metabolic interaction between St. John's wort and theophylline. Ann Pharmacother 1999; 33:502.
90. Groning R, Breitkreutz J, Muller RS. Physico-chemical interactions between extracts of Hypericum perforatum L. and drugs. Eur J Pharm Biopharm 2003; 56:231-6.
91. Roby CA, Anderson GD, Kantor E, et al. St. John's wort: Effect on CYP3A4 activity. Clin Pharmacol Ther 2000; 67:451-7.

Most read articles by the same author(s)

1 2 3 4 5 6 7 8 9 10 > >>