St. John's Wort (Hypericum
Be aware that the U.S. Food and Drug Administration does not strictly
regulate herbs and dietary supplements. There is no guarantee of strength,
purity or safety of products containing or claiming to contain shark cartilage.
Decisions to use herbs or supplements should be carefully considered. Individuals
using prescription drugs should discuss taking herbs or supplements with
their pharmacists or health care providers before starting.
Scientists have studied St. John's wort for the following health problems:
Many small studies over the past 20 years report that St. John's wort is
more effective than placebo (sugar pill) and equally effective as tricyclic
antidepressant drugs in the short-term treatment of mild-to-moderate depression
(one to three months). It is not clear if St. John's wort has the same benefits
as selective serotonin reuptake inhibitors (SSRIs), which are commonly used
for depression in the United States. Two recent well-designed studies have
found no benefit of St. John's wort, although the results of these studies
raise questions about whether they are reliable. Other data suggest that
St. Johns wort may be just as effective as SSRIs with fewer side effects.
The use of St. John's wort remains controversial, but most natural medicine
experts and textbooks continue to believe that this product is effective.
Safety concerns exist, as they do with most conventional and complementary
Studies of St. John's wort for depression have also reported reductions in
anxiety. However, there is currently not enough evidence to recommend St.
John's wort for the primary treatment of anxiety disorders.
Because of a lack of well-designed studies, there is not enough evidence
to recommend St. John's wort for the management of obsessive-compulsive disorder.
Better studies are needed before a recommendation can be made.
Antiviral effects noted in laboratory tests have not been noted in humans.
There are multiple reports of significant adverse effects and interactions
with prescription HIV and AIDS drugs (protease inhibitors and non-nucleoside
reverse transcriptase inhibitors). Therefore, there are reasons to recommend
against the use of St. John's wort in patients with HIV or AIDS.
Early study of hypericum cream in the topical treatment of mild to moderate
atopic dermatitis shows positive results. The therapeutic efficacy of the
hypericum cream, however, has to be evaluated in further studies with larger
patient populations and in comparison with therapeutic standards (such as
glucocorticoids) before a firm recommendation can be made.
Results of early study fail to provide evidence for the efficacy of St.
Johns wort in social phobia.
Early scientific evidence on St. John's wort for treating perimenopausal
symptoms, including depressed mood, premenstrual syndrome, seasonal depressive
disorder, or somatoform disorders, remains controversial.
St. John's wort has been suggested for many other uses, based on tradition
or on scientific theories. However, these uses have not been thoroughly studied
in humans, and there is limited scientific evidence about safety or
effectiveness. Some of these suggested uses are for conditions that are
potentially serious and even life-threatening. You should consult a health
care provider before using St. John's wort for any unproven use.
|Abrasions used topically
Bacterial skin infections used topically
Bruises used topically
Burns used topically
Chronic ear infections
Herpes virus infection
Painful menstrual periods
Wound healing used topically
Rare allergic skin reactions such as itchy rash have been reported in studies
in humans. People allergic to plants in the Hypericaceae family should avoid
use of St. John's wort.
In published studies, St. John's wort has been generally well tolerated at
recommended doses for up to one to three months. The most common adverse
effects include gastrointestinal symptoms, skin sensitivity to the sun
(photosensitivity), fatigue, sedation, restlessness, anxiety, insomnia,
dizziness, headache, nausea, muscle cramping, weakness and dry mouth. Many
studies show that St. John's wort has no more side effects than placebos
(sugar pills) do and has fewer side effects than prescription antidepressant
Infrequent allergic skin reactions, including itchy rash, have been reported.
Loss of hair on the scalp and eyebrows, headache, numbness, tingling and
nerve pain or damage has been reported. Increased blood pressure and pulse,
increased sweating, flushing, tremors, heartburn, anorexia, diarrhea and
constipation have been reported in studies. There are few reports of sexual
dysfunction associated with St. John's wort.
Pregnancy And Breast-Feeding
Although case reports of St. John's wort use during pregnancy exist, there
are insufficient data available at this time to recommend use during pregnancy
Interactions with drugs, supplements and other herbs have not been thoroughly
studied. The interactions listed below have been reported in scientific
publications. If you are taking prescription drugs, speak with your health
care provider or pharmacist before using herbs or dietary supplements.
Interactions With Drugs
St. John's wort may alter the blood levels of drugs that are broken down
by certain liver enzymes. This affects many different drugs, with potentially
serious effects. If you are considering taking St. Johns wort with other
drugs, herbs, supplements or vitamins, it is important for you to speak with
your health care provider and pharmacist first.
The U.S. Food and Drug Administration suggests that you avoid St. John's
wort if you are taking HIV and AIDS drugs called protease inhibitors, such
as indinavir (Crixivan), or non-nucleoside reverse transcriptase inhibitors,
such as nevirapine (Viramune). There is a risk of lowering the levels of
these drugs in your body if you take them with St. John's wort. St. John's
wort may also decrease the effects of tricyclic antidepressants, such as
amitriptyline (Elavil); cholesterol-lowering drugs, such as lovastatin (Mevacor);
nifedipine (Procardia); midazolam (Versed); digoxin; and theophylline. Avoid
St. John's wort if you are taking an immunosuppressant drug such as cyclosporine,
tacrolimus, or myophenic acid, especially if you have received an organ
transplant; there have been multiple reports of significant reductions in
drug levels and possible organ rejection.
St. John's wort may increase the risk of sun sensitivity when used with drugs
such as tetracycline or tretinoin (Retin-A). St. John's wort may decrease
the effects of the blood-thinning drug warfarin. Be careful if you take monoamine
oxidase inhibitors, such as phenelzine (Nardil), or selective serotonin reuptake
inhibitors, such as fluoxetine (Prozac), because of the potential for increased
side effects when taken with St. John's wort.
Use St. John's wort cautiously if you are taking birth control pills, because
of reports of altered menstrual flow, bleeding and unwanted pregnancies.
St. John's wort may reduce the thyroid activity of drugs such as levothyroxine
(Synthroid). St. John's wort may increase the anti-inflammatory effects of
cyclooxygenase (COX-2) inhibitors, such as celecoxib (Celebrex), or nonsteroidal
anti-inflammatory drugs, such as ibuprofen (Motrin).
St. John's wort may increase imatinib clearance. Thus, patients taking imatinib
should avoid taking St. John's wort. Concomitant use of enzyme inducers,
including St. John's wort, may necessitate an increase in the imatinib dose
to maintain effectiveness.
St. John's wort has been shown to decrease the blood concentrations of omeprazole
and affect the levels of tolbutamide, caffeine, dextromethorphan, fexofenadine,
carbamazepine, and cimetidine, among other medications.
Interactions With Herbs And Dietary Supplements
St. John's wort may alter the levels of herbs or supplements that are broken
down by certain liver enzymes. St. John's wort may add to the effects of
other herbs and supplements that also affect the same liver enzymes, such
(Humulus lupulus). Iron absorption may be affected by St. John's wort.
Herbs with selective serotonin reuptake inhibitor or monoamine oxidase inhibitor
activity may have increased levels if taken with St. John's wort. An example
Levels of foxglove,
and cholesterol-lowering herbs may be reduced when these herbs are taken
with St. John's wort. St. John's wort may increase sun sensitivity when used
with other agents with similar effects, such as capsaicin. St. John's wort
may decrease the thyroid activity of certain herbs.
The doses listed below are based on scientific research, publications
or traditional use. Because most herbs and supplements have not been thoroughly
studied or monitored, safety and effectiveness may not be proven. Brands
may be made differently, with variable ingredients even within the same brand.
Combination products often contain small amounts of each ingredient and may
not be effective. Appropriate dosing should be discussed with a health care
provider before starting therapy; always read the recommendations on a product's
label. The dosing for unproven uses should be approached cautiously, because
scientific information is limited in these areas.
For Depression Adults (Aged 18 Or Older)
Capsules/extract: A dose of 300 milligrams three times daily by mouth
of standardized 0.3 percent hypericin extract (can be standardized or 0.5
percent to 5 percent hyperforin as well) has been used. A dose of 900 to
1,800 milligrams of extract has been studied. Depression is a serious illness.
Please discuss with a qualified health care provider before self-medicating
with St. John's wort.
For Social Phobia Adults (Aged 18 Or Older)
Capsules/extract: A dose of 600 to 1,800 millgrams has been taken
For Somatoform Disorders Adults (Aged 18 Or Older)
Capsules/extract: A dose of 300 milligrams has been takeng twice daily.
For Cardiovascular Regulation Adults (Aged 18 Or Older)
Capsules/extract: A dose of 300 milligrams three times daily has been
For Atopic Dermatitis Adults (Aged 18 Or Older)
Topical: A dose of 1.5 percent hyperforin (verum) has been applied
to the skin.
Children (Younger Than 18): There is insufficient available evidence to recommend
St. John's wort in children.
Although St. John's wort has been suggested for many conditions, it has been
most studied as a treatment for mild to moderate depression. St. John's wort
has not been proven for any other health condition. It has been studied for
up to three months, but it has not been proven safe for longer use. Although
research does not report many serious side effects, there are potentially
dangerous interactions if St. John's wort is used with other drugs. For example,
people taking certain drugs for HIV or AIDS, organ transplants, birth control,
high cholesterol, high blood pressure and thyroid conditions should not use
St. John's wort. These individuals should speak with a health care provider
or pharmacist if considering its use. St. John's wort may interact with other
drugs used for depression. Many other serious interactions are possible.
St. John's wort should be avoided in pregnant or breast-feeding women and
in children, because there is not enough information about safety. Consult
your health care provider immediately if you experience side effects.
The information in this monograph was prepared by the professional staff
at Natural Standard, based on thorough systematic review of scientific evidence.
The material was reviewed by the Faculty of the Harvard Medical School with
final editing approved by Natural Standard.
Standard: An organization that produces scientifically based reviews
of complementary and alternative medicine topics.
for Complementary and Alternative Medicine (NCCAM): A division of the
U.S. Department of Health & Human Services dedicated to research.
Selected Scientific Studies: St. John's Wort
Some of the more recent studies are listed below:
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;Feb, 55(2):203-211.
Behnke K, Jensen GS, Graubaum HJ, Gruenwald J. Hypericum perforatum
versus fluoxetine in the treatment of mild to moderate depression. Adv Ther
Findling RL, McNamara NK, O'Riordan MA, et al. An open-label pilot study
of St. John's wort in juvenile depression. J Am Acad Child Adolesc Psychiatry
Frye RF, Fitzgerald SM, Lagattuta TF, et al. Effect of St John's wort on
imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004;76(4):323-329.
Gelenberg AJ, Shelton RC, Crits-Christoph P, et al. The effectiveness of
St. John's wort in major depressive disorder: a naturalistic phase 2 follow-up
in which nonresponders were provided alternate medication. J Clin Psychiatry
Hall SD, Wang Z, Huang SM, et al. The interaction between St John's wort
and an oral contraceptive. Clin Pharmacol Ther 2003;74(6):525-535.
Hammerness P, Basch E, Ulbricht C, et al. St. John's wort: a systematic review
of adverse effects and drug interactions for the consultation psychiatrist.
Hebert MF, Park JM, Chen YL, et al. Effects of St. John's wort (Hypericum
perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin
Hicks SM, Walker AF, Gallagher J, et al. The significance of "nonsignificance"
in randomized controlled studies: a discussion inspired by a double-blinded
study on St. John's wort (Hypericum perforatum L.) for premenstrual
symptoms. J Altern Complement Med 2004;10(6):925-932.
Jiang X, Williams KM, Liauw WS, et al. Effect of St. John's wort and ginseng
on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.
Br J Clin Pharmacol 2004;57(5):592-599.
Johne A, Schmider J, Brockmoller J, et al. Decreased plasma levels of
amitriptyline and its metabolites on comedication with an extract from St.
John's wort (Hypericum perforatum). J Clin Psychopharmacol
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(4):338-345.
Kalb R, Trautmann-Sponsel RD, Kieser M. Efficacy and tolerability of hypericum
extract WS 5572 versus placebo in mildly to moderately depressed patients:
a randomized double-blind multicenter clinical trial. Pharmacopsych
Kawaguchi A, Ohmori M, Tsuruoka S, et al. Drug interaction between St John's
Wort and quazepam. Br J Clin Pharmacol 2004;58(4):403-410.
Kim HL, Streltzer J, Goebert D. St. John's wort for depression: a meta-analysis
of well-defined clinical trials. J Nerv Ment Dis 1999;187(9):532-539.
Linde K, Mulrow CD. St John's wort for depression. Cochrane Database Syst
Linde K, Ramirez G, Mulrow CD, et al. St John's wort for depression: an overview
and meta-analysis of randomised clinical trials. BMJ 1996;313(7052):253-258.
Mai I, Bauer S, Perloff ES, et al. Hyperforin content determines the magnitude
of the St. John's wort-cyclosporine drug interaction. Clin Pharmacol Ther
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(4):819-822.
Mauro VF, Mauro LS, Kleshinski JF, et al. Impact of ginkgo biloba on the
pharmacokinetics of digoxin. Am J Ther 2003;10(4):247-251.
Miller LG. Drug interactions known or potentially associated with St. John's
wort. J Herbal Pharmacother 2001;1(3):51-64.
Mills E, Montori VM, Wu P, et al. Interaction of St. John's wort with
conventional drugs: systematic review of clinical trials. BMJ
Parker V, Wong AH, Boon HS, et al. Adverse reactions to St John's wort. Can
J Psychiatry 2001;46(1):77-79.
Morimoto T, Kotegawa T, Tsutsumi K, et al. Effect of St. John's wort on the
pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol
Mueller SC, Uehleke B, Woehling H, et al. Effect of St. John's wort dose
and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther
Muller D, Pfeil T, von den Driesch V. Treating depression comorbid with anxiety:
results of an open, practice-oriented study with St. John's wort WS 5572
and valerian extract in high doses. Phytomedicine 2003;10(Suppl 4):25-30.
Muller T, Mannel M, Murck H, Rahlfs VW. Treatment of somatoform disorders
with St. John's wort: a randomized, double-blind and placebo-controlled trial.
Psychosom Med 2004;66(4):538-547.
Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St. John's wort
with low-dose oral contraceptive therapy: a randomized controlled trial.
Br J Clin Pharmacol 2003;56(6):683-690.
Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo
in patients with moderate depression: randomised multicentre study of treatment
for eight weeks. BMJ 1999; 319(7224):1534-1538.
Schempp CM, Windeck T, Hezel S, Simon JC. Topical treatment of atopic dermatitis
with St. John's wort cream: a randomized, placebo controlled, double blind
half-side comparison. Phytomedicine 2003;10(Suppl 4):31-37.
Schroeder C, Tank J, Goldstein DS, et al. Influence of St. John's wort on
catecholamine turnover and cardiovascular regulation in humans. Clin Pharmacol
Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort
in major depression: a randomized controlled trial. JAMA 2001;285(15):1978-1986.
Siepmann M, Kirch W, Krause S, et al. The effects of St. John's wort extract
and amitriptyline on autonomic responses of blood vessels and sweat glands
in healthy volunteers. J Clin Psychopharmacol 2004;24(1):79-82.
Smith P, Bullock JM, Booker BM, et al. The influence of St. John's wort on
the pharmacokinetics and protein binding of imatinib mesylate. Pharmacotherapy
Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe
depression with hypericum extract WS 5570 (St. John's wort): randomised
controlled double blind non-inferiority trial versus paroxetine. BMJ
Tannergren C, Engman H, Knutson L, et al. St John's wort decreases the
bioavailability of R- and S-verapamil through induction of the first-pass
metabolism. Clin Pharmacol Ther 2004;75(4):298-309.
Wang LS, Zhou G, Zhu B, et al. St. John's wort induces both cytochrome P450
3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole.
Clin Pharmacol Ther 2004;75(3):191-197.
Wenk M, Todesco L, Krahenbuhl S. Effect 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;57(4):495-499.
Wheatley D. Safety of St John's wort (Hypericum perforatum). Lancet 2000;
Last updated June 23, 2005