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St. John’s Wort

Uses

Common names:
Hypericum, Klamath Weed
Botanical names:
Hypericum perforatum

Parts Used & Where Grown

St. John’s wort is found in Europe and the United States. It is especially abundant in northern California and southern Oregon. The above-ground (aerial) parts of the plant are gathered during the flowering season.

What Are Star Ratings?

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

This supplement has been used in connection with the following health conditions:

Used for Why
2 Stars
Anxiety
Refer to label instructions
St. John’s wort has been reported in one double-blind study to reduce anxiety.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.1 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

St. John’s wort has been reported in one double-blind study to reduce anxiety.2

2 Stars
Depression
600 to 1,200 mg daily of a standardized herbal extract containing of 0.3% hypericin, after consulting with a qualified healthcare professional
St. John’s wort can help with mild to moderate depression—but talk to your doctor first as St. John's wort can interact with certain medications.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.3 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

St. John’s wort extracts are among the leading medicines used in Germany by medical doctors for the treatment of mild to moderate depression. Using St. John’s wort extract can significantly relieve the symptoms of depression. People taking St. John’s wort show an improvement in mood and ability to carry out their daily routine. Symptoms such as sadness, hopelessness, worthlessness, exhaustion, and poor sleep also decrease.4 , 5 , 6

St. John’s wort extract has been compared to the prescription tricyclic antidepressants imipramine (Tofranil),7 , 8 , 9 amitriptyline (Elavil),10 fluoxetine (Prozac®),11 and maprotiline (Ludiomil).12 The improvement in symptoms of mild to moderate depression was similar, with notably fewer side effects, in people taking St. John’s wort.

In a double-blind trial using standard amounts of fluoxetine (Prozac)—20 mg per day—St. John’s wort extract in the amount of 400 mg twice daily was equally effective at relieving depression in people aged 60–80 years.13 Another trial found that 250 mg of St. John’s wort extract two times per day was also as effective as 20 mg of fluoxetine in treating adults with mild to moderate depression.14 In both trials comparing St. John’s wort to fluoxetine, there were far fewer side effects reported by people taking St. John’s wort.

One clinical trial compared a higher amount of the St. John’s wort extract LI 160 (1,800 mg per day) with a higher amount of imipramine (150 mg per day) in more severely depressed people.15 Again, the improvement was virtually the same for both groups with far fewer side effects for the St. John’s wort group. While this may point to St. John’s wort as a possible treatment for more severe cases of depression, this treatment should only be pursued under the guidance of a healthcare professional.

Two well-publicized double-blind studies published in the Journal of the American Medical Association (JAMA) concluded that St. John's wort is not an effective treatment for depression. However, each of these studies had potential flaws. In the first study,16 900–1,200 mg of St. John's wort per day was slightly more effective than a placebo, as assessed by the Hamilton Rating Scale for Depression. However, the difference was not statistically significant. Although the remission rate was significantly greater with St. John's wort than with placebo, only 14.3% of the patients who received the herb went into remission, causing the authors of the report to question St. John's wort's efficacy. However, the 4.9% remission rate in the placebo group was far below the placebo response rate seen in other studies of depression. That finding suggests that many of the patients recruited for this study would have been unlikely to respond to any treatment.

In the second JAMA study, depressed patients were given one of three treatments: St. John's wort, placebo, or an antidepressant medication with proven efficacy (e.g., sertraline; Zoloft). Although St. John's wort was no more effective than the placebo, by many measures neither was sertraline.17 The relatively poor outcome with sertraline makes one wonder whether the design of the study, or the criteria used to select participants, may have somehow skewed the results to make St. John's wort appear less effective than it really is.

Despite these two negative studies, the bulk of the scientific evidence indicates that St. John's wort is an effective treatment for mild to moderate depression.

Recent European trials have successfully treated mild to moderate depression using 500 to 1,050 mg of St. John’s wort per day. As an antidepressant, St. John’s wort should be taken for four to six weeks before judging its effectiveness.

2 Stars
Eczema
Apply a cream containing 5% of an herbal extract standardized to 1.5% hyperforin twice per day
A topical cream containing St. John’s wort was shown in one study to greatly improve the severity of eczema. The herb appears to have anti-inflammatory and antibacterial effects.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.18 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

In a double-blind trial, people with eczema applied a cream containing an extract of St. John’s wort to the affected areas on one side of the body, and a placebo (the same cream without the St. John’s wort) to the other side. The treatment was administered twice a day for four weeks. The severity of the eczema improved to a significantly greater extent on the side treated with St. John’s wort than on the side treated with placebo.19 Although the mechanism by which St. John’s wort relieves eczema is not known, it might be due to the anti-inflammatory and antibacterial effects of hyperforin, one of its constituents. The cream used in this study contained 5% of an extract of St. John’s wort (standardized to 1.5% hyperforin). As topical application of St. John’s wort can cause sensitivity to the sun, care should be taken to avoid excessive sun exposure when using this treatment.
2 Stars
Menopause and Depression (Black Cohosh)
Two tablets twice a day for 8 weeks, then one tablet twice a day for 8 weeks, each tablet supplying 1 mg of triterpene glycosides from black cohosh and 0.25 mg of hypericin from St. John's wort
Menopausal and depression symptoms improved in post-menopausal women after they took a combination of black cohosh and St. John's wort.
In a double-blind study of postmenopausal women who were experiencing psychological symptoms, a combination of black cohosh and St. John's wort was significantly more effective than a placebo in improving both menopausal symptoms and depression. The product used in this study contained (per tablet) black cohosh standardized to 1 mg of triterpene glycosides and St. John's wort standardized to 0.25 mg of hypericin. The amount taken was two tablets twice a day for eight weeks, followed by one tablet twice a day for eight weeks.20
2 Stars
Seasonal Affective Disorder
Consult a qualified healthcare practitioner
St. John’s wort, an herb well known for its antidepressant activity, may improve SAD symptoms.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.21 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort. 

St. John’s wort , an herb well known for its antidepressant activity,22 has been examined for its effectiveness in treating SAD. In a preliminary trial, patients with seasonal depression were given 900 mg per day of St. John’s wort in addition to either bright light (3,000 lux for two hours) or a dim light (300 lux for two hours) placebo.23 Both groups had significant improvement in depressive symptoms, but there was no difference between the groups. The authors concluded that St. John’s wort was beneficial with or without bright light therapy, but a placebo effect from the herb cannot be ruled out in this study. Another preliminary study asked 301 SAD patients to report the changes in their symptoms resulting from the use of St. John’s wort at 300 mg three times daily.24 Significant overall improvement was reported by these patients. Some of the subjects used light therapy in addition to St. John’s wort. They reported more improvement in sleep, but overall improvement was not significantly different from those using St. John’s wort alone. Double-blind research is needed to confirm the usefulness of St. John’s wort for treating SAD.

1 Star
Cold Sores
Refer to label instructions
In traditional herbal medicine, tinctures of various herbs including St. John’s wort have been applied topically to herpes outbreaks in order to promote healing.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.26 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort. 

In traditional herbal medicine, tinctures of various herbs, including St. John’s wort, chaparral, goldenseal, myrrh, and echinacea, have been applied topically to herpes outbreaks in order to promote healing.

1 Star
Ear Infections
Refer to label instructions
Ear drops with mullein, St. John’s wort, and garlic in an oil or glycerin base are traditional remedies used to alleviate symptoms, particularly pain, during acute ear infections.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.27 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

Ear drops with mullein, St. John’s wort, and garlic in an oil or glycerin base are traditional remedies used to alleviate symptoms, particularly pain, during acute ear infections. No clinical trials have investigated the effects of these herbs in people with ear infections. Moreover, oil preparations may obscure a physician’s view of the ear drum and should only be used with a healthcare professional’s directions.
1 Star
HIV and AIDS Support
Refer to label instructions
A preliminary trial found that people infected with HIV who took hypericin, a constituent from St. John’s wort, had some improvements in CD4+ cell counts.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.28 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

A constituent from St. John’s wort known as hypericin has been extensively studied as a potential way to kill HIV. A preliminary trial found that people infected with HIV who took 1 mg of hypericin per day by mouth had some improvements in CD4+ cell counts, particularly if they had not previously used AZT.29 A small number of people developed signs of mild liver damage in this study. Another much longer preliminary trial used injectable extracts of St. John’s wort twice a week combined with three tablets of a standardized extract of St. John’s wort taken three times per day by mouth. This study found not only improvements in CD4+ counts but only 2 of 16 participants developed opportunistic infections.30 No liver damage or any other side effects were noted in this trial. In a later study, much higher amounts of injectable or oral hypericin (0.25 mg/kg body weight or higher) led to serious side effects, primarily extreme sensitivity to sunlight.31 At this point, it is unlikely that isolated hypericin or supplements of St. John’s wort extract supplying very high levels of hypericin can safely be used by people with HIV infection, particularly given St. John’s wort’s many drug interactions.
1 Star
Infection
Refer to label instructions
St. John’s wort is an herb that directly attack microbes.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.32 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

Herbs that directly attack microbes include the following: chaparral, eucalyptus, garlic, green tea, lemon balm (antiviral), lomatium, myrrh, olive leaf, onion, oregano, pau d’arco (antifungal), rosemary, sage, sandalwood, St. John’s wort, tea tree oil, thyme, and usnea.
1 Star
Menopause
Refer to label instructions
Supplementing with St. John’s wort may improve psychological symptoms, including sexual well-being, in menopausal women.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.33 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

In a double-blind study of postmenopausal women who were experiencing psychological symptoms, a combination of black cohosh and St. John's wort was significantly more effective than a placebo in improving both menopausal symptoms and depression. The product used in this study contained (per tablet) black cohosh standardized to 1 mg of triterpene glycosides and St. John's wort standardized to 0.25 mg of hypericin. The amount taken was two tablets twice a day for eight weeks, followed by one tablet twice a day for eight weeks.34

Preliminary evidence suggests that supplementation with St. John’s wort extract (300 mg three times daily for 12 weeks) may improve psychological symptoms, including sexual well-being, in menopausal women.35 36

1 Star
Ulcerative Colitis
Refer to label instructions
St. John’s wort, administered as an enema, may be beneficial for people with ulcerative colitis.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.37 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

Enemas of oil of St. John’s wort may be beneficial for ulcerative colitis.38 Consult with a doctor before using St. John’s wort oil enemas.
1 Star
Wound Healing
Refer to label instructions
Topically applied St. John’s wort can be used to speed wound healing.

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.39 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

Traditional herbalists sometimes recommend the topical use of herbs such as St. John’s wort, calendula, chamomile, and plantain, either alone or in combination, to speed wound healing. Clinical trial in humans have not yet validated this traditional practice.

Traditional Use (May Not Be Supported by Scientific Studies)

In ancient Greece, St. John’s wort was used to treat many ailments, including sciatica and poisonous reptile bites. In Europe, St. John’s wort was used by herbalists for the topical treatment of wounds and burns. It is also a folk remedy for kidney and lung ailments as well as for depression.

How It Works

Common names:
Hypericum, Klamath Weed
Botanical names:
Hypericum perforatum

How It Works

The major constituents in St. John’s wort include hypericin and other dianthrones, flavonoids, xanthones, and hyperforin.40 While it was previously thought the antidepressant actions of St. John’s wort were due to hypericin and the inhibition of the enzyme monoamine oxidase,41 current research has challenged this belief, focusing on other constituents, such as hyperforin, and flavonoids.42 , 43 , 44 Test tube studies suggest that St. John’s wort extracts may exert their antidepressant actions by inhibiting the reuptake of the neurotransmitters serotonin, norepinephrine, and dopamine.45 This action is possibly due to the constituent hyperforin.46 St. John’s wort is able to act as an antidepressant, by making more of these neurotransmitters available to the brain.

How to Use It

The standard recommendation for mild to moderate depression is 500–1,050 mg of St. John’s wort extract per day.47 , 48 , 49 Results may be noted as early as two weeks. Length of use should be discussed with a healthcare professional. For more severe depression, higher intakes may be used, under the supervision of a healthcare professional.

Interactions

Common names:
Hypericum, Klamath Weed
Botanical names:
Hypericum perforatum

Interactions with Supplements, Foods, & Other Compounds

Caution: It is likely that there are many drug interactions with St. John's wort that have not yet been identified. St. John's wort stimulates a drug-metabolizing enzyme (cytochrome P450 3A4) that metabolizes at least 50% of the drugs on the market.50 Therefore, it could potentially cause a number of drug interactions that have not yet been reported. People taking any medication should consult with a doctor or pharmacist before taking St. John's wort.

Interactions with Medicines

Certain medicines interact with this supplement.

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • none

Reduce Side Effects

  • none

Support Medicine

  • none

Reduces Effectiveness

  • Atazanavir

    Taking St. John’s wort (Hypericum perforatum) when taking atazanavir might result in reduced blood levels of the drug, which could lead to reduced effectiveness and eventual resistance. Individuals taking atazanavir should avoid taking St. John’s wort at the same time.

  • Atorvastatin
    St. John's wort increases the activity of an enzyme in the body that metabolizes atorvastatin 58. Consequently, supplementation with St. John's wort may increase the metabolism of, and therefore reduce the activity of, atorvastatin.
    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Cyclosporine

    Pharmacological research from Europe suggests that St. John’s wort (Hypericum perforatum) may reduce plasma levels of cyclosporine.62 Two case reports also describe heart transplant patients taking cyclosporine who showed signs of acute transplant rejection after taking St. John’s wort extract.63 In both cases, reduced plasma concentrations of cyclosporine were found. One report cites similar findings in three patients taking cyclosporine and St. John’s wort together.64 Finally, similar drops in cyclosporine blood levels were reported in 45 kidney or liver transplant patients who began taking St. John’s wort.65 Until more is known, people taking cyclosporine should avoid the use of St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Digoxin

    One preliminary trial has suggested that St. John’s  wort(Hypericum perforatum) may reduce blood levels of digoxin.71 In this study, healthy volunteers took digoxin for five days, after which they added 900 mg per day of St. John’s wort while continuing the daily digoxin. A normal blood level of digoxin was reached after five days of taking the drug, but this level dropped significantly when St. John’s wort was added. This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.72 , 73 Until more is known, people taking digoxin should avoid St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Fosamprenavir

    Taking St. John’s wort (Hypericum perforatum) when taking fosamprenavir might result in reduced blood levels of the drug, which could lead to reduced effectiveness and eventual resistance. Individuals taking fosamprenavir should avoid taking St. John’s wort at the same time.

  • Indinavir

    Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir.94 , 95 Therefore, people taking indinavir should not take St. John’s wort.

    Indinavir is a protease inhibitor used to treat people with HIV infection. A pharmacological study gave indinavir to healthy volunteers for two days.96 On day 3, volunteers added 900 mg of St. John’s wort extract per day. At the end of the study, it was found that St. John’s wort led to a significant reduction in serum levels of indinavir. Until more is known, people taking indinavir or other antiretroviral drugs for HIV infection should avoid using St. John’s wort.

  • Lovastatin
    St. John's wort increases the activity of an enzyme in the body that metabolizes lovastatin 101. Consequently, supplementation with St. John's wort may increase the metabolism of, and therefore reduce the activity of, lovastatin.
  • Omeprazole

    In a study of healthy human volunteers, supplementing with St. John's wort greatly decreased omeprazole blood levels by accelerating the metabolism of the drug.109 Use of St. John's wort may, therefore, interfere with the actions of omeprazole.

  • Simvastatin
    In patients taking simvastatin, treatment with St. John's wort increased serum cholesterol levels, apparently because St. John's wort interfered with the effect of the medication.118
  • Theophylline

    One case study of a 42-year old asthmatic woman reported that taking 300 mg per day of St. John’s wort extract led to a significant decrease in blood levels of theophylline.119 Following discontinuation of St. John’s wort, the patient’s blood levels of theophylline returned to an acceptable therapeutic level. This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.120 , 121 Until more is known, people taking theophylline should avoid St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Warfarin

    According to a preliminary report, volunteers taking 900 mg per day of St. John’s wort were given a single dose of an anticoagulant similar in action to warfarin.126 There was a significant drop in the amount of the drug measured in the blood. Seven case studies reported to the Medical Products Agency in Sweden also found a decrease in the anticoagulant activity of warfarin when St. John’s wort was taken at the same time.127 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.128 , 129 People taking warfarin should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Zolpidem
    In healthy volunteers, supplementation with St. John's wort (Hypericum perforatum) along with zolpidem decreased blood levels of zolpidem, apparently by accelerating the metabolism of the drug.130

Potential Negative Interaction

  • Alprazolam
    St. John's wort increases the activity of an enzyme in the body that metabolizes alprazolam51. Consequently, supplementation with St. John's wort may increase the metabolism of, and therefore reduce the activity of, alprazolam.
  • Amitriptyline

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.52 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.53 , 54 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Amoxapine

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.55 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.56 , 57 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Chlordiazepoxide

    In a study of healthy volunteers, administration of St. John's wort (Hypericum perforatum) along with alprazolam decreased blood levels of alprazolam, compared with the levels when alprazolam was taken by itself.3 Individuals taking alprazolam should not take St. John's wort without supervision by a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Clomipramine

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.59 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.60 , 61 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Clonazepam

    In a study of healthy volunteers, administration of St. John's wort (Hypericum perforatum) along with alprazolam decreased blood levels of alprazolam, compared with the levels when alprazolam was taken by itself.3 Individuals taking alprazolam should not take St. John's wort without supervision by a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Desipramine

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.66 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.67 , 68 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Desogestrel-Ethinyl Estradiol

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.69 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.70 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Diazepam

    In a study of healthy volunteers, administration of St. John's wort (Hypericum perforatum) along with alprazolam decreased blood levels of alprazolam, compared with the levels when alprazolam was taken by itself.3 Individuals taking alprazolam should not take St. John's wort without supervision by a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Doxepin

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.74 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.75 , 76 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Estazolam

    In a study of healthy volunteers, administration of St. John's wort (Hypericum perforatum) along with alprazolam decreased blood levels of alprazolam, compared with the levels when alprazolam was taken by itself.3 Individuals taking alprazolam should not take St. John's wort without supervision by a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Ethinyl Estradiol and Levonorgestrel

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.77 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.78 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Ethinyl Estradiol and Norethindrone

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.79 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.80 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Ethinyl Estradiol and Norgestimate

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.81 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.82 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Ethinyl Estradiol and Norgestrel

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.83 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.84 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Fluoxetine

    There have been no published reports about negative consequences of combining St. John’s wort (Hypericum perforatum)  (Hypericum perforatum)  (Hypericum perforatum) and fluoxetine. One case has been reported of an interaction between St. John’s wort and a weak serotonin reuptake inhibitor drug known as trazodone that is vaguely similar to fluoxetine.85 In another case, a patient experienced grogginess, lethargy, nausea, weakness, and fatigue after taking one dose of paroxetine (Paxil®, another SSRI drug) after ten days of St. John’s wort use.86 Nevertheless, some doctors are concerned about the possibility of an interaction between St. John’s wort and fluoxetine causing side effects (e.g., mental confusion, muscle twitching, sweating, flushing) known collectively as serotonin syndrome.87 , 88 Until more is known about interactions and adverse actions, people taking any SSRI drugs, including fluoxetine, should avoid St. John’s wort, unless they are being closely monitored by a doctor.

  • Fluvoxamine

    One report describes a case of serotonin syndrome in a patient who took St. John’s wort and trazodone, a weak SSRI drug.89 The patient experienced mental confusion, muscle twitching, sweating, flushing, and ataxia. In another case, a patient experienced grogginess, lethargy, nausea, weakness, and fatigue after taking one dose of paroxetine (Paxil®, an SSRI drug related to fluvoxamine) after ten days of St. John’s wort.90 Until more is known about interactions and adverse actions, people taking any SSRI drugs, including fluvoxamine, should avoid St. John’s wort, unless they are being closely monitored by a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Imipramine

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.91 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.92 , 93 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Levonorgestrel

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.97 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.98 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Levonorgestrel-Ethinyl Estrad

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.99 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.100 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Lorazepam

    In a study of healthy volunteers, administration of St. John's wort (Hypericum perforatum) along with alprazolam decreased blood levels of alprazolam, compared with the levels when alprazolam was taken by itself.3 Individuals taking alprazolam should not take St. John's wort without supervision by a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Mestranol and Norethindrone

    Cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.102 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.103 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Nefazodone

    Although there have been no interactions reported in the medical literature, it is best to avoid using nefazodone with St. John’s wort unless you are under the supervision of a qualified healthcare professional.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Norgestimate-Ethinyl Estradiol

    Eight cases reported to the Medical Products Agency of Sweden suggest that St. John’s wort may interact with oral contraceptives and cause intramenstrual bleeding and/or changes in menstrual bleeding.104 One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol.105 It should be noted, however, that only three of the eight Swedish women returned to normal menstrual cycles after stopping St. John’s wort. Women taking oral contraceptives for birth control should consult with their doctor before taking St. John’s wort.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Nortriptyline

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.106 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.107 , 108 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Paroxetine

    One report described a case of serotonin syndrome in a patient who took St. John’s wort and trazodone, a weak SSRI drug.110 The patient reportedly experienced mental confusion, muscle twitching, sweating, flushing, and ataxia. In another case, a patient experienced grogginess, lethargy, nausea, weakness, and fatigue after taking one dose of paroxetine after ten days of St. John’s wort use.111

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Phenelzine

    Although St. John’s wort contains chemicals that bind MAO in test tubes, it is believed that the action of St. John’s wort is not due to MAOI activity.112 However, because St. John’s wort may have serotonin reuptake inhibiting action (similar to the action of drugs such as Prozac®, it is best to avoid concomitant use of St. John’s wort with MAOI drugs.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Protriptyline

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.113 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.114 , 115 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Sertraline

    One report described a case of serotonin syndrome in a patient who took St. John’s wort and trazodone, a weak SSRI drug.116 The patient reportedly experienced mental confusion, muscle twitching, sweating, flushing, and ataxia. In another case, a patient experienced grogginess, lethargy, nausea, weakness, and fatigue after taking one dose of paroxetine (Paxil®, another SSRI drug) after ten days of St. John’s wort use.117

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Temazepam

    In a study of healthy volunteers, administration of St. John's wort (Hypericum perforatum) along with alprazolam decreased blood levels of alprazolam, compared with the levels when alprazolam was taken by itself.3 Individuals taking alprazolam should not take St. John's wort without supervision by a doctor.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Trazodone

    One report described a case of serotonin syndrome in a patient who took St. John’s wort and trazodone.122 The patient reportedly experienced mental confusion, muscle twitching, sweating, flushing, and ataxia. Until more is known, St. John’s wort should not be combined with trazodone except under expert clinical supervision.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Trimipramine

    Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline.123 This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs.124 , 125 Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.

  • Venlafaxine

    Although there have been no interactions reported in the medical literature, it is best to avoid using venlafaxine with St. John’s wort unless you are under the supervision of a qualified healthcare professional.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Explanation Required

  • Fexofenadine

    In a study of healthy volunteers, administration of 900 mg of St. John's wort one hour prior to fexofenadine resulted in a significant increase in blood levels of fexofenadine, compared with the blood levels after taking fexofenadine alone.131 On the other hand, long-term administration of St. John's wort (300 mg three times per day for two weeks) did not alter blood levels of fexofenadine. Until more is known, St. John's wort should not be combined with fexofenadine, except under the supervision of a doctor.

The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a supplement with your doctor or pharmacist.

Side Effects

Common names:
Hypericum, Klamath Weed
Botanical names:
Hypericum perforatum

Side Effects

St. John’s wort has a low incidence of side effects compared to prescription antidepressants. An adverse events profile of St. John’s wort found that, of 14 controlled clinical trials, seven reported no adverse reactions, two had no information, and five reported a total of seven mild reactions.132 Adverse effects reported included stomach upset, fatigue, itching, sleep disturbance, and skin rash. The rate of adverse reactions was always similar to that of the placebo. Additionally, in seven trials comparing St. John’s wort with other antidepressants, the adverse reaction rate for St. John’s wort was consistently lower than that of the antidepressant drugs with which it was compared.

St. John’s wort can make the skin more sensitive to sunlight.133 Therefore, fair-skinned people should be alert for any rashes or burns following exposure to the sun. Three cases of severe blistering and burns were reported in people taking St. John’s wort internally or applying it topically and then being exposed to sunlight.134 There is a case report of a woman experiencing neuropathy (nerve injury and pain) in sun-exposed skin areas after taking 500 mg of whole St. John’s wort for four weeks.135 Although St. John’s wort has photosensitizing properties, the severity of this reaction is not typical for people taking the herb.

People with a history of manic-depressive illness (bipolar disorder) or a less severe condition known as hypomania, should avoid use of St. John’s wort as it may trigger a manic episode.136 , 137 , 138 , 139

There is a single case report in which ingestion of St. John's wort appeared to cause high blood pressure in a 56-year-old man. The blood pressure returned to normal when the herb was discontinued.140

References

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92. Nebel A, Schneider BJ, Baker RK, Kroll DJ. Potential metabolic interaction between St. John’s wortand theophylline [letter]. Ann Pharmacother 1999;33:502.

93. Mai I, Schmider J, et al. Unpublished results, May, 1999. Reported in: Johne A, Brockmöller, 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.

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