St. John’s Wort
Uses
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.
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 StarsReliable and relatively consistent scientific data showing a substantial health benefit.
2 StarsContradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1 StarFor 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. 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. has been reported in one double-blind study to reduce anxiety. |
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. 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. 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.St. John’s wort extract has been compared to the prescription tricyclic antidepressants imipramine (Tofranil), amitriptyline (Elavil), fluoxetine (Prozac®), and maprotiline (Ludiomil). 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. 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. 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. 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, 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. 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. 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 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. 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 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. |
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. 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. , an herb well known for its antidepressant activity, 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. 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. 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. 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 , 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. 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, , 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. 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 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. 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. 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. 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. 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, , 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. 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 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.Preliminary evidence suggests that supplementation with extract (300 mg three times daily for 12 weeks) may improve psychological symptoms, including sexual well-being, in menopausal women. |
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. 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 may be beneficial for ulcerative colitis. 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. 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 , 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
The major constituents in St. John’s wort include hypericin and other dianthrones, flavonoids, xanthones, and hyperforin.1 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,2 current research has challenged this belief, focusing on other constituents, such as hyperforin, and flavonoids.3, 4, 5 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.6 This action is possibly due to the constituent hyperforin.7 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.8, 9, 10 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 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.11 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.
Replenish Depleted Nutrients
none
Reduce Side Effects
none
Support Medicine
none
Reduces Effectiveness
- Amprenavir
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- Atazanavir
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- Atazanavir-Cobicistat
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- AtorvastatinSt. John's wort increases the activity of an enzyme in the body that metabolizes atorvastatin . Consequently, supplementation with St. John's wort may increase the metabolism of, and therefore reduce the activity of, atorvastatin.
- Cyclosporine
Pharmacological research from Europe suggests that St. John’s wort (Hypericum perforatum) may reduce plasma levels of cyclosporine. Two case reports also describe heart transplant patients taking cyclosporine who showed signs of acute transplant rejection after taking St. John’s wort extract. 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. Finally, similar drops in cyclosporine blood levels were reported in 45 kidney or liver transplant patients who began taking St. John’s wort. Until more is known, people taking cyclosporine should avoid the use of St. John’s wort.
- Digoxin
One preliminary trial has suggested that St. John’s wort(Hypericum perforatum) may reduce blood levels of digoxin. 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. Until more is known, people taking digoxin should avoid St. John’s wort.
- Fosamprenavir
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- Indinavir
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- Ketamine is given primarily by injection as an anesthetic and to relieve pain. It can also be used orally to treat chronic pain. In a study of healthy volunteers, administration of St. John's wort along with ketamine, decreased blood levels of the drug, which suggests that St. John's wort would decrease the effectiveness of orally administered ketamine.
- LovastatinSt. John's wort increases the activity of an enzyme in the body that metabolizes lovastatin . Consequently, supplementation with St. John's wort may increase the metabolism of, and therefore reduce the activity of, lovastatin.
- Nelfinavir
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- 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. Use of St. John's wort may, therefore, interfere with the actions of omeprazole.
- Ritonavir
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- Saquinavir
Studies have shown that taking indinavir together with St. John’s wort results in increased breakdown and dramatically reduced blood levels of indinavir. 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. 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.
- SimvastatinSt. John's wort increases the activity of an enzyme in the body that metabolizes lovastatin . Consequently, supplementation with St. John's wort may increase the metabolism of, and therefore reduce the activity of, lovastatin.
- 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. 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. Until more is known, people taking theophylline should avoid St. John’s wort.
- 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. 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. 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. People taking warfarin should consult with their doctor before taking St. John’s wort.
- ZolpidemIn 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.
Potential Negative Interaction
- AlprazolamSt. John's wort increases the activity of an enzyme in the body that metabolizes alprazolam. 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. 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. 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. 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. 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.
- Clomipramine
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. 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. 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.
- Desipramine
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. 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. 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- 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.
- Doxepin
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. 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. 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.
- 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- Fluvoxamine
One report describes a case of serotonin syndrome in a patient who took St. John’s wort and trazodone, a weak SSRI drug. 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. 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.
- Imipramine Pamoate
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. 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. 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- 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.
- 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- 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.
- 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. One reviewer has suggested that St. John’s wort may reduce serum levels of estradiol. 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.
- Nortriptyline
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. 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. Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.
- Paroxetine
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. 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. 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. 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.
- Paroxetine Mesylate
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. 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. 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. 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.
- 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. 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.
- Protriptyline
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. 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. Until more is known, people taking tricyclic antidepressants should avoid St. John’s wort.
- Sertraline
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. 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. 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. 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.
- 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.
- Trazodone
One report described a case of serotonin syndrome in a patient who took St. John’s wort and trazodone. 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.
- Trimipramine
Preliminary research has suggested that St. John’s wort (Hypericum perforatum) may reduce blood levels of the tricyclic antidepressant amitriptyline. 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. 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.
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. 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.
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.12 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.13 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.14 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.15 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.16, 17, 18, 19
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.20
1. Gruenwald J. Standardized St. John's wort clinical monograph. Quart Rev Nat Med 1997;Winter:289-99.
2. Suzuki O, Katsumata Y, Oya M. Inhibition of monoamine oxidase by hypericin. Planta Med 1984;50:272-4.
3. Holzl J, Demisch L, Gollnik B. Investigations about antidepressive and mood changing effects of Hypericum perforatum. Planta Med 1989;55:643.
4. Chatterjee SS, Koch E, Noldner M, et al. Hyperforin with hypericum extract: Interactions with some neurotransmitter systems. Quart Rev Nat Med 1997;Summer:110.
5. Calapai G, Crupi A, Firenzuoli F, et al. Effects of Hypericum perforatum on levels of 5-hydroxytryptamine, noradrenaline and dopamine in the cortex, diencephalon and brainstem of the rat. J Pharm Pharmacol 1999;51:723-8.
6. Müller WE, Rolli M, Schäfer C, Hafner U. Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 1997;30(suppl):102-7.
7. Müller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998;31(suppl):16-21.
8. Brown DJ. Herbal Prescriptions for Better Health. Rocklin, CA: Prima Publishing, 1996, 159-65.
9. Woelk H. Comparison of St. John's wort and imipramine for treating depression: Randomized controlled trial. BMJ 2000;321:536-9.
10. Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomized multicenter study of treatment for eight weeks. BMJ 1999;319:1534-9.
11. 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.
12. Ernst E, Rand JI, Barnes J, et al. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.) Eur J Clin Pharmacol 1998;54:589-94.
13. Brockmöller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: Pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30(suppl):94–101.
14. Lane-Brown MM. Photosensitivity associated with herbal preparations of St. John's wort (Hypericum perforatum). MJA 2000;172:302[Letter].
15. Bove GM. Acute neuropathy after exposure to sun in a patient treated with St John's Wort. Lancet 1998;352:1121-2 [letter].
16. Nierenberg AA, Burt T, Matthews J, Weiss AP. Mania associated with St. John's wort. Biol Psychiatry 1999;46:1707-8.
17. Moses EL, Mallinger AG. St. John's wort: Three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115-7.
18. O'Breasail AM, Argouarch S. Hypomania and St John's wort. Can J Psychiatry 1998;43:746-7 [letter].
19. Schneck C. St. John's wort and hypomania. J Clin Psychiatry 1998;59:689 [letter].
20. Zullino D, Borgeat F. Hypertension induced by St. John's Wort: a case report. Pharmacopsychiatry. 2003;36:32.
Last Review: 05-23-2015
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