Natural Standard® Patient Monograph, Copyright © 2014 (www.naturalstandard.com). All Rights Reserved. Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

Background

Extracts of Hypericum perforatum L. (St. John's wort) have been recommended traditionally for a wide range of medical conditions. The most common modern-day use of St. John's wort is for depression. Studies have shown St. John's wort may be equally effective as tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitor (SSRI) antidepressants for mild to moderate depression.

Overall, the evidence suggests St. John's wort may be effective for in mild-to-moderate depression. The evidence for severe depression remains unclear.

St. John's wort may cause serious interactions with prescription drugs, herbs, or supplements. Therefore, people using any medications should consult their healthcare providers, including a pharmacist, prior to starting therapy.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (over 18 years old)

For anxiety, 900 milligrams of St. John's wort has been taken by mouth twice daily for several weeks.

For cancer, 0.05-0.50 milligrams per kilogram of hypericin has been taken by mouth for up to three months.

For mild to moderate depression, 20-1,800 milligrams St. John's wort has been taken by mouth once to three times for 4-52 weeks. Extracts of St. John's wort used in studies included WS® 5570, WS 5572, WS 5573, ZE 117, STW 3-VI, STW3, PM235, LoHyp-57, LI 160, Psychotonin® forte extract,and Hyperforat® and were generally standardized to contain 0.3% hypericin and 2-5% hyperforin.

For severe depression, 900-1,800 milligrams of St. John's wort (extracts LI 160 and WS® 5570) has been taken by mouth daily for 8-12 weeks.

For HIV, 0.5 milligrams per kilogram of hypericin has been taken by mouth, without evidence of benefit.

For irritable bowel syndrome, 450 milligrams of St. John's wort has been taken twice daily for 12 weeks, without evidence benefit.

For nerve pain, three 900 microgram hypericin tablets were taken by mouth for two treatment periods of five weeks each.

For obsessive-compulsive disorder, 450-1,800 milligrams (standardized to 0.3% hypericin) were taken by mouth daily for 12 weeks.

For pain due to burning mouth syndrome, 300 milligram capsules of St. John's wort (containing hypericin 0.31% and hyperforin 3.0%) have been taken by mouth three times daily for 12 weeks.

For menopausal symptoms, 300 milligrams St. John's wort (Kira®) has been taken by mouth three times daily for 12 weeks and 0.4mg hypericin drops (Hyperforat®) has been taken by mouth daily for 12 weeks.

For premenstrual syndrome (PMS), 300-900 milligrams St. John's wort (standardized to 3.38% hyperforin and 0.18% hypericin) or 1,360 micrograms of hypericin have been taken by mouth daily for two menstrual cycles.

For seasonal affective disorder (SAD), 900 milligrams and unspecified doses of St. John's wort (LI 160 and Kira®) have been taken by mouth once to three times daily with or without light therapy for 4-8 weeks.

For smoking cessation, 300 milligrams St. John's wort (LI-160 extract) has been taken by mouth once or twice daily for up to three months and a week.

For social phobia, 600-1,800 milligrams St. John's wort has been taken by mouth daily for 12 weeks.

For somatoform disorders, 300 milligrams of St. John's wort (LI 160 extract) has been taken by mouth twice daily for six weeks.

For atopic dermatitis, 1.5% hyperforin (verum) cream has been used on the skin twice daily for four weeks.

For psoriasis, St. John's wort ointment has been used two times daily on the skin for four weeks.

For wound healing, 20% St. John's wort in petroleum jelly has been used on the affected skin three times daily for 16 days.

Children (under 18 years old)

For ADHD, 300 milligrams of St. John's wort (standardized to 0.3% hypericin) has been used in children three times daily for eight weeks, without evidence of benefit.

For depression, 150-1,800 milligrams St. John's wort was taken by mouth once to three times daily for up to eight weeks.

Evidence

These uses have been tested in humans or animals.  Safety and effectiveness have not always been proven.  Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Key to grades

A
Strong scientific evidence for this use
B
Good scientific evidence for this use
C
Unclear scientific evidence for this use
D
Fair scientific evidence against this use (it may not work)
F
Strong scientific evidence against this use (it likely does not work)

Grading rationale

Evidence gradeCondition to which grade level applies
A

Depression (mild-to-moderate)

Human research suggests that St. John's wort is more effective than placebo and equally as effective as TCAs and SSRIs in the short-term for mild-to-moderate depression. Although St. John's wort has been shown to have fewer side effects than SSRIs, it should be used with caution and guidance of a medical professional.
B

Somatoform disorders

Somatoform disorders are mental symptoms such as pain and fear that lack a physical source or reason for their existence. Early evidence shows that St. John's wort may help with somatoform disorders. Further research is needed to confirm these results.
C

Anxiety disorder

Early research has shown promising effects of St. John's wort for anxiety disorders. High quality evidence is lacking. Further research is needed to make conclusions.
C

Atopic dermatitis (eczema)

Early research of hypericum-cream had shown positive results for atopic dermatitis, or itchy and scaly rashes. Further studies are needed before a firm recommendation can be made.
C

ADHD (children)

It is unclear whether St. John's wort is an effective treatment in children with ADHD. More study is needed to confirm these findings.
C

Bone diseases

A combination product including St. John's wort improved healing for diabetic foot ulcers and bone disease. Further study of St. John's wort alone is warranted before a conclusion may be drawn.
C

Brain tumors

Early human study showed effectiveness of St. John's wort in decreasing brain tumor size. Further study is warranted before a conclusion may be drawn.
C

Depression (children)

Early research suggested effectiveness of St. John's wort for depression in children. Higher quality research is needed before a conclusion may be drawn.
C

Depressive disorder (severe)

Although human research is promising, the effectiveness of St. John's wort for severe depression is unclear. Additional well-designed research needed before a conclusion may be made.
C

Herpes

Early research shows that a combination product containing St. John's wort improved symptoms of herpes. Further research is warranted before a conclusion may be drawn.
C

Menopausal symptoms

Sufficient evidence is lacking to recommend St. John's wort for menopausal symptoms such as depressed mood and hot flashes. More research is needed.
C

Nerve pain

Early study shows that St. John's wort may help nerve pain. Further research is needed to confirm these results.
C

Obsessive-compulsive disorder (OCD)

Evidence for the use of St. John's wort in obsessive-compulsive disorder (OCD) is conflicting. Further research is needed before a conclusion may be drawn.
C

Pain (burning mouth syndrome)

It is unclear whether St. John's wort is an effective treatment for pain associated with burning mouth syndrome. More research is needed.
C

Pain relief (after surgery)

It is unclear whether St. John's wort is an effective treatment for pain after surgery. More research is needed.
C

Premenstrual syndrome (PMS)

The effectiveness of St. John's wort for PMS symptoms such as anxiety, depression, and cravings is unclear. Further studies are needed before a conclusion can be made.
C

Seasonal affective disorder (SAD)

Although early research is promising, there is insufficient evidence supporting the use St. John's wort for depression due to SAD. Further studies are needed before a conclusion can be made.
C

Skin disorders

Limited research shows the effectiveness of St. John's wort in treating various skin disorders. Further study is warranted before a conclusion may be drawn.
C

Smoking cessation

Early research shows the effectiveness of St. John's wort for smoking cessation or in helping to quit smoking. Further research is warranted before conclusions may be made.
C

Social phobia

The effectiveness of St. John's wort for social phobia is unclear. More study is needed.
C

Weight loss

Early research shows that a combination product containing St. John's wort was effective for weight loss. Further research of St. John's wort alone is needed before a conclusion may be drawn.
C

Wound healing

Limited research shows that St. John's wort improved wound healing and decreased the formation of scars. Further study is warranted before a firm conclusion may be drawn.
D

HIV

Non-human research shows anti-viral effects of St. John's wort in AIDS/HIV, but these effects in human research are lacking. There have been multiple reports of significant adverse effects and interactions with drugs used for HIV/AIDS, such as protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Therefore, patients treated for HIV/AIDS should avoid St. John's wort.
D

Irritable bowel syndrome (IBS)

Human research shows a lack of effectiveness and possible harm of St. John's wort in IBS. Overall, there is a lack of quality research. Further research is required.

Uses based on tradition or theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Abdominal discomfort or irritation, alcoholism, allergies, antibacterial, anti-inflammatory, anti-malarial, antioxidant, antiviral, asthma, athletic performance enhancement, bacterial skin infections (topical), bedwetting, benzodiazepine withdrawal, bruises (topical), burns (topical), cancer, chronic ear infections, colitis, contusions, dental pain, diarrhea, diuretic (increasing urine flow), dyspepsia, Epstein-Barr virus infection, excessive menstrual bleeding, fatigue, gastroenteritis, heartburn, hemorrhoids, immune function, influenza, insomnia, joint pain, liver protection from toxins, psoriasis, rheumatism, snakebites, sprains, substance abuse, ulcers.

Interactions

Interactions with Drugs

St. John's wort may interfere with the way the body processes various drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be increased in the blood (causing increased effects or adverse reactions) or decreased in the blood (which may reduce effects). Examples of medications that may be affected by St. John's wort in this manner include carbamazepine, cyclosporin, irinotecan, midazolam, nifedipine, simvastatin, theophylline, warfarin, or HIV drugs such as non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs). The U.S. Food & Drug Administration (FDA) suggests that patients with HIV/AIDS taking PIs or NNRTIs should avoid taking St. John's wort.

St. John's wort may alter the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

St. John's wort may alter blood sugar levels. Caution is advised when using medications that may also alter blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

St. John's wort may affect blood pressure. Caution is advised in people taking drugs that affect blood pressure.

St. John's wort may also interact with 5HT1 agonists (triptans), agents for the eyes, agents for the skin, agents for the stomach and intestines, agents that affect the nervous system, agents that affect the immune system, agents that damage the liver, anesthetics, alcohol, anti-anxiety agents, antibiotics, antidepressant agents, antifungals, antihistamines, anti-inflammatory agents, anticancer agents, antipsychotics, antiretroviral agents, antiviral agents, benzodiazepines, calcium channel blockers, carbamazepine, cardiac glycosides, chlorzoxazone, cholesterol-lowering agents, clozapine, contraceptives, corticosteroids, cyclosporine, dextromethorphan, digoxin, drugs that may lower seizure threshold, estrogens, fertility agents, fexofenadine, heart rate-regulating agents, hepatotoxins, HMG-CoA reductase inhibitors, hormonal agents, loperamide (Imodium®), methylphenidate, monoamine oxidase inhibitors (MAOIs), mood stabilizers, morphine, non-nucleoside reverse transcriptase inhibitors (NNRTIs), omeprazole, opiates, pain relievers, PDE5 selective inhibitors, P-glycoprotein-regulated drugs, photosensitizing agents, protease inhibitors, sedatives, selective serotonin reuptake inhibitors (SSRIs), smoking cessation agents, testosterone, theophylline, thyroid hormones, tricyclic antidepressants (TCAs), Viagra®, weight loss agents, wound healing agents, zolpidem.

Interactions with Herbs and Dietary Supplements

St. John's wort may interfere with the way the body processes herbs and supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of these herbs and supplements may be increased in the blood (causing increased effects or potentially serious adverse reactions) or decreased in the blood (which may reduce the intended effects).

St. John's wort may alter the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto.

St. John's wort may alter blood sugar levels. Caution is advised when using herbs or supplements that may also alter blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

St. John's wort may affect blood pressure. Caution is advised in people taking herbs and supplements that affect blood pressure.

St. John's wort may also interact with alcohol, anesthetics, anti-anxiety herbs and supplements, antibacterials, antidepressant herbs and supplements, antifungals, antihistamines, anti-inflammatory herbs and supplements, anticancer herbs and supplements, antioxidants, antipsychotics, antiviral herbs and supplements, cardiac glycosides, chasteberry, cholesterol-lowering herbs and supplements, contraceptives, fertility herbs and supplements, heart rate-regulating herbs and supplements, herbs and supplements for the eyes, herbs and supplements for the skin, herbs and supplements for the stomach and intestines, herbs and supplements that affect the nervous system, herbs and supplements that affect the immune system, herbs and supplements that damage the liver, herbs and supplements that lower seizure threshold, hormonal herbs and supplements, iron, melatonin, monoamine oxidase inhibitors (MAOIs), mood stabilizers, neurologic herbs and supplements, pain relievers, P-glycoprotein-regulated herbs and supplements, photosensitizing herbs and supplements, phytoestrogens, sedatives, selective serotonin reuptake inhibitors (SSRIs), smoking cessation herbs and supplements, thyroid hormones, tricyclic antidepressants (TCAs), valerian, weight loss herbs and supplements, wound healing herbs and supplements.

Methodology

This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Monograph methodology

Related terms

Adhyperforin, Amber touch-and-heal, amino acids, arnica of the nerves, balm-of-warrior's wound, balsana, bassant, Blutkraut, bossant, Calmigen®, corancillo, dendlu, devil's scorge, Eisenblut, flor de São João, flavonoids, fuga daemonum, goatweed hartheu, heofarigo on, herba de millepertius, herba hyperici, Herrgottsblut, Hexenkraut, hierba de San Juan (Spanish), hipericão (Portuguese), hipérico (Spanish), hipericon, HP, hyperforin, hypericin, Hypericum extract ZE 117, Hypericum perforatum L, isorhamnetin, Jarsin, Johanniskraut, klammath weed, Liebeskraut, LI 160, LoHyp-57, lord God's wonder plant, melatonin, millepertius pelicao, naphthodianthrones, oligomeric procyanidines, perforate, phloroglucinols, pinillo de oro, PM235, pseudohypericin, quercetin, rosin rose, rutin, Sedariston®, SJW, SJW extract LI 160, St. John's wort WS 5572, STW 3-VI, tenturotou, Teufelsflucht, touch and heal, Walpurgiskraut (German), witcher's herb, WS® 5570, WS 5572, WS 5573, xanthones, ZE117.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Avoid in people with known allergy or sensitivity to St. John's wort or to any of its parts.

Infrequent allergic skin reactions, including rash and itching, have been reported.

Side Effects and Warnings

Extensive research supports the safe use of St. John's wort for a short duration (<3 months) at recommended doses in individuals that lack other medication intake.

St. John's wort may cause anxiety, headache, muscle cramps, sweating, weakness, dry mouth, or skin irritation.

Use with caution when using St. John's wort with drugs metabolized by cytochrome P450, as decreased drug effectiveness may occur.

St. John's wort may increase the risk of photosensitivity. Use cautiously in people with sensitive skin or those taking photosensitizing drugs.

St. John's wort may increase the risk of serotonin syndrome. Use cautiously in people taking agents that increase the risk of serotonin syndrome.

St. John's wort may result in altered menstrual flow, bleeding, unwanted pregnancies, and hormone level changes. Use cautiously in women taking contraceptives or other estrogen agents by mouth.

St. John's wort may alter drug levels. Use cautiously in people taking agents for bacterial or fungal infections, agents for erectile dysfunction, antianxiety agents, antihistamines, fertility agents, P-glycoprotein agents, pain relievers, or theophylline.

St. John's wort may cause mania or psychosis. Use cautiously in people with mental illnesses and those taking antipsychotics.

St. John's wort may change how sugar is processed in the body. Use cautiously in people with diabetes or in those taking anti-diabetic agents.

St. John's wort may cause high levels of thyroid-stimulating hormone (TSH). Use cautiously in people with thyroid disorders or those using thyroid hormones.

Use cautiously in people with cataracts, due to the potential association between an element St. John's wort and cataracts.

St. John's wort may cause heart burn, loss of appetite, diarrhea, nausea, vomiting, and constipation. Use cautiously in people with stomach and intestine problems.

St. John's wort may cause liver damage. Use cautiously in people with liver problems or those taking agents that damage the liver.

St. John's wort may alter blood pressure and cause increased or uneven heart rate. Use cautiously in people with high blood pressure or abnormal heart rhythms.

St. John's wort may cause swelling. Use caution in people prone to swelling.

St. John's wort may cause dizziness, tiredness, insomnia, problems with the nervous system, skin tingling or prickling, and nerve pain. Use cautiously in people taking agents that affect the nervous system.

St. John's wort may lower the seizure threshold. Use cautiously in individuals with seizures, and drugs that may lower the seizure threshold.

St. John's wort may lower cholesterol drug concentration and may increase cholesterol. Use cautiously in people with high cholesterol and those taking agents to lower levels of cholesterol.

St. John's wort may stimulate release of certain hormones. Use cautiously with hormonal agents.

Avoid in people with a known allergy or sensitivity to St. John's wort or to any of its parts.

St. John's wort has decreased levels of drugs for HIV/AIDs. Avoid in people with HIV/AIDS who are taking protease inhibitors or non-nucleoside reverse transcriptase inhibitors, as suggested by the U.S. Food & Drug Administration (FDA).

St. John's wort has decreased levels of drugs that suppress the immune system. Avoid in individuals receiving transplants and taking agents that suppress the immune system (particularly cyclosporine).

Avoid in people with suicidal thoughts.

St. John's wort resulted in difficulty inducing anesthesia and relaxation. Avoid before surgery.

St. John's wort use with cancer agents may result in reduced effectiveness and treatment failure. Avoid in people using cancer agents.

St. John's wort may result in result in reduced digoxin efficacy. Avoid using with cardiac glycosides such as digoxin.

St. John's wort may decrease effectiveness of agents that thin blood. Avoid use in people with bleeding disorders or in those taking drugs that thin blood.

Avoid in pregnant and lactating women due to a lack of information.

Pregnancy and Breastfeeding

There is a lack of scientific evidence on the use of St. John's wort during pregnancy or lactation.

Selected references

  1. Anyzewska M, Kowalczuk A, Lozak A, et al. Determination of total hypericins in St. John's wort and herbal medicinal products. Acta Pol.Pharm. 2010;67(6):586-592.
  2. Bitran S, Farabaugh AH, Ameral VE, et al. Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among depressed outpatients? Comparison of two controlled trials of St John's wort (Hypericum perforatum) versus a SSRI. Int.Clin.Psychopharmacol. 2011;26(4):206-212.
  3. Canning S, Waterman M, Orsi N, et al. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS.Drugs 2010;24(3):207-225.
  4. Clewell A, Barnes M, Endres JR, et al. Efficacy and tolerability assessment of a topical formulation containing copper sulfate and hypericum perforatum on patients with herpes skin lesions: a comparative, randomized controlled trial. J.Drugs Dermatol. 2012;11(2):209-215.
  5. Couldwell WT, Surnock AA, Tobia AJ, et al. A phase 1/2 study of orally administered synthetic hypericin for treatment of recurrent malignant gliomas. Cancer 11-1-2011;117(21):4905-4915.
  6. Ghazanfarpour M, Kaviani M, Asadi N, et al. Hypericum perforatum for the treatment of premenstrual syndrome. Int.J.Gynaecol.Obstet. 2011;113(1):84-85.
  7. Hojo Y, Echizenya M, Ohkubo T, et al. Drug interaction between St John's wort and zolpidem in healthy subjects. J.Clin.Pharm.Ther. 2011;36(6):711-715.
  8. Laakmann E, Grajecki D, Doege K, et al. Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the treatment of climacteric complaints: a systematic review. Gynecol.Endocrinol. 2012;28(9):703-709.
  9. Najafizadeh P, Hashemian F, Mansouri P, et al. The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study. Australas.J.Dermatol. 2012;53(2):131-135.
  10. Rook AH, Wood GS, Duvic M, et al. A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis. J.Am.Acad.Dermatol. 2010;63(6):984-990.
  11. Saito YA, Rey E, Almazar-Elder AE, Harmsen WS, et al. A randomized, double-blind, placebo-controlled trial of St John's wort for treating irritable bowel syndrome. Am.J.Gastroenterol. 2010;105(1):170-177.
  12. Samadi S, Khadivzadeh T, Emami A, et al. The effect of Hypericum perforatum on the wound healing and scar of cesarean. J.Altern.Complement Med. 2010;16(1):113-117.
  13. Sarris J, Panossian A, Schweitzer I, et al. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur.Neuropsychopharmacol. 2011;21(12):841-860.
  14. Singer A, Schmidt M, Hauke W, et al. Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: a reanalysis of data from a controlled clinical trial. Phytomedicine. 6-15-2011;18(8-9):739-742.
  15. Tardivo JP, Wainwright M, and Baptista MS. Local clinical phototreatment of herpes infection in Sao Paulo. Photodiagnosis.Photodyn.Ther. 2012;9(2):118-121.

This evidence-based monograph was prepared by The Natural Standard Research Collaboration

www.naturalstandard.com