St. John's Wort

Effects and Benefits

Core Identification

Common Names:
- St. John's Wort
- Hypericum
- Klamath Weed
- Goatweed
- Tipton's Weed

Latin Name: Hypericum perforatum

Category: Herb

Uses

Traditional Uses

• Wound healing and burns - European folk medicine since ancient Greece
• Protection against "evil spirits" and melancholy - Medieval European tradition
• Nerve pain and neuralgia - Traditional Western herbalism
• Liver and digestive support - European folk medicine based on doctrine of signatures (yellow color)
• Insect repellent - Folk remedy application

Modern Uses

• Mild to Moderate Depression - Primary modern indication | Research quality: Strong
• Key findings: Meta-analyses of 25+ randomized clinical trials show St. John's Wort is more effective than placebo and comparable to tricyclic antidepressants (imipramine, amitriptyline) with fewer side effects. One study showed 65% of participants improved taking 900 mg daily. Officially approved by German Commission E for this use. Between 60-80% of patients show improvement in mood. Beneficial effects typically appear within 2-6 weeks.

• Source citations: Linde et al., British Medical Journal 1996; Szegedi et al., BMJ 2005; Multiple Cochrane reviews

• Seasonal Affective Disorder (SAD) - Winter depression treatment | Research quality: Moderate

• Key findings: Study of 168 patients showed reduced anxiety, improved libido, and better sleep with or without phototherapy.

• Source citations: Chopra Center Herbal Handbook

• Anxiety and Sleep Quality - Mood and sleep support | Research quality: Moderate

• Key findings: Increases slow-wave sleep (stages 3 and 4) which contributes to antidepressant effects. Three patients with generalized anxiety disorder experienced symptom relief from 900 mg twice daily, with benefits persisting for one year.

• Source citations: Schulz & Jobert, Journal of Geriatric Psychiatry and Neurology 1994

• Nerve Pain (Neuralgia, Sciatica) - Topical and internal use | Research quality: Moderate

• Key findings: Has locally analgesic action on nerve pains. Useful for diabetic neuropathy as alternative to tricyclic antidepressants without drowsiness or blood pressure effects.

• Source citations: Balch, Prescription for Herbal Healing; A-Z of Herbal Remedies

• Wound Healing and Burns - Topical oil application | Research quality: Moderate

• Key findings: Promotes cellular regeneration. Studies show calendula and hypericum promote wound healing in rats. Topical hypericum cream effective for atopic dermatitis in randomized controlled trial.

• Source citations: Rao et al., Fitoterapia 1991; Schempp et al., Der Hautarzt 2003

• Herpes Simplex Virus (Cold Sores) - Antiviral activity | Research quality: Preliminary

• Key findings: Hypericin and pseudohypericin inhibit herpes simplex 1 virus and other herpesviruses including cytomegalovirus in laboratory studies. Antiviral process enhanced by sunlight exposure.

• Source citations: Laboratory cell line studies

• Ear Infection Pain - Naturopathic ear drops | Research quality: Moderate

• Key findings: Otikon Otic Solution containing hypericum reduced ear pain as effectively as topical anesthetics, working within 2-3 days without antibiotics.
• Source citations: Sarrell et al., Pediatrics 2003

Active Compounds

Primary Active Ingredients:
- Hypericin - Red pigment responsible for photosensitizing effects; influences serotonin receptor availability and uptake inhibition; has antiviral and potential anticancer activity
- Pseudohypericin - Related to hypericin; contributes to antiviral activity against herpesviruses
- Hyperforin - Major antidepressant constituent; inhibits serotonin, norepinephrine, and dopamine reuptake by elevating intracellular sodium; responsible for many drug interactions via CYP3A4 induction
- Flavonoids (including quercetin, rutin, amentoflavone) - Provide antioxidant, anti-inflammatory, and blood vessel-relaxing effects; amentoflavone is antiulcerogenic
- Procyanidins - Vasoactive compounds affecting coronary arteries

Dosage Information

Standard Dosage:
- Form: Standardized extract (capsule/tablet)
- Amount: 300 mg three times daily (900 mg total)
- Standardization: 0.3% hypericin (providing ~900 mcg hypericin daily) or 2-5% hyperforin
- Frequency: Three times daily with meals

Therapeutic Dosage:
- Form: Standardized extract
- Amount: 300-600 mg three times daily (900-1,800 mg total)
- Purpose: Depression, anxiety, nerve pain
- Duration: Minimum 2-6 weeks to assess effectiveness; can be used long-term if beneficial

General Use (Whole Herb):
- Form: Dried herb (tea/infusion)
- Amount: 2-4 grams per day
- Preparation: 1 teaspoon dried or 2 teaspoons fresh herb to 250 ml boiling water, steep 5-10 minutes

Maximum Safe Dosage:
- Daily maximum: 1,800 mg standardized extract
- Warning threshold: Higher doses increase photosensitivity risk; do not exceed without medical supervision

Bioavailability Notes:
- Hypericin reaches peak plasma levels in 4-6 hours
- Steady-state concentrations achieved after 4-5 days of regular dosing
- Fat-soluble compounds; absorption may be improved with food

How to Take It

Timing:
- Take with meals to improve absorption and reduce potential stomach upset
- Divide daily dose into 2-3 portions throughout the day
- Consistency is important - take at the same times daily
- Allow 2-6 weeks to assess antidepressant effects; do not discontinue prematurely

Synergies - What It Works Well With

Complementary Supplements:
1. Black Cohosh - Combined for menopausal hot flashes | Enhanced effectiveness for vasomotor symptoms in multiple clinical trials
2. Valerian - Combined for sleep support | Complementary sedative actions for improved sleep quality
3. Lemon Balm - Combined for anxiety and stress | Both herbs support calm mood and nervous system

Avoidance - What NOT to Combine With

Supplement Interactions:
1. 5-HTP - Both affect serotonin levels | Risk of serotonin syndrome; do not combine
2. SAMe - Both have antidepressant effects via serotonin | Potential additive serotonergic effects
3. Kava - Both have sedative properties | May cause excessive sedation

Drug Interactions:
1. SSRIs (Prozac, Zoloft, Paxil, etc.) - Both affect serotonin | Risk of serotonin syndrome (confusion, fever, muscle twitching, sweating, agitation) | Severity: Severe
2. Tricyclic Antidepressants (amitriptyline, imipramine) - St. John's Wort reduces drug levels by 22-42% via CYP3A4 induction | Reduced effectiveness; serotonin syndrome risk | Severity: Severe
3. MAO Inhibitors - Overlapping mechanisms | Risk of severe hypertensive crisis | Severity: Severe
4. Warfarin (Coumadin) - Induces drug metabolism | Reduces anticoagulant effectiveness; up to 30% binding reduction | Severity: Severe
5. Cyclosporine - Induces CYP3A4 and P-glycoprotein | Can cause organ transplant rejection | Severity: Severe
6. Digoxin - Induces P-glycoprotein transport | Reduces digoxin plasma levels significantly | Severity: Severe
7. Birth Control Pills - Induces estrogen metabolism | Breakthrough bleeding reported; possible contraceptive failure | Severity: Moderate-Severe
8. HIV Protease Inhibitors (indinavir, etc.) - Induces drug metabolism | Reduces plasma levels by up to 57%; may cause treatment failure | Severity: Severe
9. Non-nucleoside Reverse Transcriptase Inhibitors (nevirapine) - Induces metabolism | Reduces drug effectiveness | Severity: Severe
10. Triptans (sumatriptan, Imitrex, etc.) - Both affect serotonin | Risk of serotonin syndrome and cerebral vasoconstriction | Severity: Moderate-Severe
11. Tramadol (Ultram) - Both affect serotonin | Serotonin syndrome risk | Severity: Moderate-Severe
12. Theophylline - Induces metabolism | Reduces drug levels | Severity: Moderate
13. Alprazolam (Xanax) - Induces CYP3A4 | Reduces half-life from 12.4 to 6 hours; doubled clearance | Severity: Moderate
14. Barbiturates - Decreases barbiturate-induced sleep time | Altered drug effects | Severity: Moderate
15. Chemotherapy drugs - May alter drug metabolism | Potential reduced effectiveness | Severity: Severe - Consult oncologist

Food Interactions:
- Earlier concerns about tyramine-rich foods (aged cheese, chocolate, red wine) have not been replicated in studies
- No significant food interactions confirmed

Safety Information

Contraindications:
- Do not use with prescription antidepressants of any class
- Do not use with immunosuppressant medications
- Do not use with HIV medications
- Avoid if taking organ transplant rejection drugs
- Avoid during pregnancy (mild uterine activity reported in vitro)
- Avoid during breastfeeding (insufficient safety data)
- Use caution with fair skin and high sun exposure
- Avoid if scheduled for surgery (potential anesthetic interactions; discontinue 2 weeks prior)
- Not recommended for severe depression or suicidal ideation - seek professional help

Side Effects:
- Common: Mild stomach upset, restlessness, fatigue, headache, dry mouth
- Uncommon: Photosensitivity (increased sunburn risk in fair-skinned individuals)
- Rare: Vivid dreams, insomnia, anxiety, dizziness, allergic reactions
- Very Rare: Reports of mania induction in bipolar patients; anxiety and schizophrenia relapse reported

Photosensitivity Note:
- Over 60 million doses dispensed annually in Germany with fewer than a dozen photosensitivity reactions reported
- Risk increases with higher doses (above standard 900 mg/day)
- Avoid tanning beds and prolonged sun exposure, especially if fair-skinned
- More significant concern at very high doses or with IV administration

Long-Term Use:
- Generally considered safe for extended use when beneficial
- No specific cycling recommendations for standard doses
- Monitor for any new medication interactions if prescriptions change
- German approval supports long-term use for maintenance of mood

Special Precautions:
- Surgery: Discontinue at least 2 weeks before scheduled surgery due to potential anesthetic interactions
- Pregnancy: Avoid due to potential uterine activity; insufficient safety data
- Children: Some evidence of safety and efficacy in children under 12 with depression symptoms, but should be supervised by healthcare provider
- Elderly: Generally well-tolerated; monitor for drug interactions with common medications
- Bipolar Disorder: May induce hypomania; use only under medical supervision

Primary Uses At-a-Glance

Primary:
- Mild to moderate depression
- Seasonal affective disorder (SAD)
- Anxiety and stress
- Sleep quality support
- Nerve pain (neuralgia, sciatica)

Secondary:
- Wound healing (topical oil)
- Burns (topical oil)
- Herpes simplex (cold sores)
- Ear infection pain (in combination products)
- Menopausal hot flashes (combined with black cohosh)

Sources

Local Library:
- Barrett, Marilyn - The Handbook of Clinically Tested Herbal Remedies Vol 1 & 2
- Balch, Phyllis - Prescription for Herbal Healing
- Bruton-Seal, Julie - Backyard Medicine
- Bruton-Seal, Julie - The Big Book of Backyard Medicine
- Simon, David - The Chopra Center Herbal Handbook
- Brewer, Sarah - Encyclopedia of Vitamins
- Duke, James A. - Handbook of Medicinal Herbs
- Moyad, Mark - The Supplement Handbook
- Gaby, Alan R. - A-Z Guide to Drug-Herb-Vitamin Interactions
- WRCHM - Herb-Drug-Nutrient Interaction
- Green, James - The Herbal Medicine-Makers Handbook
- Dunn, Peter - A-Z of Herbal Remedies
- Smith, Rachel - Prepper's Survival Natural Medicine
- WRCHM - Herbal Pharmacy

General Knowledge:
- German Commission E Monographs
- European Scientific Cooperative on Phytotherapy (ESCOP)
- American Herbal Pharmacopoeia
- Cochrane Database systematic reviews
- Multiple randomized controlled clinical trials