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Compound

St Johns Wort

Also known as hypericum, hypericum perforatum, johnswort, sjw

43 Research sources
99/100 Market safety
300.0 mg Median dose
280 Products on market

Key takeaways

  • St. John's Wort is more effective than placebo for major depression across a large patient population (N=5489) (PMID: 18843608).
  • Hypericum extract showed efficacy comparable to imipramine in patients with moderate depression (PMID: 10591711).
  • Meta-analyses confirm its utility in treating depressive disorders with a favorable tolerability profile compared to SSRIs (PMID: 19028540).
Evidence

What the research shows

AI-synthesized from 43 peer-reviewed sources · Updated 2025

St. John's Wort (Hypericum perforatum) is a herbal supplement widely used for the treatment of depressive disorders. Extensive research, including multiple Cochrane reviews and meta-analyses, suggests it is more effective than placebo and comparable to standard antidepressants for mild-to-moderate depression.

By condition

Major Depressive Disorder (Mild-to-Moderate) Strong
Multiple systematic reviews and meta-analyses indicate that St. John's Wort is effective for treating mild-to-moderate depression, often showing similar efficacy to standard antidepressants with fewer side effects.

Menopausal Symptoms/Depression Moderate
Evidence suggests it may be effective in managing depressive symptoms associated with menopause.

Cognitive Enhancement Weak
Some evidence of cognitive enhancement exists in rodent models, but human data is insufficient.

Effective doses

Specific dose ranges were not detailed in the provided abstracts, though one RCT mentioned the use of STEI 300 extract.

Safety & interactions

St. John's Wort is known for significant drug-drug interactions due to its effect on cytochrome P450 enzymes and may interact with various prescription medications.

Limitations

While evidence for mild-to-moderate depression is strong, there is a lack of consistent evidence for its efficacy in severe major depressive disorder. Some studies are limited by small sample sizes or are based on animal models.

Products

Top-rated St Johns Wort products

Ranked by safety score and evidence coverage

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Interactions

Drug–supplement interactions

133 documented interactions

DrugSeverityMechanismEvidence
Abemaciclib Critical Interaction identified from DDInter 2.0 database. Specific drugs: Abemaciclib ddinter-verified
Abiraterone Critical Interaction identified from DDInter 2.0 database. Specific drugs: Abiraterone ddinter-verified
Acalabrutinib Critical Interaction identified from DDInter 2.0 database. Specific drugs: Acalabrutinib ddinter-verified
Alpelisib Critical Interaction identified from DDInter 2.0 database. Specific drugs: Alpelisib ddinter-verified
Antiarrhythmics Critical St Johns Wort is a moderate inducer of CYP2C9, which increases metabolism of CYP cyp-inferred
Anticoagulants Critical Interaction identified from DDInter 2.0 database. Specific drugs: Apixaban, Edox ddinter-verified
Anticonvulsants Critical St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A cyp-inferred
Antidiarrheals Critical St Johns Wort is a strong inducer of P-gp, which increases metabolism of P-gp su cyp-inferred
Antifungals Critical St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A cyp-inferred
Antiplatelet Drugs Critical Interaction identified from DDInter 2.0 database. Specific drugs: Cilostazol, Ti ddinter-verified
Marketplace

How it's sold

Data aggregated from 280 product labels

Forms
Top brands
Claims vs evidence
100% Evidence-backed
78% Structure/function
0% Unsupported
Sources

Research evidence

Showing top 10 of 43 sources, sorted by quality

Systematic Review· The Cochrane database of systematic reviews· 2008· n=5489· PMID 18843608

**Linde et al., 2008** | Cochrane Database Syst Rev | Systematic Review Linde Klaus, Berner Michael M, Kriston Levente. St John's wort for major depression. Cochrane Database Syst Rev. 2008-Oct-08;2008(4):CD000448. doi:10.1002/14651858.CD00…

Meta Analysis· Journal of affective disorders· 2017· n=3808· PMID 28064110

INTRODUCTION: St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. However, conflicting data regarding its be…

Meta Analysis· Systematic reviews· 2016· n=2922· PMID 27589952

**Apaydin et al., 2016** | Syst Rev | Meta Analysis Apaydin Eric A, Maher Alicia R, ... Hempel Susanne. A systematic review of St. John's wort for major depressive disorder. Syst Rev. 2016-Sep-02;5(1):148. doi:10.1186/s13643-016-0325-2 BACK…

Systematic Review· The Cochrane database of systematic reviews· 2000· n=2291· PMID 10796719

**Linde et al., 2000** | Cochrane Database Syst Rev | Systematic Review Linde K, Mulrow C D. St John's wort for depression. Cochrane Database Syst Rev. 2000(2):CD000448 BACKGROUND: Extracts of the plant Hypericum perforatum L. (popularly ca…

Meta Analysis· Neuropsychopharmacology reports· 2025· n=1049· PMID 40014460

**Urata et al., 2025** | Neuropsychopharmacol Rep | Meta Analysis Urata Minoru, Sakurai Hitoshi, ... Watanabe Koichiro. Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis. Neuropsychopharma…

Meta Analysis· The Cochrane database of systematic reviews· 2005· n=37· PMID 15846605

**Linde et al., 2005** | Cochrane Database Syst Rev | Meta Analysis Linde K, Mulrow C D, ... Egger M. St John's wort for depression. Cochrane Database Syst Rev. 2005-Apr-18(2):CD000448 BACKGROUND: Extracts of the plant Hypericum perforatum …

Meta Analysis· The British journal of psychiatry : the journal of mental science· 2005· PMID 15684231

**Linde et al., 2005** | Br J Psychiatry | Meta Analysis Linde Klaus, Berner Michael, ... Mulrow Cynthia. St John's wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatry. 2005-Feb;186:99-107 BACKGROUND: Extract…

Rct· Complementary therapies in medicine· 2019· n=40· PMID 31331546

**Eatemadnia et al., 2019** | Complement Ther Med | Rct Eatemadnia Alieh, Ansari Somayeh, ... Najar Shahnaz. The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial. Complement Ther Med. 2…

Rct· BMJ (Clinical research ed.)· 1999· n=263· PMID 10591711

OBJECTIVES: To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression. DESIGN: Randomised, …

Meta Analysis· Scientific reports· 2016· PMID 27762349

**Ben-Eliezer et al., 2016** | Sci Rep | Meta Analysis Ben-Eliezer Daniel, Yechiam Eldad. Hypericum perforatum as a cognitive enhancer in rodents: A meta-analysis. Sci Rep. 2016-Oct-20;6:35700. doi:10.1038/srep35700 Considered an antidepres…

FAQ

Frequently asked questions

What is St. John's Wort and what is it used for?

St. John's Wort (Hypericum perforatum) is a herbal supplement widely used for treating depressive disorders. Extensive research, including multiple Cochrane reviews, suggests it is more effective than a placebo for mild-to-moderate depression.

Does St. John's Wort work for depression?

Yes, there is strong evidence that St. John's Wort is effective for mild-to-moderate depression, often showing similar efficacy to standard antidepressants with fewer side effects. Meta-analyses confirm its utility in treating depressive disorders with a favorable tolerability profile compared to SSRIs.

Can St. John's Wort help with menopausal symptoms?

There is moderate evidence suggesting it may be effective in managing depressive symptoms associated with menopause. However, research is not as robust for this specific use case compared to its primary application for general depressive disorders.

Does St. John's Wort improve cognitive function?

Evidence for cognitive enhancement is weak, as human data is currently insufficient. While some evidence of cognitive benefits exists in rodent models, this has not been confirmed in human studies.

What are the serious drug interactions with St. John's Wort?

St. John's Wort is known for significant drug-drug interactions because it induces cytochrome P450 enzymes and P-glycoprotein, which can dramatically reduce the effectiveness of other medications. Critical interactions include those with antiretrovirals, immunosuppressants like cyclosporine, and digoxin, which can lead to dangerously low plasma levels of these drugs.

Who should avoid taking St. John's Wort?

Individuals taking prescription medications, particularly antiretrovirals, benzodiazepines, or immunosuppressants, should avoid St. John's Wort due to critical interaction risks. It is also important to consult a healthcare provider before use, especially if you are pregnant or managing a complex medical condition.

What is the effective dose of St. John's Wort?

Specific dose ranges were not detailed in the provided evidence summaries, though one RCT mentioned the use of STEI 300 extract. Because dosing can vary and interactions are significant, you should consult a healthcare provider for personalized advice rather than relying on general guidelines.