St. John's Wort

Also known as: Hypericum perforatum, SJW, Ze 117

Grade A — Strong Evidenceherbantidepressant
300–900 mgWith meals, 3x/day. Full antidepressant effect at 4-6 weeks.

Cochrane-validated antidepressant comparable to SSRIs for mild-moderate depression. CRITICAL: interacts with many drugs via CYP induction.

😊Mood
Last reviewed: 2026-03-11

Evidence

Grade A

Studies

3

Interactions

5

Forms

1

Evidence Rating: Grade A — Strong Evidence

Multiple high-quality RCTs, systematic reviews, or meta-analyses with consistent findings.

Interaction Warnings

Oral contraceptivesHigh Risk

Reduces efficacy — CONTRACEPTIVE FAILURE possible via CYP3A4 induction

WarfarinHigh Risk

Reduces efficacy — INCREASED CLOTTING RISK

HIV antiretroviralsHigh Risk

CONTRAINDICATED — subtherapeutic drug levels

Cyclosporine/tacrolimusHigh Risk

Organ rejection risk — CONTRAINDICATED

SSRIs/SNRIsHigh Risk

Serotonin syndrome risk

⚠️ Important Notes

  • ⚠️ MAJOR CYP3A4/CYP2C9/P-gp INDUCER — affects many drugs
  • Must inform ALL prescribing physicians
  • Avoid in bipolar disorder
  • Only for MILD-MODERATE depression

Clinical Evidence (3 studies)

Cochrane review: SJW for depression

Linde K et al. (2008) — Cochrane Database Syst Rev

More effective than placebo for depression, similar to SSRIs, fewer side effects

View on PubMed

SJW not effective for SEVERE depression

Shelton RC et al. (2001) — JAMA

Important negative study: not for severe depression

View on PubMed

SJW Ze 117 vs fluoxetine: non-inferiority

Kasper S et al. (2006) — Int Clin Psychopharmacol

Non-inferiority to fluoxetine confirmed

View on PubMed

Alternatives to Consider

These supplements target similar goals and may be worth considering alongside or instead of St. John's Wort.

Ashwagandha

Grade A

Ayurvedic adaptogen with strong clinical evidence for cortisol reduction (15-30%), stress relief, and exercise performance.

😊 Mood

Saffron

Grade A

Potent natural antidepressant with multiple RCTs showing comparable efficacy to fluoxetine at just 30mg/day. Also supports eye health.

😊 Mood

Rhodiola Rosea

Grade B

Adaptogenic herb with strong evidence for reducing stress-related fatigue. Comparable to low-dose antidepressants for mild depression.

😊 Mood

Related Supplements

Ashwagandha

Grade A — Strong Evidence

Ayurvedic adaptogen with strong clinical evidence for cortisol reduction (15-30%), stress relief, and exercise performance.

Rhodiola Rosea

Grade B — Moderate Evidence

Adaptogenic herb with strong evidence for reducing stress-related fatigue. Comparable to low-dose antidepressants for mild depression.

Tongkat Ali

Grade C — Preliminary

Southeast Asian herb with emerging evidence for cortisol reduction and hormonal support.

Saffron

Grade A — Strong Evidence

Potent natural antidepressant with multiple RCTs showing comparable efficacy to fluoxetine at just 30mg/day. Also supports eye health.

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⚕️ Important Disclaimer

This information is for educational purposes only. It is not medical advice. Always consult a healthcare provider before starting any supplement regimen, especially if you take medications or have health conditions.

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