Supplement Scholar
Herb

St. John's Wort

Buy on Amazon ↗

Affiliate link: we may earn a commission at no extra cost to you. Disclosures

St. John's Wort. Mild-moderate antidepressant with significant CYP450 drug interactions.

How it works. Inhibits reuptake of serotonin, NE, dopamine; potent CYP3A4 and P-gp inducer.

What the research supports. 1 graded claims. Strongest: Effective for mild-moderate depression (strong).

How much to take. Typical dose: 300 mg × 3 (0.3% hypericin standardized).

Side effects and interactions. 3 medication interactions listed. Serious: Serotonin syndrome with SSRIs.

Stacking. Pairs well with A high-quality multivitamin, Omega-3 (EPA/DHA). Avoid combining with Most prescription drugs.

Common forms. Available as Standardized hypericin/hyperforin.

Key studies. 8 studies cited. The strongest are listed with links to PubMed.

Community. Experiences from people who have tried St. John's Wort. Anecdotes are not medical advice.

St. John's Wort. Mild-moderate antidepressant with significant CYP450 drug interactions.

Key compound: hyperforinC35H52O4 · 536.8 g/mol

What it is

Mild-moderate antidepressant with significant CYP450 drug interactions.

Also called

Hypericum perforatum

Food sources

Hypericum perforatum

Goals

Mood & Anxiety

How it works

Inhibits reuptake of serotonin, NE, dopamine; potent CYP3A4 and P-gp inducer.

Pathways

  • Monoamine reuptake inhibition
  • CYP3A4 induction

Effects

  • +Mood (mild-moderate depression) supports

What the research supports

Effective for mild-moderate depressionstrong

Strong: consistent results across large trials or meta-analyses. Moderate: several trials, mostly positive. Limited: small or mixed studies. Preclinical: animal or cell research only.

Typical dose
300 mg × 3 (0.3% hypericin standardized)
TimingConsistent daily timing recommended; split larger doses if GI tolerance is a concern.
With foodEither with or without food.
Best formMost evidence is based on the standardized hypericin/hyperforin form.
Shop St. John's Wort on Amazon ↗

As an Amazon Associate I earn from qualifying purchases. Look for USP, NSF or Informed Sport seals before you buy.

Side effects & interactions

Common side effects

  • Photosensitivity
  • GI upset

Serious

  • Serotonin syndrome with SSRIs

Medication interactions

Oral contraceptivessevere

Reduces efficacy — pregnancy risk.

Warfarin / digoxin / cyclosporine / antiretrovirals / chemotherapysevere

CYP3A4 induction reduces drug levels significantly.

SSRIs / MAOIssevere

Serotonin syndrome.

Check any supplement–medication combination with your pharmacist before starting.

Combines with

Pairs well

  • A high-quality multivitaminCovers micronutrient cofactors that support most supplement pathways.
  • Omega-3 (EPA/DHA)Foundational anti-inflammatory support that complements most regimens.

Avoid combining

  • Most prescription drugsMajor CYP3A4 and P-gp induction.

Common forms

  • Standardized hypericin/hyperforin

Key studies

8 studies cited in total.

St John's wort for major depression ↗
Meta-analysis · Cochrane Database · 2008

Comparable efficacy to standard antidepressants in mild-moderate depression.

PubMed: St. John's Wort — Effective for mild-moderate depression ↗
Systematic review · PubMed (NLM) · 2026

Opens current human and preclinical literature matching St. John's Wort and "Effective for mild-moderate depression". Filter by RCT, meta-analysis, or year on the results page.

PubMed: St. John's Wort — randomized controlled trial ↗
Systematic review · PubMed (NLM) · 2026

Opens current human and preclinical literature matching St. John's Wort and "randomized controlled trial". Filter by RCT, meta-analysis, or year on the results page.

Discussion

Loading discussion…