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evidence · mechanism · dose
Supplements/Herb

St. John's Wort

aka Hypericum perforatum

Mild-moderate antidepressant with significant CYP450 drug interactions.

Mood & Anxiety

Overview

Mild-moderate antidepressant with significant CYP450 drug interactions.

Natural sources
  • Hypericum perforatum
Common forms
  • Standardized hypericin/hyperforin

Mechanism of action

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

Pathways
  • · Monoamine reuptake inhibition
  • · CYP3A4 induction

Effects on the body

Supports
Mood (mild-moderate depression)

Organ system effects

Brain & CNS

Comparable to SSRIs in mild-moderate depression.

Evidence-based benefits

Effective for mild-moderate depression

Strong evidence

Potential side effects

Common
  • · Photosensitivity
  • · GI upset
Rare
    Serious
    • · Serotonin syndrome with SSRIs

    Drug interactions

    Oral contraceptives
    Reduces efficacy — pregnancy risk.
    severe
    Warfarin / digoxin / cyclosporine / antiretrovirals / chemotherapy
    CYP3A4 induction reduces drug levels significantly.
    severe
    SSRIs / MAOIs
    Serotonin syndrome.
    severe

    Safety & non-supplemental interactions

    Educational summary — always confirm with your clinician or pharmacist before starting, stopping, or combining with prescription therapy.

    Avoid if you are
    • ·Pregnant or breastfeeding (insufficient safety data)
    • ·Children under 18 (unless directed by a clinician)
    • ·Pregnant or breastfeeding
    Avoid with these conditions
    • ·Bipolar disorder (mania risk)
    • ·Major depression on prescription antidepressants
    • ·Photosensitivity disorders
    Avoid / monitor with these medications
    • ·SSRIs, SNRIs, MAOIs, triptans (serotonin syndrome)
    • ·Hormonal contraceptives (loss of efficacy — unintended pregnancy reported)
    • ·Warfarin, digoxin, cyclosporine, tacrolimus (induces CYP3A4 — reduced levels)
    • ·HIV antiretrovirals, oncology drugs (imatinib, irinotecan)
    • ·Statins, calcium-channel blockers
    Other notes
    • ·Photosensitivity — use sunscreen at higher doses.

    Supplement interactions

    Pairs well with

    None listed.

    Avoid combining with
    • Most prescription drugs
      Major CYP3A4 and P-gp induction.

    Dosing & bioavailability

    Typical dose
    300 mg × 3 (0.3% hypericin standardized)

    Where to buy

    Affiliate-style search links to reputable retailers. We don't endorse specific brands — verify third-party testing (USP, NSF, Informed Sport) before purchase.

    Herb
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    Thorne
    Practitioner-grade · NSF tested

    Scientific evidence (8)

    Meta-analysisCochrane Database · 2008

    St John's wort for major depression

    Linde K, et al.

    Cochrane review of 29 trials.

    Key findings

    Comparable efficacy to standard antidepressants in mild-moderate depression.

    Open study
    Systematic reviewPubMed (NLM) · 1970

    PubMed: St. John's Wort — Effective for mild-moderate depression

    Live PubMed search

    Live results for "St. John's Wort Effective for mild-moderate depression" across the PubMed/MEDLINE peer-reviewed index.

    Key findings

    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.

    Open study
    Systematic reviewPubMed (NLM) · 1970

    PubMed: St. John's Wort — randomized controlled trial

    Live PubMed search

    Live results for "St. John's Wort randomized controlled trial" across the PubMed/MEDLINE peer-reviewed index.

    Key findings

    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.

    Open study
    Systematic reviewPubMed (NLM) · 1970

    PubMed: St. John's Wort — meta-analysis

    Live PubMed search

    Live results for "St. John's Wort meta-analysis" across the PubMed/MEDLINE peer-reviewed index.

    Key findings

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

    Open study
    Systematic reviewPubMed (NLM) · 1970

    PubMed: St. John's Wort — pharmacokinetics

    Live PubMed search

    Live results for "St. John's Wort pharmacokinetics" across the PubMed/MEDLINE peer-reviewed index.

    Key findings

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

    Open study
    Systematic reviewPubMed (NLM) · 1970

    PubMed: St. John's Wort — safety adverse events

    Live PubMed search

    Live results for "St. John's Wort safety adverse events" across the PubMed/MEDLINE peer-reviewed index.

    Key findings

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

    Open study
    Systematic reviewPubMed (NLM) · 1970

    PubMed: St. John's Wort — dose response

    Live PubMed search

    Live results for "St. John's Wort dose response" across the PubMed/MEDLINE peer-reviewed index.

    Key findings

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

    Open study
    Systematic reviewGoogle Scholar · 1970

    Google Scholar: St. John's Wort — clinical evidence

    Live Scholar search

    Cross-database citation index for St. John's Wort as it relates to "clinical evidence".

    Key findings

    Includes preprints, theses, and journal articles. Useful for tracking citation counts and follow-on work.

    Open study
    Educational use only. This profile is not medical advice. Consult a qualified healthcare professional before starting any supplement, especially if you take prescription medication or have a chronic condition.