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HomeIngredientsSt. John's Wort
Reviewed by the Scan Dose Research Team and Clinical Advisory Board

St. John's Wort

STRONG EVIDENCESupplementLast updated April 2026

SCAN DOSE SUMMARY

St. John's Wort is one of the most evidence-backed herbal antidepressants — comparable to SSRIs for mild-to-moderate depression in multiple meta-analyses. Our research also identifies it as the MOST DANGEROUS supplement for drug interactions in our entire database. It's a potent CYP3A4 inducer that reduces the effectiveness of birth control, HIV medications, organ transplant drugs, and dozens of other medications. It should never be combined with prescription antidepressants.

EVIDENCE GRADES

Mild-to-moderate depressionStrong — Cochrane review of 29 RCTs (PMID: 18843608)
A
Severe depressionNegative — not effective for severe MDD
C-
AnxietyLimited direct evidence; secondary to depression improvement
C+
Menopausal symptomsSmall positive trials
C
ADHDVery preliminary
C

OPTIMAL DOSAGE

  • Depression: 300mg 3x/day standardized to 0.3% hypericin (or 3-5% hyperforin)
  • WS 5570 / WS 5572 (branded): Most studied extracts
  • LI 160: 300mg 3x/day
  • Duration: 4-6 weeks minimum for antidepressant effect
  • Standardization: Hypericin was originally thought to be the active compound; hyperforin is now considered more important for antidepressant action
Scan a supplement containing St. John's Wort

DRUG INTERACTIONS

SSRIs / SNRIs (all)Severe

Serotonin syndrome risk + CYP-mediated interaction

Oral contraceptivesSevere

CYP3A4 induction REDUCES hormone levels → breakthrough bleeding → PREGNANCY

Cyclosporine / tacrolimusSevere

CYP3A4 induction → organ transplant REJECTION (documented cases)

HIV protease inhibitors (indinavir)Severe

Reduces drug levels by 50-80% → treatment failure

WarfarinSevere

CYP induction reduces warfarin levels → clotting risk

DigoxinSevere

P-gp induction reduces digoxin levels

Statins (simvastatin, atorvastatin)Moderate

CYP3A4 induction reduces statin levels

Benzodiazepines (alprazolam, midazolam)Moderate

CYP3A4 induction reduces levels

Chemotherapy drugsSevere

Reduces drug levels — treatment failure risk

MethadoneSevere

Reduced levels → withdrawal symptoms

Triptans (sumatriptan)Severe

Serotonin syndrome risk

TheophyllineModerate

Reduced levels

Omeprazole (PPI)Moderate

CYP2C19 induction reduces levels

Irinotecan (chemo)Severe

Reduces SN-38 levels by 42%

SAFETY PROFILE

⚠️ MOST DRUG INTERACTIONS OF ANY SUPPLEMENT

St. John's Wort is a POTENT inducer of CYP3A4, CYP2C9, CYP2C19, CYP1A2, and P-glycoprotein. This means it DECREASES blood levels of dozens of medications. This is not theoretical — these interactions have caused treatment failures, organ transplant rejections, and unintended pregnancies.

Drug Interactions

Side Effects

  • Photosensitivity (fair-skinned individuals — wear sunscreen)
  • GI upset, dizziness, confusion
  • Vivid dreams, restlessness
  • Dry mouth

Pregnancy & Lactation

  • AVOID — CYP induction affects many medications; limited direct pregnancy safety data; may reduce effectiveness of any co-administered drugs

WADA Status

Not Prohibited

HOW SCAN DOSE SCORES THIS

THE HIGHEST INTERACTION RISK SUPPLEMENT IN OUR DATABASE
If ANY prescription medication is in the user's profile, St. John's Wort must trigger a comprehensive drug interaction review
Birth control users: automatic SEVERE warning (documented pregnancy risk)
SSRI/SNRI users: automatic CONTRAINDICATED alert
Transplant patients: absolute contraindication
Products should carry prominent drug interaction warnings — score penalty for products that don't
For users on NO medications with mild-to-moderate depression: legitimate option with strong evidence

CLINICAL REFERENCES

1.

Linde K et al. St John's wort for major depression. *Cochrane Database Syst Rev.* 2008.

(2008). PMID: 18843608

2.

Markowitz JS et al. Effect of St John's wort on drug metabolism by induction of CYP3A4.

PMID: 10789117

3.

Ruschitzka F et al. Acute heart transplant rejection due to Saint John's wort. *Lancet.* 2000.

(2000). PMID: 10861149

4.

Piscitelli SC et al. Indinavir concentrations and St John's wort. *Lancet.* 2000.

(2000). PMID: 12622848

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Scan Your St. John's Wort SupplementBrowse all ingredients

Reviewed by the Scan Dose Research Team and Clinical Advisory Board | Last updated: April 2026

Not medical advice. Based on published clinical research and systematic reviews.

Safety

St. John's Wort: Drug Interactions

The most interaction-prone supplement in common use. St. John's Wort induces multiple drug-metabolism enzymes and can cause treatment failure across many drug classes.

Mechanism: St. John's Wort is a potent inducer of CYP3A4, CYP2C9, CYP1A2, and P-glycoprotein. It reduces the blood levels of almost every drug metabolized by these enzymes.

Do not combine

Dangerous interactions. Talk to your prescriber before using this supplement if you take any of these.

  • SSRIs (Prozac, Zoloft, Lexapro)

    Additive serotonergic effect.

    RiskSerotonin syndrome, potentially fatal.
    ActionNever combine.

    Source: PMID: 27444983

  • SNRIs (Effexor, Cymbalta)

    Additive serotonergic effect.

    RiskSerotonin syndrome.
    ActionNever combine.

    Source: FDA warning

  • Oral contraceptives

    Induces CYP3A4, accelerating estrogen metabolism.

    RiskUnplanned pregnancy from contraceptive failure.
    ActionNever combine. Use backup contraception.

    Source: PMID: 19719333

  • Cyclosporine

    Induces CYP3A4, dramatically reducing cyclosporine levels.

    RiskOrgan rejection in transplant patients.
    ActionAbsolutely never combine.

    Source: FDA black box warning

  • HIV protease inhibitors (ritonavir, indinavir)

    Induces CYP3A4, reducing drug levels.

    RiskTreatment failure and viral rebound.
    ActionNever combine.

    Source: FDA warning

  • Warfarin

    Induces CYP enzymes, reducing warfarin levels.

    RiskBlood clots from subtherapeutic INR.
    ActionNever combine.

    Source: PMID: 19719333

  • Digoxin

    Induces P-glycoprotein, reducing digoxin levels.

    RiskHeart failure from subtherapeutic levels.
    ActionNever combine.

    Source: Clinical pharmacology

  • Chemotherapy agents

    Induces CYP3A4, reducing drug levels.

    RiskTreatment failure.
    ActionNever combine.

    Source: FDA warning

  • Theophylline

    Induces CYP1A2, reducing levels.

    RiskLoss of asthma or COPD control.
    ActionAvoid.

    Source: Clinical pharmacology

  • Triptans (sumatriptan)

    Additive serotonergic effect.

    RiskSerotonin syndrome risk.
    ActionAvoid.

    Source: FDA warning

Stop 2 weeks before surgery

Anesthesia interactions from CYP enzyme induction.

Educational information only. This is not medical advice. These statements have not been evaluated by the FDA. Talk to your prescriber before starting, stopping, or combining any supplement with prescription medication.

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