{
  "slug": "st-johns-wort",
  "name": "St. John's Wort (Hypericum perforatum)",
  "alternate_names": [
    "Hypericum perforatum",
    "St John's Wort",
    "Hypericin",
    "Hyperforin",
    "WS 5570",
    "LI 160",
    "STW 3-VI",
    "Ze 117"
  ],
  "mechanism": [
    "Triple monoamine reuptake inhibition (5-HT / NE / DA) by hyperforin (proposed antidepressant mechanism in research models)",
    "PXR (pregnane X receptor) activation driving CYP3A4 / CYP1A2 / CYP2C9 and P-glycoprotein induction (well-documented pharmacokinetic-interaction mechanism)",
    "NF-kB pathway suppression (anti-inflammatory, preclinical)",
    "Modulation of GABA and glutamate receptor signaling (preclinical)"
  ],
  "target": [
    "5-HT transporter (SERT)",
    "Norepinephrine transporter (NET)",
    "Dopamine transporter (DAT)",
    "Pregnane X receptor (PXR) / CYP3A4",
    "P-glycoprotein (MDR1)"
  ],
  "use_case": [
    "mild-to-moderate depression symptom rating scales (research-context)",
    "menopausal / perimenopausal hot-flash frequency and severity (research-context)",
    "perimenopausal mood and quality-of-life markers (research-context)",
    "drug-metabolism / pharmacokinetic-interaction studies (research-context, safety axis)"
  ],
  "body_system": [
    "MOOD",
    "NEURO",
    "ENDO"
  ],
  "evidence_tier": "B",
  "evidence_anchor_pmid_count": 39,
  "evidence_breakdown": {
    "meta_sr": 4,
    "human_rct": 0,
    "total_indexed": 39
  },
  "dosage_range": "600-900 mg/day standardized extract (typically standardized to ~0.3% hypericin and/or 1-6% hyperforin), most commonly 300 mg x 3/day for 6-12 weeks in depression-rating RCTs; ~900 mg/day for 8-16 weeks in menopause/hot-flash trials. The most-studied standardized extracts are WS 5570, LI 160, STW 3-VI and Ze 117. Educational reference, not a dosing recommendation.",
  "safety_notes": "Generally well tolerated in clinical trials at 600-900 mg/day standardized extract, with adverse-event rates typically lower than SSRIs (mild GI upset, headache, dry mouth; dose-dependent photosensitivity at high doses). CRITICAL DRUG-INTERACTION SIGNAL: St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein via PXR activation, which can substantially LOWER blood levels and effectiveness of many prescription medicines — including oral contraceptives, warfarin, ciclosporin, HIV protease inhibitors, digoxin and certain statins. Combining it with SSRIs/SNRIs/triptans carries a serotonin-syndrome risk. Anyone taking prescription medication should consult a doctor before use. Pregnancy/lactation safety is not established; caution in bipolar disorder (possible mania induction). Not a substitute for prescribed antidepressant therapy.",
  "regulatory": {
    "fda": "Legal dietary-supplement ingredient under DSHEA (structure/function claims only); FDA expects labeling to disclose the drug-interaction risk; no FDA-authorized disease/health claim.",
    "efsa": "No authorized Reg 1924/2006 health claim; an EMA/HMPC traditional-use herbal monograph exists for mild depressive symptoms, and several EU member states license standardized extracts as herbal medicinal products (e.g. Germany's Jarsin/Laif, Commission E approved). Marketable via traditional-herbal-medicine frameworks rather than as an EFSA-claim supplement.",
    "anvisa": "Listed as a traditional herbal medicine (fitoterapico tradicional) by ANVISA; permitted with drug-interaction labeling; no Anexo functional health claim authorized."
  },
  "regulatory_markets": [
    {
      "market": "US",
      "status": "DSHEA supplement",
      "tier": "permitted"
    },
    {
      "market": "EU",
      "status": "Authorized claim",
      "tier": "authorized"
    },
    {
      "market": "CN",
      "status": "Supplement (CBEC)",
      "tier": "permitted"
    },
    {
      "market": "BR",
      "status": "ANVISA supplement",
      "tier": "permitted"
    }
  ],
  "ingredient_hub_url": "https://asxan.ai/ingredients/st-johns-wort/",
  "related_goal_slugs": [],
  "related_lifestyle_slugs": [],
  "last_evidence_review": "2026-06-27",
  "schema_version": "nc-public-v0.2",
  "api_version": "nc-public-v0.3",
  "_meta": {
    "last_evidence_review": "2026-06-27",
    "ip_axes_disclosed": {
      "public_axes": [
        "mechanism",
        "target",
        "use_case",
        "body_system",
        "evidence_tier",
        "dosage_range",
        "safety_notes",
        "regulatory",
        "authorized_claims"
      ],
      "ip_axes_not_exposed": [
        "proprietary_formula_ratios",
        "clinical_protocol_internals",
        "proprietary_research_compounds",
        "supplier_specific_grade_specifications",
        "unpublished_endpoint_data"
      ],
      "rationale": "asxan.ai surfaces the educational, evidence-tier-disclosed slice. Formula composition and clinical-protocol internals are intentionally outside this public surface."
    }
  }
}