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St. John's Wort (Hypericum perforatum)

Herboral · inferred

Standardized herbal extract (typically 0.3% hypericin or 3% hyperforin). Potent CYP3A4 and P-glycoprotein inducer causing numerous drug interactions. Acts as a weak non-selective monoamine reuptake inhibitor with established modest efficacy in mild-to-moderate depression. One of the most clinically important herb-drug interaction profiles in all of phytomedicine.

Projected serum levels — 900 mg, once daily

St. John's Wort (Hypericum perforatum)
St. John's Wort (Hypericum perforatum) modeled serum levels, 900 mg once daily over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 6.3 12.5 18.8 25 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1

Maintenance schedule: 900 mg once daily (oral).

Modeled steady state after ~1 days: peak ≈ 24.2 mg, trough ≈ 0.000 mg body load. Population-based estimate over 15 days for a 900 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Herb
Route modeled
Oral
Model confidence
inferred
Half-life
26 min
Common dose
900 mg
Suggested maximum
1.8k mg/day
Reference dose range
450–1.8k mg (single dose)
Suggested cadence
once daily

Documented interactions

  • contraindicated
    Efavirenz (Sustiva) + St. John's Wort (Hypericum perforatum) CYP induction

    Efavirenz (Sustiva) inducer of CYP3A4 predicted to change St. John's Wort (Hypericum perforatum) AUC by ~0.16x

  • contraindicated
    Rifampin + St. John's Wort (Hypericum perforatum) CYP induction

    Rifampin inducer of CYP3A4 predicted to change St. John's Wort (Hypericum perforatum) AUC by ~0.16x

  • danger
    1P-LSD (1-Propionyl-LSD) + St. John's Wort (Hypericum perforatum) Serotonin risk

    1P-LSD (1-Propionyl-LSD) and St. John's Wort (Hypericum perforatum) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability, altered mental status).

  • danger
    25I-NBOMe + St. John's Wort (Hypericum perforatum) Serotonin risk

    25I-NBOMe and St. John's Wort (Hypericum perforatum) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability, altered mental status).

  • danger
    2C-I (2,5-Dimethoxy-4-iodophenethylamine) + St. John's Wort (Hypericum perforatum) Serotonin risk

    2C-I (2,5-Dimethoxy-4-iodophenethylamine) and St. John's Wort (Hypericum perforatum) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability,…

  • danger
    2C-B (4-Bromo-2,5-dimethoxyphenethylamine) + St. John's Wort (Hypericum perforatum) Serotonin risk

    2C-B (4-Bromo-2,5-dimethoxyphenethylamine) and St. John's Wort (Hypericum perforatum) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability,…

Serum checks 665 modeled interaction pairings for st. john's wort (hypericum perforatum) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor Watkins RE et al. · Proceedings of the National Academy of Sciences, 2001 DOI

    Landmark study demonstrating PXR activation mechanism.

  2. Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures Budzinski JW et al. · Drug Metabolism and Disposition, 2000 DOI

    Hyperforin-mediated CYP3A4 induction.

  3. Clinical relevance of St. John's wort drug interactions revisited Nicolussi A et al. · British Journal of Pharmacology, 2020 DOI

    Comprehensive clinical drug interaction review.

3 published studies referenced in the app, each with a plain-language summary.