St. John's Wort

St. John's Wort (SJW) (Hypericum perforatum) is a plant used as a herbal medicine for many centuries in the treatment of mood disorders. The active ingredient is thought to be from hypericin/hyperforin and other flavonoids.

Pharmacokinetics of St. John's Wort

St. John's Wort: Cytochrome P450 Metabolism

Substrate of (Metabolized by)
Induces 3A4 (potent!)[1]
  • St. John's wort's is thought to have a direct effect on serotonin receptors, monoamine oxidase inhibition, and neuroendocrine and ion channel modulation.

Dosing for St. John's Wort

Starting 300 mg TID (or 450 mg BID)
Titration Plasma levels gradually rise over several weeks
Maximum 1800 mg
  • The typical treatment duration in major depressive disorder is between 4 to 12 weeks.[3][4]
  • St. John's Wort comes in oral tablets typically.
  • One of the main concerns with the use of St. John's wort is it is an inducer of cytochrome (CYP) P450 3A4 activity (a substantial number of medications are metabolized via this pathway).
  • High potency extracts can interfere with the metabolism of various medications.
  • St. John's wort is typically better tolerated than many first-line antidepressants.
  • Side effects include headaches, gastrointestinal upset, skin irritation, photosensitivity, and dry mouth.
  • Transient photosensitivity is the most common side effect and occurs more commonly at higher dosages