St John's wort
Herbal products and dietary supplements
Herbal products and dietary supplementsPregnancy: avoid
Avoid in pregnancy. It may be unsafe in pregnancy; breastfed infants of mothers who take it may have colic, drowsiness and lethargy.
A plant extract (Hypericum perforatum) that may help mild to moderate depression but induces CYP3A4 and P-glycoprotein, causing dangerous interactions.
Also called: Hypericum perforatum, Hyperici herba, Hypericum
Quick facts
- Group
- Herbal products and dietary supplements
- Target
- Pregnane X receptor (PXR), which switches on CYP3A4 and P-glycoprotein; also monoamine reuptake
- Used for
- Mild to moderate depression
- Key effects
- Photosensitive skin reactions · Dizziness
- Monitor
- Drug levels or effect
- ATC
- N06AX25
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows hyperforin, the constituent that causes the interactions, bound to the ligand-binding domain of human PXR.
Its antidepressant effect is attributed mainly to hyperforin (with other constituents), which inhibits the reuptake of serotonin, noradrenaline and dopamine. Hyperforin also activates the nuclear pregnane X receptor (PXR) in the liver and gut, which switches on the genes for CYP3A4, P-glycoprotein and other drug-handling enzymes. Many medicines are then metabolised or pumped out faster and lose effect. Hypericin, another constituent, makes the skin sensitive to light.
- Hyperforin inhibits serotonin, noradrenaline and dopamine reuptake
- Hyperforin also activates PXR in liver and gut
- More CYP3A4 and P-glycoprotein are made
- Other drugs fall to subtherapeutic levels
Indications
- Mild to moderate depression: better than placebo and about as effective as standard antidepressants in trials; uncertain for severe depression or long-term use Major depressive disorder →
Adverse effects
Common
- Photosensitive skin reactions
- Diarrhoea and stomach upset
- Dizziness
- Insomnia and restlessness
Contraindications
- Use with medicines whose levels must stay stable: ciclosporin and tacrolimus, HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, warfarin, digoxin, irinotecan and other anticancer drugs
- Use with SSRIs or MAOIs
Key interactions
- Oral contraceptives
- Lower hormone levels: breakthrough bleeding and unintended pregnancy
- Ciclosporin, tacrolimus
- Lower levels and risk of transplant rejection
- Warfarin, digoxin, simvastatin, ivabradine
- Reduced effect
- HIV drugs (for example indinavir, nevirapine) and anticancer drugs (irinotecan, imatinib, docetaxel)
- Subtherapeutic levels and treatment failure
- SSRIs, triptans and other serotonergic drugs
- Serotonin syndrome
What is monitored
- Drug levels or effect of interacting medicines (ciclosporin, tacrolimus, INR, digoxin, HIV viral load)
- Mood and suicide risk in depression
- Skin reactions after sun exposure
Pregnancy and breastfeeding
Avoid in pregnancy. It may be unsafe in pregnancy; breastfed infants of mothers who take it may have colic, drowsiness and lethargy.
Nursing care
- Ask every patient about herbal products and supplements and record them with the medicine list
- Flag transplant, HIV, anticoagulant and contraceptive users: they are the highest-risk groups
- Advise sun protection while it is used
- Remember that stopping the herb can make levels of other drugs rise again
- Teach that «natural» does not mean safe and that supplements are not approved as medicines before sale
Pharmacokinetics
- Absorption
- Taken by mouth as extracts; products differ in their hyperforin and hypericin content
- Metabolism
- Its constituents induce intestinal and hepatic CYP3A4 and P-glycoprotein
Test yourself
Think of the answer, then tap the question to see it.
Which constituent of St John's wort causes its drug interactions, and how?
Hyperforin activates PXR, which induces CYP3A4 and P-glycoprotein, so many drugs are cleared faster.
What can happen to a transplant patient on ciclosporin who starts St John's wort?
Ciclosporin levels fall and the graft can be rejected.
For which kind of depression is the evidence for St John's wort best?
Mild to moderate depression; it is uncertain in severe depression.
Why is St John's wort dangerous with an SSRI?
It adds serotonergic activity and can cause serotonin syndrome.
Connections
← Back to the class: Herbal products and dietary supplements
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: St. John's Wort: Usefulness and Safety (National Center for Complementary and Integrative Health (NCCIH), 2025); Guía para el Manejo de Emergencias Toxicológicas (Ministerio de Salud y Protección Social; Organización Panamericana de la Salud, 2017).
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Representative model, for educational purposes only.