[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Herbal products and dietary supplements](https://durgical.com/en/pharmacology/classes/herbal-products-and-dietary-supplements/) › St John's wort

# St John's wort

## Herbal products and dietary supplements?

Herbal products and dietary supplements

## Pregnancy: 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.

Updated Nov 1, 2026

Also called: Hypericum perforatum, Hyperici herba, Hypericum

## Quick facts

**Group**
[Herbal products and dietary supplements](https://durgical.com/en/pharmacology/classes/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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

◎**Pregnane X receptor (PXR), which switches on CYP3A4 and P-glycoprotein; also monoamine reuptake**St John's wort

ⓘ The figure shows hyperforin, the constituent that causes the interactions, bound to the ligand-binding domain of human PXR.

**Target in 3D:** Pregnane X receptor (PXR), which switches on CYP3A4 and P-glycoprotein; also monoamine reuptake. PDB structure 1M13 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/1M13) · Drag to rotate · pinch to zoom

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 →](https://durgical.com/en/conditions/major-depressive-disorder/)

## Adverse effects

### Common

- Photosensitive skin reactions
- Diarrhoea and stomach upset
- Dizziness
- Insomnia and restlessness

### Serious (rare, important)

- Treatment failure of critical medicines (transplant rejection, unintended pregnancy, HIV resistance, thrombosis)
- Serotonin syndrome with SSRIs, triptans and other serotonergic drugs

## 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

## Memory aid

St John's wort «washes out» drugs: PXR → CYP3A4 + P-gp up → the Pill, ciclosporin, digoxin, warfarin, HIV drugs go down.

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/st-john-s-wort/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**Pregnancy: avoid**
Avoid in pregnancy. It may be unsafe in pregnancy; breastfed infants of mothers who take it may have colic, drowsiness and lethargy.

## Connections

## Related drugs 4

- [Ciclosporin](https://durgical.com/en/pharmacology/ciclosporin/)
- [Warfarin](https://durgical.com/en/pharmacology/warfarin/)
- [Digoxin](https://durgical.com/en/pharmacology/digoxin/)
- [Sertraline](https://durgical.com/en/pharmacology/sertraline/)

## Related conditions 1

- [Major depressive disorder](https://durgical.com/en/conditions/major-depressive-disorder/)

[← Back to the class: Herbal products and dietary supplements](https://durgical.com/en/pharmacology/classes/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](https://www.nccih.nih.gov/health/st-johns-wort) (National Center for Complementary and Integrative Health (NCCIH), 2025); [Guía para el Manejo de Emergencias Toxicológicas](https://minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/DE/GT/guias-manejo-emergencias-toxicologicas-outpout.pdf) (Ministerio de Salud y Protección Social; Organización Panamericana de la Salud, 2017).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/st-john-s-wort/