St John's wort — interactions

The canonical INDUCER, and the reason "natural" says nothing about safety. It activates the pregnane X receptor, raising CYP3A4 and P-glycoprotein together — so the drug is destroyed faster AND absorbed less. It has also caused documented transplant rejection and HIV treatment failure. Separately, it is serotonergic.

Also known as: Hypericum perforatum, hypericum, SJW. Category: supplement.

What it does, mechanism by mechanism

CYP3A4 induction — induces, strong

Increases CYP3A4 expression, usually via the pregnane X receptor. The mirror hazard: the drug is destroyed faster and silently stops working. Transplant rejection, HIV breakthrough, contraceptive failure.

Moore et al. identified PXR activation as the mechanism. Ruschitzka et al. reported acute heart transplant rejection from ciclosporin level collapse; Piscitelli et al. measured a 57% median fall in indinavir AUC in healthy volunteers.

Sources: Moore LB 2000, Ruschitzka F 2000, Piscitelli SC 2000, Henderson L 2002 · more on CYP3A4 induction

P-glycoprotein induction — induces, strong

Increases the efflux pump, lowering absorption. St John's wort does this and CYP3A4 induction at the same time — two mechanisms pointing the same way.

Johne et al. measured reduced digoxin exposure with hypericum extract.

Sources: Johne A 1999 · more on P-glycoprotein induction

Serotonin reuptake inhibition — inhibits, moderate

Blocks the serotonin transporter (SERT), raising synaptic serotonin. Additive with anything else that raises serotonin; combined with MAO inhibition it is the classic lethal pairing.

Serotonin syndrome has been reported with SJW plus SSRIs.

Sources: Henderson L 2002, Boyer EW 2005 · more on Serotonin reuptake inhibition

What it reaches in this dataset

Via CYP3A4 induction

Via P-glycoprotein induction

This list is what is IN the table. It is not the set of substances this interacts with — that set is larger and partly unknown, and the mechanism is the thing to carry to a substance we have not listed.

Specific combinations

What a clean result means here

A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.

In this dataset

  • Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
  • Serotonergic drugs and the serotonin-toxicity mechanism
  • Dietary tyramine and L-dopa loads
  • The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
  • P-glycoprotein inhibition and induction
  • 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
  • QT prolongation as an additive pharmacodynamic axis
  • Culinary seasonings and common foods with documented pharmacological activity
  • A selected set of narrow-therapeutic-index drugs where those shifts matter most

Not in this dataset

  • Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
  • Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
  • Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
  • Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
  • Renal and hepatic impairment, age, pregnancy, and body composition.
  • Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
  • Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
  • Allergy, intolerance, and contamination or adulteration of unregulated products.
  • Anything published after the last-reviewed date below.

72 substances, 20 mechanisms, 64 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.

References

  1. Moore LB, Goodwin B, Jones SA, et al. (2000). St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. PNAS. doi:10.1073/pnas.130155097
  2. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G (2000). Acute heart transplant rejection due to Saint John's wort. The Lancet. doi:10.1016/S0140-6736(99)05467-7
  3. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J (2000). Indinavir concentrations and St John's wort. The Lancet. doi:10.1016/S0140-6736(99)05712-8
  4. Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P (2002). St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. British Journal of Clinical Pharmacology. doi:10.1046/j.1365-2125.2002.01683.x
  5. Johne A, Brockmöller J, Bauer S, Maurer A, Langheinrich M, Roots I (1999). Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clinical Pharmacology & Therapeutics. doi:10.1053/cp.1999.v66.a101944
  6. Boyer EW, Shannon M (2005). The Serotonin Syndrome. New England Journal of Medicine. doi:10.1056/NEJMra041867

Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.

Last reviewed . All interaction pages.