Clinical relevance of St. John's wort drug interactions revisited.
Can you check every one of my prescriptions against St. John's wort — including anything I take for transplant, HIV, blood thinning, heart rhythm, or seizures — before I start or stop it?
Weak or heavily disputed. Treat as a question, not an answer. how we score evidence
Caveat on this rating: Three of the four authors are employees of Max Zeller Söhne AG, a manufacturer of a St. John's wort herbal medicinal product, and this is a narrative review rather than a systematic one — so it sits at the bottom of the evidence rubric and its framing should be read with the authors' commercial interest in mind. Note the direction of that interest: authors paid by an SJW manufacturer nonetheless document the interactions, which makes the interaction findings harder, not softer.
In the United States St. John's wort is sold as a dietary supplement under DSHEA, which means it reaches the shelf without FDA review of efficacy, safety, or potency and the FDA can act only after a problem emerges. It has never been FDA-approved to treat depression or anything else. The FDA issued a Public Health Advisory on 10 February 2000 warning that St. John's wort substantially lowered blood levels of the HIV drug indinavir through CYP3A4 induction and that the same mechanism would affect many other medicines. In Germany and several other European countries, by contrast, standardised hypericum extracts are licensed medicines that doctors prescribe for depression, which is why most of the trial evidence comes from German-speaking countries. Because US products are supplements rather than drugs, hypericin and hyperforin content varies widely between brands and batches — and hyperforin content is what drives the drug interactions, so two bottles labelled identically can behave very differently.
Twenty years after St. John's wort caused acute graft rejection in two heart transplant patients on cyclosporine, this review confirms the mechanism: St. John's wort activates the pregnane-X receptor, inducing CYP3A4 and P-glycoprotein, and so lowers blood levels of cyclosporine, tacrolimus, digoxin, indinavir, warfarin, alprazolam, simvastatin, and oral contraceptives. The degree of CYP3A4 induction correlates significantly with how much hyperforin the particular preparation contains, which is why interaction risk differs between products bearing the same name.
Worth asking
Can you check every one of my prescriptions against St. John's wort — including anything I take for transplant, HIV, blood thinning, heart rhythm, or seizures — before I start or stop it?
What to watch for
Evidence quality tells you whether to trust the finding — not whether the treatment is safe. These are the risks this research reports.
- Serotonin syndrome
- Psychosis & mania
- Interactions with other medicines
- Fertility & pregnancy risk
- Unverified product content
- Acne & skin effects
Source
Clinical relevance of St. John's wort drug interactions revisited. — Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. (2020)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1111/bph.14936
DOI: 10.1111/bph.14936
How this was scored
- Study design
- Narrative review
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- not recorded
- Preregistered
- No
- Conflicts disclosed
- Yes
- Independent of proponent
- No
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026. Last verified September 10, 2026.
Where we put this study in context
Questions
How strong is the evidence behind this?
veisund rates this source "contested". Weak or heavily disputed. Treat as a question, not an answer. It scores 32 out of 100 on our published rubric. One caveat travels with that badge: Three of the four authors are employees of Max Zeller Söhne AG, a manufacturer of a St. John's wort herbal medicinal product, and this is a narrative review rather than a systematic one — so it sits at the bottom of the evidence rubric and its framing should be read with the authors' commercial interest in mind. Note the direction of that interest: authors paid by an SJW manufacturer nonetheless document the interactions, which makes the interaction findings harder, not softer. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Clinical relevance of St. John's wort drug interactions revisited. — Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. (2020). Published in: Reputable peer-reviewed journal. DOI: 10.1111/bph.14936. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Narrative review. Funding: Funding not disclosed. The researchers were not independent of whoever benefits from the result. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is st-johns-wort, hypericum perforatum, sjw, hypericum, klamath weed, tipton's weed, li 160, ws 5570, stw3-vi, ze 117 FDA approved for this use?
No. Its current status is: Not FDA-evaluated for this use. In the United States St. John's wort is sold as a dietary supplement under DSHEA, which means it reaches the shelf without FDA review of efficacy, safety, or potency and the FDA can act only after a problem emerges. It has never been FDA-approved to treat depression or anything else. The FDA issued a Public Health Advisory on 10 February 2000 warning that St. John's wort substantially lowered blood levels of the HIV drug indinavir through CYP3A4 induction and that the same mechanism would affect many other medicines. In Germany and several other European countries, by contrast, standardised hypericum extracts are licensed medicines that doctors prescribe for depression, which is why most of the trial evidence comes from German-speaking countries. Because US products are supplements rather than drugs, hypericin and hyperforin content varies widely between brands and batches — and hyperforin content is what drives the drug interactions, so two bottles labelled identically can behave very differently.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.