St John's Wort and medications.
St John's Wort is not in the Distil recommendation database. We surface it here deliberately, because why a compound is left out is as useful as what we recommend.
St John's Wort is one of the most interaction-heavy supplements in clinical pharmacology, and that is why it sits outside the Distil database. It is a strong inducer of the CYP3A4 enzyme and the P-glycoprotein transporter, so it lowers the blood levels of a long list of prescription medicines. Warfarin, ciclosporin and tacrolimus, the combined oral contraceptive pill, and several antidepressants are all on that list. A dropped contraceptive level can mean an unplanned pregnancy. A dropped immunosuppressant level can mean transplant rejection.
It is also serotonergic, so taken alongside an SSRI or SNRI it adds to the risk of serotonin syndrome. The interaction surface is wide enough, and the consequences serious enough, that we will not place it in a personalised stack. The documented pairs below are real. If you already take St John's Wort, the priority is checking it against your prescriptions, not swapping it out.
What to consider instead. Every option below is in the Distil database, so you can check each against your own medications:
- Saffron Extract: has antidepressant trial evidence and does not induce drug-metabolising enzymes
- Omega-3 EPA: EPA-dominant omega-3 has the better mood evidence of the two fatty acids
- Vitamin D3: worth checking and correcting a low level before anything else
We still hold the documented interactions for St John's Wort, which is why it stays in the interactions checker even though we do not recommend it. Below are the 56 documented pairs we have explicitly assessed: 32 red, 22 amber, and 2 green. Every call is cited to a clinical reference (PMID) or the British National Formulary.
Documented interactions
CYP induction
St John's Wort speeds up how the body clears acenocoumarol, which can make the blood thinner much less effective and dangerously raise the risk of a clot. This is a serious interaction. Do not take St John's Wort with acenocoumarol, and if you already take both, tell your anticoagulant clinic before stopping either.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort can cause your body to clear ciclosporin too quickly, dropping its level below the protective range and raising rejection risk. Do not combine.
St John's Wort speeds up how the body clears the HIV medicine efavirenz, which can drop the drug level too low to control the virus and let HIV become resistant. This is a serious interaction and the two should not be combined. If you take efavirenz, do not start St John's Wort, and if you already take both, tell your HIV team before changing anything.
St John's Wort can cause your body to clear tacrolimus too quickly, dropping its level below the protective range and raising rejection risk. Do not combine.
St John's Wort can cause your body to clear warfarin too quickly, dropping your INR and raising clot risk. Do not combine.
St John's Wort can speed up how the body clears amitriptyline, lowering the drug level in your blood and making it work less well for low mood or pain. In a study, it cut amitriptyline levels by about a fifth. If you take amitriptyline, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Carbamazepine is a strong enzyme-inducer that already speeds up its own breakdown, and St John's Wort works the same way. In the one controlled study, adding St John's Wort did not lower carbamazepine levels further, but combining two enzyme-inducers is still best avoided without specialist input, especially when carbamazepine is being started or its dose changed. Do not start or stop St John's Wort while taking carbamazepine without telling whoever prescribes it.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Clomipramine is a tricyclic antidepressant broken down by the same liver enzymes that St John's Wort speeds up, so St John's Wort may lower its level and make it work less well. If you take clomipramine, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Dosulepin is a tricyclic antidepressant broken down by the same liver enzymes that St John's Wort speeds up, so St John's Wort may lower its level and make it work less well. If you take dosulepin, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Doxepin is a tricyclic antidepressant broken down by the same liver enzymes that St John's Wort speeds up, so St John's Wort may lower its level and make it work less well. If you take doxepin, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Imipramine is a tricyclic antidepressant broken down by the same liver enzymes that St John's Wort speeds up, so St John's Wort may lower its level and make it work less well. If you take imipramine, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Lofepramine is a tricyclic antidepressant broken down by the same liver enzymes that St John's Wort speeds up, so St John's Wort may lower its level and make it work less well. If you take lofepramine, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort can speed up how the body clears nortriptyline, lowering its level in your blood so it works less well for low mood or pain. In a study, blood levels of nortriptyline dropped by about 40 percent. If you take nortriptyline, mention St John's Wort to your GP or pharmacist rather than starting it on your own, and watch for symptoms returning.
St John's Wort speeds up several of the liver enzymes that clear phenytoin, so it could lower your phenytoin level and let seizures break through. Phenytoin has a narrow safe range and small changes matter. Do not start or stop St John's Wort while taking phenytoin without telling whoever prescribes it, so your level and dose can be checked.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort can speed up how the body clears theophylline, which may lower the level in your blood and make it less effective at keeping your airways open. Theophylline has a narrow safe range, so do not start or stop St John's Wort while taking it without telling whoever prescribes it, as your dose and blood levels may need checking.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
CYP3A4 induction
St John's Wort speeds up how the body clears HIV protease inhibitors like atazanavir, which can drop the drug level too low to control the virus and let HIV become resistant. This is a serious interaction and these medicines should not be combined. If you take atazanavir, do not start St John's Wort, and if you already take both, tell your HIV team before changing anything.
St John's Wort can reduce circulating oestrogen levels by speeding up its breakdown. For people taking HRT with conjugated oestrogens (Premarin, Prempak-C), this can mean returning menopausal symptoms (hot flushes, sleep disruption) despite a dose that was previously working, and breakthrough bleeding is a warning sign. We treat this as a do-not-combine pair without specialist sign-off.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort speeds up how the body clears HIV protease inhibitors like darunavir, which can drop the drug level too low to control the virus and let HIV become resistant. This is a serious interaction and these medicines should not be combined. If you take darunavir, do not start St John's Wort, and if you already take both, tell your HIV team before changing anything.
St John's Wort can reduce the contraceptive reliability of the progestogen-only pill. Because there is no oestrogen backup in the progestogen-only pill, the consequence of reduced hormone levels is more direct. We treat this as a do-not-combine pair.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort can reduce circulating oestradiol levels by speeding up its breakdown. For people taking HRT, this can mean returning menopausal symptoms (hot flushes, sleep disruption) despite a prescribed dose that was previously working. We treat this as a do-not-combine pair without specialist sign-off.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort can reduce the contraceptive reliability of the combined pill. Breakthrough bleeding is the warning sign, and unintended pregnancies have been reported on this combination. We treat this as a do-not-combine pair.
St John's Wort can reduce the contraceptive reliability of the combined pill. Breakthrough bleeding is the warning sign, and unintended pregnancies have been reported on this combination. We treat this as a do-not-combine pair.
St John's Wort speeds up how the body clears HIV protease inhibitors like lopinavir (Kaletra), which can drop the drug level too low to control the virus and let HIV become resistant. This is a serious interaction and these medicines should not be combined. If you take lopinavir, do not start St John's Wort, and if you already take both, tell your HIV team before changing anything.
St John's Wort can speed up the breakdown of norethisterone, lowering its level in your blood. In an HRT or period-control setting this can mean breakthrough bleeding and reduced effect, and where norethisterone is providing contraceptive cover that cover can become unreliable. We treat this as a do-not-combine pair without specialist sign-off.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort speeds up how the body clears HIV protease inhibitors like ritonavir, which can drop the drug level too low to control the virus and let HIV become resistant. This is a serious interaction and these medicines should not be combined. If you take ritonavir, do not start St John's Wort, and if you already take both, tell your HIV team before changing anything.
St John's Wort speeds up how the body clears HIV protease inhibitors like saquinavir, which can drop the drug level too low to control the virus and let HIV become resistant. This is a serious interaction and these medicines should not be combined. If you take saquinavir, do not start St John's Wort, and if you already take both, tell your HIV team before changing anything.
St John's Wort can reduce circulating tibolone metabolite levels by speeding up its breakdown. For HRT users this means menopausal symptom control may slip. We treat this as a do-not-combine pair without specialist sign-off.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort speeds up the breakdown of alprazolam, which can leave it less effective than expected at the prescribed dose and may mean anxiety symptoms return. Talk to whoever prescribed it before combining.
St John's Wort tends to reduce how well atorvastatin lowers your cholesterol by speeding up its breakdown. If you take St John's Wort with atorvastatin, talk to whoever prescribes it, as your cholesterol may need rechecking and your dose may need adjusting.
St John's Wort speeds up a liver enzyme called CYP3A4, which is one of the routes the body uses to clear clarithromycin. Taking the two together may lower the amount of clarithromycin in your blood and could make the antibiotic less effective at clearing the infection. If you are prescribed clarithromycin, it is sensible to pause St John's Wort for the course and tell whoever prescribed it that you take it.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort can speed up the breakdown of diazepam, which may mean it is less effective than expected at the prescribed dose. Talk to whoever prescribed it before combining.
St John's Wort can reduce circulating dydrogesterone levels by speeding up its breakdown. Dydrogesterone is the progestogen in HRT combinations such as Femoston, so for HRT users this can mean menopausal symptom control slips and breakthrough bleeding becomes more likely. Mention St John's Wort to your prescriber rather than starting it alongside HRT on your own.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort speeds up a liver enzyme called CYP3A4, which helps clear erythromycin from the body. Taking the two together may lower the amount of erythromycin in your blood and could make the antibiotic less effective. If you are prescribed erythromycin, it is sensible to pause St John's Wort for the course and tell whoever prescribed it that you take it.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort can speed up the breakdown of reboxetine, which may leave it less effective than expected at the prescribed dose. Talk to whoever prescribed it before combining.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort tends to lower the amount of active simvastatin in your blood, which may reduce its cholesterol-lowering effect. If you take St John's Wort with simvastatin, talk to whoever prescribes it, as your cholesterol may need rechecking.
Additive serotonergic activity
St John's Wort and buspirone both raise serotonin activity, and a published case linked the combination to serotonin syndrome, a potentially serious reaction. St John's Wort can also speed up the breakdown of buspirone and make it less effective. Because of the serotonin risk we treat this as a do-not-combine pair without specialist sign-off.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort and citalopram both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
St John's Wort and duloxetine both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
St John's Wort and escitalopram both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
St John's Wort and fluoxetine both raise serotonin levels. Combined, they can cause serotonin syndrome (agitation, sweating, tremor, raised heart rate, confusion). Do not combine.
St John's Wort with an MAOI like isocarboxazid can cause hypertensive crisis and serotonin syndrome. This is a strict do-not-combine.
St John's Wort raises serotonin in the brain, and linezolid is an antibiotic that also acts as an MAOI, blocking serotonin breakdown. Combining them risks serotonin syndrome. This is a strict do-not-combine.
St John's Wort raises serotonin in the brain, and moclobemide is an MAOI (the reversible kind) that blocks serotonin breakdown. Combining them risks serotonin syndrome. This is a strict do-not-combine.
St John's Wort and paroxetine both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
St John's Wort with an MAOI like phenelzine can cause hypertensive crisis and serotonin syndrome. This is a strict do-not-combine.
Rasagiline is an MAO-B inhibitor used for Parkinson's. Combined with St John's Wort, serotonin can rise to dangerous levels because there is less MAO available to break it down. We treat this as a do-not-combine pair.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Selegiline is an MAO-B inhibitor used for Parkinson's. Combined with St John's Wort, serotonin can rise to dangerous levels because there is less MAO available to break it down. We treat this as a do-not-combine pair.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort and sertraline both raise serotonin levels. Combined, they can cause serotonin syndrome (agitation, sweating, tremor, raised heart rate, confusion). Do not combine.
St John's Wort with an MAOI like tranylcypromine can cause hypertensive crisis and serotonin syndrome. This is a strict do-not-combine.
St John's Wort and venlafaxine both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
St John's Wort raises serotonin in its own right, and sumatriptan is a serotonin-receptor drug for migraine. In theory the two could add up, though the evidence that triptans trigger serotonin syndrome is weak and most people tolerate the combination. Be alert to agitation, sweating, tremor, shivering or a racing heart, and mention the St John's Wort to your GP, especially if you also take an antidepressant.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Tramadol raises serotonin as part of how it relieves pain, and St John's Wort raises serotonin too. Taking them together may increase the risk of serotonin syndrome (agitation, sweating, tremor, shivering, a racing heart, confusion). This is not a strict do-not-combine like St John's Wort plus an SSRI, but it is one to avoid stacking without your prescriber's involvement, especially if your tramadol dose has recently gone up.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort raises serotonin in its own right, and zolmitriptan is a serotonin-receptor drug for migraine. In theory the two could add up, though the evidence that triptans trigger serotonin syndrome is weak and most people tolerate the combination. Be alert to agitation, sweating, tremor, shivering or a racing heart, and mention the St John's Wort to your GP, especially if you also take an antidepressant.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
P-glycoprotein interaction
St John's Wort tends to reduce how much digoxin reaches your bloodstream, which may make it less effective at the prescribed dose. Because digoxin has a narrow safe range, do not start or stop St John's Wort while on digoxin without telling whoever prescribes it, so your dose and levels can be checked.
Glucuronidation (no CYP interaction)
Lorazepam is broken down by a different enzyme system (glucuronidation) than the one St John's Wort affects. We treat this pair as no expected interaction.
Temazepam is broken down by a different enzyme system (glucuronidation) than the one St John's Wort affects. We treat this pair as no expected interaction.
What this page does not say. Leaving a compound out of our recommendations is not a verdict that it is useless for everyone. It is a statement about safety, evidence, or interaction load in the context Distil screens for. Discuss any supplement decision with whoever manages your prescriptions.
How we grade severity, choose what's in scope, and what we exclude.
Every call on this page is reasoned. We publish the full rubric for severity tiers, the medication inclusion logic, the evidence grades we accept, and what we deliberately leave out. About three thousand words. Worth reading once if you use this tool more than occasionally.
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- the evidence-backed compounds worth adding, and the ones worth dropping
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