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 60 documented pairs we have explicitly assessed: 33 red, 25 amber, and 2 green. Every call is cited to a clinical reference (PMID) or the British National Formulary.
Documented interactions
Last reviewed 30 June 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
CYP induction
Red Does interact with Acenocoumarol?
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.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Ciclosporin?
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.
Evidence: Supported by human study data.
Red Does interact with Efavirenz?
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.
Evidence: Supported by human study data.
Red Does interact with Tacrolimus?
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.
Evidence: Supported by human study data.
Red Does interact with Warfarin sodium?
St John's Wort can cause your body to clear warfarin too quickly, dropping your INR and raising clot risk. Do not combine.
Evidence: Supported by human study data.
Amber Does interact with Amitriptyline?
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.
Evidence: Supported by human study data.
Amber Does interact with Carbamazepine?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Clomipramine?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Dosulepin?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Doxepin?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Imipramine?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Lofepramine?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Nortriptyline?
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.
Evidence: Supported by human study data.
Amber Does interact with Phenytoin?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Theophylline?
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.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
CYP3A4 induction
Red Does interact with Conjugated oestrogens?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Desogestrel?
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.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Estradiol?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Ethinylestradiol with desogestrel?
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.
Evidence: Supported by human study data.
Red Does interact with Ethinylestradiol with levonorgestrel?
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.
Evidence: Supported by human study data.
Red Does interact with Norethisterone?
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.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Tibolone?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Alprazolam?
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.
Evidence: Supported by human study data.
Amber Does interact with Atorvastatin?
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, tell whoever prescribes it, as they may need to recheck your cholesterol and adjust your dose. Do not change your atorvastatin dose yourself.
Evidence: Supported by human study data.
Amber Does interact with Clarithromycin?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Diazepam?
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.
Evidence: Limited human data, based on case reports and a known mechanism.
Amber Does interact with Dydrogesterone?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Erythromycin?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Reboxetine?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Simvastatin?
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.
Evidence: Supported by human study data.
Additive serotonergic activity
Red Does interact with Buspirone?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Citalopram?
St John's Wort and citalopram both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
Evidence: Supported by human study data.
Red Does interact with Duloxetine hydrochloride?
St John's Wort and duloxetine both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
Evidence: Supported by human study data.
Red Does interact with Escitalopram?
St John's Wort and escitalopram both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
Evidence: Supported by human study data.
Red Does interact with Fluoxetine hydrochloride?
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.
Evidence: Supported by human study data.
Red Does interact with Fluvoxamine?
St John's Wort and fluvoxamine both raise serotonin levels. Combined, they can cause serotonin syndrome (agitation, sweating, tremor, raised heart rate, confusion). Do not combine.
Evidence: Supported by human study data.
Red Does interact with Isocarboxazid?
St John's Wort with an MAOI like isocarboxazid can cause hypertensive crisis and serotonin syndrome. This is a strict do-not-combine.
Evidence: Supported by human study data.
Red Does interact with Linezolid?
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.
Evidence: Supported by human study data.
Red Does interact with Moclobemide?
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.
Evidence: Supported by human study data.
Red Does interact with Paroxetine hydrochloride?
St John's Wort and paroxetine both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
Evidence: Supported by human study data.
Red Does interact with Phenelzine?
St John's Wort with an MAOI like phenelzine can cause hypertensive crisis and serotonin syndrome. This is a strict do-not-combine.
Evidence: Supported by human study data.
Red Does interact with Rasagiline?
Taking St John's Wort with rasagiline (an MAO-B inhibitor used for Parkinson's) can push serotonin to dangerous levels, because there is less MAO available to break it down, so we treat this as a do-not-combine pair.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Selegiline?
Taking St John's Wort with selegiline (an MAO-B inhibitor used for Parkinson's) can push serotonin to dangerous levels, because there is less MAO available to break it down, so we treat this as a do-not-combine pair.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Red Does interact with Sertraline?
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.
Evidence: Supported by human study data.
Red Does interact with Tranylcypromine?
St John's Wort with an MAOI like tranylcypromine can cause hypertensive crisis and serotonin syndrome. This is a strict do-not-combine.
Evidence: Supported by human study data.
Red Does interact with Venlafaxine?
St John's Wort and venlafaxine both raise serotonin levels. Combined, they can cause serotonin syndrome. Do not combine.
Evidence: Supported by human study data.
Amber Does interact with Lithium carbonate?
St John's Wort raises serotonin activity, and lithium can add to serotonergic effects, so combining them may raise the risk of serotonin syndrome (agitation, sweating, tremor, confusion). Lithium also needs careful blood-level monitoring, so speak to your GP or specialist before adding St John's Wort.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Sumatriptan succinate?
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.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Tramadol hydrochloride?
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.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Trazodone hydrochloride?
St John's Wort and trazodone both act on serotonin, so combining them may raise the risk of serotonin syndrome (agitation, sweating, tremor, confusion). Talk to your GP or pharmacist before taking them together.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Vortioxetine?
St John's Wort and vortioxetine both raise serotonin activity, so taking them together may raise the risk of serotonin syndrome (agitation, sweating, tremor, confusion). Check with your GP or pharmacist before combining them.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does interact with Zolmitriptan?
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.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
P-glycoprotein induction (lowers drug levels)
Amber Does interact with Digoxin?
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.
Evidence: Supported by human study data.
Glucuronidation (no CYP interaction)
Green Does interact with Lorazepam?
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.
Evidence: Supported by human study data.
Green Does interact with Temazepam?
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.
Evidence: Supported by human study data.
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.
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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 free checker answers one interaction question at a time. A Distil report reviews the bigger picture: your goals, diet, medications, current supplements and any blood results you provide, then shows what appears worth keeping, changing, adding or leaving out.
- what your diet already covers, so you are not adding a capsule for something food is already handling
- which evidence-graded compounds are worth considering for your goals, and which were considered but left out
- what to keep, change or stop from what you already take, plus the order to introduce anything new
- how your medications and complete supplement stack fit together, with daily timing and a clear point for reassessment
The interaction check is one section of the full report. You also get the reasoning behind each recommendation and the evidence references used.
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