Supplement·Interactions·Reviewed June 9, 2026
St. John's Wort interactions.
St. John's Wort has 113 documented interactions in the NutriStack database: 78 to avoid or watch closely and 35 that need timing or caution. The full list, with what each pairing does, is below.
In short
St. John's Wort at a glance.
A quick, data-grounded summary. The full table is below.
St. John's Wort has 113 documented interactions in the NutriStack database: 78 to avoid or watch closely and 35 that need timing or caution. The full list, with what each pairing does, is below.
Interactions
Everything that interacts with st. john's wort.
Every supplement and medication in the NutriStack database with a documented interaction with this substance, highest-severity first. Open any pair for the mechanism and sources.
| Substance | Interaction | What happens |
|---|---|---|
| 5-HTP | Contraindicated | St. John's Wort inhibits serotonin reuptake while 5-HTP floods serotonin synthesis. Combined use risks serotonin syndrome: a potentially fatal... details → |
| Citalopram | Contraindicated | Dual serotonin reuptake inhibition from citalopram and St. John's Wort creates serotonin syndrome risk. |
| Clomipramine | Contraindicated | St. John's Wort can add serotonergic activity and can alter metabolism of many drugs. |
| Combined Oral Contraceptive | Contraindicated | St. John's Wort induces CYP3A4, dramatically reducing levels of ethinyl estradiol and progestins. This causes contraceptive failure and unintended... details → |
| Cyclosporine | Contraindicated | St. John's Wort can markedly reduce cyclosporine concentrations and has been associated with transplant rejection. |
| Desvenlafaxine | Contraindicated | St. John's Wort has antidepressant-like serotonergic activity and is a major herb-drug interaction trigger. Combining it with desvenlafaxine can add... details → |
| Duloxetine | Contraindicated | Combining duloxetine (an SNRI) with St. John's Wort creates a serious risk of serotonin syndrome. Both agents increase synaptic serotonin through... details → |
| Escitalopram | Contraindicated | Combining escitalopram with St. John's Wort significantly increases the risk of serotonin syndrome. Escitalopram is the most selective SSRI, and... details → |
| Fluoxetine | Contraindicated | Combining fluoxetine with St. John's Wort creates a high risk of serotonin syndrome. Fluoxetine has a long half-life (including its active... details → |
| Fluvoxamine | Contraindicated | St. John's Wort has SSRI-like activity and is a strong CYP3A4/2C9 inducer. Combined with fluvoxamine, the additive serotonergic load can trigger... details → |
| Itraconazole | Contraindicated | St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Itraconazole exposure or undermine therapy. |
| L-Tryptophan | Contraindicated | St. John's Wort inhibits serotonin reuptake while L-Tryptophan increases serotonin synthesis. Risk of serotonin syndrome. |
| Levomilnacipran | Contraindicated | St. John's Wort can increase serotonergic activity and can induce drug-metabolizing pathways. |
| Linezolid | Contraindicated | St. John's Wort can increase serotonergic tone and is unsafe with Linezolid's monoamine oxidase inhibitory activity. |
| Lurasidone | Contraindicated | St. John's Wort is a strong CYP3A4 inducer and can markedly lower lurasidone exposure. |
| Paroxetine | Contraindicated | Dual serotonin reuptake inhibition from paroxetine and St. John's Wort creates high serotonin syndrome risk. |
| Phenelzine | Contraindicated | St. John's Wort is serotonergic and is inappropriate with irreversible MAOIs. |
| Quetiapine | Contraindicated | St. John's Wort is a potent CYP3A4 inducer that can reduce quetiapine plasma concentrations by up to 80%, essentially rendering the medication... details → |
| Rasagiline | Contraindicated | St. John's Wort is listed among contraindicated products with rasagiline because of serotonin syndrome risk. |
| Selegiline | Contraindicated | St. John's Wort is explicitly contraindicated with selegiline transdermal labeling and is unsafe with MAOI therapy because of serotonergic effects. |
| Sertraline | Contraindicated | Combining sertraline (an SSRI) with St. John's Wort creates a serious risk of serotonin syndrome, a potentially life-threatening condition. St.... details → |
| Tacrolimus | Contraindicated | St. John's Wort can markedly lower tacrolimus concentrations and cause rejection risk. |
| Tapentadol | Contraindicated | St. John's Wort has serotonergic activity and can interact unpredictably with centrally acting analgesics, increasing serotonin syndrome concern. |
| Tramadol | Contraindicated | Combining tramadol with St. John's Wort creates dual risks: serotonin syndrome from additive serotonergic effects, and potential loss of tramadol's... details → |
| Tranylcypromine | Contraindicated | St. John's Wort has serotonergic effects and is unsafe with irreversible MAOIs. |
| Venlafaxine | Contraindicated | Combining venlafaxine with St. John's Wort creates a dangerous risk of serotonin syndrome. Multiple case reports have documented this interaction.... details → |
| Vilazodone | Contraindicated | St. John's Wort has serotonergic effects and can also induce CYP3A4, making both toxicity and loss of antidepressant control possible. |
| Voriconazole | Contraindicated | St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Voriconazole exposure or undermine therapy. |
| Vortioxetine | Contraindicated | St. John's Wort has serotonergic activity and can interact unpredictably with antidepressants. |
| Warfarin | Contraindicated | St. John's Wort is a potent inducer of CYP3A4, CYP2C9, and P-glycoprotein, which dramatically accelerates warfarin metabolism and reduces its plasma... details → |
| Amiodarone | Conflict | St. John's Wort induces CYP3A4, which is a major metabolic pathway for amiodarone. This can significantly reduce amiodarone plasma levels,... details → |
| Amlodipine | Conflict | St. John's Wort is a potent inducer of CYP3A4 via pregnane X receptor (PXR) activation. Amlodipine is primarily metabolized by CYP3A4.... details → |
| Apixaban | Conflict | St. John's Wort potently induces CYP3A4 and P-glycoprotein, both of which are major pathways for apixaban metabolism and transport. This induction... details → |
| Aripiprazole | Conflict | St. John's Wort induces CYP3A4 and CYP2D6, both of which metabolize aripiprazole. This can reduce aripiprazole levels by 50% or more, potentially... details → |
| Atorvastatin | Conflict | St. John's Wort is a potent CYP3A4 inducer that significantly increases atorvastatin metabolism, reducing its plasma levels and cholesterol-lowering... details → |
| Budesonide Inhaled | Conflict | St. John's Wort induces CYP3A4, and budesonide is extensively metabolized by CYP3A. This may lower budesonide exposure and weaken asthma or airway... details → |
| Carbamazepine | Conflict | Both carbamazepine and St. John's Wort are potent CYP3A4 inducers. Combining them creates unpredictable effects on drug metabolism, potentially... details → |
| Cinacalcet | Conflict | St. John's Wort can induce CYP3A4 and may reduce cinacalcet exposure, destabilizing calcium and PTH control. |
| Clarithromycin | Conflict | St. John's Wort is a potent inducer of CYP3A4, the primary enzyme that metabolizes clarithromycin. Co-administration substantially lowers... details → |
| Clozapine | Conflict | St. John's Wort induces drug-metabolizing enzymes and transporters and may lower exposure to some antipsychotics or destabilize psychiatric treatment. |
| Dabigatran | Conflict | St. John's wort is a potent P-glycoprotein and CYP3A4 inducer. Because dabigatran etexilate's oral absorption depends on P-gp, induction can... details → |
| Dexamethasone | Conflict | St. John's Wort can induce CYP3A4, and dexamethasone exposure is strongly affected by CYP3A4 activity. Taking St. John's Wort during dexamethasone... details → |
| Diazepam | Conflict | St. John's Wort induces CYP3A4 and CYP2C19, both of which metabolize diazepam. This can reduce diazepam levels, causing breakthrough anxiety or... details → |
| Digoxin | Conflict | St. John's Wort significantly reduces digoxin levels through potent P-glycoprotein induction. A landmark study showed that St. John's Wort reduced... details → |
| Diltiazem | Conflict | St. John's Wort induces CYP3A4, reducing diltiazem plasma levels significantly. This can lead to uncontrolled hypertension or angina. |
| Doxepin | Conflict | St. John's Wort can add serotonergic effects and alter metabolism of many drugs. |
| Dutasteride | Conflict | Dutasteride exposure is vulnerable to CYP3A-related changes, and St. John's Wort is a clinically important inducer of CYP3A4 and P-glycoprotein.... |
| Erythromycin | Conflict | St. John's Wort is a potent inducer of CYP3A4 and intestinal P-glycoprotein. Erythromycin is metabolized by CYP3A4 and is a P-gp substrate, so... |
| Estradiol | Conflict | St. John's Wort induces CYP3A4, which metabolizes estradiol. This can reduce estradiol levels by 20-40%, potentially causing breakthrough bleeding,... details → |
| Felodipine | Conflict | St. John's Wort is a potent inducer of intestinal and hepatic CYP3A4, the primary enzyme that metabolizes felodipine, which already has very low... |
| Finasteride | Conflict | St. John's Wort can lower finasteride exposure. In healthy men, 14 days of St. John's Wort pretreatment significantly reduced finasteride Cmax, AUC,... details → |
| Fluconazole | Conflict | St. John's Wort is a strong inducer of CYP3A4 (via PXR activation by hyperforin) and P-glycoprotein. Because fluconazole is partly metabolized by... details → |
| Fluticasone Inhaled | Conflict | St. John's Wort can induce CYP3A4, and fluticasone is cleared primarily by CYP3A4. Induction may lower systemic and possibly airway steroid... details → |
| Fluticasone Nasal | Conflict | St. John's Wort induces CYP3A4, the main pathway that clears fluticasone. With daily nasal fluticasone, this may lower steroid exposure and reduce... details → |
| Ivabradine | Conflict | St. John's Wort can induce CYP3A4 and P-glycoprotein, and systematic reviews identify ivabradine as a drug whose exposure can be reduced by this... details → |
| Lamotrigine | Conflict | St. John's Wort can induce UGT glucuronidation enzymes responsible for lamotrigine metabolism, potentially reducing lamotrigine blood levels and... details → |
| Losartan | Conflict | Losartan is a prodrug metabolized by CYP2C9 and CYP3A4 to its active metabolite E-3174, which is 10-40 times more potent than the parent compound.... details → |
| Lovastatin | Conflict | St. John's Wort can induce CYP3A4 and P-glycoprotein, which may lower exposure to CYP3A4-metabolized statins. Human data show a major reduction in... details → |
| MDMA | Conflict | St. John's Wort both adds to serotonergic load and induces drug-metabolizing enzymes, so combined with MDMA it can raise serotonin syndrome risk... details → |
| Methotrexate | Conflict | St. John's Wort induces CYP enzymes and P-glycoprotein that may affect methotrexate metabolism and transport. While methotrexate is primarily... details → |
| Methylprednisolone | Conflict | St. John's Wort products high in hyperforin induce CYP3A, and methylprednisolone is a CYP3A-sensitive steroid. This may lower methylprednisolone... details → |
| Nifedipine | Conflict | St. John's Wort induces CYP3A4, which is the primary metabolic pathway for nifedipine. This can dramatically reduce nifedipine levels and blood... details → |
| Olanzapine | Conflict | St. John's Wort induces CYP1A2, the primary metabolic pathway for olanzapine. This can reduce olanzapine levels, causing psychotic relapse. |
| Ranolazine | Conflict | St. John's Wort is a clinically important inducer of CYP3A4 and P-glycoprotein. Ranolazine is extensively metabolized by CYP3A and is also linked to... |
| Risperidone | Conflict | St. John's Wort induces CYP3A4, which metabolizes risperidone. Reduced risperidone levels can cause psychotic relapse. |
| Rivaroxaban | Conflict | St. John's Wort potently induces CYP3A4 and P-glycoprotein, the primary metabolic pathways for rivaroxaban. This can substantially reduce... details → |
| Roflumilast | Conflict | St. John's Wort can induce CYP3A4 and may reduce roflumilast exposure, potentially decreasing COPD exacerbation prevention. |
| Rosuvastatin | Conflict | St. John's Wort induces CYP3A4 and P-glycoprotein, which can reduce rosuvastatin levels. While rosuvastatin is less dependent on CYP3A4 than other... details → |
| Salmeterol/Fluticasone | Conflict | St. John's Wort can induce CYP3A4 and may lower exposure to CYP3A4 substrates, potentially making controller response less predictable. |
| Sildenafil | Conflict | St. John's Wort induces CYP3A4, the primary enzyme metabolizing sildenafil. This can reduce sildenafil effectiveness. |
| Silodosin | Conflict | St. John's Wort can induce CYP3A4 and P-glycoprotein and may reduce silodosin exposure. |
| Simvastatin | Conflict | St. John's Wort dramatically reduces simvastatin levels through potent CYP3A4 induction. Simvastatin is highly dependent on CYP3A4 for metabolism,... details → |
| Solifenacin | Conflict | St. John's Wort can induce CYP3A4 and may reduce solifenacin exposure, decreasing bladder symptom control. |
| Tadalafil | Conflict | St. John's Wort can induce CYP3A4, the main metabolic pathway for tadalafil. This may lower tadalafil exposure and reduce its effectiveness for... details → |
| Theophylline | Conflict | St. John's Wort may induce drug-metabolizing pathways and make theophylline exposure less predictable. |
| Ticagrelor | Conflict | Ticagrelor is metabolised by CYP3A4 and is a P-glycoprotein substrate. St. John's wort potently induces both, and the model CYP3A4/P-gp inducer... details → |
| Tolterodine | Conflict | St. John's Wort may induce CYP3A4 and reduce tolterodine exposure, lowering symptom control. |
| Verapamil | Conflict | St. John's Wort induces CYP3A4, the primary enzyme metabolizing verapamil. This can reduce verapamil levels by 40-80%, leading to loss of heart... details → |
| Alprazolam | Caution | St. John's Wort can induce CYP3A4, the main enzyme clearing alprazolam. High-hyperforin St. John's Wort products may lower alprazolam exposure and... details → |
| American Ginseng | Caution | St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein and may accelerate the metabolism of ginsenosides, potentially reducing the... |
| Amitriptyline | Caution | St. John's Wort can substantially lower amitriptyline and nortriptyline exposure, which may cause loss of antidepressant, migraine, sleep, or... details → |
| Black Cohosh | Caution | Both herbs carry independent hepatic safety signals, so combining them can complicate monitoring and attribution if liver enzymes rise or symptoms... |
| Bupropion | Caution | Both bupropion and St. John's Wort lower the seizure threshold, and combining them may significantly increase seizure risk. Bupropion already... details → |
| Buspirone | Caution | A published case report describes serotonin syndrome after combining buspirone with St. John's Wort. St. John's Wort also has broad drug-interaction... details → |
| Cerebrolysin | Caution | St. John's Wort can affect mood and drug metabolism, complicating neurologic care. |
| Clopidogrel | Caution | St. John's Wort induces CYP3A4 and CYP2C19, which are the key enzymes responsible for converting clopidogrel from its inactive prodrug form to its... details → |
| Crocin (Saffron Extract) | Caution | Both saffron and St. John's Wort have serotonergic activity. Combining them may additively increase serotonergic tone and, in theory, the risk of... |
| Dihexa | Caution | St. John's Wort can alter mood and drug metabolism, complicating neuropsychiatric monitoring. |
| Dong Quai | Caution | St. John's Wort can alter drug metabolism and complicate hormonal or anticoagulant therapy contexts where dong quai is already risky. |
| Fexofenadine | Caution | St. John's Wort can change fexofenadine exposure through transporter effects. A single St. John's Wort dose increased fexofenadine peak... details → |
| Galantamine | Caution | St. John's Wort induces CYP3A4 and may lower exposure to drugs with CYP3A4 metabolism, including galantamine. |
| Gotu Kola | Caution | St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein and is associated with photosensitivity, while gotu kola is metabolized hepatically... |
| Luteolin | Caution | Luteolin inhibits several cytochrome P450 enzymes (including CYP3A4 and CYP1A2) and drug transporters, whereas St. John's Wort is a potent inducer... |
| Metoclopramide | Caution | Metoclopramide has rare reports of serotonin syndrome, especially when combined with serotonergic drugs. St. John's Wort has serotonergic activity... |
| Nebivolol | Caution | St. John's Wort is a broad inducer of drug-metabolizing enzymes. While nebivolol is primarily a CYP2D6 substrate, St. John's Wort can reduce the... |
| Noopept | Caution | St. John's Wort can alter drug metabolism and has neuropsychiatric effects; noopept interaction data are lacking. |
| Oxcarbazepine | Caution | St. John's Wort is an inducer of CYP3A4 and P-glycoprotein. Oxcarbazepine also induces CYP3A4, so the combination can amplify interaction burden for... |
| Oxycodone | Caution | St. John's Wort can induce CYP3A activity, and oxycodone exposure is clinically sensitive to CYP3A induction and inhibition. Using them together may... details → |
| Pioglitazone | Caution | St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Pioglitazone exposure or undermine therapy. |
| Primidone | Caution | St. John's Wort adds enzyme induction to primidone's enzyme-inducing metabolite burden and can reduce exposure to many co-medications. |
| Psilocybin | Caution | St. John's Wort has serotonergic and weak monoamine-oxidase-modulating activity, so combining it with the serotonergic psychedelic psilocybin raises... |
| Pueraria Mirifica | Caution | St. John's Wort may alter metabolism of many drugs and hormone therapies, making estrogenic supplement effects harder to predict. |
| Repaglinide | Caution | St. John's Wort can induce drug-metabolizing enzymes and transporters and may lower Repaglinide exposure or undermine therapy. |
| Rhodiola Rosea | Caution | Rhodiola and St. John's Wort both have CNS-active and possible serotonergic effects. Human interaction evidence is limited, but combining them can... |
| Rifampin | Caution | St. John's Wort and rifampin are both strong induction concerns for drug-metabolizing enzymes and transporters; the main danger is failure of other... |
| Rizatriptan | Caution | St. John's wort has serotonergic antidepressant activity and has documented interaction concerns with antidepressant drugs. Rizatriptan is a... details → |
| Saffron Extract | Caution | St. John's Wort is serotonergic and a strong CYP/P-gp inducer; combining with saffron complicates psychiatric and drug-interaction risk. |
| Sumatriptan | Caution | St. John's wort has serotonergic antidepressant activity and has been linked to clinically important interactions with antidepressant drugs.... details → |
| Suvorexant | Caution | Suvorexant exposure is sensitive to CYP3A modulation, and St. John's Wort can induce CYP3A4. Combining them may lower suvorexant levels and reduce... |
| Trazodone | Caution | St. John's Wort has SSRI-like activity and induces CYP3A4, which is the primary enzyme that metabolizes trazodone. The combination both adds... details → |
| Vitex (Chasteberry) | Caution | St. John's Wort can alter drug metabolism and hormonal contraceptive effectiveness, complicating Vitex use for cycle symptoms. |
| Wild Yam | Caution | St. John's Wort can reduce effectiveness of many medications, including hormonal therapies, while wild yam users may be treating hormone symptoms. |
| Zolpidem | Caution | St. John's Wort can induce CYP3A4 and P-glycoprotein, while zolpidem is partly cleared through CYP3A-mediated metabolism. The combination may reduce... |
Go deeper
The full st. john's wort profile.
Benefits, dosing by goal, forms, and the cited evidence for this supplement.
FAQ
Common st. john's wort questions.
Quick answers drawn from the table above.
What interacts with St. John's Wort?
In the NutriStack database, St. John's Wort has 113 documented interactions with other supplements and medications. The most notable include 5-HTP, Citalopram, Clomipramine, Combined Oral Contraceptive, and Cyclosporine.
What should you not take with St. John's Wort?
St. John's Wort is flagged against 78 substances in the database, including 5-HTP, Citalopram, Clomipramine, Combined Oral Contraceptive, Cyclosporine, and Desvenlafaxine. Review these with a clinician before combining, especially alongside prescription medications.
Can you take St. John's Wort with 5-HTP?
NutriStack classifies the St. John's Wort and 5-HTP pairing as contraindicated: St. John's Wort inhibits serotonin reuptake while 5-HTP floods serotonin synthesis. Combined use risks serotonin syndrome: a potentially fatal condition. Do NOT combine. Both increase serotonergic activity through different mechanisms.
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