St. John's Wort Interactions

Sertraline is an SSRI that blocks serotonin reuptake, and St. John's wort independently raises central serotonin through constituents such as hyperforin and hypericin. Combining them can trigger serotonin syndrome, a potentially life-threatening reaction marked by altered mental status, autonomic instability, and neuromuscular hyperactivity. St. John's wort also induces CYP3A4 and CYP2C19, which can lower sertraline levels and undermine treatment.

St. John's wort is a potent inducer of CYP3A4 and P-glycoprotein, the enzyme and transporter that clear cyclosporine. Taking the two together markedly lowers cyclosporine blood levels, which can render the drug subtherapeutic. This has caused documented acute organ rejection in transplant recipients, making the combination a contraindication.

St. John's Wort induces CYP3A4 and P-glycoprotein, increasing the clearance of contraceptive hormones and reducing the effectiveness of hormonal contraceptives.

St. John's Wort raises brain serotonin, norepinephrine, and dopamine through reuptake inhibition and shows weak monoamine oxidase inhibition. Layered on a prescription MAOI, which blocks the breakdown of those same monoamines, the combination can push monoamine signaling to dangerous levels and is contraindicated because of the risk of serotonin syndrome and hypertensive crisis.

Paroxetine is an SSRI that raises serotonin by blocking its reuptake. St. John's wort independently raises serotonin and also induces drug-metabolizing enzymes and P-glycoprotein. Taken together, the additive serotonin effect can precipitate serotonin syndrome, and paroxetine is among the most frequently implicated SSRIs in published St. John's wort case reports.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). St. John's wort independently inhibits serotonin (and to a lesser extent norepinephrine and dopamine) reuptake. Combining them can drive synaptic serotonin higher and trigger serotonin syndrome, and St. John's wort can also reduce venlafaxine exposure by inducing drug-metabolizing enzymes such as CYP3A4.

St. John's wort induces the CYP3A4 enzyme and the P-glycoprotein transporter, which speeds up clearance of tacrolimus and lowers its blood levels, raising the risk of transplant rejection. Stopping the herb after the body has adjusted can let tacrolimus levels rebound, which has been linked to kidney toxicity.

St. John's Wort is pharmacologically active, not a harmless herb, and it interacts with SSRIs in two overlapping and hard-to-predict ways. The result is a combination most clinicians prefer to avoid rather than manage.

St. John's wort revs up a gut transporter that digoxin depends on for absorption, so combining them quietly drains digoxin from the bloodstream. Because digoxin has so little room to spare, that drop can leave the drug too weak to control your heart.

Adderall (mixed amphetamine salts) raises synaptic norepinephrine, dopamine, and to a lesser extent serotonin. St. John's Wort inhibits reuptake of those same monoamines. Together they can push the serotonergic system far enough to risk serotonin syndrome and can add cardiovascular strain. Separately, St. John's Wort strongly induces the CYP3A4 enzyme and P-glycoprotein, which can blunt the effect of many co-taken medicines.

St. John's wort strongly induces both CYP3A4 (apixaban's main metabolizing enzyme) and P-glycoprotein (its efflux transporter). Taken together, it speeds apixaban's breakdown and clearance, lowering blood levels and weakening clot protection, which raises the risk of stroke or thromboembolism.

St. John's wort is a potent inducer of intestinal CYP3A4 and P-glycoprotein, the same enzymes that break down verapamil before it reaches the bloodstream. Taking the two together sharply lowers verapamil's systemic exposure and can erase its therapeutic effect on blood pressure, heart rhythm, or migraine prevention.

Duloxetine and St. John's wort both increase serotonergic activity, and combining them can raise serotonin to levels associated with serotonin syndrome.

Fluoxetine and St. John's wort both increase serotonin activity, and combining them can add to the same effect and contribute to serotonin syndrome.

St. John's Wort activates the pregnane X receptor and induces drug-metabolizing enzymes (CYP3A4, CYP2C9, CYP2C19) and P-glycoprotein. Because phenytoin is cleared mainly by CYP2C9 and CYP2C19, taking St. John's Wort alongside it could speed phenytoin's breakdown and lower its blood levels, raising the theoretical risk of breakthrough seizures. Direct human data for phenytoin specifically are limited, so regulators treat this as a mechanism-based precaution rather than a documented loss of control.

Tramadol inhibits serotonin and norepinephrine reuptake, and St. John's Wort increases central serotonergic activity, so combining them can add together and raise the risk of serotonin syndrome. St. John's Wort also induces CYP3A4 and CYP2B6, enzymes involved in tramadol metabolism, which may lower levels of tramadol's active M1 metabolite and weaken pain relief.

St. John's Wort strongly induces CYP3A4, the main enzyme that clears oxycodone. In a controlled trial, taking St. John's Wort for about two weeks markedly lowered oxycodone blood levels and weakened its pain-relieving effect, so combining the two can leave pain poorly controlled.

St. John's wort induces the CYP3A4 enzyme and the P-glycoprotein transporter that simvastatin depends on, sharply increasing the drug's first-pass breakdown. In a controlled crossover study of healthy volunteers, two weeks of St. John's wort substantially lowered the amount of active simvastatin reaching the bloodstream, weakening its cholesterol-lowering effect.

St. John's wort induces the cytochrome P450 enzymes (and the P-glycoprotein transporter) that clear amitriptyline, measurably lowering amitriptyline blood levels and reducing its antidepressant and pain-relieving effect. Because both also raise serotonin signaling, combining them adds a theoretical risk of serotonin syndrome. The net effect can be a weaker antidepressant plus an added safety concern.

St. John's wort induces the liver enzymes CYP3A4 and CYP2C19 that break down omeprazole. Taking the two together speeds up omeprazole clearance, lowers its blood levels, and can weaken its acid-suppressing effect — potentially undermining treatment of GERD, ulcers, or H. pylori eradication.

Escitalopram is a selective SSRI cleared mainly by CYP2C19 and CYP3A4. St. John's wort independently raises serotonin tone and is a strong inducer of those same enzymes and P-glycoprotein. Taken together, the combination can add to serotonergic effects and, through enzyme induction, lower escitalopram levels and blunt its antidepressant effect. Documented serotonin syndrome cases with St. John's wort involve other SSRIs rather than escitalopram specifically, so the combination is best avoided rather than treated as a guaranteed emergency.

Both carbamazepine and St. John's Wort induce CYP3A4, the liver enzyme that primarily breaks carbamazepine down. The combined effect is hard to predict: carbamazepine already induces its own metabolism, so adding the herb may lower exposure most before that self-induction is fully established. The bigger danger comes at transitions — especially stopping St. John's Wort while still on carbamazepine, when the loss of enzyme induction can let carbamazepine levels climb toward toxicity.

St. John's wort induces the liver enzymes (chiefly CYP3A4, via the pregnane X receptor) that help clear nortriptyline, which can lower nortriptyline blood levels and weaken its antidepressant effect. The herb also adds serotonergic activity, which gives an additive, theoretical increase in the risk of serotonin syndrome.

St. John's wort is a strong inducer of the CYP3A4 enzyme system that clears the statin-like compound (monacolin K, chemically identical to lovastatin) in red yeast rice. Taking them together speeds up how the body breaks down that compound, lowering its levels and weakening red yeast rice's cholesterol-lowering effect. The concern here is loss of benefit rather than toxicity, and the direction is the opposite of CYP3A4-inhibitor interactions, so it does not raise muscle-injury risk.

Methylphenidate treats ADHD by inhibiting reuptake of dopamine and norepinephrine. St. John's Wort adds its own monoamine reuptake activity and is a strong inducer of the CYP3A4 drug-metabolising enzyme. A small published observation suggests St. John's Wort can blunt methylphenidate's effect on ADHD symptoms. There is also a theoretical, additive serotonergic risk, mainly relevant if other serotonergic drugs are present, but no confirmed serotonin syndrome cases have been reported for this specific pair.

Carvedilol is partly broken down by liver enzymes (including CYP2C9 and CYP3A4) and is also a P-glycoprotein substrate. St. John's Wort induces several of these enzymes and P-glycoprotein, which can speed carvedilol clearance and lower its blood levels, potentially weakening its blood-pressure and heart-failure effects. The interaction is mechanism-based and extrapolated from St. John's Wort's effect on similar drugs; no direct human study of this specific pair has been published.

St. John's wort can modestly induce the P-glycoprotein (P-gp) transporter that dabigatran depends on for absorption. With repeated use this may lower dabigatran blood levels somewhat, in theory reducing clot protection. The measured effect in human studies is weak and there are no reported thrombosis cases from the pairing, but because dabigatran is given for serious clotting conditions and the herb's effect lingers after stopping, the combination is best avoided.

St. John's Wort induces CYP3A4 and P-glycoprotein through PXR activation. Because oral ketoconazole is cleared by CYP3A4, regular St. John's Wort use can speed its breakdown, lower antifungal blood levels, and risk reduced effectiveness. The effect is established by mechanism and by analogy with other azole antifungals; topical ketoconazole is not a practical concern.

St. John's wort induces CYP3A4, the enzyme that metabolizes atorvastatin, lowering statin exposure and weakening cholesterol-lowering efficacy over time.

St. John's Wort induces several liver drug-metabolizing enzymes, including CYP1A2 and CYP3A4, plus the transporter P-glycoprotein. Propranolol is cleared mainly through CYP1A2 and CYP2D6, so regular St. John's Wort use can plausibly speed up its breakdown and weaken its effect. Direct studies of this specific pair are lacking; the concern is based on St. John's Wort's confirmed enzyme-inducing action, its documented lowering of theophylline (which shares propranolol's CYP1A2 pathway), and a case report of lost intraocular-pressure control in a glaucoma patient on a topical beta-blocker.

St. John's wort induces drug-metabolizing enzymes that can lower bupropion blood levels and weaken its effect. A human case report also links the pair to a prolonged movement (dystonic) reaction from overlapping effects on brain chemicals. The often-cited additive seizure risk rests mainly on animal extract studies and is not well supported in people.