St John's wort and medicines: how it interacts, and who should be careful

By Milen Cholakov, MPharm · 26 September 2026 · 4 min read

St John's wort (Hypericum perforatum) is a herbal remedy that is often sold for low mood, sometimes on the same shelf as vitamins. Because it is a plant product, people often don't mention it when a doctor prescribes something new. Yet it is one of the best-documented herbs for interactions with medicines. The US National Center for Complementary and Integrative Health puts it plainly: it has been clearly shown that St John's wort can interact in dangerous, sometimes life-threatening ways with a variety of medicines [3].

How St John's wort changes other medicines

Your body clears many medicines with enzymes in the liver and gut, and the most important of them is CYP3A4. Transporter proteins also move medicines around; one of them, P-glycoprotein, pumps many drugs back out of the cells lining the gut.

St John's wort turns these systems up. According to the European Medicines Agency (EMA) monograph, St John's wort preparations induce the activity of CYP3A4, CYP2B6, CYP2C9, CYP2C19 and P-glycoprotein [1]. The switch behind this is a receptor called PXR (pregnane X receptor), and the degree of CYP3A4 induction correlates with the product's hyperforin content [2]. The result is that affected medicines are cleared faster, their blood levels fall, and they may stop working as well as they should [1].

Two practical details follow from the EMA text:

• The effect outlasts the last capsule. The raised enzyme activity returns to normal within about one week after stopping [1]. That means levels of another medicine can keep changing for days after St John's wort is stopped, so starting or stopping it on top of an important medicine is best planned with the prescriber.
• The preparation matters. The monograph distinguishes products delivering no more than 1 mg of hyperforin a day; for these, used for up to two weeks, no clinically relevant interactions have been reported for the enzymes studied [1]. Unless the product information clearly says so, it is safest to assume a St John's wort product can interact.

Medicines where this matters most

The EMA monograph lists combinations that are contraindicated, meaning they should not be used together [1]:

• Transplant medicines such as ciclosporin, tacrolimus, sirolimus and everolimus. In 2000, an interaction between St John's wort and ciclosporin caused acute rejection in two heart transplant patients [2].
• Coumarin-type anticoagulants such as warfarin [1, 3].
• Some HIV medicines, including indinavir and other protease inhibitors, and nucleoside reverse transcriptase inhibitors [1].

Hormonal contraceptives need a special mention. Lower hormone levels may lead to breakthrough (intermenstrual) bleeding and reduced protection against pregnancy, and the EMA advises women using hormonal contraceptives to take additional contraceptive measures [1].

The monograph also asks for special care with other medicines handled by the same enzymes, giving examples such as amitriptyline, alprazolam, diazepam, midazolam, methadone, simvastatin, digoxin, fexofenadine and finasteride [1]. NCCIH adds seizure medicines such as phenytoin and carbamazepine, and some heart medicines such as ivabradine [3]. Levothyroxine is affected too: its product information notes that St John's wort speeds up its metabolism, so a higher thyroid dose may be needed [4]. (See also: levothyroxine with calcium, iron, magnesium or coffee.)

Antidepressants and serotonin syndrome

A second problem has nothing to do with enzymes. St John's wort may add to the effects of serotonin when combined with antidepressants such as SSRIs (for example sertraline or paroxetine) or with buspirone [1]. Very rarely this causes serotonin syndrome, with symptoms such as sweating, a fast heart rate, diarrhoea, fever, agitation, disorientation, tremor or muscle jerks [1]. This is a real risk when someone adds St John's wort to a prescribed antidepressant, or switches from one to the other without advice.

Before surgery

The EMA advises that before planned surgery, possible interactions with anaesthetic medicines should be identified and, if necessary, St John's wort should be stopped [1]. Tell the surgical team if you take it.

When to talk to your doctor or pharmacist

• Before starting St John's wort if you take any prescription medicine. The EMA monograph itself advises this [1].
• If you use hormonal contraception, or take a transplant, anticoagulant, HIV, seizure, heart or thyroid medicine.
• Before stopping St John's wort if you are already taking it together with another medicine.
• Straight away if you get agitation, sweating, a racing heart, tremor or fever after combining it with an antidepressant.
• If you have a planned operation.
• If low mood is the reason you're considering it: depression can be a serious illness and deserves a proper assessment [3].

This article is general information, not medical advice, diagnosis or treatment. Don't start, stop or change a medicine without talking to your doctor or pharmacist.