St John's wort

Is St John's wort safe?

The herb is not very toxic. Its side effects are usually mild, and there is no consistent pattern of liver damage. If you take nothing else, the risks are modest.

Almost nobody is in that position. St John's wort is one of the most interacting substances you can buy over the counterOver-the-counterA medicine you can buy without a prescription, in a pharmacy or shop, with directions on the pack for safe use without a doctor.More in the glossary. It switches on the liver and gut machinery that clears drugs from the body, so many medicines stop working properly. The NIH's complementary health centre rates it as carrying an overall high risk of drug interactions, and that is why we give it the lowest interactions score in this section.

How the interaction works

St John's wort, mostly through the compound hyperforin, activates CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary and other drug-metabolising enzymes in the liver, and P-glycoprotein, a pump in the gut wall that pushes drugs back out. The result is lower blood levels of a long list of medicines. In the US, St John's wort appears in the drug interaction section of the labels of more than 150 different medicines, and about 20 list it as a contraindicationContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary, most of them HIV drugs, plus voriconazole, ranolazine, lurasidone, rasagiline and the COVID-19 treatment Paxlovid. The effect builds over about a week and takes one to two weeks to fade after stopping.

Separately, St John's wort raises serotonin activity in the brain. Combined with antidepressants, it can cause serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary.

The interactions that matter most

Drug group	Examples	What can happen
Hormonal contraception	Combined pill, progestogen-only pill, implant	Breakthrough bleeding, unplanned pregnancy
Anticoagulants	Warfarin	Lower INR, risk of clots
Transplant drugs	Ciclosporin, tacrolimus	Organ rejection
HIV medicines	Indinavir, nevirapine	Treatment failure, drug resistance
Heart drugs	Digoxin, ivabradine	Lower effect
Cancer drugs	Irinotecan, imatinib, docetaxel	Lower effect
Antidepressants	Sertraline and other SSRIs, SNRIs, triptans	Serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary
Epilepsy medicines	Phenytoin, carbamazepine	Seizures from lower levels
Statins	Simvastatin	Less cholesterol lowering

Two reports published in 2000 made regulators take this seriously: heart transplant patients who showed signs of rejection after starting St John's wort, and a study in healthy volunteers in which blood levels of the HIV drug indinavir fell by more than half. Reports of unplanned pregnancies in women on the pill followed.

The risk is not theoretical. A Wake Forest study of US doctor visits from 1993 to 2010, published in 2014, found that 28% of people recorded as taking St John's wort were also on a drug with which it could interact dangerously.

Regulators' responses

Countries took different routes. France leaves St John's wort off its 2014 list of plants allowed in food supplements. Ireland lists it as a prescription-only medicinePrescription-only medicineA medicine that can be supplied only with a prescription from a doctor or another authorised prescriber.More in the glossary, apart from products for external use. Germany and the UK treat it as a herbal medicine, with standardised extracts and mandatory interaction warnings in the patient leaflet. In the US it is sold as a supplement with no requirement to warn.

The European Medicines Agency's herbal monograph, revised in 2022, says products must not be combined with warfarin-type anticoagulants, ciclosporin, tacrolimus, sirolimus, everolimus, HIV protease inhibitors and some other HIV drugs, irinotecan, imatinib and other cancer drugs cleared by the same enzymes. Women on hormonal contraception are told to use an extra method. The one exception is low-hyperforin products: at no more than 1 mg of hyperforin a day, used for up to two weeks, the monograph reports no clinically relevant interactions.

Other side effects

At usual doses, people report stomach upset, dizziness, dry mouth, insomnia, fatigue and restlessness. High doses can make skin more sensitive to sunlight; the EU monograph notes tingling and sunburn-like reactions in fair-skinned people in strong sun. The licensed extracts in Europe are taken at 600 to 1,800 mg a day depending on the product, so follow the label of the specific one. Like other antidepressants, it can trigger mania in people with bipolar disorder. NCCIH advises avoiding it in pregnancy, where it may increase the risk of birth defects, and when breastfeeding.

Product strength

Products differ widely in hypericin and hyperforin content. That matters twice: for whether it works and for how strong the interactions are. A 2020 review in the British Journal of Pharmacology found that the degree of CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary induction correlates with the hyperforin dose. In Europe, choose a product with a traditional herbal registration (THR) mark in the UK or a licensed herbal medicine, which are standardised. In the US, a USP VerifiedThird-party testingTesting of a supplement by an independent lab to check that it contains what the label says and is free of set contaminants.More in the glossary mark is the best available check, though few St John's wort products carry it.

Before you take it

• Show your full medicine list to a pharmacist first. This is the single most useful step.
• Do not combine it with any antidepressant, or switch between them, without your doctor.
• If you use hormonal contraception, assume it is less reliable and use condoms or a copper IUD.
• Tell your surgeon and anaesthetist, and every new prescriber, that you take it.
• Do not stop suddenly if other drug doses have been adjusted around it.

Depression is a medical condition, and choosing a treatment should involve your doctor. For other herbs with mood claims, see ashwagandha and kava.

How we scored it

Organ toxicity (85) is good and dose safety (75) acceptable. Interactions (20) is one of the lowest factor scores on SafetyScorer, because failures of the pill, transplant drugs and HIV treatment are well documented. Regulatory actions (45) reflect the French exclusion from food supplements, the Irish prescription rule and the EU contraindicationContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary list.