St John’s Wort: Drug Interactions, Side Effects and What Research Shows

St John’s wort is a yellow-flowered herb, Hypericum perforatum, sold as a dietary supplement and promoted mainly for mood. The most important fact about it is not its research record but its drug interactions: the National Center for Complementary and Integrative Health (NCCIH) says it has been clearly shown to interact in dangerous, sometimes life-threatening ways with a variety of medicines, including birth control pills, transplant drugs, blood thinners and HIV medicines. This guide covers those interactions first, then side effects and a neutral summary of what trials found.

Peptide Labs sells dietary supplements, but it does not sell St John’s wort, and none of the product labels in our catalog list it. This article is general information, not medical advice.

What is St John's wort?

Hypericum perforatum is a flowering plant used in Greek, Islamic and Chinese traditional medicine. NCCIH explains that the name likely refers to John the Baptist, because the plant blooms around his feast day in late June. Other common names include hypericum, Klamath weed and goatweed. Historically it was used for stomach ulcers, colds and wounds as well as low mood.

Today it is sold in the United States as capsules, tablets, teas and liquid extracts, mostly marketed for mood and sometimes for menopause symptoms, and as creams and oils for the skin. As a supplement it is not reviewed by FDA before sale, so quality depends on the maker. A seal from an independent tester tells you the label matches the bottle; our guide to third-party tested supplements explains what those seals cover.

St John's wort interactions: the core safety issue

St John’s wort interactions happen mainly because the herb switches on drug-clearing systems in the body, especially the CYP3A enzymes, as a 2003 study of birth control pills confirmed. When these work faster, many medicines are removed from the body sooner, so blood levels fall and the medicine may stop working as intended. The table lists the medicine groups NCCIH names.

St John's wort and birth control

St John’s wort and birth control is one of the most thoroughly documented interactions. In a 2003 study in Clinical Pharmacology and Therapeutics, 12 healthy women on a combination pill took St John’s wort for two cycles. The body cleared the pill’s hormones faster, and breakthrough bleeding rose from 2 of 12 women to 7 of 12. A 2005 study of 16 women on a lower-hormone pill, published in Contraception, found 13 to 15 percent lower hormone exposure, more breakthrough bleeding and signs of follicle growth and probable ovulation. The 2003 authors advised that women on the pill who use St John’s wort consider adding a barrier method. Ask your clinician or pharmacist about your own method.

St John’s wort is not the only supplement with this kind of warning. Memorial Sloan Kettering advises people on birth control pills to avoid DIM as well, as our DIM supplement guide explains.

Transplant, HIV and blood-thinning medicines

Some of the earliest warnings came from transplant and HIV medicine. In 2000 The Lancet published a report titled “Acute heart transplant rejection due to Saint John’s wort” and, in the same issue, a study of lower indinavir concentrations in people taking the herb. These are drugs where small drops in blood levels can have serious consequences. NCCIH also lists warfarin, digoxin and several cancer drugs. If you take any of them, do not start or stop St John’s wort without talking to the clinician who manages that medicine, because stopping the herb can also change drug levels.

Antidepressants and serotonin

NCCIH warns that taking St John’s wort with certain antidepressants or other drugs that affect serotonin may lead to increased serotonin-related side effects, which can be serious. Never combine it with a prescribed antidepressant, or swap one for the other, without your prescriber. Other supplements that act on serotonin raise similar questions; see our guide to 5-HTP. If you also use hemp products, our article on CBD drug interactions covers the same enzyme system from another angle.

St John's wort side effects

St John’s wort side effects are usually mild in people who take no other medicines. NCCIH says it appears safe for most such adults for up to 12 weeks, and some studies suggest longer use can be safe. Reported problems include:

• Sun sensitivity: large amounts by mouth, or use on the skin, might cause severe skin reactions after sun exposure.
• Common complaints: diarrhea, dizziness, trouble sleeping, restlessness and skin tingling. Headache was more frequent than with placebo in one US trial.
• Pregnancy: NCCIH says it may be unsafe because it may increase the risk of birth defects.
• Breastfeeding: infants of mothers who take it can have colic, drowsiness and lethargy.

What the research on mood shows

Most St John’s wort research tested it in people diagnosed with depression, and the results disagree. NCCIH summarizes the evidence as suggesting it may be helpful for mild or moderate depression, with uncertainty about severe depression and use beyond 12 weeks. The individual studies show why the picture is mixed:

• A 2008 Cochrane review of 29 trials with 5,489 patients found extracts did better than placebo and about as well as standard antidepressants, with fewer dropouts for side effects. The authors noted that trials from German-speaking countries reported more favorable results, which complicates interpretation.
• A 2001 JAMA trial of 200 adults at 11 US medical centers found no significant benefit over placebo on the main outcome over 8 weeks.
• A 2002 JAMA trial of 340 adults at 12 US clinics compared St John’s wort with placebo and the antidepressant sertraline. Neither active pill beat placebo on the main outcomes, so the trial may not have been able to detect a difference.
• A 2008 JAMA trial in 54 children and teens with ADHD found no improvement over placebo.

Depression can be a serious illness. If you or someone close to you may be depressed, talk to a health care provider rather than choosing a supplement on your own. If you are interested in the research on other herbs studied for mood or stress, our guides to saffron and lemon balm describe evidence of similar or weaker quality. For a related herb with its own serious safety record, see our guide to kava.

Who should avoid St John's wort

• Anyone taking a prescription medicine, unless their prescriber or pharmacist has checked it.
• People using hormonal birth control who are relying on it to avoid pregnancy.
• Transplant recipients and people taking HIV medicines, warfarin, digoxin or cancer drugs.
• People taking antidepressants or other drugs that affect serotonin.
• Anyone pregnant or breastfeeding.
• Anyone scheduled for surgery or a new prescription: tell the clinician you take it.

Frequently Asked Questions

Questions about a label? Contact us or read our Buyer’s Guide. Follow the label and ask a healthcare provider before starting any supplement, especially if you take medicines or are pregnant. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Last reviewed October 2026.

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