St John's Wort History: Traditional Use to Drug Interactions
St John's wort has a long record in traditional medicine and a mixed record in depression trials. Its interaction record, which includes birth control pills and transplant drugs, is the part readers should check first.
The history of St John's wort runs through Greek, Islamic and Chinese traditional medicine, and its modern story is as much about the medicines it changes as about mood. The record is mixed on mood and clear on interactions. **Interaction warning:** St John's wort can weaken the effect of many prescription medicines, including birth control pills, warfarin, cyclosporine and some HIV drugs. If you take any medicine, talk with a clinician or pharmacist before you start an herb, and do not stop a prescribed medicine on your own. Depression can be serious, so see a health care provider if you or a family member may have it. **Jump to:** [Early use and the name](#early-use-and-the-name), [Depression reviews](#what-the-depression-reviews-found), [Interactions](#why-the-interaction-record-grew), [Frequently asked questions](#frequently-asked-questions), [Bottom line](#bottom-line) ## Early use and the name The [National Center for Complementary and Integrative Health (NCCIH)](https://www.nccih.nih.gov/health/st-johns-wort) says the plant has been widely used in traditional medicine, including Greek, Islamic and Chinese systems. Historically it was used for depression, stomach ulcers, colds and wound healing, and today it is promoted mainly for depression. The name apparently refers to John the Baptist, since the plant blooms near his late June feast, NCCIH says. We did not verify a classical author, so this page names none. For another herb with a long traditional record, see the [turmeric history](/blog/history/history-of-turmeric-and-curcumin-from-ayurveda-to-isolation), which covers Eastern texts and the capsule. ## What the depression reviews found According to PubMed, the [2008 Cochrane review](https://doi.org/10.1002/14651858.CD000448.pub3) pooled 29 trials with 5,489 patients. Its placebo comparisons showed marked heterogeneity, and the nine larger trials gave a response rate ratio of 1.28 for the herb against placebo. Against standard antidepressants, the response ratios were close to 1.0, and fewer people stopped the herb because of side effects than stopped older antidepressants or SSRIs. The authors also noted that trials from German-speaking countries reported results more favorable to the herb. According to PubMed, a [2016 systematic review by Apaydin and colleagues](https://doi.org/10.1186/s13643-016-0325-2) covered 35 studies and 6,993 patients. It found more treatment responders than placebo, no significant difference from antidepressants in mild and moderate depression, and fewer adverse events than antidepressants. | Source | Year | Scope | Main finding | |---|---|---|---| | Linde, Berner and Kriston (Cochrane review) | 2008 | 29 trials, 5,489 patients | Superior to placebo in pooled results, with marked heterogeneity; similar to standard antidepressants; fewer dropouts for side effects | | Apaydin and colleagues (systematic review) | 2016 | 35 studies, 6,993 patients | More responders than placebo; no significant difference from antidepressants in mild and moderate depression; little research on severe depression | | NCCIH fact sheet | 2025 | Summary of the research | Appears more effective than placebo and as effective as standard antidepressants for mild or moderate depression; uncertain for severe depression or use beyond 12 weeks | Both reviews point in the same direction, and both flag heterogeneity among the trials. For the wider stress and sleep picture, see our [sleep and stress guide](/health/sleep-stress-complete-guide). ## Why the interaction record grew According to PubMed, a [2020 review by Nicolussi and colleagues](https://doi.org/10.1111/bph.14936) traces these interactions to activation of the pregnane-X-receptor, which induces CYP3A4 and P-glycoprotein. The review reports that the herb altered the pharmacokinetics of drugs including digoxin, tacrolimus, indinavir, warfarin, alprazolam, simvastatin and oral contraceptives. It also says CYP3A4 induction tracks the hyperforin content of a preparation, so products differ. Three of its four authors list Max Zeller Söhne AG as their affiliation, and readers should weigh that link. The first clinical alarm came in 2000. A [Lancet letter by Ruschitzka and colleagues](https://doi.org/10.1016/S0140-6736(99)05467-7) described acute rejection in two transplant patients, which the authors attributed to a metabolic interaction between St John's wort and cyclosporin. In 2003, a [study of 12 healthy women by Hall and colleagues](https://doi.org/10.1016/j.clpt.2003.08.009) found that the herb roughly halved the half-life of ethinyl estradiol, from 23.4 to 12.2 hours on average. Breakthrough bleeding rose to 7 of 12 women, from 2 of 12 in the control cycle. A [randomized trial of 18 women by Pfrunder and colleagues](https://doi.org/10.1046/j.1365-2125.2003.02005.x) found more intracyclic bleeding when the herb was added to a low-dose contraceptive. Between 13 and 15 of 17 women bled in the two St John's wort cycles, compared with 6 of 17 on the pill alone. [NCCIH's fact sheet](https://www.nccih.nih.gov/health/st-johns-wort) lists more: antidepressants such as amitriptyline and bupropion, anti-seizure drugs such as phenytoin and carbamazepine, heart drugs such as digoxin and ivabradine, and cancer drugs such as irinotecan and imatinib. It also warns that combining the herb with certain antidepressants or other serotonin-acting drugs may lead to serious serotonin-related side effects. ## Frequently asked questions ### Why is St John's wort named after St John? [NCCIH](https://www.nccih.nih.gov/health/st-johns-wort) says the name apparently refers to John the Baptist, because the plant blooms around the time of his feast in late June. The word "apparently" matters. The fact sheet presents this as the likely explanation, not a documented origin. We did not find a dated source that records the naming, so this page does not claim one. Until then, read the link as probable. ### Which classical writers recorded St John's wort? We did not verify a classical writer or passage for this plant in this review, so this page does not name one. [NCCIH](https://www.nccih.nih.gov/health/st-johns-wort) describes its use in Greek, Islamic and Chinese medicine. That traditional record is the history we could confirm, and readers who want a named classical source should check a primary text directly before they cite it. Any dated claim should be checked before it is repeated. ### What did the depression reviews find? The [2008 Cochrane review](https://doi.org/10.1002/14651858.CD000448.pub3) and the [2016 systematic review](https://doi.org/10.1186/s13643-016-0325-2) both found St John's wort better than placebo in pooled results. Neither found a significant difference from standard antidepressants in the comparisons it ran. Both flagged heterogeneity among the trials, and the 2016 review pointed to little research on severe depression. [NCCIH](https://www.nccih.nih.gov/health/st-johns-wort) says the evidence is uncertain for severe depression and for use longer than 12 weeks, so those cases remain open. These are results for trial participants, not a promise for any one person. ### Why does St John's wort interact with so many medicines? According to PubMed, the [2020 review by Nicolussi and colleagues](https://doi.org/10.1111/bph.14936) traces these interactions to activation of the pregnane-X-receptor, which induces CYP3A4 and P-glycoprotein. The degree of CYP3A4 induction tracks the hyperforin content, so the effect can differ between products. That mechanism is why the herb can change the levels of drugs as different as warfarin and birth control pills. Readers should treat the mechanism as a reason for caution, not a dosing guide. ### Is St John's wort safe with birth control pills or transplant drugs? Not without a clinician's review. A [2000 Lancet letter](https://doi.org/10.1016/S0140-6736(99)05467-7) linked acute rejection in two transplant patients to an interaction with cyclosporin. A [2003 study of 12 women](https://doi.org/10.1016/j.clpt.2003.08.009) found more breakthrough bleeding on the herb, and its authors advised counseling women to expect that and to consider a barrier method of contraception. [NCCIH](https://www.nccih.nih.gov/health/st-johns-wort) says that for adults not taking other medicines, the herb appears safe for up to 12 weeks. Other side effects can include diarrhea, dizziness, trouble sleeping and skin tingling. This page cannot tell you whether an interaction applies to your medicine, so ask your prescriber or pharmacist first. ### Is St John's wort regulated like a drug in the United States? No. [NCCIH](https://www.nccih.nih.gov/health/st-johns-wort) says many herbal products taken by mouth are sold as dietary supplements, and unlike drugs, they are not approved by the U.S. Food and Drug Administration before sale. Manufacturers are responsible for the safety and labeling of their products, and the FDA can act when public health concerns arise. We did not verify how other countries classify the herb, so this page does not describe them. For how to read a supplement label, see our [supplement safety guide](/health/vitamin-d-complete-guide/supplement-safety-quality-testing-guide). ## Bottom line St John's wort has a long record in traditional medicine and a mixed record in depression trials, with mild to moderate depression as its best-supported use. The interaction record is the part most readers should act on before they start it. Check each prescription and over-the-counter medicine with a clinician or pharmacist before combining it with the herb, and ask again when the answer is unclear. In the [2003 study of 12 women](https://doi.org/10.1016/j.clpt.2003.08.009), seven had breakthrough bleeding on the herb, compared with two during the control cycle. **Next reads** - [Supplement safety guide](/health/vitamin-d-complete-guide/supplement-safety-quality-testing-guide): how to read a supplement label before you buy. - [Turmeric and Curcumin: From Eastern Texts to the Capsule](/blog/history/history-of-turmeric-and-curcumin-from-ayurveda-to-isolation): another herb's history, from Eastern texts to the capsule. ### Related reading - [milk thistle's history and its liver trials](/blog/history/history-of-milk-thistle-from-dioscorides-to-silymarin) - [valerian's history and its sleep trial record](/blog/history/history-of-valerian-from-galen-to-sleep-tea)