Short answer: Yes, with many. NCCIH says St. John's wort can interact in dangerous, sometimes life-threatening ways with medicines, and can weaken birth control pills, warfarin, some statins, some antidepressants, transplant, seizure, heart, HIV and cancer drugs. Taken with some antidepressants it may cause serious serotonin side effects. In one study, breakthrough bleeding on the pill rose from 2 of 12 women to 7 of 12.
The NCCIH clinical digest says St. John's wort has an overall high risk of drug interactions because it strongly switches on cytochrome P450 enzymes and intestinal P-glycoprotein, which the body uses to break down and move many drugs. More enzyme activity means many medicines are cleared faster and their levels drop.
NCCIH says that although telling health care providers about any supplement matters, it is especially crucial for St. John's wort because it interacts with so many medicines.
| Group | Examples NCCIH names |
|---|---|
| Birth control | Birth control pills |
| Blood thinner | Warfarin |
| Cholesterol | Certain statins, including simvastatin |
| Antidepressants | Some, including amitriptyline and bupropion |
| Transplant | Cyclosporine |
| Seizure | Phenytoin, carbamazepine |
| Heart | Digoxin, ivabradine |
| HIV | Indinavir, nevirapine |
| Cancer | Irinotecan, imatinib, docetaxel |
The digest adds benzodiazepines to the documented list. The MedlinePlus warfarin page also lists St. John's wort among herbal products that may interact with warfarin. The estradiol tablet label names it among products that may lower estrogen levels.
In a 2003 study, 12 women on a combined birth control pill took 300 mg of St. John's wort three times a day for two cycles. The half-life of ethinyl estradiol, the estrogen in the pill, fell from about 23 hours to about 12 hours, and the body cleared the progestin norethindrone faster.
Breakthrough bleeding happened in 2 of 12 women before St. John's wort and 7 of 12 while taking it. The authors concluded women on the pill should expect breakthrough bleeding and should consider adding a barrier method while using St. John's wort.
NCCIH says 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. It also says large doses by mouth, or use on the skin, may cause severe skin reactions after sun exposure, and that it may be unsafe in pregnancy.
For adults not taking any medicine, NCCIH says it appears safe for up to 12 weeks. Anyone on a prescription who is thinking about it, or wants to stop it, can ask a prescriber or pharmacist first, since stopping can also change drug levels. Dose Track keeps supplements and prescriptions in one list you can show at a visit.
Read more on Dose Track: St. John's wort guide · Tirzepatide and the birth control pill · Estradiol tablets side effects · Interaction checker