St. John's wort interactions: What drugs clash with this herbal supplement?

When you take St. John's wort, a herbal supplement often used for mild depression. Also known as Hypericum perforatum, it may seem harmless because it’s natural—but it doesn’t play nice with many prescription drugs. This herb doesn’t just float through your system. It kicks your liver into high gear, forcing it to break down other medications faster than they’re meant to. That means your pills might not work at all—or worse, they could build up and cause toxic side effects.

One of the biggest risks is with antidepressants, including SSRIs like sertraline and fluoxetine. Mixing St. John’s wort with these can trigger serotonin syndrome—a dangerous spike in brain chemicals that causes shaking, rapid heartbeat, confusion, and even seizures. It’s not a myth. Emergency rooms see this every year. Then there’s birth control pills, used by millions to prevent pregnancy. St. John’s wort lowers hormone levels so much that breakthrough bleeding and unintended pregnancies happen. It’s not a small risk. It’s a real one.

And it doesn’t stop there. Blood thinners like warfarin, a common medication to prevent clots, can become less effective, raising your risk of stroke or pulmonary embolism. Even drugs for HIV, cancer, and heart conditions like digoxin, used to treat irregular heartbeats can be thrown off balance. The reason? St. John’s wort affects the CYP3A4 and CYP2C9 enzymes—your body’s main drug-processing system. If you’re on anything that’s metabolized by these enzymes, you’re playing with fire.

People often don’t realize they’re at risk because they think herbal means safe. But if you’re taking a pill for a chronic condition, you can’t treat St. John’s wort like a vitamin. Doctors don’t always ask about supplements. You have to speak up. Keep a list of everything you take—prescriptions, over-the-counter meds, teas, and herbs—and bring it to every appointment.

Below, you’ll find real cases from people who learned the hard way—what happened when St. John’s wort mixed with their meds, how they caught it, and what they did next. These aren’t warnings. They’re survival guides.