What happens when you take bupropion with st. john's wort?
Bupropion is an antidepressant that increases the brain chemicals norepinephrine and dopamine. It is prescribed for major depression (Wellbutrin), seasonal mood changes, and smoking cessation (Zyban). St. John's wort (Hypericum perforatum) is a herbal extract sold for low mood. The two can interact in a few different ways.
- Enzyme induction lowers bupropion levels. St. John's wort, mainly through its component hyperforin, switches on liver enzymes (including the CYP450 family) and the P-glycoprotein transporter. In a human pharmacokinetic study, this lowered bupropion exposure modestly, which can weaken the medicine's effect over time.
- Overlapping effects on brain chemicals. Both products act on monoamines: bupropion raises norepinephrine and dopamine, while St. John's wort influences serotonin, norepinephrine, and dopamine. A published case report describes a prolonged facial movement (dystonic) reaction in a woman taking both together, consistent with this overlap.
- A rebound effect if the herb is stopped. Because enzyme induction takes one to two weeks to wear off, stopping St. John's wort abruptly while continuing bupropion can let bupropion levels drift back up, sometimes bringing on restlessness, insomnia, or anxiety.
You may also notice additive activation — jitteriness, trouble sleeping, or a faster heartbeat — because both products are stimulating rather than calming.
Why is this important?
The most reliable concern is that St. John's wort can quietly reduce how well bupropion works. If you are taking bupropion for depression, a weaker effect can let symptoms creep back. If you are taking it (as Zyban) to quit smoking, a reduced effect may make a relapse more likely.
The herb is also unpredictable. Its enzyme-inducing strength varies between products and between batches, so the size of the interaction is hard to forecast. Stopping the herb suddenly can shift bupropion levels in the other direction.
An older worry that the combination sharply raises seizure risk is not well supported in people. Bupropion does lower the seizure threshold on its own, and that is why it is avoided in people with seizure disorders, eating disorders, or alcohol or sedative withdrawal. But the idea that St. John's wort meaningfully adds to that risk comes mostly from one type of animal extract, while other extracts of the same plant were actually protective. There is no good human seizure evidence for the pair. The honest summary is that the herb may blunt bupropion's benefit and has been linked to a movement reaction — not that it reliably triggers seizures.
What should you do?
Before any change: Tell your prescriber and pharmacist about every supplement you take, including "mood," "calm," "energy," and smoking-cessation products, since St. John's wort hides inside many of them. Do not start St. John's wort on your own while you are on bupropion.
Every day on bupropion: If you are not taking the herb, simply keep it out of your routine and stick with approaches your prescriber supports — psychotherapy, exercise, light exposure, or a dose review. Avoid stacking other stimulating or seizure-lowering factors such as heavy alcohol use, crash dieting, or sleep deprivation.
When stopping or switching: If you are already taking St. John's wort and your prescriber wants to start bupropion, stop the herb under guidance and allow time for the enzyme effect to wear off before bupropion is started or adjusted. Never stop or start either product abruptly without telling your prescriber, because the interaction can shift in both directions.
Seek prompt care for any seizure, unusual muscle stiffness or twisting movements, severe agitation, or a return of strong depressive thoughts.
Which specific products are affected?
Bupropion products include generic bupropion (immediate-, sustained-, and extended-release), Wellbutrin SR and Wellbutrin XL, Aplenzin, Forfivo XL, and Zyban for smoking cessation. The interaction applies to all of these. Combination products such as Contrave (bupropion with naltrexone, used for weight management) are affected too.
St. John's wort is sold as standalone capsules, tinctures, and teas, and is also blended into many "mood," "calm," "PMS," and herbal antidepressant products under names such as Kira, Perika, and Movana. Read the full ingredient list of any mood-support product before adding it to a prescription regimen.
The science behind it
The strongest human evidence for this pair is limited but real. Milton and colleagues reported a 58-year-old woman who developed a prolonged oro-facial dystonia (a sustained involuntary movement reaction) while taking bupropion together with St. John's wort, consistent with overlapping effects on dopamine and serotonin (PMID 17578477). On the pharmacokinetic side, Lei and colleagues gave St. John's wort to healthy volunteers and measured a modest reduction in bupropion exposure, in keeping with enzyme induction (PMID 20102294).
The seizure concern is weaker than older write-ups imply. A kindling study of Hypericum extracts in animals found that water and butanol extracts were anticonvulsant and only an ether extract was pro-convulsant, with no human seizure data (PMC6264782). Bupropion's own dose-related seizure risk is documented in its FDA prescribing information, but that is a property of the drug, not proof that the herb adds to it. Overall, the evidence supports a real but moderate interaction driven by reduced drug levels and a movement-reaction case report, rather than a strong additive seizure hazard.
Frequently Asked Questions
Is it dangerous to take St. John's wort with bupropion?
It is best avoided. The main, well-supported problem is that the herb can lower how well bupropion works. A movement-reaction case report exists as well. It is generally considered a moderate interaction rather than an emergency-level one, but you should not combine them without your prescriber's input.
Will St. John's wort cause a seizure if I am on bupropion?
There is no good human evidence that the herb meaningfully adds to bupropion's seizure risk. That worry comes mostly from one type of plant extract tested in animals. Bupropion can lower the seizure threshold on its own, so it is still wise to avoid other seizure-lowering factors.
Can St. John's wort stop my antidepressant from working?
It can reduce the effect. By switching on enzymes that break bupropion down, St. John's wort can lower its levels and let depressive symptoms return. This is the most consistent reason to keep the two apart.
What if I have been taking both already?
Do not stop either one abruptly on your own. Contact your prescriber, who can help you taper safely — stopping the herb suddenly can let bupropion levels rise and cause restlessness or insomnia.
I take Zyban to quit smoking. Does this apply to me?
Yes. Zyban is bupropion, so the same interaction applies. Lowering its levels with St. John's wort could make it harder to stay off cigarettes.
What can I use for mood support instead?
Ask your prescriber. Options that do not interfere with bupropion include psychotherapy, regular exercise, light therapy for seasonal symptoms, and adjusting your prescribed regimen rather than adding an herb.
Key takeaways
- St. John's wort can lower bupropion's blood levels and weaken its effect — the most consistent reason to avoid the pair.
- A human case report links the combination to a prolonged movement (dystonic) reaction from overlapping effects on brain chemicals.
- The often-repeated additive seizure risk is overstated; it rests on animal extract data, not human evidence. This is a moderate, not severe, interaction.
- Do not start or stop either product abruptly — the interaction can shift in both directions.
- Tell every prescriber and pharmacist about all supplements, since St. John's wort hides in many mood and energy products, and review any change with them first.