Drug & supplement interaction

St. John's Wort + Bupropion

Bupropion brand names: Wellbutrin, Wellbutrin SR, Zyban, Wellbutrin XL, Aplenzin, and others.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Bupropion falls into 2 drug categories that St. John's Wort can interact with; the most serious is rated moderate. St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

St. John's Wort and Bupropion

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

St. John's Wort interacts with whole categories of medication. Bupropion falls into 2 of those categories, so it can interact with St. John's Wort in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

1 of 2

Why this applies to Bupropion

Bupropion falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES — the group St. John's Wort interacts with.

St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion, a CYP2B6 substrate, reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: St. John's wort tends to speed up the enzyme (CYP2B6) that your body uses to clear bupropion. When you take them together, your bupropion can be broken down a little faster, so blood levels drop. In one clinical study, levels fell by roughly 14% with a 20% bump in clearance. That's a modest change, not a dramatic one.

In real life, this could mean your bupropion works a bit less than expected, so your depression, seasonal mood symptoms, or quit-smoking support might not feel as strong. Since St. John's wort is also used for mood, doubling up on antidepressant-type effects raises other concerns too. Please don't change anything on your own. Check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lei HP, Yu XY, Xie HT, et al. Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica 2010;40(4):275-81. PubMed
Moderate

BUPROPION (Wellbutrin)

2 of 2
St. John's wort might reduce the levels and effects of bupropion.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort.
Severity Moderate Likelihood Probable Evidence B

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know if you take bupropion (Wellbutrin) and are thinking about St. John's wort. This herb tends to speed up a liver enzyme called CYP2B6, which is one of the main pathways your body uses to process bupropion. In one clinical study, people clearing bupropion about 20% faster, so blood levels dropped a bit. The practical worry is weaker treatment, meaning your depression, seasonal symptoms, or quit-smoking support may not work as well.

The change here was fairly modest, not dramatic, but it points in the direction of less benefit. Both products also work on mood chemicals, so combining them is something your prescriber should weigh in on. Please loop in your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lei HP, Yu XY, Xie HT, et al. Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica 2010;40(4):275-81. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

St. John's Wort Also Interacts With Other Medications

St. John's Wort has 755 major, 387 moderate known drug interactions in our database — the Bupropion one above is among them. If you take anything else, check it against the full list below.

Major 755 Moderate 387 No known interaction 1,688 (incl. Bupropion)
Taking anything else?

Check Another of Your Medications Against St. John's Wort

Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.

From our Q&A

Questions About St. John's Wort or Bupropion

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers St. John's Wort or Bupropion, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Bupropion

This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Bupropion page lists 46 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (moderate), African Wild Potato (moderate), Artichoke (moderate) and Astaxanthin (moderate).

By severity: 1 major · 33 moderate · 12 minor.

From our pharmacist’s overview on the Bupropion page

“Bupropion (Wellbutrin, Zyban) deserves genuine care around supplements, and the entry to understand first is activated charcoal, the only major-rated interaction on this list. Charcoal and similar bulk products can soak up the drug in the gut and blunt its effect, so space them well apart from your dose.”

Reviewed by 2 · Jul 18, 2026

Open the Bupropion interaction page

One more smart check

Taking St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Bupropion too, on top of St. John's Wort — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where St. John's Wort and Bupropion Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement St. John's Wort
Top 25%

#156 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Bupropion
Top 1%

#21 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About St. John's Wort

What is St. John's Wort?

St. John's Wort
  • Mild to moderate depression
  • Anxiety and stress
  • Sleep problems
  • Menopausal symptoms
  • Wound healing (topical)

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.

Read the full St. John's Wort monograph & all interactions
Medication

About Bupropion

What Is Bupropion Used For?

Brand names: Wellbutrin, Wellbutrin SR, Zyban, Wellbutrin XL, Aplenzin, Forfivo XL

Bupropion is FDA-approved to treat major depressive disorder (MDD) — a form of clinical depression. Extended-release formulations (XL and hydrobromide versions, including Aplenzin) are also approved for the prevention of seasonal affective disorder (SAD), the pattern of depression that tends to arrive in autumn and winter.

Not all formulations share every indication. Aplenzin (bupropion hydrobromide extended-release) and bupropion hydrochloride extended-release tablets (XL) are indicated for both MDD and SAD. Bupropion hydrochloride extended-release tablets (SR) and bupropion hydrochloride immediate-release tablets are indicated for MDD only.

See full Bupropion drug information
Keep checking

Other Drugs & St. John's Wort

Browse every other medication we’ve checked against St. John's Wort — both the ones with a known interaction and the ones without. Select any drug for the full detail.

755Major
387Moderate
0Minor
1,687No known interaction
755 Major 387 Moderate 1,687 No interaction
Major

755 interactions

Showing 60 of 755 major interactions — see all 755 on the St. John's Wort page.

Moderate

387 interactions

Showing 60 of 387 moderate interactions — see all 387 on the St. John's Wort page.

No interaction 1,687 drugs checked — show the list

We also checked St. John's Wort against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,687 medications checked with no known interaction — see the full St. John's Wort list.

See the full St. John's Wort interactions page
See every supplement checked against Bupropion, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
St. John's Wort monograph › Uses, safety, and every drug interaction in one place Bupropion supplement interactions › Every supplement checked against Bupropion, ranked by severity Bupropion drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking St. John's Wort and Bupropion Together: Common Questions

Can you take St. John's Wort with Bupropion?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for St. John's Wort and Bupropion?
Bupropion belongs to more than one drug category, and St. John's Wort interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the St. John's Wort and Bupropion interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Bupropion and St. John's Wort?

Our pharmacists answer your medication & supplement questions — free.

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.