Drug & supplement interaction

Grape + Buproprion, Dextromethorphan

Buproprion, Dextromethorphan brand name: Auvelity.

Moderate Interaction
The bottom line Moderate

Buproprion, Dextromethorphan falls into 2 drug categories that Grape can interact with; the most serious is rated moderate. Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.

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

Grape and Buproprion, Dextromethorphan

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

Why Are There 2 Interactions?

Grape interacts with whole categories of medication. Buproprion, Dextromethorphan falls into 2 of those categories, so it can interact with Grape 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 2D6 (CYP2D6) SUBSTRATES

1 of 2

Why this applies to Buproprion, Dextromethorphan

Buproprion, Dextromethorphan falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Grape interacts with.

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

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

Auvelity is a combo of bupropion and dextromethorphan, and here's the clever part: the bupropion is actually there to block the CYP2D6 enzyme so your body doesn't break down the dextromethorphan too fast. That keeps the dextromethorphan working in your brain. Grape seed extract has shown, in lab dish studies only, that it might also slow down CYP2D6.

So in theory, a concentrated grape seed supplement could nudge dextromethorphan levels a little higher, which might mean more dizziness, drowsiness, or nausea. I want to stress this is only test-tube data and has never been seen in real people, and eating grapes or drinking grape juice won't do this. Still, before starting any grape seed capsule, run it past your pharmacist or doctor first.

References
  1. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Buproprion, Dextromethorphan also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

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

Auvelity combines bupropion and dextromethorphan, and the bupropion part actually works to slow the breakdown of dextromethorphan so it stays active in your brain longer. The bigger question with grape products is CYP3A4, an enzyme involved in processing many medicines. The catch is that the science here is genuinely murky. Lab (test tube) studies hint that concentrated grape seed extract might block CYP3A4, while animal studies suggest it might speed it up. We just don't have human reports either way.

Because the evidence is so preliminary and conflicting, I wouldn't lose sleep over eating grapes. With concentrated grape seed extract supplements, it's worth a quick check with your pharmacist, mainly because Auvelity can already cause dizziness, nausea, or trouble sleeping.

References
  1. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  2. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu

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

Grape Also Interacts With Other Medications

Grape has 867 moderate, 42 minor known drug interactions in our database — the Buproprion, Dextromethorphan one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Grape

Covers the 2,830 medications we’ve checked against Grape. Pick one to open its full report.

From our Q&A

Questions About Grape or Buproprion, Dextromethorphan

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grape or Buproprion, Dextromethorphan, 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 Buproprion, Dextromethorphan

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Buproprion, Dextromethorphan page lists 178 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lithium (major), St. John's Wort (major) and 1,3-dmaa (moderate).

By severity: 4 major · 134 moderate · 40 minor.

From our pharmacist’s overview on the Buproprion, Dextromethorphan page

“Auvelity pairs dextromethorphan with bupropion to treat depression, and its interaction list is one to approach carefully, with 178 supplements on file and four of them rated major. St.”

Reviewed by 2 · Jul 18, 2026

Open the Buproprion, Dextromethorphan interaction page

One more smart check

Taking Grape as Part of a Dietary Supplement Product? Check It for Interactions

We hold 8,053 real supplement products containing Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grape. Your product may carry other ingredients that interact with Buproprion, Dextromethorphan too, on top of Grape — 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 Grape and Buproprion, Dextromethorphan 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 Grape
Top 5%

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

29 days ago today
Medication Buproprion, Dextromethorphan
Steady interest

#1,881 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 Grape

What is Grape?

Grape
  • Antioxidant support
  • Heart and circulation health
  • Vein problems (such as varicose veins)
  • Eye health
  • General anti-inflammatory support

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is healthy and generally safe, the supplement evidence for treating specific conditions is mostly limited or preliminary. Talk with your pharmacist or doctor before starting a grape supplement.

Read the full Grape monograph & all interactions
Medication

About Dextromethorphan and Bupropion

What Is Dextromethorphan and Bupropion Used For?

Brand name: Auvelity

Auvelity (dextromethorphan/bupropion) is approved to treat major depressive disorder (MDD) in adults. It is also approved to treat agitation associated with dementia due to Alzheimer's disease in adults.

For Alzheimer's-related agitation, Auvelity is not meant to be taken only when agitation flares up — it is a scheduled, ongoing treatment, not an as-needed medication.

See full Dextromethorphan and Bupropion drug information
Keep checking

Other Drugs & Grape

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

0Major
867Moderate
42Minor
1,920No known interaction
Moderate

867 interactions

Showing 60 of 867 moderate interactions — see all 867 on the Grape page.

Minor

42 interactions

No interaction 1,920 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Grape and Buproprion, Dextromethorphan Together: Common Questions

Can you take Grape with Buproprion, Dextromethorphan?
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 Grape and Buproprion, Dextromethorphan?
Buproprion, Dextromethorphan belongs to more than one drug category, and Grape 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 Grape and Buproprion, Dextromethorphan 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

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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.