Drug & supplement interaction

Grape + Methadone

Methadone brand name: Dolophine.

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

Methadone 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 Methadone

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. Methadone 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 Methadone

Methadone 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

Here's the basic idea with grape seed extract and your methadone. Lab studies (done in test tubes, not in people) hint that concentrated grape seed extract might slow down an enzyme called CYP2D6, which is one of the pathways your body uses to clear methadone. If that enzyme works slower, methadone could in theory build up a bit. Since methadone is an active drug (not a prodrug that needs switching on), more of it in your system could mean stronger effects like extra drowsiness, slowed breathing, or constipation.

That said, this is only a theoretical concern and hasn't actually been seen in humans, and eating grapes or drinking grape juice is very unlikely to matter. Concentrated supplements are the question mark. Methadone is a sensitive medicine, so check with your pharmacist or doctor before starting a grape seed product.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Methadone 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

Here's the honest picture: your body uses an enzyme called CYP3A4 to help clear methadone. Grape seed extract may tug on that enzyme, but the research pulls in two directions. Lab (test tube) studies hint it might slow CYP3A4, which could let methadone build up and raise side effects like heavy drowsiness, slowed breathing, or constipation. Animal studies suggest the opposite, that it might speed up the enzyme, which could weaken methadone and risk withdrawal-type symptoms.

The key thing to know is that none of this has actually been seen in people, so it stays theoretical for now. Still, methadone is a drug where small shifts matter, so please check with your pharmacist or doctor before adding a grape seed supplement. Eating grapes as food isn't a concern.

Contact Dr. Brian directly if you have additional questions on this interaction
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 869 moderate, 42 minor known drug interactions in our database — the Methadone one above is among them. If you take anything else, check it against the full list below.

Moderate 869 Minor 42 No known interaction 1,919 (incl. Methadone)
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 Methadone

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 Methadone, 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 Methadone

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methadone page lists 223 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 10 major · 174 moderate · 39 minor.

From our pharmacist’s overview on the Methadone page

“If you take methadone, choose your supplements with genuine care. Of the 223 ingredients on this page, most either add to methadone's sedating effect or change how fast your body clears it, which can push its blood level up or down.”

Reviewed by 2 · Jul 18, 2026

Open the Methadone 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 Methadone 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 Methadone 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%

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

29 days ago today
Medication Methadone
Top 25%

#514 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 Methadone

What Is Methadone Used For?

Brand name: Dolophine

Methadone treats two main problems. Some products are used for severe, persistent pain that needs daily, around-the-clock opioid treatment when other options are not adequate. Some products are used for opioid addiction (heroin or other morphine-like drugs), as detoxification or as maintenance treatment along with social and medical services.

Not every product is approved for every use. Methadone tablets, oral solution and oral concentrate (Intensol) list both pain and opioid addiction. Diskets, Methadose Dispersible tablets and the Methadose and Methadone Hydrocloride oral concentrates are labeled only for opioid addiction. Methadone injection is for severe pain, and for short-term treatment of opioid dependence in people who cannot take medicine by mouth, such as hospitalized patients. It is not approved for outpatient opioid dependence treatment. Methadone is not meant to be used as an as-needed pain reliever.

See full Methadone 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
869Moderate
42Minor
1,918No known interaction
869 Moderate 42 Minor 1,918 No interaction
Moderate

869 interactions

Showing 60 of 869 moderate interactions — see all 869 on the Grape page.

Minor

42 interactions

No interaction 1,918 drugs checked — show the list

We also checked Grape against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,918 medications checked with no known interaction — see the full Grape list.

See the full Grape interactions page
See every supplement checked against Methadone, 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
Grape monograph › Uses, safety, and every drug interaction in one place Methadone supplement interactions › Every supplement checked against Methadone, ranked by severity Methadone 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 Grape and Methadone Together: Common Questions

Can you take Grape with Methadone?
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 Methadone?
Methadone 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 Methadone 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 Methadone and Grape?

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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.