Drug & supplement interaction

European Barberry + Methadone

Methadone brand name: Dolophine.

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

Methadone falls into 2 drug categories that European Barberry can interact with; the most serious is rated moderate. Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.

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

European Barberry and Methadone

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

Why Are There 2 Interactions?

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

Moderate

CNS DEPRESSANTS

1 of 2

Why this applies to Methadone

Methadone falls under CNS DEPRESSANTS — the group European Barberry interacts with.

Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.
Animal research suggests that berberine, a constituent of European barberry, might have sedative effects. Theoretically, European barberry might have a similar effect.
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 short version: berberine, the main active part of European barberry, has shown sedative (calming, drowsy) effects in animal studies. Methadone is already a strong opioid that can make you sleepy, slow your breathing, and lower your alertness. The concern is that stacking the two could add up, leaving you more drowsy or foggy than expected.

I want to be honest about the strength of this: it's theoretical, based on how berberine behaves in lab and animal research, not on real cases in people taking methadone. Still, methadone is a medication where extra sedation is worth taking seriously. Don't change anything on your own. Just check with your pharmacist or doctor before adding barberry so they can keep an eye on you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
  2. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Methadone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, European barberry might increase the levels and clinical effects of CYP3A4 substrates.
There is very preliminary evidence suggesting that berberine, a constituent of European barberry, might inhibit the CYP3A4 enzyme. Theoretically, European barberry might have a similar effect.
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 gist for methadone. Your liver uses an enzyme called CYP3A4 to help break this medicine down. Berberine, the main active compound in European barberry, may gently slow that enzyme. If it does, your body could clear methadone a bit more slowly, letting levels creep up. Methadone is active as-is (not a prodrug), so higher levels mean stronger opioid effects: more drowsiness, slowed breathing, confusion, or constipation.

I want to be honest about the evidence here. This is theoretical, based on how berberine behaves in the lab, not real patient cases. Still, methadone is a drug where small shifts matter, so please don't add barberry without checking with your prescriber or pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. 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

European Barberry Also Interacts With Other Medications

European Barberry has 1,209 moderate 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 1,209 No known interaction 1,621 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against European Barberry

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

From our Q&A

Questions About European Barberry 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 European Barberry 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 European Barberry 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 European Barberry as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2 real supplement products containing European Barberry, each one broken down to its full ingredient list — and combination products often carry several ingredients besides European Barberry. Your product may carry other ingredients that interact with Methadone too, on top of European Barberry — 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 European Barberry 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 European Barberry
Steady interest

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

29 days ago today
Medication Methadone
Top 25%

#699 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 European Barberry

What is European Barberry?

European Barberry
  • Digestive upset
  • Antimicrobial support
  • Blood sugar support
  • Cholesterol and metabolic support
  • Skin conditions

European barberry is a shrub whose root, bark, and berries contain berberine, a bitter plant alkaloid that has been studied mostly in isolated form. Some early research on berberine is promising for blood sugar and cholesterol, but high-quality evidence for the whole barberry herb is limited. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full European Barberry monograph & all interactions
Medication

About Methadone

What Is Methadone Used For?

Brand name: Dolophine

Methadone treats severe and persistent pain that requires daily, around-the-clock, long-term opioid treatment and cannot be managed adequately with other options. It is available in several forms for this use, including oral solution, oral tablets, oral concentrate, and injectable forms (intravenous, intramuscular, and subcutaneous). Injectable methadone is not approved for outpatient pain treatment — it is reserved for hospitalized patients unable to take oral medication.

Methadone is also used for the detoxification and maintenance treatment of opioid addiction (dependence on heroin or other morphine-like drugs). Oral forms — including tablets, dispersible tablets (such as Methadose Dispersible and DISKETS), and oral concentrates (such as Methadone Hydrochloride Intensol™, Methadose, and others) — are approved for this use. By law, methadone for opioid addiction treatment must be dispensed only by certified opioid treatment programs. Injectable methadone is not approved for outpatient addiction treatment.

See full Methadone drug information
Keep checking

Other Drugs & European Barberry

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

0Major
1,209Moderate
0Minor
1,620No known interaction
1,209 Moderate 1,620 No interaction
Moderate

1,209 interactions

Showing 60 of 1,209 moderate interactions — see all 1,209 on the European Barberry page.

No interaction 1,620 drugs checked — show the list

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

Showing the 60 most looked-up of 1,620 medications checked with no known interaction — see the full European Barberry list.

See the full European Barberry 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
European Barberry 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 European Barberry and Methadone Together: Common Questions

Can you take European Barberry 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 European Barberry and Methadone?
Methadone belongs to more than one drug category, and European Barberry 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 European Barberry 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 European Barberry?

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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.