Drug & supplement interaction

Goldenseal + Methadone

Methadone brand name: Dolophine.

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

Methadone falls into 3 drug categories that Goldenseal can interact with; the most serious is rated moderate. Theoretically, goldenseal might increase the sedative effects of CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Goldenseal and Methadone

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Goldenseal interacts with whole categories of medication. Methadone falls into 3 of those categories, so it can interact with Goldenseal in 3 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 3

Why this applies to Methadone

Methadone falls under CNS DEPRESSANTS — the group Goldenseal interacts with.

Theoretically, goldenseal might increase the sedative effects of CNS depressants.
Goldenseal contains berberine. Animal research shows that berberine can have sedative effects. However, this effect 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 short version on combining goldenseal with methadone. Goldenseal contains berberine, and in animal studies that compound showed some sedating, calming effects. The thinking is that it could add to the drowsiness that methadone already causes, potentially making you feel more sleepy, foggy, or slowed down.

I want to be honest about the evidence here: this is theoretical. The sedation was seen in animals, not actually reported in people, so we're being cautious rather than sounding an alarm. Still, because methadone is a powerful opioid that already slows your breathing and your thinking, it makes sense to play it safe. Please check with your pharmacist or doctor before adding goldenseal, and don't change your methadone on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
  2. 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
  3. Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
  4. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

Methadone also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Goldenseal might increase serum levels of drugs metabolized by CYP2D6.
Clinical and in vitro research shows that goldenseal can significantly inhibit CYP2D6 enzymes, potentially increasing levels of drugs metabolized by CYP2D6.
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 gist with goldenseal and methadone: goldenseal contains berberine, which can block a liver enzyme called CYP2D6. Methadone is partly broken down by this enzyme (along with others). When you slow that breakdown, more methadone can linger in your body than usual. Methadone is not a prodrug, so this means a stronger opioid effect, not a weaker one.

What could that look like? More drowsiness, slowed or shallow breathing, constipation, or feeling overly sedated. Methadone is a drug where small changes really matter, so I'd treat this seriously. The evidence here is moderate, not rock-solid, but please don't add goldenseal without first checking with your pharmacist or the prescriber managing your methadone.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  2. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
  3. Sevior, D. K., Hokkanen, J., Tolonen, A., Abass, K., Tursas, L., Pelkonen, O., and Ahokas, J. T. Rapid screening of commercially available herbal products for the inhibition of major human hepatic cytochrome P450 enzymes using the N-in-one cocktail. Xeno PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Goldenseal might increase serum levels of drugs metabolized by CYP3A4.
Most clinical and in vitro research shows that goldenseal inhibits CYP3A4 enzyme activity and increases serum levels of CYP3A4 substrates, such as midazolam. However, in one small clinical study, goldenseal did not affect the levels of indinavir, a CYP3A4 substrate, in healthy volunteers. This is likely due to the fact that indinavir has a high oral bioavailability, making it an inadequate probe for CYP3A4 interactions and/or that it is primarily metabolized by hepatic CYP3A, while goldenseal has more potential to inhibit intestinal CYP3A enzyme activity. Both goldenseal extract and its isolated constituents berberine and hydrastine inhibit CYP3A, with hydrastine possibly having more inhibitory potential than berberine.
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 with goldenseal and methadone. Your liver uses an enzyme called CYP3A4 to help break methadone down. Goldenseal appears to slow that enzyme, so methadone may not clear as quickly. That can let levels creep up in your body.

Methadone is an active drug (not a prodrug), so higher levels usually mean stronger opioid effects, things like extra drowsiness, slowed or shallow breathing, constipation, and confusion. Methadone can also affect heart rhythm, so any buildup deserves caution. The evidence here is moderate, not certain, but methadone has a narrow safety margin, so even small shifts matter. Please don't stop or change anything on your own. Talk with your pharmacist or doctor before combining these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. Sandhu RS, Prescilla RP, Simonelli TM, Edwards DJ. Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol 2003;43:1283-8.. PubMed
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
  5. Gurley BJ, et al. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activitiy In Vivo. Clin Pharmacol Ther. 2008;83(1):61-69.
  6. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  7. Nguyen JT, Tian DD, Tanna RS, et al. An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Ob

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

Goldenseal Also Interacts With Other Medications

Goldenseal has 1,235 moderate, 1 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 1,235 Minor 1 No known interaction 1,594 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against Goldenseal

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

From our Q&A

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

We hold 1,726 real supplement products containing Goldenseal, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Goldenseal. Your product may carry other ingredients that interact with Methadone too, on top of Goldenseal — 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 Goldenseal 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 Goldenseal
Top 10%

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

29 days ago today
Medication Methadone
Top half

#766 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 Goldenseal

What is Goldenseal?

Goldenseal
  • Digestive upset and diarrhea
  • Colds and respiratory infections
  • Sore throat and mouth sores
  • Skin and eye irritation (topical/traditional)
  • Antimicrobial support

Goldenseal is a popular North American herb that contains berberine, a compound studied for antimicrobial effects. However, strong human evidence for its many traditional uses is largely lacking, and it should be avoided during pregnancy and breastfeeding. Talk to a pharmacist or doctor before using it.

Read the full Goldenseal 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 & Goldenseal

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

0Major
1,235Moderate
1Minor
1,593No known interaction
1,235 Moderate 1 Minor 1,593 No interaction
Moderate

1,235 interactions

Showing 60 of 1,235 moderate interactions — see all 1,235 on the Goldenseal page.

Minor

1 interaction

No interaction 1,593 drugs checked — show the list

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

Showing the 60 most looked-up of 1,593 medications checked with no known interaction — see the full Goldenseal list.

See the full Goldenseal 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
Goldenseal 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 Goldenseal and Methadone Together: Common Questions

Can you take Goldenseal 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 3 interactions listed for Goldenseal and Methadone?
Methadone belongs to more than one drug category, and Goldenseal 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 Goldenseal 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 Goldenseal?

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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.