Drug & supplement interaction

Goldenseal + Diphenhydramine

Diphenhydramine brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, and others.

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

Goldenseal has a moderate interaction with Diphenhydramine. Theoretically, goldenseal might increase the sedative effects of CNS depressants.

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

Goldenseal and Diphenhydramine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CNS DEPRESSANTS

Why this applies to Diphenhydramine

Diphenhydramine 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 gist: diphenhydramine (Benadryl) already makes a lot of people drowsy, and that's actually the point when folks use it for sleep. Goldenseal contains berberine, which in animal studies showed some calming, sleepy effects. So the concern is that pairing the two might pile on extra sedation, leaving you groggier, dizzier, or more foggy-headed than you'd expect.

I want to be straight with you, though: this is a theoretical worry. The sedation from berberine hasn't actually been seen in people, so it's based on lab and animal data, not strong human evidence. Still, since both lean the same direction, it's reasonable to go easy and check with your pharmacist or doctor, especially before driving or if you already feel knocked out by Benadryl.

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.

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 Diphenhydramine one above is one of them. If you take anything else, check it against the full list below.

Moderate 1,235 Minor 1 No known interaction 1,594 (incl. Diphenhydramine)
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 Diphenhydramine

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 Diphenhydramine, 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 Diphenhydramine

This page covers Goldenseal only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine page lists 147 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 Henbane (major).

By severity: 9 major · 119 moderate · 19 minor.

From our pharmacist’s overview on the Diphenhydramine page

“Diphenhydramine (Benadryl, Simply Sleep) is sedating by design, and most of the 147 supplements and herbal ingredients on this list lean into that. Seventy-eight are sedating substances themselves, alcohol and kava the standouts, and stacking them can slow breathing and reflexes well beyond ordinary drowsiness.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine 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 Diphenhydramine 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 Diphenhydramine 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%

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

29 days ago today
Medication Diphenhydramine
Top 25%

#370 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 Diphenhydramine

What Is Diphenhydramine Used For?

Brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, Simply Sleep, Sominex, Diphenhydramine, Compoz, Sleep Aid, Benadryl cream, Benadryl spray, Dermamycin cream, Ziradryl, Nytol

Diphenhydramine temporarily relieves symptoms of hay fever, other upper respiratory allergies, and the common cold — including runny nose, sneezing, itchy or watery eyes, and itching of the nose or throat.

After Bite Xtra gel is formulated for topical use and is approved to temporarily relieve pain and itching from minor burns, minor cuts and scrapes, insect bites, minor skin irritations, and rashes from poison ivy, poison oak, and poison sumac.

See full Diphenhydramine 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 Diphenhydramine, 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 Diphenhydramine supplement interactions › Every supplement checked against Diphenhydramine, ranked by severity Diphenhydramine 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 Diphenhydramine Together: Common Questions

Can you take Goldenseal with Diphenhydramine?
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.
How serious is the Goldenseal and Diphenhydramine 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 Diphenhydramine 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.