Drug & supplement interaction

Goldenseal + Zaleplon

Zaleplon brand names: Sonata, Starnoc.

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

Zaleplon falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Goldenseal and Zaleplon

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

Why Are There 2 Interactions?

Goldenseal interacts with whole categories of medication. Zaleplon falls into 2 of those categories, so it can interact with Goldenseal 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 Zaleplon

Zaleplon 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

Zaleplon (Sonata) is already a sleep aid that quiets brain activity to help you drift off, so it's worth knowing what goldenseal might add to that. Goldenseal contains berberine, and in animal studies berberine has shown some mild sedative effects of its own. The concern here is simple: stacking two things that calm the brain could, in theory, leave you feeling more drowsy, groggy, or unsteady than zaleplon alone would.

I want to be honest about the strength of this one. It's a theoretical interaction based on lab and animal data, and this added sedation hasn't actually been reported in people. So don't panic, but if you take goldenseal regularly and notice extra morning grogginess or dizziness, check in with your pharmacist or doctor before changing anything.

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 3A4 (CYP3A4) SUBSTRATES

2 of 2

Zaleplon 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 for Zaleplon (Sonata): your body relies on an enzyme called CYP3A4 to break this sleep aid down and clear it out. Goldenseal appears to slow that enzyme down. When the cleanup crew works slower, more zaleplon can hang around in your system than expected.

For you, that usually means a stronger or longer-lasting effect. Think extra drowsiness the next morning, dizziness, grogginess, or feeling unsteady on your feet. Zaleplon isn't a prodrug, so this goes in the direction of more drug effect, not less. The evidence here is moderate, not rock-solid, but it's worth taking seriously since it touches your alertness. Please check with your pharmacist or doctor before combining the two so they can weigh in on your situation.

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 Zaleplon 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. Zaleplon)
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 Zaleplon

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 Zaleplon, 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 Zaleplon

This page covers Goldenseal only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Zaleplon page lists 195 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: 9 major · 147 moderate · 39 minor.

Open the Zaleplon 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 Zaleplon 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 Zaleplon 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%

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

29 days ago today
Medication Zaleplon
Steady interest

#2,533 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 Zaleplon

What Is Zaleplon Used For?

Brand names: Sonata, Starnoc

Zaleplon capsules are approved for the short-term treatment of insomnia. Specifically, they help reduce the time it takes to fall asleep (sleep onset). Clinical studies showed this benefit for up to 30 days of use.

Zaleplon has not been shown to increase total sleep time or reduce the number of times you wake up during the night. It is intended for short-term use, and if sleep problems continue beyond 7–10 days, a doctor should evaluate you for an underlying cause.

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

Can you take Goldenseal with Zaleplon?
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 Goldenseal and Zaleplon?
Zaleplon 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 Zaleplon 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 Zaleplon 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.