Drug & supplement interaction

Phellodendron + Midazolam

Midazolam brand names: Versed, Seizalam, Nayzilam.

Moderate Interaction
The bottom line Moderate

Midazolam falls into 3 drug categories that Phellodendron can interact with; the most serious is rated moderate. Theoretically, phellodendron 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

Phellodendron and Midazolam

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

Why Are There 3 Interactions?

Phellodendron interacts with whole categories of medication. Midazolam falls into 3 of those categories, so it can interact with Phellodendron 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 Midazolam

Midazolam falls under CNS DEPRESSANTS — the group Phellodendron interacts with.

Theoretically, phellodendron might increase the sedative effects of CNS depressants.
Phellodendron contains berberine. Animal research suggests that berberine may have sedative effects. Theoretically, phellodendron might also have CNS depressants effects.
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 midazolam (Versed, Nayzilam). This is a benzodiazepine, so it already slows down brain activity to make you drowsy and relaxed. Phellodendron contains berberine, and in animal studies berberine has shown its own mild calming, sedative-type effects. So the concern is simple addition: pairing the two could pile on extra sleepiness.

If that happened, you might feel groggier, more lightheaded, slower to wake up, or unsteady after the procedure. I want to be straight with you, though. This warning is theoretical, based on lab and animal data, not real human reports, so I wouldn't lose sleep over it. Still, please mention any phellodendron or berberine product to your doctor or pharmacist before a procedure so they can plan around it.

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 3

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

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP3A4.
Phellodendron contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, phellodendron might also inhibit CYP3A4.
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 simple version. Your body relies on a liver enzyme called CYP3A4 to break down and clear midazolam. The berberine in phellodendron may slow that enzyme down a bit. If midazolam isn't cleared as quickly, more of it can hang around, which could make its effects (deeper drowsiness, more sedation, slower breathing, and stronger memory-blocking) stronger or longer-lasting than expected.

Now, the good news: this is a theoretical concern based mostly on lab work, not a proven problem in people. Midazolam is also usually given by a trained professional who's watching you closely. Still, since both calm the body, it's worth mentioning your phellodendron use to your pharmacist or doctor before any procedure so they can plan accordingly.

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
  2. 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
  3. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  4. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
Moderate

MIDAZOLAM (Versed)

3 of 3
Theoretically, phellodendron might reduce metabolism of midazolam, which might increase the risk of severe adverse effects.
Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam. Theoretically, phellodendron might also inhibit the metabolism of midazolam.
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 midazolam (Versed): your liver clears it using an enzyme called CYP3A4. The berberine in phellodendron can slow that enzyme down. When midazolam isn't broken down as quickly, more of it sticks around in your body, so its calming, sleepy effects can hit harder and last longer.

In real terms, that could mean extra drowsiness, deeper sedation, confusion, or slowed breathing. The good news is this concern is mostly theoretical, based on how berberine behaves rather than strong human studies. Still, midazolam is potent and usually given for procedures, so it's worth mentioning. Please tell the anesthesia team or your pharmacist about any phellodendron or berberine products before you receive midazolam.

References
  1. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. 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

Phellodendron Also Interacts With Other Medications

Phellodendron has 1,159 moderate known drug interactions in our database — the Midazolam one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Phellodendron

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

Everything else you take

See Every Supplement That Interacts With Midazolam

This page covers Phellodendron only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Midazolam page lists 202 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), Bitter Orange (major) and Fever Bark (major).

By severity: 11 major · 153 moderate · 38 minor.

From our pharmacist’s overview on the Midazolam page

“Sedation stacked on sedation is the headline risk with midazolam (Versed, Seizalam, Nayzilam). Midazolam is a benzodiazepine used for sedation and seizure emergencies, and 78 of the 202 interacting ingredients here, beer and wine included, add their own drowsiness, which can slide into dangerously slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Midazolam interaction page

One more smart check

Taking Phellodendron as Part of a Dietary Supplement Product? Check It for Interactions

We hold 393 real supplement products containing Phellodendron, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phellodendron. Your product may carry other ingredients that interact with Midazolam too, on top of Phellodendron — 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 Phellodendron and Midazolam 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 Phellodendron
Top 25%

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

29 days ago today
Medication Midazolam
Steady interest

#1,816 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 Phellodendron

What is Phellodendron?

Phellodendron
  • Digestive complaints and diarrhea
  • Inflammation and joint discomfort
  • Stress and weight management (in combination products)
  • Skin conditions (topical, traditional)
  • Antimicrobial support

Phellodendron is a traditional Chinese medicine bark (Huang Bai) that contains berberine and other plant compounds with antimicrobial and anti-inflammatory activity in lab studies. Human evidence for most uses is limited, and it is often sold in combination with other herbs, making its individual effects hard to judge. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Phellodendron monograph & all interactions
Medication

About Midazolam

What Is Midazolam Used For?

Brand names: Versed, Seizalam, Nayzilam

Midazolam is used in several different forms depending on the setting. Injectable midazolam (given by IV or IM shot) is used before and during surgery or procedures — such as endoscopy, cardiac catheterization, or bronchoscopy — to cause sedation, reduce anxiety, and prevent memory of the event. It can also be used to start general anesthesia or to keep heavily sedated, ventilated patients comfortable in a critical care unit. Midazolam HCl oral syrup is used specifically in children for sedation and anxiety relief before procedures or anesthesia induction, in a monitored medical setting only.

Nayzilam nasal spray is indicated for a different purpose: the acute treatment of seizure clusters (also called acute repetitive seizures) in people aged 12 and older who have epilepsy. It is used intermittently — not as a daily seizure medicine — when a cluster of seizures breaks through the person's usual pattern.

See full Midazolam drug information
Keep checking

Other Drugs & Phellodendron

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

0Major
1,159Moderate
0Minor
1,670No known interaction
Moderate

1,159 interactions

Showing 60 of 1,159 moderate interactions — see all 1,159 on the Phellodendron page.

No interaction 1,670 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Phellodendron and Midazolam Together: Common Questions

Can you take Phellodendron with Midazolam?
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 Phellodendron and Midazolam?
Midazolam belongs to more than one drug category, and Phellodendron 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 Phellodendron and Midazolam 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 Midazolam and Phellodendron?

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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.