Drug & supplement interaction

Phellodendron + Ramelteon

Ramelteon brand name: Rozerem.

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

Ramelteon 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 Ramelteon

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. Ramelteon 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 Ramelteon

Ramelteon 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

Ramelteon (Rozerem) is a sleep aid that gently nudges your brain's melatonin signals to help you drift off. Phellodendron contains berberine, and in animal studies berberine has shown some calming, sedative-like activity. So the concern here is simple: stacking the two could add up and make you more drowsy than you bargained for.

If that happened, you might feel extra groggy, lightheaded, or slow to wake up the next morning, with a higher chance of feeling unsteady if you get up during the night. I want to be honest though: this is a theoretical caution based on lab and animal data, not proven in people. Real-world risk is likely low, but please run it by your pharmacist or doctor before combining them.

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 2C9 (CYP2C9) SUBSTRATES

2 of 3

Ramelteon also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP2C9.
Phellodendron contains berberine. Preliminary clinical research shows that berberine can inhibit CYP2C9. Theoretically, phellodendron might also inhibit CYP2C9.
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 Rozerem (ramelteon). Your body uses certain liver enzymes to break this sleep aid down. Phellodendron, mainly because of the berberine in it, may slow one of those enzymes (CYP2C9). If that enzyme works slower, a little more ramelteon could linger in your system, which might make you feel groggier, drowsier the next morning, or more dizzy than usual.

I want to be honest about how solid this is: it's a theoretical concern based on how these compounds behave, not something proven in people taking the two together. Ramelteon isn't a prodrug, so the worry here is stronger effect, not weaker. Still, before pairing them, run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Ramelteon 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 short version: your body clears Ramelteon mainly through a liver enzyme called CYP3A4. The berberine in Phellodendron may slow that enzyme down a bit. If it does, Ramelteon could hang around in your system longer than usual, which might make it stronger than expected. With a sleep aid, that could mean feeling extra drowsy, groggy, or foggy the next morning.

I want to be honest about the evidence, though. This concern is theoretical, based on how berberine behaves in lab studies, not on real cases with Ramelteon. So it may not amount to much in practice. Still, since both affect how sleepy you feel, it's worth a quick chat with your pharmacist or doctor before combining them.

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
  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

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

Moderate 1,159 No known interaction 1,671 (incl. Ramelteon)
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.

From our Q&A

Questions About Phellodendron or Ramelteon

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Phellodendron or Ramelteon, 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 Ramelteon

This page covers Phellodendron only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ramelteon page lists 228 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 · 173 moderate · 46 minor.

From our pharmacist’s overview on the Ramelteon page

“Ramelteon (Rozerem) is a prescription sleep aid, and its 228 interacting supplements call for real care, starting with the nine rated major. The frustrating part is that the things sleepless people typically reach for, kava, CBD, a glass of wine before bed, sit at the heart of the problem.”

Reviewed by 2 · Jul 18, 2026

Open the Ramelteon 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 Ramelteon 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 Ramelteon 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%

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

29 days ago today
Medication Ramelteon
Steady interest

#1,453 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 Ramelteon

What Is Ramelteon Used For?

Brand name: Rozerem

Ramelteon treats insomnia marked by difficulty with sleep onset, meaning trouble falling asleep.

This use is supported for Rozerem and for ramelteon tablets (including film-coated tablets). The studies behind it lasted up to six months.

See full Ramelteon 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
1,159 Moderate 1,670 No 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

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

Showing the 60 most looked-up of 1,670 medications checked with no known interaction — see the full Phellodendron list.

See the full Phellodendron interactions page
See every supplement checked against Ramelteon, 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
Phellodendron monograph › Uses, safety, and every drug interaction in one place Ramelteon supplement interactions › Every supplement checked against Ramelteon, ranked by severity Ramelteon 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 Phellodendron and Ramelteon Together: Common Questions

Can you take Phellodendron with Ramelteon?
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 Ramelteon?
Ramelteon 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 Ramelteon 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 Ramelteon 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.