Drug & supplement interaction

Berberine + Aspirin, Caffeine, Dihydrocodeine Bitartrate

Aspirin, Caffeine, Dihydrocodeine Bitartrate brand name: Synalgos DC.

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

Aspirin, Caffeine, Dihydrocodeine Bitartrate falls into 4 drug categories that Berberine can interact with; the most serious is rated moderate. Theoretically, berberine might increase the sedative effects of CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Berberine and Aspirin, Caffeine, Dihydrocodeine Bitartrate

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Berberine interacts with whole categories of medication. Aspirin, Caffeine, Dihydrocodeine Bitartrate falls into 4 of those categories, so it can interact with Berberine in 4 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 4

Why this applies to Aspirin, Caffeine, Dihydrocodeine Bitartrate

Aspirin, Caffeine, Dihydrocodeine Bitartrate falls under CNS DEPRESSANTS — the group Berberine interacts with.

Theoretically, berberine might increase the sedative effects of CNS depressants.
Animal research suggests that berberine may have sedative effects. Theoretically, use of berberine along with CNS depressants might produce additive therapeutic and adverse 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

Synalgos DC contains dihydrocodeine, an opioid pain reliever that can already make you feel drowsy, foggy, or slowed down. The concern here is simple: berberine has shown mild sedative effects in animal studies, so in theory pairing it with this medication could add to that sleepiness. We're talking about possible extra grogginess, slower thinking, or feeling more wiped out than usual.

I want to be honest about the strength of this, though. This is a theoretical concern based on lab and animal research, not strong human data, so for most people it's likely a minor issue. Still, since opioids carry their own sedation risk, it's worth a quick chat with your pharmacist or doctor before combining them, especially before you drive or operate 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 2D6 (CYP2D6) SUBSTRATES

2 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, berberine might increase serum levels of drugs metabolized by CYP2D6.
In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6. Theoretically, use of berberine with drugs metabolized by CYP2D6 might increase drug levels and increase the risk of adverse effects.
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 wrinkle with this combo: the dihydrocodeine part of Synalgos DC is a prodrug. Your body uses an enzyme called CYP2D6 to turn it into the stronger active painkiller. Berberine appears to slow that same enzyme down, so in theory it could mean less of the drug gets switched on, leaving you with weaker pain relief than expected.

I'll be honest, this is mostly based on lab work and a little early human data, so it's more of a theoretical caution than a sure thing. The aspirin and caffeine pieces aren't really affected here. If you're leaning on this medicine for real pain and want to try berberine, just run it by your pharmacist or doctor first so they can keep an eye on how well your pain stays controlled.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. 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
  3. 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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, berberine might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, use of berberine with drugs metabolized by CYP3A4 might increase drug levels and increase the risk of adverse effects.
Severity Moderate Likelihood Possible Evidence A

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

This combination product (Synalgos DC) blends aspirin, caffeine, and dihydrocodeine. The piece to watch here is the dihydrocodeine, an opioid pain reliever that's partly handled by the CYP3A4 enzyme. Berberine appears to mildly slow that enzyme down. In theory, that could let a bit more of the opioid linger in your system, which might mean stronger effects like extra drowsiness, dizziness, constipation, or slowed breathing.

Keep in mind this is mostly a theoretical concern based on lab work and early studies, so it may not cause real trouble for most people. Caffeine and aspirin aren't the main worry. Still, since this medicine contains an opioid, I'd run it by your pharmacist or doctor before adding berberine, and watch for unusual sleepiness if you do take both.

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
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

4 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, berberine might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
In vitro and in vivo research suggest that berberine can inhibit platelet aggregation. Theoretically, berberine might have additive effects when used with anticoagulant and antiplatelet drugs and increase the risk of bleeding.
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

The piece of this combo pill I want to focus on is the aspirin. Aspirin is a blood thinner that keeps your platelets (the cells that clump together to form clots) from sticking as well. Berberine appears to do something similar in the test tube, gently slowing platelet activity. Put the two together and the worry is simply additive: a bit more thinning than aspirin alone, which could mean easier bruising, nosebleeds, or bleeding that takes longer to stop.

Now, the honest part: this concern comes from lab and animal research only, not strong human studies, so it stays theoretical. Still, since you are already on a daily aspirin product, it is worth a quick chat with your pharmacist or doctor before adding berberine, especially if you notice any unusual bleeding.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
  2. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.

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

Berberine Also Interacts With Other Medications

Berberine has 1 major, 1,158 moderate known drug interactions in our database — the Aspirin, Caffeine, Dihydrocodeine Bitartrate one above is among them. If you take anything else, check it against the full list below.

Major 1 Moderate 1,158 No known interaction 1,671 (incl. Aspirin, Caffeine, Dihydrocodeine Bitartrate)
Taking anything else?

Check Another of Your Medications Against Berberine

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

From our Q&A

Questions About Berberine or Aspirin, Caffeine, Dihydrocodeine Bitartrate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Berberine or Aspirin, Caffeine, Dihydrocodeine Bitartrate, 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate

This page covers Berberine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Dihydrocodeine Bitartrate page lists 398 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), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

Open the Aspirin, Caffeine, Dihydrocodeine Bitartrate interaction page

One more smart check

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

We hold 908 real supplement products containing Berberine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Berberine. Your product may carry other ingredients that interact with Aspirin, Caffeine, Dihydrocodeine Bitartrate too, on top of Berberine — 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 Berberine and Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 Berberine
Top 10%

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

29 days ago today
Medication Aspirin, Caffeine, Dihydrocodeine Bitartrate
Steady interest

#1,526 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 Berberine

What is Berberine?

Berberine
  • Blood sugar control
  • High cholesterol
  • Heart and metabolic health
  • Digestive upset
  • Antimicrobial support
  • Weight management

Berberine is a yellow plant compound that has shown promise for lowering blood sugar and cholesterol in some studies, but the quality of research varies and it is not a replacement for prescribed medicine. It can cause stomach upset and should be avoided during pregnancy and breastfeeding. Always check with your pharmacist or doctor before starting it, especially if you take other medications.

Read the full Berberine monograph & all interactions
Keep checking

Other Drugs & Berberine

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

1Major
1,158Moderate
0Minor
1,670No known interaction
1 Major 1,158 Moderate 1,670 No interaction
Major

1 interaction

Moderate

1,158 interactions

Showing 60 of 1,158 moderate interactions — see all 1,158 on the Berberine page.

No interaction 1,670 drugs checked — show the list

We also checked Berberine 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 Berberine list.

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

Can you take Berberine with Aspirin, Caffeine, Dihydrocodeine Bitartrate?
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 4 interactions listed for Berberine and Aspirin, Caffeine, Dihydrocodeine Bitartrate?
Aspirin, Caffeine, Dihydrocodeine Bitartrate belongs to more than one drug category, and Berberine 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 Berberine and Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate and Berberine?

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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.