Drug & supplement interaction

Cubebs + Caffeine (OTC drug)

Caffeine (OTC drug) brand names: Vivarin, Overtime, Molie.

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

Cubebs has a moderate interaction with Caffeine (OTC drug). Several compounds isolated from cubebs can inhibit cytochrome P450 3A4 (CYP3A4) in vitro.

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

Cubebs and Caffeine (OTC drug)

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Caffeine (OTC drug)

Caffeine (OTC drug) falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Cubebs interacts with.

Several compounds isolated from cubebs can inhibit cytochrome P450 3A4 (CYP3A4) in vitro. So far, this effect has not been reported in humans. Theoretically, cubebs might increase the effects and side effects of drugs metabolized by CYP3A4. These include lovastatin (Mevacor), clarithromycin (Biaxin), cyclosporine (Neoral, Sandimmune), diltiazem (Cardizem), estrogens, indinavir (Crixivan), triazolam (Halcion), and numerous others.
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 honest picture with cubebs and your caffeine pill. The concern on file is that compounds in cubeb berries can slow down a liver enzyme called CYP3A4 in the test tube. If that happened in your body, drugs cleared by that pathway could build up a bit and hit harder. The thing is, caffeine isn't really a CYP3A4 drug. It's mostly broken down by a different enzyme, CYP1A2, so this particular interaction is a poor fit for caffeine and probably won't change much.

On top of that, this is only lab and animal data, never shown in people, so it's quite theoretical. Still, if you ever feel extra jittery, wired, or notice a racing heart or trouble sleeping, that's worth a chat with your pharmacist. A sprinkle of cubeb as a spice is very unlikely to matter compared to concentrated extracts or oils.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Usia T, Watabe T, Kadota S, Tezuka Y. Potent CYP3A4 inhibitory constituents of Piper cubeba. J Nat Prod 2005;68(1):64-8.

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

Cubebs Also Interacts With Other Medications

Cubebs has 642 moderate, 22 minor known drug interactions in our database — the Caffeine (OTC drug) one above is one of them. If you take anything else, check it against the full list below.

Moderate 642 Minor 22 No known interaction 2,166 (incl. Caffeine (OTC drug))
Taking anything else?

Check Another of Your Medications Against Cubebs

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

Everything else you take

See Every Supplement That Interacts With Caffeine (OTC drug)

This page covers Cubebs only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Caffeine (OTC drug) page lists 208 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Peyote (major) and Rauvolfia Vomitoria (major).

By severity: 7 major · 155 moderate · 46 minor.

From our pharmacist’s overview on the Caffeine (OTC drug) page

“The person swallowing a caffeine pill like Vivarin to power through a shift is often the same person drinking coffee, taking an herbal energy blend, or scooping pre-workout powder, and that overlap is exactly where the danger sits. Seven of the 208 supplement ingredients on file carry a major rating, and those seven are worth understan…”

Reviewed by 2 · Jul 18, 2026

Open the Caffeine (OTC drug) interaction page

One more smart check

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

We hold 19 real supplement products containing Cubebs, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cubebs. Your product may carry other ingredients that interact with Caffeine (OTC drug) too, on top of Cubebs — 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 Cubebs and Caffeine (OTC drug) 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 Cubebs
Steady interest

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

29 days ago today
Medication Caffeine (OTC drug)
Top 10%

#148 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 Cubebs

What is Cubebs?

Cubebs
  • Coughs and bronchitis
  • Indigestion and gas
  • Urinary tract complaints
  • Sore throat
  • Culinary spice

Cubebs are spicy, peppery berries from a vine in the pepper family that have long been used in traditional medicine for coughs, digestion, and urinary problems. Modern human studies are very limited, so its benefits are not well proven. Use it cautiously as a food spice, and talk to your pharmacist or doctor before using concentrated extracts or oils.

Read the full Cubebs monograph & all interactions
Keep checking

Other Drugs & Cubebs

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

0Major
642Moderate
22Minor
2,165No known interaction
642 Moderate 22 Minor 2,165 No interaction
Moderate

642 interactions

Showing 60 of 642 moderate interactions — see all 642 on the Cubebs page.

Minor

22 interactions

No interaction 2,165 drugs checked — show the list

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

Showing the 60 most looked-up of 2,165 medications checked with no known interaction — see the full Cubebs list.

See the full Cubebs interactions page
See every supplement checked against Caffeine (OTC drug), 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
Cubebs monograph › Uses, safety, and every drug interaction in one place Caffeine (OTC drug) supplement interactions › Every supplement checked against Caffeine (OTC drug), 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 Cubebs and Caffeine (OTC drug) Together: Common Questions

Can you take Cubebs with Caffeine (OTC drug)?
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 Cubebs and Caffeine (OTC drug) 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 Caffeine (OTC drug) and Cubebs?

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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.