Drug & supplement interaction

Cubebs + Mestranol, Norethindrone

Mestranol, Norethindrone brand names: Necon 1/50, Ortho Novum 21, Ortho-Novum 1/50-28, Norinyl 1 50 21 Day, Ortho Novum 1 Plus 50, and others.

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

Cubebs has a moderate interaction with Mestranol, Norethindrone. 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 Mestranol, Norethindrone

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Mestranol, Norethindrone

Mestranol, Norethindrone 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

Your birth control pill here combines an estrogen (mestranol) with a progestin (norethindrone), and your liver uses an enzyme called CYP3A4 to help clear these hormones. In test tube studies, certain compounds from cubebs appear to slow that enzyme down. If that happened in the body, the hormones could clear a little more slowly and build up, which in theory might bump up estrogen-type side effects like nausea, breast tenderness, bloating, headaches, or mood changes.

I want to be honest about how soft this evidence is: it comes only from lab research, not from people, so this is more theoretical than proven. A sprinkle of cubeb as a kitchen spice is very unlikely to matter. Concentrated extracts or oils are the bigger question mark, so check with your pharmacist or doctor before using those.

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 Mestranol, Norethindrone 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. Mestranol, Norethindrone)
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 Mestranol, Norethindrone

This page covers Cubebs only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Mestranol, Norethindrone page lists 193 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 147 moderate · 40 minor.

Open the Mestranol, Norethindrone 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 Mestranol, Norethindrone 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 Mestranol, Norethindrone 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
Top half

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

29 days ago today
Medication Mestranol, Norethindrone
Top half

#1,062 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 Mestranol, Norethindrone, 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 Mestranol, Norethindrone supplement interactions › Every supplement checked against Mestranol, Norethindrone, 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 Mestranol, Norethindrone Together: Common Questions

Can you take Cubebs with Mestranol, Norethindrone?
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 Mestranol, Norethindrone 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 Mestranol, Norethindrone 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.