Drug & supplement interaction

Cannabidiol (cbd) + 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

Mestranol, Norethindrone falls into 3 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase cannabidiol levels.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Mestranol, Norethindrone

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

Why Are There 3 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Mestranol, Norethindrone falls into 3 of those categories, so it can interact with Cannabidiol (cbd) in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

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Why this applies to Mestranol, Norethindrone

Mestranol, Norethindrone falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Cannabidiol (cbd) interacts with.

Theoretically, CYP3A4 inhibitors might increase cannabidiol levels.
Cannabidiol is a substrate of CYP3A4 enzymes. Theoretically, drugs that inhibit CYP3A4 enzymes might increase levels of cannabidiol, increasing its effects 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

Here's a twist worth understanding: in this pairing, it's the CBD that may be affected, not your birth control pill. The estrogen and progestin in this combo pill (mestranol and norethindrone) can mildly slow down a liver enzyme called CYP3A4, which happens to be one of the pathways that breaks down CBD. So in theory, taking them together could let CBD build up a bit, making its effects (and side effects like drowsiness, loose stools, or appetite changes) a little stronger.

I want to be honest that this is only a theoretical concern based on how these compounds work, not something proven in studies. Your pill should still work fine. If you notice you feel more sedated than usual on your CBD, just loop in your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Product information for Marinol. AbbVie. North Chicago, IL 60064. August 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Mestranol, Norethindrone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Cannabidiol may increase levels of drugs that are metabolized by CYP3A4.
In vitro and animal research shows that cannabidiol inhibits CYP3A4. In human studies and case reports, cannabidiol has been associated with an increase in plasma levels of the CYP3A4 substrates zonisamide, tacrolimus, everolimus, citalopram, midazolam, and methadone.
Severity Moderate Likelihood Probable Evidence A

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This birth control pill combines two hormones, and your liver clears them using an enzyme called CYP3A4. CBD can slow that enzyme down a bit. In theory, that means the hormones could hang around at slightly higher levels than usual. With estrogen and progestin pills, higher exposure tends to nudge up the more common side effects, things like nausea, breast tenderness, headaches, mood changes, or some spotting.

The good news: this is not the kind of interaction that makes your birth control stop working, and these aren't dangerous medicines to have a little extra of. Most of the strong human evidence here is for other drugs, not this exact pill. Still, if you're adding CBD, it's worth a quick chat with your pharmacist or doctor so you can keep an eye on how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yamaori S, Ebisawa J, Okushima Y, et al. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci 2011;88(15-16):730-6. PubMed
  2. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  3. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  4. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
  5. Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transplant. 2019;19(10):2944-2948. PubMed
  6. Wiemer-Kruel A, Stiller B, Bast T. Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex. Neuropediatrics. 2019. PubMed
  7. Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
  8. Anderson LL, Doohan PT, Oldfield L, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. J Clin Psychopharmacol. 2021. PubMed
  9. Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
  10. Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. PubMed
  11. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
Moderate

CYTOCHROME P450 2C19 (CYP2C19) INDUCERS

3 of 3

Mestranol, Norethindrone also falls under CYTOCHROME P450 2C19 (CYP2C19) INDUCERS.

Theoretically, CYP2C19 inducers might decrease cannabidiol levels.
Cannabidiol is a substrate of CYP2C19 enzymes. Theoretically, drugs that induce CYP2C19 enzymes might decrease the levels and effects of cannabidiol.
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 thing to keep in mind with this pairing: the concern runs in one direction, and it's about your CBD, not your birth control pill. This combination pill (mestranol/norethindrone) can act as a mild nudge on a liver enzyme called CYP2C19, which is one of the enzymes that helps break down CBD. In theory, that could clear CBD out a little faster and leave you with somewhat weaker CBD effects.

I want to be honest that this is purely a theoretical interaction based on how these things work on paper, not something proven in real people. There's no good evidence your pill will make your CBD stop working, and nothing here suggests your birth control becomes less reliable. If you rely on CBD for a specific reason, just mention it to your pharmacist so you can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)

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

Cannabidiol (cbd) Also Interacts With Other Medications

Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Mestranol, Norethindrone one above is among them. If you take anything else, check it against the full list below.

Moderate 1,050 No known interaction 1,780 (incl. Mestranol, Norethindrone)
Taking anything else?

Check Another of Your Medications Against Cannabidiol (cbd)

Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Mestranol, Norethindrone

This page covers Cannabidiol (cbd) 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

How much people look this up

Where Cannabidiol (cbd) 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 Cannabidiol (cbd)
Top half

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

29 days ago today
Medication Mestranol, Norethindrone
Top 25%

#550 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 Cannabidiol (cbd)

What is Cannabidiol (cbd)?

  • Anxiety and stress
  • Sleep problems
  • Chronic pain
  • Certain seizure disorders
  • Inflammation

CBD is a compound from the cannabis (hemp) plant that does not cause a 'high.' It has strong evidence only for certain rare seizure disorders (as a prescription drug), while most other popular uses are still backed by limited or early research. Product quality varies a lot, so talk with your pharmacist or doctor before using it, especially if you take other medicines.

Read the full Cannabidiol (cbd) monograph & all interactions
Keep checking

Other Drugs & Cannabidiol (cbd)

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

0Major
1,050Moderate
0Minor
1,779No known interaction
1,050 Moderate 1,779 No interaction
Moderate

1,050 interactions

Showing 60 of 1,050 moderate interactions — see all 1,050 on the Cannabidiol (cbd) page.

No interaction 1,779 drugs checked — show the list

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

Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) list.

See the full Cannabidiol (cbd) 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
Cannabidiol (cbd) 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 Cannabidiol (cbd) and Mestranol, Norethindrone Together: Common Questions

Can you take Cannabidiol (cbd) 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.
Why are there 3 interactions listed for Cannabidiol (cbd) and Mestranol, Norethindrone?
Mestranol, Norethindrone belongs to more than one drug category, and Cannabidiol (cbd) 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 Cannabidiol (cbd) 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

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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.