Drug & supplement interaction

Cannabidiol (cbd) + Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone brand names: Femhrt, Loestrin 21, Ovcon 35 21, Ovcon 50 28, Necon 0.5 35 21, and others.

Moderate Interaction
The bottom line Moderate

Ethinyl Estradiol, Norethindrone falls into 4 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Cannabidiol may increase levels of drugs metabolized by CYP1A2.

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

Cannabidiol (cbd) and Ethinyl Estradiol, Norethindrone

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

Why Are There 4 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Ethinyl Estradiol, Norethindrone falls into 4 of those categories, so it can interact with Cannabidiol (cbd) in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 4

Why this applies to Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Cannabidiol (cbd) interacts with.

Cannabidiol may increase levels of drugs metabolized by CYP1A2.
In vitro research shows that cannabidiol inhibits CYP1A2. Furthermore, clinical studies show that cannabidiol may inhibit the metabolism of caffeine, a CYP1A2 substrate. Two pharmacokinetic studies in healthy adults show that taking cannabidiol dosed 640 mg once up to 750 twice daily increases the area under the curve of caffeine. However, results are mixed over whether cannabidiol impacts peak serum levels of caffeine.
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

Here's the thing to know about pairing CBD with your birth control pill (Loestrin, Ovcon, and similar brands). CBD can slow down a liver enzyme called CYP1A2, and in lab and human studies it has blocked the breakdown of drugs that rely on that pathway. When a drug clears more slowly, its levels can creep up.

For your pill, that could mean a bit more estrogen and progestin hanging around, which sometimes shows up as nausea, breast tenderness, bloating, or breakthrough spotting. To be fair, the strongest evidence here used very high CBD doses (hundreds of milligrams), and combined hormone pills aren't broken down mainly by CYP1A2, so the real-world effect on your pill is likely small. Still, before you start a CBD product, it's worth a quick chat with your pharmacist or doctor.

References
  1. Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective potent inhibitors of human CYP1 enzymes. Biochem Pharmacol 2010;79(11):1691-8.
  2. Thai C, Tayo B, Critchley D. A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects. Clin Pharmacol Drug Dev. 2021. PubMed
  3. 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
  4. 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 3A4 (CYP3A4) INHIBITORS

2 of 4

Ethinyl Estradiol, Norethindrone also falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS.

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, your birth control pill (Ethinyl Estradiol with Norethindrone) is acting on the CBD, not the other way around. The estrogen component can mildly block a liver enzyme called CYP3A4, which is one of the pathways that breaks down CBD. If that pathway slows down, CBD may build up a little, and you might notice more of CBD's typical effects like drowsiness, lightheadedness, dry mouth, or an upset stomach.

The good news is this is only a theoretical concern based on how these compounds behave, not something proven in real patients, so it's rated fairly low risk. Still, if you start feeling unusually sleepy or off after adding CBD, mention it to your pharmacist or doctor before making any changes.

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

3 of 4

Ethinyl Estradiol, 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

Your birth control pill combines two hormones, ethinyl estradiol and norethindrone, and both are cleared from your body in part by a liver enzyme called CYP3A4. CBD can slow that enzyme down. In theory, that could let a little more of these hormones build up in your bloodstream, which may nudge up the usual estrogen-type side effects like nausea, breast tenderness, headaches, or spotting.

Honestly, this is more of a 'good to know' than a reason to panic. The strongest CBD interactions have shown up with other medicines, not this exact combo, and food or trace amounts of CBD are unlikely to matter much. Concentrated CBD products are the bigger question mark. Before pairing them, run it by your pharmacist or doctor so they can keep an eye on how you feel.

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

4 of 4

Ethinyl Estradiol, 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 a helpful twist with this pairing: the concern isn't that your birth control pill (the ethinyl estradiol and norethindrone combo) changes because of CBD. It's the other way around. Your hormone pill can act as a mild nudge on a liver enzyme called CYP2C19, which happens to be one of the pathways your body uses to break down CBD. In theory, that could speed up how fast you clear the CBD and leave a little less of it working in your system.

I want to be honest about how soft this evidence is. This is purely theoretical, based on how the enzymes line up on paper, not on real-world studies in people. For most folks it likely won't be noticeable, and your contraceptive protection isn't expected to change. Still, if your CBD seems less effective, mention it to your pharmacist or doctor so they can take a look.

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

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 Ethinyl Estradiol, Norethindrone

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Norethindrone page lists 240 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 · 196 moderate · 38 minor.

From our pharmacist’s overview on the Ethinyl Estradiol, Norethindrone page

“If you take a birth control pill or hormone therapy containing ethinyl estradiol and norethindrone (Loestrin, Femhrt, and others), a few supplements can genuinely undermine it, so read this page with care. Six of the 240 ingredients on file are rated major, and those six come first.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl Estradiol, Norethindrone interaction page

How much people look this up

Where Cannabidiol (cbd) and Ethinyl Estradiol, 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

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

29 days ago today
Medication Ethinyl Estradiol, Norethindrone
Top 10%

#283 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
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
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

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Pharmacist Counseling Corner

Taking Cannabidiol (cbd) and Ethinyl Estradiol, Norethindrone Together: Common Questions

Can you take Cannabidiol (cbd) with Ethinyl Estradiol, 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 4 interactions listed for Cannabidiol (cbd) and Ethinyl Estradiol, Norethindrone?
Ethinyl Estradiol, 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 Ethinyl Estradiol, 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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