Drug & supplement interaction

Cannabis + Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate brand name: Activella.

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

Estradiol, Norethindrone Acetate falls into 3 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of cannabis.

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

Cannabis and Estradiol, Norethindrone Acetate

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

Why Are There 3 Interactions?

Cannabis interacts with whole categories of medication. Estradiol, Norethindrone Acetate falls into 3 of those categories, so it can interact with Cannabis 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

1 of 3

Why this applies to Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Cannabis interacts with.

Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of cannabis.
Delta-9-tetrahydrocannabinol (THC), an active constituent of cannabis, is a substrate of CYP3A4 enzymes.
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 gist of this one: your Activella (a combo of estradiol and norethindrone) can act as a mild blocker of an enzyme called CYP3A4. That same enzyme helps your body break down THC, the active part of cannabis. So in theory, taking them together could slow down THC's breakdown a bit, letting it linger and feel stronger. That might mean more pronounced effects like drowsiness, dizziness, a stronger high, dry mouth, or a faster heartbeat.

I want to be honest with you though: this is a theoretical concern based on how these compounds behave in the lab, not something proven in real patients. For most people it's unlikely to cause major trouble. Still, if you use cannabis regularly while on Activella, it's worth a quick chat with your pharmacist or doctor, especially if you notice extra grogginess.

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

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

Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.
In vitro research shows that cannabis can inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. In vitro research also shows that cannabis extracts modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids CBD and cannabigerol (CBG) had stronger inhibitory effects than extracts containing THC and CBD.
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 Activella combines two hormones, estradiol and norethindrone, and your liver uses an enzyme called CYP3A4 to help break them down. Lab studies suggest that compounds in cannabis (especially CBD and CBG) may slow that same enzyme. In theory, that could let a little more of these hormones linger in your body rather than being cleared at the usual pace.

If that happened, you might notice more of the typical estrogen-related effects, such as breast tenderness, bloating, nausea, headaches, or breakthrough spotting. I want to be straight with you though: this is based only on test-tube and animal research, not real people, so the effect (if any) is likely small. Still, it's worth mentioning to your doctor or pharmacist, especially if you use cannabis regularly.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pellinen, P., Honkakoski, P., Stenback, F., Niemitz, M., Alhava, E., Pelkonen, O., Lang, M. A., and Pasanen, M. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur.J Pharmacol 1-3-1994;2 PubMed
  2. 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
Moderate

P-GLYCOPROTEIN SUBSTRATES

3 of 3

Estradiol, Norethindrone Acetate also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, cannabis might alter levels of drugs that are substrates of P-glycoprotein (P-gp).
Most in vitro research suggests that constituents of cannabis, including cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), can inhibit P-gp and increase the accumulation of probe compounds by reducing P-gp mediated drug efflux. In vitro studies in kidney cell lines show that a 1-hour exposure to CBD and THC inhibits P-gp. Cannabis may also alter the expression of P-gp, although this effect appears to vary based on duration of exposure. Some in vitro research in lymphoblastoid leukemia cell lines indicates that a 1-hour exposure to cannabinoids does not affect P-gp expression, while a prolonged 72-hour exposure decreases P-gp expression. Other in vitro research in these cell lines shows that a 4-hour exposure to THC and CBD induces P-gp gene expression, while exposure for longer than 4 hours and up to 48 hours does not induce P-gp gene expression.
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 short version: Activella combines two hormones (estradiol and norethindrone), and they're handled in part by a transporter protein called P-glycoprotein, which acts like a pump moving substances out of cells. In lab and animal studies, cannabis compounds (THC and CBD) appear to slow that pump down. In theory, that could let a little more of these hormones build up in your system.

I want to be honest about how shaky this is. This is based only on cell and animal research, not real people taking Activella, so we don't actually know if it matters in everyday life. If it did nudge hormone levels up, you might notice things like breast tenderness, bloating, nausea, headaches, or breakthrough spotting. Nothing here means you should stop either one, but do mention your cannabis use to your doctor or pharmacist so they can keep an eye on you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhu, H. J., Wang, J. S., Markowitz, J. S., Donovan, J. L., Gibson, B. B., Gefroh, H. A., and Devane, C. L. Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp.Ther. 2006;317(2):850-857. PubMed
  2. Holland, M. L., Panetta, J. A., Hoskins, J. M., Bebawy, M., Roufogalis, B. D., Allen, J. D., and Arnold, J. C. The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. Biochem.Pharmacol 4-14-2006;71(8):1146-115 PubMed
  3. Tournier N, Lucie Chevillard L, Megarbane B, et al. Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Int J Neuropsychopharmacol. 2010;13(7):905-15. PubMed
  4. Arnold JC, Hone P, Holland ML, Allen JD. CB2 and TRPV1 receptors mediate cannabinoid actions on MDR1 expression in multidrug resistant cells. Pharmacol Rep. 2012;64(3):751-7. PubMed

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

Cannabis Also Interacts With Other Medications

Cannabis has 2 major, 1,108 moderate, 25 minor known drug interactions in our database — the Estradiol, Norethindrone Acetate one above is among them. If you take anything else, check it against the full list below.

Major 2 Moderate 1,108 Minor 25 No known interaction 1,695 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Cannabis

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

From our Q&A

Questions About Cannabis or Estradiol, Norethindrone Acetate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabis or Estradiol, Norethindrone Acetate, 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 Estradiol, Norethindrone Acetate

This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norethindrone Acetate page lists 212 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 171 moderate · 38 minor.

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

“Activella pairs estradiol with norethindrone as hormone therapy, and because the treatment depends on steady hormone levels in the blood, supplements that raise or lower those levels warrant real scrutiny. Three of the 212 interacting ingredients rate major, and all three hit that weak point: St.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norethindrone Acetate interaction page

One more smart check

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

We hold 21 real supplement products containing Cannabis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cannabis. Your product may carry other ingredients that interact with Estradiol, Norethindrone Acetate too, on top of Cannabis — 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 Cannabis and Estradiol, Norethindrone Acetate 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 Cannabis
Top 25%

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,374 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 Cannabis

What is Cannabis?

Cannabis
  • Chronic pain
  • Nausea and vomiting from chemotherapy
  • Muscle spasticity (e.g., multiple sclerosis)
  • Anxiety and stress
  • Sleep problems
  • Appetite stimulation

Cannabis contains many active compounds, mainly THC (which causes a 'high') and CBD (which does not). Some uses, such as chemotherapy-related nausea, certain seizure disorders, and muscle spasticity, have meaningful evidence, while many other popular uses are not well proven. It can cause real side effects and impairment, so talk to your doctor or pharmacist and follow your local laws before using it.

Read the full Cannabis monograph & all interactions
Keep checking

Other Drugs & Cannabis

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

2Major
1,108Moderate
25Minor
1,694No known interaction
2 Major 1,108 Moderate 25 Minor 1,694 No interaction
Major

2 interactions

Moderate

1,108 interactions

Showing 60 of 1,108 moderate interactions — see all 1,108 on the Cannabis page.

Minor

25 interactions

No interaction 1,694 drugs checked — show the list

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

Showing the 60 most looked-up of 1,694 medications checked with no known interaction — see the full Cannabis list.

See the full Cannabis interactions page
See every supplement checked against Estradiol, Norethindrone Acetate, 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
Cannabis monograph › Uses, safety, and every drug interaction in one place Estradiol, Norethindrone Acetate supplement interactions › Every supplement checked against Estradiol, Norethindrone Acetate, 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 Cannabis and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Cannabis with Estradiol, Norethindrone Acetate?
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 Cannabis and Estradiol, Norethindrone Acetate?
Estradiol, Norethindrone Acetate belongs to more than one drug category, and Cannabis 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 Cannabis and Estradiol, Norethindrone Acetate 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.