Drug & supplement interaction

Cannabis + Elagolix Sodium

Elagolix Sodium brand name: Orilissa.

Moderate Interaction
The bottom line Moderate

Elagolix Sodium falls into 3 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.

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

Cannabis and Elagolix Sodium

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. Elagolix Sodium 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) SUBSTRATES

1 of 3

Why this applies to Elagolix Sodium

Elagolix Sodium falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Cannabis interacts with.

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

Here's the short version for Orilissa (elagolix): your body clears this medicine partly through a liver enzyme called CYP3A4. Lab studies suggest cannabis can mildly slow that enzyme down. In theory, that could let a bit more elagolix linger in your system, which might nudge up its usual side effects, things like hot flashes, headaches, nausea, trouble sleeping, mood changes, or joint pain.

I want to be honest about how shaky this evidence is. This comes only from test-tube research, not real people, so we don't truly know if it matters in everyday use. Elagolix isn't a prodrug, so the direction (slightly stronger effect) makes sense, but the actual risk looks low. Still, it's worth a quick chat with your pharmacist or doctor, especially since cannabis can add to drowsiness or mood effects on its own.

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

2 of 3

Elagolix Sodium 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 simple version: Orilissa (elagolix) is moved around your body partly by a transporter called P-glycoprotein, which acts like a little pump that pushes the drug back out of cells. Lab studies suggest the compounds in cannabis (THC and CBD) may slow that pump down. If the pump works less, a bit more elagolix could stay in your system, which in theory might mean stronger effects or more side effects like hot flashes, headache, nausea, mood changes, or trouble sleeping.

I want to be honest though: this is based only on test-tube and cell studies, not on real people taking both together, so it's quite uncertain. It's worth mentioning to your doctor or pharmacist, but there's no need to panic. Don't change how you take Orilissa on your own.

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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

3 of 3

Elagolix Sodium also falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS.

Theoretically, CYP3A4 inducers might reduce the levels and clinical 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 key thing to understand: this interaction runs from your medication onto the cannabis, not the other way around. Orilissa (elagolix) can act as a mild CYP3A4 inducer, meaning it can speed up the enzyme that helps break down THC, the active compound in cannabis. In plain terms, your elagolix may cause your body to clear THC a bit faster, so the cannabis could feel weaker or wear off sooner than you'd expect.

This is theoretical, based on how these compounds behave in the lab rather than strong human studies, so I wouldn't lose sleep over it. Your elagolix should keep working normally for your endometriosis pain. Still, since cannabis can add to side effects like dizziness, mood changes, or tiredness, it's worth a quick chat with your doctor or pharmacist before combining them.

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.

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 Elagolix Sodium 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 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 Elagolix Sodium

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 Elagolix Sodium, 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 Elagolix Sodium

This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Elagolix Sodium page lists 159 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 · 118 moderate · 38 minor.

From our pharmacist’s overview on the Elagolix Sodium page

“The list of supplements that interact with elagolix sodium (Orilissa), a pill taken daily for endometriosis pain, is one I would read carefully, starting with its three major entries. Grapefruit can raise elagolix blood levels by blocking the liver enzyme that clears it, inviting more side effects.”

Reviewed by 2 · Jul 18, 2026

Open the Elagolix Sodium 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 Elagolix Sodium 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 Elagolix Sodium 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%

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

29 days ago today
Medication Elagolix Sodium
Steady interest

#2,195 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
Medication

About Elagolix

What Is Elagolix Used For?

Brand name: Orilissa

Orilissa (elagolix) is used to treat moderate to severe pain associated with endometriosis — a condition where tissue similar to the uterine lining grows outside the uterus, causing significant pain.

This includes general pelvic pain as well as pain during sex (dyspareunia). How long you can take it depends on your dose and your overall health, so your prescriber will tailor the treatment duration to you.

See full Elagolix drug information
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
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
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
Pharmacist Counseling Corner

Taking Cannabis and Elagolix Sodium Together: Common Questions

Can you take Cannabis with Elagolix Sodium?
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 Elagolix Sodium?
Elagolix Sodium 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 Elagolix Sodium 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.