Drug & supplement interaction

Cannabidiol (cbd) + Naproxen, Sumatriptan

Naproxen, Sumatriptan brand name: Treximet.

Moderate Interaction
The bottom line Moderate

Naproxen, Sumatriptan falls into 2 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
Interactions2
EvidenceA
What do Severity, Likelihood & Evidence mean?
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Interaction report

Cannabidiol (cbd) and Naproxen, Sumatriptan

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Cannabidiol (cbd) interacts with whole categories of medication. Naproxen, Sumatriptan falls into 2 of those categories, so it can interact with Cannabidiol (cbd) in 2 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 2

Why this applies to Naproxen, Sumatriptan

Naproxen, Sumatriptan 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

Treximet combines two active medicines, naproxen and sumatriptan, neither of which is a prodrug. The part that matters here is the naproxen piece. Naproxen is partly broken down by an enzyme called CYP1A2, and CBD can slow that enzyme down. When the enzyme works slower, naproxen can hang around in your body a little longer and build up.

In real life that could mean a bit more of naproxen's usual side effects, like stomach upset, heartburn, or a higher chance of stomach irritation. The effect is likely modest, and concentrated CBD doses matter more than a tiny amount. Still, before pairing the two regularly, check with your pharmacist or doctor so they can keep an eye on things.

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 2C9 (CYP2C9) SUBSTRATES

2 of 2

Naproxen, Sumatriptan also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Cannabidiol may increase levels of drugs metabolized by CYP2C9.
In vitro and animal research shows that cannabidiol inhibits CYP2C9. In human studies, cannabidiol has been associated with an increase in plasma levels of topiramate and losartan, CYP2C9 substrates. Concomitant use of cannabidiol with CYP2C9 substrates may increase the risk for adverse effects from these substrates.
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

Treximet combines two medicines, and the naproxen part is the one to watch here. Naproxen is cleared partly by a liver enzyme called CYP2C9, and CBD can slow that enzyme down. That can let naproxen build up a bit more than usual in your body. We have solid human data showing CBD raises levels of other CYP2C9 drugs, so this is a real, well-documented effect, not just a theory.

Practically, more naproxen in your system can mean a higher chance of stomach upset, heartburn, or, with regular use, irritation or bleeding in the gut, plus extra strain on the kidneys. The sumatriptan half isn't affected much this way. Nothing here means you must avoid CBD, but please check with your pharmacist or doctor before pairing them.

References
  1. Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
  2. Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
  3. 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
  4. 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
  5. 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
  6. Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.

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 Naproxen, Sumatriptan 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 Naproxen, Sumatriptan

This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Naproxen, Sumatriptan page lists 332 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Asarabacca (major) and Beer (major).

By severity: 14 major · 273 moderate · 45 minor.

From our pharmacist’s overview on the Naproxen, Sumatriptan page

“Treximet combines naproxen, an anti-inflammatory painkiller, with sumatriptan for migraine, and that pairing gives its interaction list real teeth. Of the 332 supplements and herbs on file, 14 carry a major rating, and those are the entries to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Naproxen, Sumatriptan interaction page

How much people look this up

Where Cannabidiol (cbd) and Naproxen, Sumatriptan 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

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

29 days ago today
Medication Naproxen, Sumatriptan
Steady interest

#2,133 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 Naproxen, Sumatriptan Together: Common Questions

Can you take Cannabidiol (cbd) with Naproxen, Sumatriptan?
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 2 interactions listed for Cannabidiol (cbd) and Naproxen, Sumatriptan?
Naproxen, Sumatriptan 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 Naproxen, Sumatriptan 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.