Drug & supplement interaction

Delta-9-tetrahydrocannabinol (thc) + Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.

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

Acetaminophen, Aspirin, Caffeine falls into 3 drug categories that Delta-9-tetrahydrocannabinol (thc) can interact with; the most serious is rated moderate. Theoretically, THC might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.

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

Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Aspirin, Caffeine

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

Why Are There 3 Interactions?

Delta-9-tetrahydrocannabinol (thc) interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 3 of those categories, so it can interact with Delta-9-tetrahydrocannabinol (thc) in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

1 of 3

Why this applies to Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Delta-9-tetrahydrocannabinol (thc) interacts with.

Theoretically, THC might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs.
In vitro research shows that THC inhibits platelet aggregation.
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

The piece of Excedrin that matters here is the aspirin. Aspirin already makes your platelets less sticky, which is part of how it eases pain and reduces clotting. Lab studies suggest THC may also nudge platelets toward being less sticky. Put the two together and, in theory, you could bleed or bruise a little more easily.

I want to be honest about the evidence though: this is only a test-tube finding, not something proven in real people, so for most folks taking occasional Excedrin it is likely a small concern. Still, if you notice easy bruising, nosebleeds, or stomach upset, or you take aspirin daily, check in with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Levy, R., Schurr, A., Nathan, I., Dvilanski, A., and Livne, A. Impairment of ADP-induced platelet aggregation by hashish components. Thromb.Haemost. 12-31-1976;36(3):634-640. DOI
  2. Formukong, E. A., Evans, A. T., and Evans, F. J. The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation. J.Pharm.Pharmacol. 1989;41(10):705-709.
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

2 of 3

Acetaminophen, Aspirin, Caffeine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, THC might decrease the levels and clinical effects of CYP2E1 substrates.
In vitro research shows that cannabis containing THC can induce the activity of CYP2E1, which might increase the metabolism of CYP2E1 substrates. It is unclear if this effect is due to THC, other constituents, or the combination.
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: this is a very theoretical concern, based only on lab research, not on real people. The idea is that THC might speed up an enzyme called CYP2E1. Acetaminophen (the Tylenol part of Excedrin) is partly handled by that enzyme. If THC nudged it to work faster, slightly more acetaminophen could be turned into a byproduct that's harder on the liver. In everyday use, this is far from proven and isn't a typical reason for problems.

What I'd actually keep an eye on is the bigger picture: don't exceed the acetaminophen limit on the label, go easy on alcohol, and remember caffeine plus THC can both affect how alert you feel. If you use cannabis regularly and take acetaminophen often, just mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sheweita, S. A. Narcotic drugs change the expression of cytochrome P450 2E1 and 2C6 and other activities of carcinogen-metabolizing enzymes in the liver of male mice. Toxicology 9-30-2003;191(2-3):133-142. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Acetaminophen, Aspirin, Caffeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, THC may increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that cannabis containing THC might modestly inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. It is unclear if this effect is due to THC, other constituents, or the combination. In vitro research also shows that cannabis extracts containing THC modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids cannabidiol (CBD) or cannabigerol (CBG) alone had stronger inhibitory effects than extracts containing both THC and CBD. Conversely, a crossover clinical study in healthy adults shows that oral THC does not inhibit CYP3A4.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the honest answer on combining THC (like cannabis or dronabinol) with Excedrin Migraine, which is just a combo of acetaminophen, aspirin, and caffeine. On paper, THC might slightly slow down a liver enzyme called CYP3A4, which could let some medicines hang around a bit longer. But this is really a non-issue for Excedrin. The acetaminophen and aspirin in it aren't cleared mainly through CYP3A4, and none of these three are prodrugs that need that enzyme to work.

The data behind this is also very weak, just lab and test-tube studies, and one human study actually showed oral THC didn't block CYP3A4 at all. So I wouldn't lose sleep over it. If you take THC regularly, it never hurts to mention it to your pharmacist.

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
  3. 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

Delta-9-tetrahydrocannabinol (thc) Also Interacts With Other Medications

Delta-9-tetrahydrocannabinol (thc) has 762 moderate, 336 minor known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is among them. If you take anything else, check it against the full list below.

Moderate 762 Minor 336 No known interaction 1,732 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Delta-9-tetrahydrocannabinol (thc)

Covers the 2,830 medications we’ve checked against Delta-9-tetrahydrocannabinol (thc). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

This page covers Delta-9-tetrahydrocannabinol (thc) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Ephedra (major).

By severity: 13 major · 312 moderate · 46 minor.

From our pharmacist’s overview on the Acetaminophen, Aspirin, Caffeine page

“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Aspirin, Caffeine interaction page

How much people look this up

Where Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Aspirin, Caffeine 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 Delta-9-tetrahydrocannabinol (thc)
Top half

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

29 days ago today
Medication Acetaminophen, Aspirin, Caffeine
Top 1%

#11 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 Delta-9-tetrahydrocannabinol (thc)

What is Delta-9-tetrahydrocannabinol (thc)?

Delta-9-tetrahydrocannabinol (thc)
  • Chronic or nerve pain
  • Nausea and vomiting from chemotherapy
  • Appetite loss and weight loss
  • Muscle spasticity
  • Sleep problems
  • Anxiety and stress

THC is the main mind-altering compound in cannabis and is best known for causing a 'high.' A prescription form (dronabinol) is approved for chemotherapy-related nausea and appetite loss, but for most other uses the evidence is mixed or limited, and THC can impair thinking and driving. It should be avoided in pregnancy and breastfeeding and used only with medical guidance.

Read the full Delta-9-tetrahydrocannabinol (thc) monograph & all interactions
Keep checking

Other Drugs & Delta-9-tetrahydrocannabinol (thc)

Browse every other medication we’ve checked against Delta-9-tetrahydrocannabinol (thc) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
762Moderate
336Minor
1,731No known interaction
762 Moderate 336 Minor 1,731 No interaction
Moderate

762 interactions

Showing 60 of 762 moderate interactions — see all 762 on the Delta-9-tetrahydrocannabinol (thc) page.

Minor

336 interactions

Showing 60 of 336 minor interactions — see all 336 on the Delta-9-tetrahydrocannabinol (thc) page.

No interaction 1,731 drugs checked — show the list

We also checked Delta-9-tetrahydrocannabinol (thc) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,731 medications checked with no known interaction — see the full Delta-9-tetrahydrocannabinol (thc) list.

See the full Delta-9-tetrahydrocannabinol (thc) interactions page
See every supplement checked against Acetaminophen, Aspirin, Caffeine, 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
Delta-9-tetrahydrocannabinol (thc) monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Aspirin, Caffeine supplement interactions › Every supplement checked against Acetaminophen, Aspirin, Caffeine, 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 Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Aspirin, Caffeine Together: Common Questions

Can you take Delta-9-tetrahydrocannabinol (thc) with Acetaminophen, Aspirin, Caffeine?
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 Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Aspirin, Caffeine?
Acetaminophen, Aspirin, Caffeine belongs to more than one drug category, and Delta-9-tetrahydrocannabinol (thc) 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 Delta-9-tetrahydrocannabinol (thc) and Acetaminophen, Aspirin, Caffeine 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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