Drug & supplement interaction

Peyote + Acetaminophen, Aspirin, Caffeine

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

Major Interaction
The bottom line Major

Peyote has a major interaction with Acetaminophen, Aspirin, Caffeine. Concomitant use of peyote with stimulant drugs may increase the risk of adverse CNS effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Peyote and Acetaminophen, Aspirin, Caffeine

Here is the interaction we found between these two, with the evidence behind it.

Major

STIMULANT DRUGS

Why this applies to Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under STIMULANT DRUGS — the group Peyote interacts with.

Concomitant use of peyote with stimulant drugs may increase the risk of adverse CNS effects. Some CNS stimulants include nicotine, cocaine, sympathomimetic amines, and amphetamines.
Severity Major Likelihood Probable Evidence D

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 a product like Excedrin Migraine: the part that matters for this interaction is the caffeine. Caffeine is a mild stimulant for your brain and nervous system. Peyote (through its active compound, mescaline) already revs up parts of the brain, so layering caffeine on top could, in theory, push those stimulant-type effects further. Think jitteriness, a racing or pounding heart, anxiety, restlessness, and trouble sleeping.

I want to be honest about the evidence here: this concern is theoretical, based on how these substances work rather than strong real-world studies. The acetaminophen and aspirin parts aren't really the issue. Still, peyote isn't a safe or legal self-treatment, so please don't mix the two without talking it through with your pharmacist or doctor first.

References
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.

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

Peyote Also Interacts With Other Medications

Peyote has 171 major, known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Peyote

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

This page covers Peyote 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 Peyote 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 Peyote
Steady interest

#1,065 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Aspirin, Caffeine
Top 10%

#171 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 Peyote

What is Peyote?

  • Traditional and religious ceremonies
  • Spiritual or visionary experiences
  • Folk use for pain and fatigue
  • Folk use for fever and skin conditions

Peyote is a small spineless cactus that contains mescaline, a powerful hallucinogen. It is a federally controlled substance in the United States (with a narrow exemption for certain Native American religious use), is not a safe or proven dietary supplement, and should not be used for self-treatment.

Read the full Peyote monograph & all interactions
Keep checking

Other Drugs & Peyote

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

171Major
0Moderate
0Minor
2,658No known interaction
Major

171 interactions

Showing 60 of 171 major interactions — see all 171 on the Peyote page.

No interaction 2,658 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 Peyote and Acetaminophen, Aspirin, Caffeine Together: Common Questions

Can you take Peyote with Acetaminophen, Aspirin, Caffeine?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Peyote and Acetaminophen, Aspirin, Caffeine interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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.