Drug & supplement interaction

Peyote + Oxymetazoline Hydrochloride

Oxymetazoline Hydrochloride brand names: Afrin, Rhofade, Upneeq.

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

Peyote has a major interaction with Oxymetazoline Hydrochloride. 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 Oxymetazoline Hydrochloride

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

Major

STIMULANT DRUGS

Why this applies to Oxymetazoline Hydrochloride

Oxymetazoline Hydrochloride 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 idea behind this one. Oxymetazoline is a sympathomimetic, meaning it acts a bit like your body's own adrenaline to tighten blood vessels. Peyote (through mescaline) revs up the nervous system in its own way. Pairing two things that both stimulate could, in theory, add up to more strain on your heart and brain, things like a racing or pounding heartbeat, higher blood pressure, jitteriness, or worsened anxiety.

I want to be honest about the strength of this: it's a theoretical concern based on how these compounds behave, not solid human studies. Also worth noting, when you use Afrin in the nose or Rhofade and Upneeq on the skin or eye, very little gets into your whole body, so real-world overlap is likely small. Even so, since peyote isn't a safe or legal product, please talk with your pharmacist or doctor before mixing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Oxymetazoline Hydrochloride one above is one of them. If you take anything else, check it against the full list below.

Major 171 No known interaction 2,659 (incl. Oxymetazoline Hydrochloride)
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 Oxymetazoline Hydrochloride

This page covers Peyote only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Oxymetazoline Hydrochloride page lists 48 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Ephedra (major), Rauvolfia Vomitoria (major), Sida Cordifolia (major), 1,3-dmaa (moderate) and 1,3-dmba (moderate).

By severity: 4 major · 39 moderate · 5 minor.

Open the Oxymetazoline Hydrochloride interaction page

How much people look this up

Where Peyote and Oxymetazoline Hydrochloride 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

#1,096 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Oxymetazoline Hydrochloride
Top half

#1,395 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
Medication

About Oxymetazoline Topical

What Is Oxymetazoline Topical Used For?

Brand names: Afrin, Rhofade, Upneeq

Rhofade (oxymetazoline hydrochloride cream, 1%) is approved to treat persistent facial erythema (redness) associated with rosacea in adults. It is applied directly to the face once daily.

Other oxymetazoline topical products — including Afrin spray and Medix Nasal Decongestant Oxymetazoline Hydrochloride and Tukol Max Action solutions — are available for nasal use. Uses for those products are not covered in the current prescribing information provided here.

See full Oxymetazoline Topical drug information
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
171 Major 2,658 No 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

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

Showing the 60 most looked-up of 2,658 medications checked with no known interaction — see the full Peyote list.

See the full Peyote interactions page
See every supplement checked against Oxymetazoline Hydrochloride, 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
Peyote monograph › Uses, safety, and every drug interaction in one place Oxymetazoline Hydrochloride supplement interactions › Every supplement checked against Oxymetazoline Hydrochloride, ranked by severity Oxymetazoline Topical drug information › The full plain-English guide to this medication 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 Peyote and Oxymetazoline Hydrochloride Together: Common Questions

Can you take Peyote with Oxymetazoline Hydrochloride?
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 Oxymetazoline Hydrochloride 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.