Drug & supplement interaction

Yerba Mate + Midazolam

Midazolam brand names: Versed, Seizalam, Nayzilam.

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

Midazolam falls into 3 drug categories that Yerba Mate can interact with; the most serious is rated moderate. Theoretically, the caffeine in yerba mate might reduce the efficacy of benzodiazepines.

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

Yerba Mate and Midazolam

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

Why Are There 3 Interactions?

Yerba Mate interacts with whole categories of medication. Midazolam falls into 3 of those categories, so it can interact with Yerba Mate in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

BENZODIAZEPINES

1 of 3

Why this applies to Midazolam

Midazolam falls under BENZODIAZEPINES — the group Yerba Mate interacts with.

Theoretically, the caffeine in yerba mate might reduce the efficacy of benzodiazepines.
Yerba mate contains caffeine. Caffeine can antagonize the anxiolytic effects of benzodiazepines.
Severity Moderate 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 simple version: midazolam (Versed) is a benzodiazepine that calms the brain to help you relax, feel sleepy, and not remember a procedure. Yerba mate, on the other hand, contains caffeine, which is a stimulant that wakes the brain up. So the two pull in opposite directions. In theory, the caffeine could work against midazolam's calming and drowsy effects, making it feel like the medicine isn't quite doing its job.

I want to be honest about the strength of this: it's based on how caffeine and these drugs behave, not on strong human studies, so it's more theoretical than proven. In real life, midazolam is usually given by a medical team right before a procedure, and they won't have you sipping mate at that point. If you regularly drink mate, just mention it to your doctor or anesthesia team beforehand.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. File SE, Bond AJ, Lister RG. Interaction between effects of caffeine and lorazepam in performance tests and self-ratings. J Clin Psychopharmacol 1982;2:102-6. DOI
  2. Mattila MJ, Palva E, Savolainen K. Caffeine antagonizes diazepam effects in man. Med Biol 1982;60:121-3.
  3. Mattila MJ, Nuotto E. Caffeine and theophylline counteract diazepam effects in man. Med Biol 1983;61:337-43.
  4. Mattila ME, Mattila MJ, Nuotto E. Caffeine moderately antagonizes the effects of triazolam and zopiclone on the psychomotor performance of healthy subjects. Pharmacol Toxicol 1992;70:286-9.
  5. Mattila MJ, Vainio P, Nurminen ML, et al. Midazolam 12 mg is moderately counteracted by 250 mg caffeine in man. Int J Clin Pharmacol Ther 2000;38:581-7. PubMed
Moderate

MIDAZOLAM (Versed)

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Theoretically, use of yerba mate with midazolam might increase midazolam metabolite levels and adverse effects.
In vitro research shows that yerba mate extract containing 6.75% chlorogenic acid significantly inhibits the metabolism of midazolam via inhibition of cytochrome P450 3A4 (CYP3A4).
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 gist: midazolam is cleared from your body by a liver enzyme called CYP3A4. In lab studies, a concentrated yerba mate extract slowed that enzyme down. If that happened in real life, your body would break midazolam down more slowly, so the drug could build up and hit harder. With a sedative like midazolam, that means more pronounced drowsiness, deeper relaxation, slower breathing, and feeling groggy or confused for longer than expected.

The good news is this is theoretical, based on a test-tube study using a specific high-strength extract, not on people drinking mate. Still, midazolam is usually given by professionals around procedures or surgery, so it's worth mentioning any yerba mate use to your anesthesia team, pharmacist, or doctor beforehand.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Feltrin C, Farias IV, Sandjo LP, Reginatto FH, Simões CMO. Effects of Standardized Medicinal Plant Extracts on Drug Metabolism Mediated by CYP3A4 and CYP2D6 Enzymes. Chem Res Toxicol 2020;33(9):2408-2419. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Midazolam also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, yerba mate might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yerba mate extract inhibits CYP3A4 enzymes. Theoretically, taking yerba mate may increase levels and adverse effects of CYP3A4 substrates.
Severity Minor 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 gist: your body relies on a liver enzyme called CYP3A4 to clear midazolam (Versed). In a lab setting, yerba mate has been shown to slow that same enzyme down a bit. In theory, if that enzyme works slower, midazolam could hang around longer and feel stronger, meaning more drowsiness, deeper sedation, or grogginess that lingers.

The good news is that this is based only on test-tube research, not real people, so the actual risk looks small. Midazolam is also usually given in a controlled medical setting where staff watch your sedation closely. Still, if you regularly drink a lot of yerba mate, it's worth mentioning to your doctor or anesthesia team beforehand so nobody is caught off guard.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Feltrin C, Farias IV, Sandjo LP, Reginatto FH, Simões CMO. Effects of Standardized Medicinal Plant Extracts on Drug Metabolism Mediated by CYP3A4 and CYP2D6 Enzymes. Chem Res Toxicol 2020;33(9):2408-2419. PubMed

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

Yerba Mate Also Interacts With Other Medications

Yerba Mate has 8 major, 504 moderate, 573 minor known drug interactions in our database — the Midazolam one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 504 Minor 573 No known interaction 1,745 (incl. Midazolam)
Taking anything else?

Check Another of Your Medications Against Yerba Mate

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

Everything else you take

See Every Supplement That Interacts With Midazolam

This page covers Yerba Mate only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Midazolam page lists 202 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Bitter Orange (major) and Fever Bark (major).

By severity: 11 major · 153 moderate · 38 minor.

From our pharmacist’s overview on the Midazolam page

“Sedation stacked on sedation is the headline risk with midazolam (Versed, Seizalam, Nayzilam). Midazolam is a benzodiazepine used for sedation and seizure emergencies, and 78 of the 202 interacting ingredients here, beer and wine included, add their own drowsiness, which can slide into dangerously slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Midazolam interaction page

One more smart check

Taking Yerba Mate as Part of a Dietary Supplement Product? Check It for Interactions

We hold 68 real supplement products containing Yerba Mate, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yerba Mate. Your product may carry other ingredients that interact with Midazolam too, on top of Yerba Mate — 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 Yerba Mate and Midazolam 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 Yerba Mate
Steady interest

#1,089 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Midazolam
Steady interest

#1,705 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 Yerba Mate

What is Yerba Mate?

Yerba Mate
  • Energy and alertness
  • Weight loss
  • Mental focus
  • Digestive support
  • Antioxidant support

Yerba mate is a caffeine-containing herbal beverage from South America that is widely enjoyed for its stimulating, coffee-like effects. While it is rich in antioxidants and is being studied for weight, blood sugar, and cholesterol, strong human evidence for most health claims is limited. Drinking very hot mate over many years has been linked to higher risk of certain cancers, so enjoy it warm and in moderation.

Read the full Yerba Mate monograph & all interactions
Medication

About Midazolam

What Is Midazolam Used For?

Brand names: Versed, Seizalam, Nayzilam

Midazolam is used in several different forms depending on the setting. Injectable midazolam (given by IV or IM shot) is used before and during surgery or procedures — such as endoscopy, cardiac catheterization, or bronchoscopy — to cause sedation, reduce anxiety, and prevent memory of the event. It can also be used to start general anesthesia or to keep heavily sedated, ventilated patients comfortable in a critical care unit. Midazolam HCl oral syrup is used specifically in children for sedation and anxiety relief before procedures or anesthesia induction, in a monitored medical setting only.

Nayzilam nasal spray is indicated for a different purpose: the acute treatment of seizure clusters (also called acute repetitive seizures) in people aged 12 and older who have epilepsy. It is used intermittently — not as a daily seizure medicine — when a cluster of seizures breaks through the person's usual pattern.

See full Midazolam drug information
Keep checking

Other Drugs & Yerba Mate

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

8Major
504Moderate
573Minor
1,744No known interaction
8 Major 504 Moderate 573 Minor 1,744 No interaction
Major

8 interactions

Moderate

504 interactions

Showing 60 of 504 moderate interactions — see all 504 on the Yerba Mate page.

Minor

573 interactions

Showing 60 of 573 minor interactions — see all 573 on the Yerba Mate page.

No interaction 1,744 drugs checked — show the list

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

Showing the 60 most looked-up of 1,744 medications checked with no known interaction — see the full Yerba Mate list.

See the full Yerba Mate interactions page
See every supplement checked against Midazolam, 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
Yerba Mate monograph › Uses, safety, and every drug interaction in one place Midazolam supplement interactions › Every supplement checked against Midazolam, ranked by severity Midazolam 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 Yerba Mate and Midazolam Together: Common Questions

Can you take Yerba Mate with Midazolam?
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 Yerba Mate and Midazolam?
Midazolam belongs to more than one drug category, and Yerba Mate 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 Yerba Mate and Midazolam 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

Still Have a Question About Midazolam and Yerba Mate?

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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.