Drug & supplement interaction

Coffee + Pentobarbital

Pentobarbital brand name: Nembutal.

Moderate Interaction
The bottom line Moderate

Coffee has a moderate interaction with Pentobarbital. Theoretically, coffee might reduce the effects of pentobarbital.

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

Coffee and Pentobarbital

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

Moderate

PENTOBARBITAL (Nembutal)

Theoretically, coffee might reduce the effects of pentobarbital.
Coffee contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital.
Severity Moderate Likelihood Possible Evidence B

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 simple version: pentobarbital is a barbiturate that calms the brain and helps you feel sleepy or sedated. Coffee does the opposite. The caffeine in it is a stimulant that wakes you up and blocks the same drowsy signals pentobarbital is trying to turn on.

So if you drink coffee while taking pentobarbital, the caffeine may partly cancel out the calming or sleep-inducing effect, leaving you more alert than expected. This is mostly a theoretical concern and isn't dangerous in itself, but it could make the medication work less well. A cup now and then probably matters little; loading up on coffee or energy drinks is more likely to push against the drug. If you're unsure how much is okay, check with your pharmacist or doctor.

References
  1. Forrest WH Jr, Bellville JW, Brown BW Jr. The interaction of caffeine with pentobarbital as a nighttime hypnotic. Anesthesiology 1972;36:37-41. 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

Coffee Also Interacts With Other Medications

Coffee has 8 major, 466 moderate, 116 minor known drug interactions in our database — the Pentobarbital 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 Coffee

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

Everything else you take

See Every Supplement That Interacts With Pentobarbital

This page covers Coffee only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Pentobarbital page lists 127 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), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 103 moderate · 17 minor.

From our pharmacist’s overview on the Pentobarbital page

“Pentobarbital (Nembutal) is a potent barbiturate sedative, and most of what interacts with it pushes in the direction the drug already goes, toward deeper sedation and slowed breathing. I would treat this list with real seriousness.”

Reviewed by 2 · Jul 18, 2026

Open the Pentobarbital interaction page

One more smart check

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

We hold 716 real supplement products containing Coffee, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Coffee. Your product may carry other ingredients that interact with Pentobarbital too, on top of Coffee — 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 Coffee and Pentobarbital 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 Coffee
Top 5%

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

29 days ago today
Medication Pentobarbital
Steady interest

#2,600 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 Coffee

What is Coffee?

  • Alertness and reducing fatigue
  • Mental focus and concentration
  • Athletic performance
  • Headache relief
  • Weight management

Coffee is a widely consumed beverage made from roasted coffee beans, valued mainly for its caffeine, which boosts alertness and energy. For most healthy adults, moderate coffee intake is generally safe and may have some health benefits, but too much can cause jitteriness, poor sleep, and a faster heartbeat. People who are pregnant, breastfeeding, or sensitive to caffeine should limit their intake and check with a doctor or pharmacist.

Read the full Coffee monograph & all interactions
Keep checking

Other Drugs & Coffee

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

8Major
466Moderate
116Minor
2,239No known interaction
Major

8 interactions

Moderate

466 interactions

Showing 60 of 466 moderate interactions — see all 466 on the Coffee page.

Minor

116 interactions

Showing 60 of 116 minor interactions — see all 116 on the Coffee page.

No interaction 2,239 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 Coffee and Pentobarbital Together: Common Questions

Can you take Coffee with Pentobarbital?
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.
How serious is the Coffee and Pentobarbital 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.