Drug & supplement interaction

Hemp + Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, and others.

Minor Interaction
The bottom line Minor

Acetaminophen, Butalbital, Caffeine falls into 2 drug categories that Hemp can interact with; the most serious is rated minor. Theoretically, hemp might decrease the levels and clinical effects of CYP1A2 substrates.

Read the full interaction report
SeverityMinor
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Hemp and Acetaminophen, Butalbital, Caffeine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Hemp interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine falls into 2 of those categories, so it can interact with Hemp in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Butalbital, Caffeine

Acetaminophen, Butalbital, Caffeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Hemp interacts with.

Theoretically, hemp might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that hemp induces CYP1A2 enzymes.
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 practical picture for your headache combo (Esgic, Fiogesic, and similar). The caffeine part of this pill is cleared by a liver enzyme called CYP1A2. Lab studies suggest hemp may speed that enzyme up a bit, which could clear the caffeine a touch faster. In plain terms, the gentle pick-me-up and headache-helping boost from the caffeine portion might feel slightly weaker. The acetaminophen and butalbital pieces aren't really driven by this enzyme, so this is mostly about the caffeine.

Honestly, this is rated minor and comes only from test-tube research, not from people, so I wouldn't lose sleep over it. Food amounts of hemp seeds or oil are very unlikely to matter. If you use concentrated hemp supplements regularly, just mention it to your pharmacist or doctor.

References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Theoretically, hemp might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that hemp induces CYP3A4 enzymes.
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 for your Esgic or Fioricet style headache medicine (acetaminophen, butalbital, and caffeine). Some lab and animal studies hint that hemp might rev up a liver enzyme called CYP3A4, which helps break down butalbital, the barbiturate piece of this combo. In theory, speeding that enzyme up could clear the drug a little faster, which might make your headache relief feel weaker. The caffeine and acetaminophen parts aren't really affected this way.

I want to be honest though: this is very weak evidence, just test-tube and animal data, not real people. Everyday hemp seeds or hemp oil in food are unlikely to cause trouble. If you take concentrated hemp supplements regularly, mention it to your pharmacist or doctor so they can keep an eye on how well your medicine works.

References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Hemp Also Interacts With Other Medications

Hemp has 41 moderate, 896 minor known drug interactions in our database — the Acetaminophen, Butalbital, Caffeine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Hemp

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine

This page covers Hemp only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine page lists 252 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), Ephedra (major) and Grapefruit (major).

By severity: 11 major · 197 moderate · 44 minor.

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

“Alcohol is the interaction I would flag first for anyone taking acetaminophen, butalbital, and caffeine (Esgic, Fiogesic, and others). Drinking raises the risk of liver injury from the acetaminophen component, and 38 of the 252 supplement ingredients on file carry that same liver concern.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Butalbital, Caffeine interaction page

One more smart check

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

We hold 720 real supplement products containing Hemp, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Hemp. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine too, on top of Hemp — 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 Hemp and Acetaminophen, Butalbital, 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 Hemp
Top 25%

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine
Steady interest

#1,689 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 Hemp

What is Hemp?

Hemp
  • Plant-based protein source
  • Heart health support
  • Skin and hair health
  • Reducing inflammation
  • General nutrition (omega fatty acids)

Hemp seeds and hemp seed oil are nutritious foods rich in protein, fiber, and healthy omega-3 and omega-6 fatty acids, and they are generally safe for most people as part of the diet. While the nutrition is real, strong human evidence that hemp supplements treat specific medical conditions is limited. Talk with your pharmacist or doctor before using hemp products for a health concern, especially if you are pregnant or breastfeeding.

Read the full Hemp monograph & all interactions
Medication

About Acetaminophen, Butalbital, and Caffeine

What Is Acetaminophen, Butalbital, and Caffeine Used For?

Brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, Esgic, Fioricet

This three-ingredient combination — butalbital, acetaminophen, and caffeine — is used to relieve the symptoms of tension headache (also called muscle contraction headache). All supported products, including tablets, capsules, and oral solution, share this same approved use.

It is worth knowing that evidence for using this combination to treat repeated, frequent tension headaches over time is limited. Because butalbital can be habit-forming, extended or repeated use is not recommended.

See full Acetaminophen, Butalbital, and Caffeine drug information
Keep checking

Other Drugs & Hemp

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

0Major
41Moderate
896Minor
1,892No known interaction
Moderate

41 interactions

Minor

896 interactions

Showing 60 of 896 minor interactions — see all 896 on the Hemp page.

No interaction 1,892 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 Hemp and Acetaminophen, Butalbital, Caffeine Together: Common Questions

Can you take Hemp with Acetaminophen, Butalbital, Caffeine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Hemp and Acetaminophen, Butalbital, Caffeine?
Acetaminophen, Butalbital, Caffeine belongs to more than one drug category, and Hemp 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 Hemp and Acetaminophen, Butalbital, Caffeine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your 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.