Drug & supplement interaction

Hemp + Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine brand names: Esgic with Codeine, Fioricet w/ Codeine.

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

Acetaminophen, Butalbital, Caffeine, Codeine 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, Codeine

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, Codeine 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, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine 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 short version: this combo pill has four ingredients, and the part that hemp could touch is the caffeine. Caffeine is cleared by a liver enzyme called CYP1A2. Lab studies (not human studies) suggest hemp may speed that enzyme up a little, which in theory could clear caffeine a bit faster. If that happened, you might notice the caffeine feels slightly less potent, so a touch less of that wide-awake, jittery lift.

Honestly, I wouldn't lose sleep over this one. The evidence is only test-tube level, the rating is minor, and it doesn't meaningfully change the acetaminophen, butalbital, or codeine in this product. Food amounts of hemp seeds are very unlikely to matter. Still, if you're using concentrated hemp supplements regularly, mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
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, Codeine 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 short version: this combination pill contains several pieces, and the lab concern is about hemp possibly speeding up a liver enzyme called CYP3A4. That same enzyme helps handle the butalbital portion, and it's part of what turns codeine into its active pain-relieving form. So if hemp truly revved up this enzyme in people, you might see slightly less reliable pain relief, or somewhat more sedation from faster butalbital changes. Honestly, the effect could go either way depending on the ingredient.

The reassuring part: this is only theoretical, based on test-tube research, not real patients. Food amounts of hemp seeds or oil almost certainly won't matter. If you use concentrated hemp supplements regularly, just mention it to your pharmacist or doctor.

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

Moderate 41 Minor 896 No known interaction 1,893 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
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, Codeine

This page covers Hemp only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine, Codeine page lists 305 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), Asarabacca (major), Beer (major) and Ephedra (major).

By severity: 15 major · 245 moderate · 45 minor.

Open the Acetaminophen, Butalbital, Caffeine, Codeine 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, Codeine 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, Codeine 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%

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine, Codeine
Top half

#921 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
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
41 Moderate 896 Minor 1,892 No 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

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

Showing the 60 most looked-up of 1,892 medications checked with no known interaction — see the full Hemp list.

See the full Hemp interactions page
See every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, 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
Hemp monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, ranked by severity 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 Hemp and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Hemp with Acetaminophen, Butalbital, Caffeine, Codeine?
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, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine 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, Codeine 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

Still Have a Question About Acetaminophen, Butalbital, Caffeine, Codeine and Hemp?

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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.