Cannabis + Acetaminophen, Butalbital, Caffeine
Acetaminophen, Butalbital, Caffeine brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, and others.
Acetaminophen, Butalbital, Caffeine falls into 3 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, cannabis may increase the levels and adverse effects of CYP3A4 substrates.
Read the full interaction reportCannabis and Acetaminophen, Butalbital, Caffeine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Cannabis interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine falls into 3 of those categories, so it can interact with Cannabis in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
1 of 3Why this applies to Acetaminophen, Butalbital, Caffeine
Acetaminophen, Butalbital, Caffeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Cannabis interacts with.
In vitro research shows that cannabis can inhibit the activity of CYP3A4 enzymes, which might decrease the metabolism of CYP3A4 substrates. In vitro research also shows that cannabis extracts modestly inhibit the CYP3A4 metabolism of testosterone; extracts providing the specific cannabinoids CBD and cannabigerol (CBG) had stronger inhibitory effects than extracts containing THC and CBD.
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.
Here's the gist with your headache medicine (Esgic, Fiogesic and similar combos). The butalbital piece, a barbiturate, is partly cleared by a liver enzyme called CYP3A4. In lab and test-tube studies, cannabis appears to gently slow that enzyme down. In theory, that could let butalbital linger a bit longer, which might add to its sedating effects, things like extra drowsiness, dizziness, slowed breathing, or feeling foggy. Both cannabis and butalbital can make you sleepy on their own, so combining them tends to stack that effect.
Keep in mind this is weak, theoretical evidence, not something proven in people. Still, before mixing the two, it's worth a quick chat with your pharmacist or doctor, especially about the combined drowsiness.
- Pellinen, P., Honkakoski, P., Stenback, F., Niemitz, M., Alhava, E., Pelkonen, O., Lang, M. A., and Pasanen, M. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur.J Pharmacol 1-3-1994;2 PubMed
- Treyer A, Reinhardt JK, Eigenmann DE, Oufir M, Hamburger M. Phytochemical comparison of medicinal cannabis extracts and study of their CYP-mediated interactions with coumarinic oral anticoagulants. Med Cannabis Cannabinoids. 2023;6(1):21-31. PubMed
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
2 of 3Acetaminophen, Butalbital, Caffeine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
In vitro research shows that cannabis can induce the activity of CYP2E1, which might increase the metabolism of CYP2E1 substrates.
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.
Here's the gist for this headache combo. The piece that matters is the acetaminophen (the Tylenol part). Your liver uses an enzyme called CYP2E1 to handle some acetaminophen, and lab studies suggest cannabis might speed that enzyme up. In theory, that could shift more acetaminophen down a pathway that produces a toxic byproduct, which is the same byproduct your liver normally has to neutralize.
I want to be honest though: this is based only on test-tube and animal research, so we don't really know how much it matters in real people. The practical takeaway is to be careful not to exceed your daily acetaminophen limit and to go easy on alcohol. If you use cannabis regularly and take this regularly, just give your pharmacist or doctor a heads-up so they can keep an eye on things.
- Sheweita, S. A. Narcotic drugs change the expression of cytochrome P450 2E1 and 2C6 and other activities of carcinogen-metabolizing enzymes in the liver of male mice. Toxicology 9-30-2003;191(2-3):133-142. PubMed
BARBITURATES
3 of 3Acetaminophen, Butalbital, Caffeine also falls under BARBITURATES.
Some research shows that synthetic delta-9-tetrahydrocannabinol (THC) increases the elimination half-life of pentobarbital by 4 hours when dosed concomitantly.
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.
The piece of this combo to watch here is the butalbital, which is a barbiturate. It's the sedating, muscle-relaxing part that calms a tension headache. There's a theory, based mostly on how these drugs behave rather than solid human studies, that cannabis might slow how your body clears barbiturates. In one small study THC stretched out how long a related barbiturate stuck around by about 4 hours.
In plain terms, mixing the two could leave more butalbital in your system and pile on the drowsiness. You might feel extra sleepy, foggy, dizzy, or slow to react, which is risky for driving. The evidence is thin, so don't panic, but please check with your pharmacist or doctor before using both together.
- Marinol Prescribing Information. Solvay Pharmaceuticals, Rev March 2008. Available at: http://www.solvaypharmaceuticals-us.com/static/wma/pdf/1/3/2/5/0/004InsertText500012RevMar2008.pdf (Accessed 2 July 2009).
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Cannabis Also Interacts With Other Medications
Cannabis has 2 major, 1,108 moderate, 25 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.
Check Another of Your Medications Against Cannabis
We haven’t checked that one against Cannabis yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Cannabis. Pick one to open its full report.
Questions About Cannabis or Acetaminophen, Butalbital, Caffeine
These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Cannabis or Acetaminophen, Butalbital, Caffeine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:
Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.
See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine
This page covers Cannabis 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
Taking Cannabis as Part of a Dietary Supplement Product? Check It for Interactions
We hold 21 real supplement products containing Cannabis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cannabis. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine too, on top of Cannabis — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where Cannabis 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.
#220 of 1,452 supplements looked up here in the last 7 days
#55 of 2,830 medications looked up here in the last 7 days
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.
About Cannabis
What is Cannabis?
- Chronic pain
- Nausea and vomiting from chemotherapy
- Muscle spasticity (e.g., multiple sclerosis)
- Anxiety and stress
- Sleep problems
- Appetite stimulation
Cannabis contains many active compounds, mainly THC (which causes a 'high') and CBD (which does not). Some uses, such as chemotherapy-related nausea, certain seizure disorders, and muscle spasticity, have meaningful evidence, while many other popular uses are not well proven. It can cause real side effects and impairment, so talk to your doctor or pharmacist and follow your local laws before using it.
About Acetaminophen, Butalbital, and Caffeine
What Is Acetaminophen, Butalbital, and Caffeine Used For?
Brand names: Tecnal, Esgic Plus, Fiogesic, Triad, Repan, Esgic, Fioricet
This combination product — available as capsules, tablets, and oral solution under various names including Fioricet — is used to relieve the symptoms of tension headaches (also called muscle contraction headaches).
All supported products, including Fioricet capsules and the oral solution, share this same indication. Because butalbital can be habit-forming, extended or repeated use is not recommended, and these products are not established as safe or effective for treating headaches that come back frequently over time.
Other Drugs & Cannabis
Browse every other medication we’ve checked against Cannabis — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
2 interactions
1,108 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Metronidazole ›
- Diphenhydramine ›
- Aspirin ›
- Hydrocortisone ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Fenofibrate ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Acetaminophen ›
- Buprenorphine ›
- Conjugated Estrogens ›
Showing 60 of 1,108 moderate interactions — see all 1,108 on the Cannabis page.
25 interactions
- Fluphenazine ›
- Asenapine ›
- Clozapine ›
- Prochlorperazine ›
- Acetophenazine ›
- Butaperazine ›
- Carphenazine ›
- Chlorprothixene ›
- Isopropamide Iodide ›
- Mesoridazine Besylate ›
- Methotrimeprazine Maleate ›
- Molindone ›
- Olanzapine ›
- Paliperidone ›
- Paliperidone Palmitate ›
- Pericyazine ›
- Perphenazine ›
- Piperacetazine ›
- Promazine ›
- Sertindole ›
- Thiothixene ›
- Trifluoperazine ›
- Triflupromazine ›
- Isopropamide, Trifluoperazine ›
- Isopropamide, Prochlorperazine ›
No interaction 1,694 drugs checked — show the list
We also checked Cannabis against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Rosuvastatin ›
- Metoprolol ›
- Escitalopram ›
- Methamphetamine ›
- Tirzepatide ›
- Docusate ›
- Sumatriptan ›
- Valacyclovir ›
- Hydroxyurea ›
- Isotretinoin ›
- Semaglutide ›
- Metformin ›
- Lisdexamfetamine ›
- Methotrexate ›
- Amphetamine ›
- Amoxicillin ›
- Lisinopril ›
- Bupropion ›
- Bendamustine ›
- Azithromycin ›
- Levothyroxine, Liothyronine ›
- Acyclovir ›
- Dextroamphetamine ›
- Duloxetine ›
- Methylene Blue ›
- Bisoprolol ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Cephalexin ›
- Cyclopentolate ›
- Ezetimibe ›
- Carbidopa, Levodopa ›
- Mannitol ›
- Insulin Degludec, Liraglutide ›
- Thyroid Hormone ›
- Levodopa ›
- Spironolactone ›
- Mitomycin ›
- Canagliflozin, Metformin ›
- Venlafaxine ›
- Alginic Acid, Aluminum Hydroxide ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Atenolol ›
- Magnesium Hydroxide (otc Drug) ›
- Minoxidil ›
- Acarbose ›
- Cefaclor ›
- Daptomycin ›
- Hydroxychloroquine ›
- Pegunigalsidase Alfa-iwxj ›
- Flutemetamol F-18 ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Amphetamine Aspartate, Amphetamine Sulfate, Dextroamphetamine Saccharate, Dextroamphetamine Sulfate ›
- Hydrochlorothiazide ›
- Atenolol, Chlorthalidone ›
- Factor 7a ›
- Bentoquatam ›
Showing the 60 most looked-up of 1,694 medications checked with no known interaction — see the full Cannabis list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Acetaminophen, Butalbital, Caffeine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Butalbital, Caffeine as a medicine that can lower these. This is not an interaction with Cannabis — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Acetaminophen, Butalbital, Caffeine nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Cannabis and Acetaminophen, Butalbital, Caffeine Together: Common Questions
Can you take Cannabis with Acetaminophen, Butalbital, Caffeine?
Why are there 3 interactions listed for Cannabis and Acetaminophen, Butalbital, Caffeine?
How serious is the Cannabis and Acetaminophen, Butalbital, Caffeine interaction?
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.