Cannabis + Acetaminophen, Butalbital, Caffeine, Codeine
Acetaminophen, Butalbital, Caffeine, Codeine brand names: Esgic with Codeine, Fioricet w/ Codeine.
Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 drug categories that Cannabis can interact with; the most serious is rated moderate. Theoretically, cannabis might have additive effects if used with other CNS depressants.
Read the full interaction reportCannabis and Acetaminophen, Butalbital, Caffeine, Codeine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Cannabis interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine, Codeine falls into 4 of those categories, so it can interact with Cannabis in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 4Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine
Acetaminophen, Butalbital, Caffeine, Codeine falls under CNS DEPRESSANTS — the group Cannabis interacts with.
Cannabis can have CNS depressant effects. Combining cannabis with other CNS depressants might result in additive or synergistic effects. A small clinical trial in healthy adults shows that inhaling a high-grade cannabis (Bedrocan International B.V., Veendam, The Netherlands) 100 mg, containing delta-9-tetrahydrocannabinol 21.8% and cannabinol 0.1%, modestly increases subjective feelings of sedation when compared with cannabis alone.
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.
This combo pill packs two ingredients that already slow down your brain and nervous system: butalbital (a barbiturate) and codeine (an opioid). Both can leave you feeling drowsy, foggy, and slowed down. Cannabis works on different receptors, but it can pile on the same kind of sedation. So putting them together may stack up the effect.
Practically speaking, you might feel extra sleepy, dizzy, slow to react, or unsteady on your feet, and in some cases breathing can become shallower. This is based on how these drugs work and a small study showing cannabis adds modest sedation, not on hard proof, but it's worth taking seriously. Avoid driving, and please check with your pharmacist or doctor before mixing the two.
- 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).
- Hollister, L. E. Interactions of cannabis with other drugs in man. NIDA Res.Monogr 1986;68:110-116. DOI
- van Dam CJ, van der Schrier R, van Velzen M, et al. Inhaled Delta(9)-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers. Br J Anaesth 2023;130(4):485-493.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 4Acetaminophen, Butalbital, Caffeine, Codeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
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.
This combo pill is a real mix: acetaminophen (Tylenol), butalbital (a barbiturate), caffeine, and codeine. The piece to watch is the butalbital, which your liver clears partly through an enzyme called CYP3A4. Lab studies suggest cannabis can slow that enzyme down, so in theory butalbital could build up a bit and leave you feeling more drowsy, foggy, dizzy, or short of breath. Stacking cannabis on top of a barbiturate and an opioid (codeine) already adds to that sedation on its own.
Keep in mind this is based on test-tube research, not strong human data, so the effect may be small. Still, with sedating medicines like these, I'd play it safe and run it by your pharmacist or doctor before mixing in cannabis.
- 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
3 of 4Acetaminophen, Butalbital, Caffeine, Codeine 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.
This combination pill has four ingredients, and the part this interaction touches is the acetaminophen (Tylenol) piece. Acetaminophen is partly broken down by an enzyme called CYP2E1. Lab and animal studies hint that cannabis might speed this enzyme up, which could nudge acetaminophen toward a byproduct that is harder on the liver. Honestly though, this is theoretical and based only on test-tube and animal work, so I wouldn't lose sleep over it.
What matters more in real life: cannabis and the codeine and butalbital in this pill can all make you drowsy, dizzy, or foggy, and that adds up fast. Codeine also needs activation to work for pain, which cannabis doesn't change here. Keep acetaminophen totals reasonable and check with your pharmacist or doctor before mixing.
- 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
4 of 4Acetaminophen, Butalbital, Caffeine, Codeine 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.
This combo pill contains butalbital, which is a barbiturate, and that's the part we're focused on here. The thinking is that cannabis might slow how your body clears butalbital, letting it hang around a little longer. In one small study, THC stretched out the half-life of a similar barbiturate by about four hours.
What that could mean in real life: more drowsiness, dizziness, slowed breathing, or feeling foggy and uncoordinated, since both cannabis and butalbital are sedating on their own. To be fair, this is theoretical and based on limited data, not strong human evidence. Still, because both can make you sleepy, it's worth a quick chat with your doctor or pharmacist before mixing them, especially when driving.
- 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, Codeine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Cannabis
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Covers the 2,830 medications we’ve checked against Cannabis. Pick one to open its full report.
Questions About Cannabis or Acetaminophen, Butalbital, Caffeine, Codeine
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, Codeine, 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, Codeine
This page covers Cannabis 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
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, Codeine 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, 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.
#222 of 1,452 supplements looked up here in the last 7 days
#988 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.
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 ›
- Metoprolol ›
- Rosuvastatin ›
- Escitalopram ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Methamphetamine ›
- Sumatriptan ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Lisdexamfetamine ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Acyclovir ›
- Bendamustine ›
- Methotrexate ›
- Amphetamine ›
- Azithromycin ›
- Dextroamphetamine ›
- Isotretinoin ›
- Methylene Blue ›
- Duloxetine ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Levothyroxine Sodium ›
- Dexmethylphenidate ›
- Spironolactone ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Minoxidil ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Venlafaxine ›
- Lenvatinib ›
- Phenylephrine ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Nortriptyline ›
- Amoxicillin, Clavulanate Potassium ›
- Procainamide ›
- Hydroxychloroquine ›
- Azelaic Acid ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
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, Codeine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Butalbital, Caffeine, Codeine 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, Codeine 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, Codeine Together: Common Questions
Can you take Cannabis with Acetaminophen, Butalbital, Caffeine, Codeine?
Why are there 4 interactions listed for Cannabis and Acetaminophen, Butalbital, Caffeine, Codeine?
How serious is the Cannabis and Acetaminophen, Butalbital, Caffeine, Codeine 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.