Cannabis + Tramadol, Acetaminophen
Tramadol, Acetaminophen brand name: Tramacet.
Tramadol, Acetaminophen falls into 3 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 Tramadol, Acetaminophen
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. Tramadol, Acetaminophen 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).
CNS DEPRESSANTS
1 of 3Why this applies to Tramadol, Acetaminophen
Tramadol, Acetaminophen 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.
Tramacet is a combo of tramadol (an opioid-type painkiller) and acetaminophen. The piece that matters here is the tramadol, which already works on your brain and nervous system and can make you feel drowsy, foggy, or slow. Cannabis can do the same thing, so using them together may stack those effects.
What that can look like in real life: more sleepiness, dizziness, trouble concentrating, slowed reaction time, and feeling lightheaded. This is mostly a theoretical, common-sense concern based on how both act, not a dramatic or dangerous reaction for most people. Still, it's worth being careful, especially before driving or if you're older. I'd check with your doctor or pharmacist before mixing them, and never change your medication on your own.
- 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 3Tramadol, Acetaminophen 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.
Here's the gist with Tramacet (tramadol plus acetaminophen) and cannabis. Tramadol partly relies on liver enzymes, including CYP3A4, to be processed. Lab-dish studies hint that cannabis can mildly slow down CYP3A4. If that happened in real life, a bit more tramadol could hang around, which might mean stronger sedation, dizziness, drowsiness, nausea, or constipation. Both tramadol and cannabis are also independently sedating, so the bigger real-world concern is feeling extra drowsy or foggy when you combine them.
I want to be honest: this enzyme effect is theoretical and based only on test-tube work, so it may not amount to much. Still, please run this combo past your doctor or pharmacist before using them together.
- 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 3Tramadol, Acetaminophen 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 honest picture with Tramacet (tramadol plus acetaminophen) and cannabis. The lab-based concern is that cannabis may speed up an enzyme called CYP2E1. For the acetaminophen part, that enzyme is one route that can turn it into a harmful liver byproduct, so in theory a faster pathway could be a little harder on the liver, especially at higher acetaminophen doses or with alcohol. But this is test-tube evidence only, so I wouldn't lose sleep over normal use.
Honestly, the bigger real-world issue is that both cannabis and tramadol can cause drowsiness, dizziness, and slowed thinking, which stack together. Please run this combo by your pharmacist or doctor, and don't exceed the acetaminophen on the label.
- 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
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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen
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 Tramadol, Acetaminophen, 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 Tramadol, Acetaminophen
This page covers Cannabis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol, Acetaminophen page lists 280 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 Gamma-hydroxybutyrate (ghb) (major).
By severity: 12 major · 224 moderate · 44 minor.
From our pharmacist’s overview on the Tramadol, Acetaminophen page
“The combinations I worry about most with tramadol and acetaminophen (Tramacet) involve anything that deepens drowsiness or strains the liver. Tramadol is an opioid, so sedating supplements like kava, along with alcohol in any form, can slow breathing on top of adding sleepiness, which is why this list deserves genuine care rather than…”
Reviewed by 2 · Jul 18, 2026
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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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.
#217 of 1,452 supplements looked up here in the last 7 days
#389 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 ›
- Metformin ›
- Lisdexamfetamine ›
- Amoxicillin ›
- Acyclovir ›
- Lisinopril ›
- Bendamustine ›
- Methotrexate ›
- Amphetamine ›
- Azithromycin ›
- Dextroamphetamine ›
- Isotretinoin ›
- Methylene Blue ›
- Duloxetine ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Mannitol ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Levothyroxine Sodium ›
- Dexmethylphenidate ›
- Spironolactone ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Mitomycin ›
- Minoxidil ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Lenvatinib ›
- Phenylephrine ›
- Venlafaxine ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Nortriptyline ›
- Procainamide ›
- Amoxicillin, Clavulanate Potassium ›
- Hydroxychloroquine ›
- Azelaic Acid ›
- Dextrothyroxine ›
- Triptorelin ›
- 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
Tramadol, Acetaminophen Is Linked to Lower Levels of One Nutrient
Natural Medicines records Tramadol, Acetaminophen 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 Tramadol, Acetaminophen 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 Tramadol, Acetaminophen Together: Common Questions
Can you take Cannabis with Tramadol, Acetaminophen?
Why are there 3 interactions listed for Cannabis and Tramadol, Acetaminophen?
How serious is the Cannabis and Tramadol, Acetaminophen 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.