Cannabidiol (cbd) + Acetaminophen, Orphenadrine
Acetaminophen, Orphenadrine brand name: Orfenagesic.
Acetaminophen, Orphenadrine falls into 4 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Cannabidiol may increase levels of drugs metabolized by CYP1A2.
Read the full interaction reportCannabidiol (cbd) and Acetaminophen, Orphenadrine
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Cannabidiol (cbd) interacts with whole categories of medication. Acetaminophen, Orphenadrine falls into 4 of those categories, so it can interact with Cannabidiol (cbd) in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
1 of 4Why this applies to Acetaminophen, Orphenadrine
Acetaminophen, Orphenadrine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Cannabidiol (cbd) interacts with.
In vitro research shows that cannabidiol inhibits CYP1A2. Furthermore, clinical studies show that cannabidiol may inhibit the metabolism of caffeine, a CYP1A2 substrate. Two pharmacokinetic studies in healthy adults show that taking cannabidiol dosed 640 mg once up to 750 twice daily increases the area under the curve of caffeine. However, results are mixed over whether cannabidiol impacts peak serum levels of caffeine.
Interaction 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..
This combination pill pairs acetaminophen (Tylenol) with orphenadrine, a muscle relaxer. The orphenadrine part is partly cleared by a liver enzyme called CYP1A2, and CBD can slow that enzyme down. When the enzyme works slower, orphenadrine can build up a bit more than usual, which may bump up its side effects.
For orphenadrine, that could mean more drowsiness, dry mouth, blurry vision, dizziness, or a faster heartbeat. Keep in mind the studies showing this used very high CBD doses, so a small everyday amount may matter less. Even so, since CBD products vary so much, it is worth checking with your pharmacist or doctor before combining them, especially if you already feel sleepy on this medicine.
- Yamaori S, Kushihara M, Yamamoto I, Watanabe K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective potent inhibitors of human CYP1 enzymes. Biochem Pharmacol 2010;79(11):1691-8.
- Thai C, Tayo B, Critchley D. A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects. Clin Pharmacol Drug Dev. 2021. PubMed
- Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
- Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
GLUCURONIDATED DRUGS
2 of 4Acetaminophen, Orphenadrine also falls under GLUCURONIDATED DRUGS.
In vitro research shows that cannabidiol inhibits uridine diphosphoglucuronosyl transferase (UGT) 1A9 and UGT2B7, enzymes responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs.
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 this combo: your pain reliever (acetaminophen, with the muscle relaxant orphenadrine) gets partly cleared by the body through a process called glucuronidation. In lab dishes, CBD has been shown to slow down some of the enzymes that do that work. The thinking is that CBD could let acetaminophen build up a little more than usual.
I want to be honest about the evidence here: this is based only on test-tube studies, not real people, so it's more of a theoretical caution than a proven problem. Still, if acetaminophen levels run higher, that's a concern for your liver, especially with regular use or any alcohol. Orphenadrine on its own can already cause drowsiness and dry mouth. Please loop in your pharmacist or doctor before pairing these, and watch your total daily acetaminophen.
- Epidiolex (cannabidiol) prescribing information. Greenwich Biosciences, Inc., Carlsbad, CA, 2019. Available at: https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf (accessed 5/9/2019)
CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES
3 of 4Acetaminophen, Orphenadrine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.
In vitro research shows that cannabidiol inhibits CYP2E1. So far, this interaction has not been reported in humans.
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 your Orfenagesic, which combines acetaminophen (Tylenol) and orphenadrine (a muscle relaxer). One of the liver enzymes that helps break down acetaminophen is called CYP2E1, and lab studies (in test tubes, not in people) suggest CBD may slow that enzyme down. In theory, that could let acetaminophen linger a bit longer in your system.
I want to be honest about how shaky this is: it has only been seen in lab dishes, never reported in actual patients. So I wouldn't lose sleep over it. The bigger practical reminder is to watch your total daily acetaminophen and avoid extra alcohol, since both stress the liver. If you use CBD regularly with this medicine, just give your pharmacist or doctor a heads-up.
- Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. PubMed
CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES
4 of 4Acetaminophen, Orphenadrine also falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES.
In vitro research shows that cannabidiol inhibits CYP2B6. However, this interaction has yet to be reported in humans. Until more is known, use with caution. Theoretically, concomitant use of cannabidiol with CYP2B6 substrates might increase the risk for adverse effects from these 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 combo pill: one of its ingredients, orphenadrine (a muscle relaxer), is partly broken down by a liver enzyme called CYP2B6. In test-tube studies, CBD slows that enzyme down. In plain terms, that could let orphenadrine build up a bit higher than usual, which might bump up its typical side effects, things like drowsiness, dry mouth, blurred vision, dizziness, or constipation. The acetaminophen part isn't really the concern here.
The big caveat: this is only theory based on lab work. It hasn't actually been seen in real people, so I wouldn't panic. Still, if you'd feel more relaxed knowing for sure, run it by your pharmacist or doctor before pairing the two, especially since both can make you sleepy.
- Yamaori S, Maeda C, Yamamoto I, Watanabe K. Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids. Forensic Toxicol 2011;29:117-24. DOI
- Nasrin S, Watson CJW, Perez-Paramo YX, Lazarus P. Cannabinoid Metabolites as Inhibitors of Major Hepatic CYP450 Enzymes, with Implications for Cannabis-Drug Interactions. Drug Metab Dispos 2021;49(12):1070-1080. 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.
Cannabidiol (cbd) Also Interacts With Other Medications
Cannabidiol (cbd) has 1,050 moderate known drug interactions in our database — the Acetaminophen, Orphenadrine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Cannabidiol (cbd)
We haven’t checked that one against Cannabidiol (cbd) yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Cannabidiol (cbd). Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Orphenadrine
This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Orphenadrine page lists 160 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), Procaine (major) and Siberian Cocklebur (major).
By severity: 6 major · 119 moderate · 35 minor.
From our pharmacist’s overview on the Acetaminophen, Orphenadrine page
“Orfenagesic combines acetaminophen with orphenadrine, a muscle relaxant, and the acetaminophen half is what makes its interaction list worth real vigilance. Six of the 160 supplement ingredients on file carry a major rating, and the largest risky cluster, 38 ingredients including beer and wine, adds to the strain acetaminophen already…”
Reviewed by 2 · Jul 18, 2026
Where Cannabidiol (cbd) and Acetaminophen, Orphenadrine 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.
#392 of 1,452 supplements looked up here in the last 7 days
#505 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 Cannabidiol (cbd)
What is Cannabidiol (cbd)?
- Anxiety and stress
- Sleep problems
- Chronic pain
- Certain seizure disorders
- Inflammation
CBD is a compound from the cannabis (hemp) plant that does not cause a 'high.' It has strong evidence only for certain rare seizure disorders (as a prescription drug), while most other popular uses are still backed by limited or early research. Product quality varies a lot, so talk with your pharmacist or doctor before using it, especially if you take other medicines.
Other Drugs & Cannabidiol (cbd)
Browse every other medication we’ve checked against Cannabidiol (cbd) — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1,050 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Ibuprofen ›
- Metronidazole ›
- Diphenhydramine ›
- Hydrocortisone ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Bupropion ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Isotretinoin ›
- Orphenadrine ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Indomethacin ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Griseofulvin ›
- Ivabradine ›
Showing 60 of 1,050 moderate interactions — see all 1,050 on the Cannabidiol (cbd) page.
No interaction 1,779 drugs checked — show the list
We also checked Cannabidiol (cbd) against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Methylphenidate ›
- Aspirin ›
- Ivermectin ›
- Rosuvastatin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Semaglutide ›
- Sumatriptan ›
- Tirzepatide ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Acyclovir ›
- Doxycycline ›
- Methotrexate ›
- Azithromycin ›
- Methylene Blue ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Spironolactone ›
- Factor 7a ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Minoxidil ›
- Mitomycin ›
- Levodopa ›
- Ezetimibe ›
- Cefaclor ›
- Phenylephrine ›
- Vancomycin ›
- Lenvatinib ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Amoxicillin, Clavulanate Potassium ›
- Procainamide ›
- Hydroxychloroquine ›
- Tenecteplase ›
- Azelaic Acid ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Pizotifen ›
- Tocainide ›
- Acetylsalicylic Acid ›
- Hydrochlorothiazide ›
- Rocuronium ›
- Succimer ›
- Mitomycin C ›
- Dabigatran ›
Showing the 60 most looked-up of 1,779 medications checked with no known interaction — see the full Cannabidiol (cbd) 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, Orphenadrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Orphenadrine as a medicine that can lower these. This is not an interaction with Cannabidiol (cbd) — 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, Orphenadrine 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 Cannabidiol (cbd) and Acetaminophen, Orphenadrine Together: Common Questions
Can you take Cannabidiol (cbd) with Acetaminophen, Orphenadrine?
Why are there 4 interactions listed for Cannabidiol (cbd) and Acetaminophen, Orphenadrine?
How serious is the Cannabidiol (cbd) and Acetaminophen, Orphenadrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Orphenadrine and Cannabidiol (cbd)?
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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.