Cannabidiol (cbd) + Acetaminophen, Codeine, Doxylamine
Acetaminophen, Codeine, Doxylamine brand name: Mersyndol.
Acetaminophen, Codeine, Doxylamine falls into 5 drug categories that Cannabidiol (cbd) can interact with; the most serious is rated moderate. Theoretically, cannabidiol might have additive effects if used with other CNS depressants.
Read the full interaction reportCannabidiol (cbd) and Acetaminophen, Codeine, Doxylamine
These two interact in 5 distinct ways. Each one is explained separately below.
Why Are There 5 Interactions?
Cannabidiol (cbd) interacts with whole categories of medication. Acetaminophen, Codeine, Doxylamine falls into 5 of those categories, so it can interact with Cannabidiol (cbd) in 5 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CNS DEPRESSANTS
1 of 5Why this applies to Acetaminophen, Codeine, Doxylamine
Acetaminophen, Codeine, Doxylamine falls under CNS DEPRESSANTS — the group Cannabidiol (cbd) interacts with.
Preliminary clinical research, case reports, and animal studies suggest that high dose cannabidiol has sedative and hypnotic effects. Theoretically, concomitant use of cannabidiol with drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.
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 thing to keep in mind with Mersyndol: two of its ingredients already make you drowsy. The codeine is an opioid pain reliever, and the doxylamine is a sedating antihistamine (the same type found in nighttime sleep aids). Both can leave you feeling sleepy, foggy, or slow.
CBD, especially at higher supplement doses, can add a calming, drowsy effect of its own. So stacking them together may pile on the sedation, more than each one alone. You might notice extra grogginess, dizziness, trouble concentrating, or feeling unsteady on your feet. This concern is mostly theoretical, based on how these substances behave rather than strong studies, but it's still worth respecting. Please check with your pharmacist or doctor before combining them, and don't drive until you know how you react.
- Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol 1981;21(8-9 Suppl):417S-27S. PubMed
- Monti JM. Hypnoticlike effects of cannabidiol in the rat. Psychopharmacology (Berl) 1977;55(3):263-5. PubMed
- Pickens JT. Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content. Br J Pharmacol 1981;72(4):649-56.
- Perez-Vilar S, Karami S, Long K, Leishear K. Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021. Clin Toxicol (Phila) 2022. PubMed
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
2 of 5Acetaminophen, Codeine, Doxylamine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
In vitro research shows that cannabidiol inhibits CYP2D6. Theoretically, concomitant use of cannabidiol with CYP2D6 substrates might increase the risk for adverse effects from these substrates. However, a clinical crossover trial in healthy adults shows that cannabidiol does not inhibit dextromethorphan, a substrate of CYP2D6.
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 wrinkle with Mersyndol: the codeine part is a prodrug. Your body uses an enzyme called CYP2D6 to turn codeine into morphine, which is what actually relieves pain. CBD has been shown in lab (test tube) studies to slow CYP2D6 down. In theory, if that enzyme is blocked, less codeine gets converted to morphine, so you might get weaker pain relief, not stronger effects.
I'll be honest though, this is theoretical and on the weaker end of the evidence. A real-world study using another CYP2D6 drug found CBD didn't actually block it much. So I wouldn't lose sleep over it, but since codeine is involved, it's worth a quick chat with your pharmacist or doctor before pairing them.
- Yamaori S, Okamoto Y, Yamamoto I, Watanabe K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 2011;39(11):2049-56. 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.
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
3 of 5Acetaminophen, Codeine, Doxylamine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.
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..
Here's the thing with Mersyndol (acetaminophen, codeine, and doxylamine): CBD can block an enzyme called CYP1A2. Of the three ingredients, the one most tied to that enzyme is doxylamine, the antihistamine that makes you drowsy. If CBD slows its breakdown, doxylamine levels can creep up, which may leave you more sedated, dizzy, dry-mouthed, or groggy than usual. Since CBD itself can be relaxing and codeine is also a sedating opioid, stacking all of this together can add up to extra sleepiness.
The CYP1A2 evidence here is solid, but it comes from high CBD doses. Everyday hemp products may matter less. Still, please check with your pharmacist or doctor before combining them, especially if you'll be driving.
- 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
4 of 5Acetaminophen, Codeine, Doxylamine 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.
This Mersyndol combo has three players, and CBD's possible effect touches a couple of them. In lab dishes, CBD blocks two glucuronidation enzymes (UGT1A9 and UGT2B7), which help your body clear certain drugs. Acetaminophen and morphine (the active form of codeine) are partly cleared this way, so in theory CBD could slow that cleanup and let levels nudge upward.
If that happened, you might notice more drowsiness, dizziness, constipation, or nausea, with the doxylamine adding to the sleepy feeling. Keep in mind this is only based on test-tube research, not real people, so it may not amount to much in practice. Still, since heavy sedation matters, please check with your pharmacist or doctor before combining them rather than adjusting anything yourself.
- 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
5 of 5Acetaminophen, Codeine, Doxylamine 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 piece of this combo product that matters most for the CBD question: the acetaminophen part. Acetaminophen is partly handled by a liver enzyme called CYP2E1, and lab (test-tube) studies suggest CBD may slow that enzyme down. In theory, that could shift how acetaminophen is broken down. The honest truth, though, is that this has only been seen in the lab, never reported in actual people, so I wouldn't lose sleep over it.
The bigger picture: this is a triple-ingredient product (acetaminophen, the opioid codeine, and the sedating antihistamine doxylamine), so pairing it with CBD can stack up drowsiness, dizziness, and grogginess. Please run it by your pharmacist or doctor before combining, especially around driving or daytime use.
- 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, Codeine, Doxylamine 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, Codeine, Doxylamine
This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Codeine, Doxylamine page lists 261 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: 11 major · 208 moderate · 42 minor.
From our pharmacist’s overview on the Acetaminophen, Codeine, Doxylamine page
“Mersyndol pairs acetaminophen with codeine and doxylamine, two sedating drugs in one tablet, so I read its interaction list with genuine vigilance. Of the 261 supplements and herbs on file, the biggest hazard is anything else that slows the brain: 78 ingredients add sedation, and that group holds several of the 11 major-rated entries,…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Codeine, Doxylamine interaction page
Where Cannabidiol (cbd) and Acetaminophen, Codeine, Doxylamine 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.
#559 of 1,452 supplements looked up here in the last 7 days
#1,776 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 ›
- Ivermectin ›
- Aspirin ›
- Rosuvastatin ›
- Docusate ›
- Tirzepatide ›
- Hydroxyurea ›
- Valacyclovir ›
- Sumatriptan ›
- Semaglutide ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Methotrexate ›
- Doxycycline ›
- Azithromycin ›
- Acyclovir ›
- Levothyroxine, Liothyronine ›
- Methylene Blue ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Cyclopentolate ›
- Cephalexin ›
- Mannitol ›
- Ezetimibe ›
- Acetylsalicylic Acid ›
- Spironolactone ›
- Carbidopa, Levodopa ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Thyroid Hormone ›
- Pizotifen ›
- Levodopa ›
- Daptomycin ›
- Hexobarbitone ›
- Mitomycin ›
- Lenvatinib ›
- Canagliflozin, Metformin ›
- Magnesium Hydroxide (otc Drug) ›
- Pegunigalsidase Alfa-iwxj ›
- Cefaclor ›
- Flutemetamol F-18 ›
- Insulin Degludec, Liraglutide ›
- Atenolol ›
- Bentoquatam ›
- Factor 7a ›
- Alglucosidase Alpha ›
- Salbutamol Sulfate ›
- Hethylphenidate Hcl ›
- Azelaic Acid ›
- Phenylephrine ›
- Vancomycin ›
- Tocainide ›
- Minoxidil ›
- Insulin Human, Sodium Chloride ›
- Hydroxychloroquine ›
- Bleomycin ›
- Ribavirin Aerosol ›
- Casanthranol, Docusate ›
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, Codeine, Doxylamine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Codeine, Doxylamine 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, Codeine, Doxylamine 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, Codeine, Doxylamine Together: Common Questions
Can you take Cannabidiol (cbd) with Acetaminophen, Codeine, Doxylamine?
Why are there 5 interactions listed for Cannabidiol (cbd) and Acetaminophen, Codeine, Doxylamine?
How serious is the Cannabidiol (cbd) and Acetaminophen, Codeine, Doxylamine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Codeine, Doxylamine 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.