Cannabidiol (cbd) + Acetaminophen, Diphenhydramine, Pseudoephedrine
Acetaminophen, Diphenhydramine, Pseudoephedrine brand names: Contac Night Allergy Relief, Children's Tylenol Allergy, Cold Control.
Acetaminophen, Diphenhydramine, Pseudoephedrine falls into 4 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, Diphenhydramine, Pseudoephedrine
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, Diphenhydramine, Pseudoephedrine 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).
CNS DEPRESSANTS
1 of 4Why this applies to Acetaminophen, Diphenhydramine, Pseudoephedrine
Acetaminophen, Diphenhydramine, Pseudoephedrine 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.
The piece of this combo product that matters here is the diphenhydramine (the same antihistamine found in Benadryl). It already makes a lot of people drowsy. CBD, especially at higher supplement doses, can also have a mild sedating effect. Put them together and that sleepiness may stack up, so you could feel groggier, foggy-headed, or more wiped out than usual.
This is a theoretical concern based mostly on pharmacology and early reports, not strong human proof, so I don't want to alarm you. Still, it's worth being careful before driving or doing anything that needs you sharp. The acetaminophen and pseudoephedrine parts aren't the issue with CBD here. Check in with your pharmacist or doctor before pairing them, especially if you notice extra drowsiness.
- 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 1A2 (CYP1A2) SUBSTRATES
2 of 4Acetaminophen, Diphenhydramine, Pseudoephedrine 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 practical picture with this combination cold and allergy product. CBD can slow down a liver enzyme called CYP1A2, and when an enzyme like that is blocked, drugs it handles can build up a bit. The good news is that none of the three ingredients in this product (acetaminophen, diphenhydramine, and pseudoephedrine) rely heavily on CYP1A2, so in everyday use this interaction is unlikely to cause real trouble.
That said, if you stack high-dose CBD with this medicine, just stay aware of overlapping effects like extra drowsiness from the diphenhydramine, or jitteriness and raised blood pressure from the pseudoephedrine. Don't start or stop anything on your own. A quick chat with your pharmacist is the safest way to be sure it's fine for you.
- 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
3 of 4Acetaminophen, Diphenhydramine, Pseudoephedrine 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 for this combo cold and allergy product. The acetaminophen in it gets cleared partly by a liver process called glucuronidation, and lab studies suggest CBD can slow that pathway a bit. In theory, that could let acetaminophen levels run a little higher than usual. The good news is this is based only on test-tube research, not real-world cases, so for most people taking normal doses it's unlikely to cause an obvious problem.
My practical advice: keep a close eye on your total daily acetaminophen, since it hides in many cold, pain, and sleep products, and going over the limit is hard on the liver. The diphenhydramine (drowsiness) and pseudoephedrine (jitteriness, higher blood pressure) parts aren't really the concern here. If you use CBD regularly, just run it by your pharmacist first.
- 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
4 of 4Acetaminophen, Diphenhydramine, Pseudoephedrine 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 that matters most in this combo product: the acetaminophen (the Tylenol part). Your liver uses an enzyme called CYP2E1 to break down a small slice of acetaminophen into a byproduct that can be hard on the liver. In lab dish studies, CBD slows that enzyme down. In theory, that could shift how acetaminophen is processed, but here's the honest part: this has not been seen in actual people, and it's based only on test-tube research.
For everyday, occasional use at normal doses, I wouldn't lose sleep over this. The bigger real-world advice is just to avoid going over the daily acetaminophen limit and to skip extra alcohol. The diphenhydramine and pseudoephedrine aren't the concern here. If you take CBD regularly or have any liver issues, run it by your pharmacist or doctor first.
- 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, Diphenhydramine, Pseudoephedrine 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, Diphenhydramine, Pseudoephedrine
This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine, Pseudoephedrine page lists 292 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 · 234 moderate · 43 minor.
From our pharmacist’s overview on the Acetaminophen, Diphenhydramine, Pseudoephedrine page
“A drink with this medicine is the risk I would flag first. Beer and wine both carry major ratings, well documented in humans, because alcohol deepens the sedation that diphenhydramine already causes.”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Diphenhydramine, Pseudoephedrine interaction page
Where Cannabidiol (cbd) and Acetaminophen, Diphenhydramine, Pseudoephedrine 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.
#523 of 1,452 supplements looked up here in the last 7 days
#215 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 ›
- Valacyclovir ›
- Hydroxyurea ›
- Sumatriptan ›
- Semaglutide ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Methotrexate ›
- Doxycycline ›
- Azithromycin ›
- Acyclovir ›
- Levothyroxine, Liothyronine ›
- Methylene Blue ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Cephalexin ›
- Cyclopentolate ›
- Ezetimibe ›
- Acetylsalicylic Acid ›
- Mannitol ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Spironolactone ›
- Levodopa ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Pizotifen ›
- Daptomycin ›
- Lenvatinib ›
- Hexobarbitone ›
- Canagliflozin, Metformin ›
- Flutemetamol F-18 ›
- Atenolol ›
- Cefaclor ›
- Mitomycin ›
- Pegunigalsidase Alfa-iwxj ›
- Hydroxychloroquine ›
- Magnesium Hydroxide (otc Drug) ›
- Insulin Degludec, Liraglutide ›
- Minoxidil ›
- Azelaic Acid ›
- Casanthranol, Docusate ›
- Bentoquatam ›
- Factor 7a ›
- Hydrochlorothiazide ›
- Salbutamol Sulfate ›
- Hethylphenidate Hcl ›
- Alglucosidase Alpha ›
- Insulin Human, Sodium Chloride ›
- Birth Control Pills ›
- Vancomycin ›
- Alginic Acid, Aluminum Hydroxide ›
- Phenylephrine ›
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, Diphenhydramine, Pseudoephedrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Diphenhydramine, Pseudoephedrine 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, Diphenhydramine, Pseudoephedrine 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, Diphenhydramine, Pseudoephedrine Together: Common Questions
Can you take Cannabidiol (cbd) with Acetaminophen, Diphenhydramine, Pseudoephedrine?
Why are there 4 interactions listed for Cannabidiol (cbd) and Acetaminophen, Diphenhydramine, Pseudoephedrine?
How serious is the Cannabidiol (cbd) and Acetaminophen, Diphenhydramine, Pseudoephedrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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