Cannabidiol (cbd) + Acetaminophen, Caffeine, Pyrilamine
Acetaminophen, Caffeine, Pyrilamine brand name: Midol Max Strength Menstrual.
Acetaminophen, Caffeine, Pyrilamine falls into 5 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, Caffeine, Pyrilamine
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, Caffeine, Pyrilamine 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).
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
1 of 5Why this applies to Acetaminophen, Caffeine, Pyrilamine
Acetaminophen, Caffeine, Pyrilamine 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..
Here's what matters with a product like Midol Max Strength, which contains caffeine alongside acetaminophen and pyrilamine. CBD can slow down a liver enzyme called CYP1A2, and caffeine is cleared by that very enzyme. So when you take CBD with this combo, caffeine can hang around longer and build up. That's not dangerous for most people, but you might feel the caffeine more than usual, things like jitteriness, a racing heart, trouble sleeping, or an upset stomach.
This effect is well documented in studies, though they used fairly high CBD doses. The acetaminophen and pyrilamine parts aren't the concern here. If you notice you feel wired or shaky, that's your cue to chat with your pharmacist or doctor about timing or dosing.
- 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.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 5Acetaminophen, Caffeine, Pyrilamine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro and animal research shows that cannabidiol inhibits CYP3A4. In human studies and case reports, cannabidiol has been associated with an increase in plasma levels of the CYP3A4 substrates zonisamide, tacrolimus, everolimus, citalopram, midazolam, and methadone.
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 Midol Max Strength (acetaminophen, caffeine, and pyrilamine) and CBD. CBD can slow down a liver enzyme called CYP3A4, which is one of the pathways your body uses to clear certain medicines. When that happens, blood levels of a CYP3A4 substrate can creep up a bit. None of these three ingredients is a prodrug, so this would mean slightly stronger or longer-lasting effects, not weaker ones.
In real life, this combo is fairly low-stakes for occasional menstrual relief. You might notice a little more caffeine jitteriness, a fast heartbeat, or extra drowsiness from the pyrilamine (an antihistamine). The bigger thing with acetaminophen is simply not overdoing the total daily dose. If you use CBD regularly, just give your pharmacist a heads-up.
- Yamaori S, Ebisawa J, Okushima Y, et al. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci 2011;88(15-16):730-6. PubMed
- Harvey DJ. Absorption, distribution, and biotransformation of the cannabinoids. Marijuana and Medicine. 1999;91-103. DOI
- Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem Pharmacol 1993;45(6):1323-31. PubMed
- Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Sep;58(9):1586-92. PubMed
- Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transplant. 2019;19(10):2944-2948. PubMed
- Wiemer-Kruel A, Stiller B, Bast T. Cannabidiol Interacts Significantly with Everolimus-Report of a Patient with Tuberous Sclerosis Complex. Neuropediatrics. 2019. PubMed
- Madden K, Tanco K, Bruera E. Clinically Significant Drug-Drug Interaction Between Methadone and Cannabidiol. Pediatrics. 2020;e20193256. PubMed
- Anderson LL, Doohan PT, Oldfield L, et al. Citalopram and Cannabidiol: In Vitro and In Vivo Evidence of Pharmacokinetic Interactions Relevant to the Treatment of Anxiety Disorders in Young People. J Clin Psychopharmacol. 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
- 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
- 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 5Acetaminophen, Caffeine, Pyrilamine 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.
If you're reaching for Midol Max Strength (which combines acetaminophen, caffeine, and an antihistamine called pyrilamine) while also using CBD, here's the gist. Your liver clears acetaminophen partly through a process called glucuronidation. In lab studies, CBD has been shown to slow down some of the enzymes (UGT1A9 and UGT2B7) that handle this step. In theory, that could let acetaminophen build up a bit higher than usual.
Keep in mind this is based only on test-tube research, not real people, so the actual risk is probably small. Still, since too much acetaminophen can stress the liver, it's smart not to exceed the dose on the label and to avoid alcohol. If you use CBD regularly, just mention it to your pharmacist so they can double-check your total acetaminophen intake.
- 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 5Acetaminophen, Caffeine, Pyrilamine 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 for Midol Max Strength: the acetaminophen part is partly handled by a liver enzyme called CYP2E1. In test-tube studies, CBD seems to slow that enzyme down. In theory, that could let a little more acetaminophen hang around than usual. The reason this gets attention is that the CYP2E1 pathway is the one that makes acetaminophen's liver-stressing byproduct, so anything touching it gets a careful look.
That said, this is only lab data and has never actually been reported in people, so I wouldn't lose sleep over it. The bigger real-world tip is to simply not stack multiple acetaminophen products and stay within the daily limit. If you use CBD regularly, just mention it to your pharmacist so we can keep an eye on your total dose.
- 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
CAFFEINE
5 of 5Acetaminophen, Caffeine, Pyrilamine also falls under CAFFEINE.
Caffeine is a substrate of CYP1A2, and cannabidiol has been shown to inhibit CYP1A2 metabolism. A pharmacokinetic study in healthy adults shows that taking oral cannabidiol, starting at 250 mg once daily and titrating to 750 twice daily over a total of 24 days, increases the peak serum level of caffeine by 15% and the overall exposure to caffeine by 95% after a single dose of caffeine 200 mg taken on day 23. Other clinical research also shows that cannabidiol modestly increases the area under the curve of caffeine but does not increase 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 piece worth knowing about Midol Max Strength: one of its three ingredients is caffeine, and that's where CBD comes in. CBD can slow down a liver enzyme called CYP1A2, which is the main pathway that clears caffeine out of your system. When that pathway is blocked, caffeine sticks around longer and your body's overall exposure to it goes up. In one good-quality study, CBD nearly doubled total caffeine exposure.
In real life, that might mean the caffeine in your Midol feels stronger than usual, more jittery, a racing or pounding heart, trouble sleeping, or an upset stomach. The acetaminophen and pyrilamine parts aren't the concern here. This isn't dangerous for most healthy people, but if you regularly use CBD, mention it to your pharmacist so you can keep an eye on the caffeine load.
- 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
- Bansal S, Zamarripa CA, Spindle TR, et al. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023.
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, Caffeine, Pyrilamine 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, Caffeine, Pyrilamine
This page covers Cannabidiol (cbd) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Pyrilamine page lists 322 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), Ephedra (major) and Grapefruit (major).
By severity: 16 major · 260 moderate · 46 minor.
Open the Acetaminophen, Caffeine, Pyrilamine interaction page
Where Cannabidiol (cbd) and Acetaminophen, Caffeine, Pyrilamine 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.
#527 of 1,452 supplements looked up here in the last 7 days
#140 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 ›
- Mannitol ›
- Acetylsalicylic Acid ›
- Carbidopa, Levodopa ›
- Spironolactone ›
- Thyroid Hormone ›
- Levodopa ›
- Dexmethylphenidate ›
- Levothyroxine Sodium ›
- Pizotifen ›
- Daptomycin ›
- Lenvatinib ›
- Canagliflozin, Metformin ›
- Hexobarbitone ›
- Cefaclor ›
- Flutemetamol F-18 ›
- Pegunigalsidase Alfa-iwxj ›
- Mitomycin ›
- Atenolol ›
- Magnesium Hydroxide (otc Drug) ›
- Hydroxychloroquine ›
- Insulin Degludec, Liraglutide ›
- Minoxidil ›
- Bentoquatam ›
- Casanthranol, Docusate ›
- Azelaic Acid ›
- Factor 7a ›
- Salbutamol Sulfate ›
- Hydrochlorothiazide ›
- Hethylphenidate Hcl ›
- Alglucosidase Alpha ›
- Vancomycin ›
- Birth Control Pills ›
- Tocainide ›
- Phenylephrine ›
- Bleomycin ›
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, Caffeine, Pyrilamine Is Linked to Lower Levels of 7 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Pyrilamine 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, Caffeine, Pyrilamine 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, Caffeine, Pyrilamine Together: Common Questions
Can you take Cannabidiol (cbd) with Acetaminophen, Caffeine, Pyrilamine?
Why are there 5 interactions listed for Cannabidiol (cbd) and Acetaminophen, Caffeine, Pyrilamine?
How serious is the Cannabidiol (cbd) and Acetaminophen, Caffeine, Pyrilamine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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