Drug & supplement interaction

Hops + Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine brand names: Tylenol PM, Tylenol PM Ex Strength.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Acetaminophen, Diphenhydramine falls into 2 drug categories that Hops can interact with; the most serious is rated moderate. Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Hops and Acetaminophen, Diphenhydramine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Hops interacts with whole categories of medication. Acetaminophen, Diphenhydramine falls into 2 of those categories, so it can interact with Hops in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 2

Why this applies to Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine falls under CNS DEPRESSANTS — the group Hops interacts with.

Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
Some animal research shows that hops has sedative effects.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to keep in mind: Tylenol PM is a combo product, and one of its ingredients, diphenhydramine (the same medicine in Benadryl), already makes most people sleepy. Hops are taken for the very same reason, to help with sleep and relaxation. So if you pair them, you may end up feeling more drowsy than you expected, with extra grogginess, a foggy head, slowed reactions, or a heavy hangover feeling the next morning.

This is a theoretical concern based mostly on how these things work plus some animal studies, so it's not a hard danger. Still, I'd be careful before driving or doing anything that needs full focus. If you take Tylenol PM regularly and want to add hops, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Schiller, H., Forster, A., Vonhoff, C., Hegger, M., Biller, A., and Winterhoff, H. Sedating effects of Humulus lupulus L. extracts. Phytomedicine. 2006;13(8):535-541. PubMed
  2. Lee KM, Jung JS, Song DK, and et al. Effects of Humulus lupulus extract on the central nervous system in mice. Planta Med 1993;59(Suppl):A691.
  3. Assessment report on Humulus lupulus L., flos. European Medicines Agency, 2014. Available at: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-humulus-lupulus-l-flos_en.pdf. Accessed September 29, 2021.
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Acetaminophen, Diphenhydramine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the good news on combining hops with Tylenol PM (which is acetaminophen plus diphenhydramine): the lab worry doesn't seem to hold up in real life. In a test tube, certain hops flavonoids slowed down a liver enzyme called CYP1A2. But when researchers actually gave people a standardized hops extract, it didn't change how their bodies processed caffeine, a drug that relies on that same enzyme. So a meaningful interaction here is unlikely.

The more practical thing to keep in mind is overlap, not metabolism. Diphenhydramine already makes you drowsy, and hops are taken to help with sleep, so together they can leave you extra sleepy or groggy. If you take both, go easy and check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Henderson MC, Miranda CL, Stevens JF, et al. In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus. Xenobiotica 2000;30:235-51.. PubMed
  2. van Breemen RB, Chen L, Tonsing-Carter A, et al. Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women. J Agric Food Chem. 2020;68(18):5212-5220. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • 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.
Evidence the quality of the studies behind the rating (graded A–D)
  • 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.

Keep it in perspective

Hops Also Interacts With Other Medications

Hops has 288 moderate, 574 minor known drug interactions in our database — the Acetaminophen, Diphenhydramine one above is among them. If you take anything else, check it against the full list below.

Moderate 288 Minor 574 No known interaction 1,968 (incl. Acetaminophen, Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Hops

Covers the 2,830 medications we’ve checked against Hops. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Diphenhydramine

This page covers Hops only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine page lists 254 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 · 204 moderate · 39 minor.

Open the Acetaminophen, Diphenhydramine interaction page

One more smart check

Taking Hops as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,325 real supplement products containing Hops, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Hops. Your product may carry other ingredients that interact with Acetaminophen, Diphenhydramine too, on top of Hops — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Hops and Acetaminophen, Diphenhydramine 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.

Supplement Hops
Top 25%

#146 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 10%

#254 of 2,830 medications looked up here in the last 7 days

29 days ago today

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.

Supplement

About Hops

What is Hops?

Hops
  • Sleep problems and insomnia
  • Anxiety and restlessness
  • Menopausal symptoms
  • Mild digestive complaints
  • Flavoring in beer and food

Hops are most often used for sleep and mild anxiety, frequently combined with valerian, but the human evidence is limited and not very strong. They are generally well tolerated when used short-term, though they may cause drowsiness, and should be avoided during pregnancy and breastfeeding because their safety is unknown.

Read the full Hops monograph & all interactions
Keep checking

Other Drugs & Hops

Browse every other medication we’ve checked against Hops — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
288Moderate
574Minor
1,967No known interaction
288 Moderate 574 Minor 1,967 No interaction
Moderate

288 interactions

Showing 60 of 288 moderate interactions — see all 288 on the Hops page.

Minor

574 interactions

Showing 60 of 574 minor interactions — see all 574 on the Hops page.

No interaction 1,967 drugs checked — show the list

We also checked Hops against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,967 medications checked with no known interaction — see the full Hops list.

See the full Hops interactions page
See every supplement checked against Acetaminophen, Diphenhydramine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

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

Keep exploring
Hops monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Diphenhydramine supplement interactions › Every supplement checked against Acetaminophen, Diphenhydramine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Hops and Acetaminophen, Diphenhydramine Together: Common Questions

Can you take Hops with Acetaminophen, Diphenhydramine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Hops and Acetaminophen, Diphenhydramine?
Acetaminophen, Diphenhydramine belongs to more than one drug category, and Hops interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Hops and Acetaminophen, Diphenhydramine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Acetaminophen, Diphenhydramine and Hops?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.