Drug & supplement interaction

Valerian + 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 Valerian can interact with; the most serious is rated moderate. Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.

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

Valerian and Acetaminophen, Diphenhydramine

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

Why Are There 2 Interactions?

Valerian interacts with whole categories of medication. Acetaminophen, Diphenhydramine falls into 2 of those categories, so it can interact with Valerian 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 Valerian interacts with.

Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
Theoretically, concomitant use of valerian and drugs with sedative and anesthetic properties may cause additive therapeutic and adverse 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 with Tylenol PM: that little PM stands for the diphenhydramine (think Benadryl), which is already a sedating antihistamine. Valerian is used to calm the nervous system too, so stacking the two means you could end up more drowsy than you bargained for. Realistically that looks like next-morning grogginess, feeling foggy or unsteady, and a higher chance of stumbles, especially for older folks.

I'll be honest with you, this concern comes mostly from lab and animal research, not solid human studies, so it's more of a theoretical add-up than a proven problem. Still, since both are working in the same calming direction, it's worth a quick chat with your pharmacist or doctor before you combine them, particularly if you drive early or are prone to falls.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999;51:505-12. PubMed
  2. Yuan CS, Mehendale S, Xiao Y, et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004;98:353-8. PubMed
  3. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009 Dec;23:1795-6.
Moderate

GLUCURONIDATED DRUGS

2 of 2

Acetaminophen, Diphenhydramine also falls under GLUCURONIDATED DRUGS.

Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
In vitro research shows that methanolic valerian extract and valerenic acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) and UGT2B7.
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 with Tylenol PM. This product already pairs acetaminophen with diphenhydramine (a sedating antihistamine), so it's designed to make you drowsy. Valerian is also used to calm and relax you, so the bigger real-world concern is simply adding sedation on top of sedation. Together they could leave you groggier than expected, dizzy, or foggy the next morning.

There's also a lab-only finding that valerian might slightly slow how the body clears acetaminophen (through a process called glucuronidation), which could nudge its levels up a bit. This is only test-tube data, so it's theoretical and probably minor at normal doses. Still, talk with your pharmacist before combining them, especially if you take other sleep aids or alcohol.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alkharfy, K. M. and Frye, R. F. Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro. Xenobiotica 2007;37(2):113-123.

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

Valerian Also Interacts With Other Medications

Valerian has 337 moderate, 564 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 337 Minor 564 No known interaction 1,929 (incl. Acetaminophen, Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Valerian

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

From our Q&A

Questions About Valerian or Acetaminophen, Diphenhydramine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Valerian or Acetaminophen, Diphenhydramine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Diphenhydramine

This page covers Valerian 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 Valerian as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2,185 real supplement products containing Valerian, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Valerian. Your product may carry other ingredients that interact with Acetaminophen, Diphenhydramine too, on top of Valerian — 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 Valerian 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 Valerian
Top 10%

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

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 10%

#216 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 Valerian

What is Valerian?

Valerian
  • Insomnia and poor sleep
  • Anxiety and stress
  • Restlessness
  • Muscle tension or cramps
  • Menstrual discomfort

Valerian is an herb whose root is widely used as a natural sleep aid and for calming nerves. The evidence is mixed and often weak, so it may help some people sleep but does not work reliably for everyone. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before starting it.

Read the full Valerian monograph & all interactions
Keep checking

Other Drugs & Valerian

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

0Major
337Moderate
564Minor
1,928No known interaction
337 Moderate 564 Minor 1,928 No interaction
Moderate

337 interactions

Showing 60 of 337 moderate interactions — see all 337 on the Valerian page.

Minor

564 interactions

Showing 60 of 564 minor interactions — see all 564 on the Valerian page.

No interaction 1,928 drugs checked — show the list

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

Showing the 60 most looked-up of 1,928 medications checked with no known interaction — see the full Valerian list.

See the full Valerian 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
Valerian 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 Valerian and Acetaminophen, Diphenhydramine Together: Common Questions

Can you take Valerian 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 Valerian and Acetaminophen, Diphenhydramine?
Acetaminophen, Diphenhydramine belongs to more than one drug category, and Valerian 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 Valerian 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 Valerian?

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.