Drug & supplement interaction

European Mandrake + 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 European Mandrake can interact with; the most serious is rated moderate. Theoretically, concurrent use might increase absorption of some drugs because of inhibited gastrointestinal (GI) motility caused by European mandrake.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

European Mandrake and Acetaminophen, Diphenhydramine

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

Why Are There 2 Interactions?

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

Moderate

ORAL DRUGS

1 of 2

Why this applies to Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine falls under ORAL DRUGS — the group European Mandrake interacts with.

Theoretically, concurrent use might increase absorption of some drugs because of inhibited gastrointestinal (GI) motility caused by European mandrake.
Severity Moderate Likelihood Probable Evidence D

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..

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

First, the honest big-picture point: European mandrake is genuinely toxic and we don't recommend taking it at all. But here's how it could clash with Tylenol PM specifically. Mandrake's tropane alkaloids (atropine-like chemicals) slow down your gut. When your stomach and intestines move more slowly, a medicine can sit there longer and get absorbed more fully, so theoretically you could end up with stronger effects from the acetaminophen and diphenhydramine.

What makes this pair worrying is that diphenhydramine (Benadryl) already has the same anticholinergic action as mandrake. Stacking them could mean heavy sedation, dry mouth, blurry vision, constipation, confusion, and a racing heart. This is theoretical, based on pharmacology, but please talk with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
Moderate

ANTICHOLINERGIC DRUGS

2 of 2

Acetaminophen, Diphenhydramine also falls under ANTICHOLINERGIC DRUGS.

Concurrent use may cause additive anticholinergic effects and adverse effects. Anticholinergic drugs include conventional medications containing tropane alkaloids such as atropine, as well as phenothiazines, amantadine, some antiparkinson drugs, glutethimide, meperidine, tricyclic antidepressants, antiarrhythmic agents, and antihistamines.
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 key thing to know: the diphenhydramine half of Tylenol PM (the same drug as Benadryl) already has built-in anticholinergic activity. European mandrake is loaded with tropane alkaloids like atropine and scopolamine that work the very same way. Stack them together and those effects can pile up. We call this additive anticholinergic load.

In real life that could mean a very dry mouth, blurry vision, constipation, trouble urinating, a racing heart, confusion, and heavy drowsiness on top of the sleepiness diphenhydramine already causes. This concern is based on how these chemicals behave (theoretical pharmacology), not strong human studies. Honestly though, mandrake is genuinely toxic and we don't recommend using it at all. Please check with your pharmacist or doctor before combining anything like this.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

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

European Mandrake Also Interacts With Other Medications

European Mandrake has 2,041 moderate 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 2,041 No known interaction 789 (incl. Acetaminophen, Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against European Mandrake

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Diphenhydramine

This page covers European Mandrake 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

How much people look this up

Where European Mandrake 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 European Mandrake
Top 25%

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

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 25%

#552 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 European Mandrake

What is European Mandrake?

European Mandrake
  • Insomnia (traditional)
  • Pain relief (historical)
  • Anxiety or depression (folk use)
  • Gout and aches (traditional)
  • Sedation or anesthesia (historical)

European mandrake is a highly toxic plant from the nightshade family that was used in ancient and medieval times as a sedative and pain reliever. It contains powerful poisons that can cause serious harm or death, and there is no proof it safely treats any condition. We strongly recommend you do not consume mandrake in any form.

Read the full European Mandrake monograph & all interactions
Keep checking

Other Drugs & European Mandrake

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

0Major
2,041Moderate
0Minor
788No known interaction
2,041 Moderate 788 No interaction
Moderate

2,041 interactions

Showing 60 of 2,041 moderate interactions — see all 2,041 on the European Mandrake page.

No interaction 788 drugs checked — show the list

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

Showing the 60 most looked-up of 788 medications checked with no known interaction — see the full European Mandrake list.

See the full European Mandrake 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
European Mandrake 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
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Taking European Mandrake and Acetaminophen, Diphenhydramine Together: Common Questions

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

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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.