Drug & supplement interaction

European Mandrake + Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine brand name: Actifed Allergy.

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

Diphenhydramine, Pseudoephedrine 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 Diphenhydramine, Pseudoephedrine

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. Diphenhydramine, Pseudoephedrine 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 Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine 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

Here's the thing with this combo: European mandrake contains atropine-like compounds that slow down your gut and dry up your body's secretions. Actifed Allergy already does some of this same work, since diphenhydramine (the antihistamine) has strong drying, sedating, anticholinergic effects, and pseudoephedrine is a stimulant decongestant. Stacking mandrake on top can pile on those effects. You could end up with a very dry mouth, blurry vision, constipation, trouble urinating, a racing heart, confusion, or heavy drowsiness.

The slowed gut may also let more of the drug get absorbed, making side effects stronger. This is a theoretical concern based on how these chemicals act, not hard human studies. Honestly, mandrake is genuinely toxic and we'd never recommend it. Please talk with your pharmacist or doctor before mixing 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.
Moderate

ANTICHOLINERGIC DRUGS

2 of 2

Diphenhydramine, Pseudoephedrine 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 short version: both European mandrake and the diphenhydramine in Actifed Allergy block the same part of your nervous system (the cholinergic system). Mandrake does it through its tropane alkaloids like atropine and scopolamine, and diphenhydramine, an older antihistamine, does it too. Stack them together and those drying, slowing effects can pile up.

What that might feel like: a very dry mouth, blurry vision, constipation, trouble urinating, confusion, and drowsiness. The pseudoephedrine side could also nudge your heart rate and blood pressure up. This warning is theoretical, based on how these chemicals work rather than reported cases, so I'm not trying to alarm you. Honestly though, mandrake itself is poisonous and I would steer clear of it entirely. Please check with your pharmacist or doctor first.

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 Diphenhydramine, Pseudoephedrine 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. Diphenhydramine, Pseudoephedrine)
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 Diphenhydramine, Pseudoephedrine

This page covers European Mandrake only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine, Pseudoephedrine page lists 185 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), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 13 major · 150 moderate · 22 minor.

From our pharmacist’s overview on the Diphenhydramine, Pseudoephedrine page

“This medicine pulls in two directions at once, which is exactly why the supplement list for diphenhydramine and pseudoephedrine (Actifed Allergy) is not one to skim. The antihistamine half is sedating, so anything else that slows the brain deepens drowsiness; beer, wine, and kava all carry major ratings, with alcohol the best documented.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine, Pseudoephedrine interaction page

How much people look this up

Where European Mandrake and 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.

Supplement European Mandrake
Top 25%

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

29 days ago today
Medication Diphenhydramine, Pseudoephedrine
Steady interest

#2,041 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 Diphenhydramine, Pseudoephedrine, 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 Diphenhydramine, Pseudoephedrine supplement interactions › Every supplement checked against Diphenhydramine, Pseudoephedrine, 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 European Mandrake and Diphenhydramine, Pseudoephedrine Together: Common Questions

Can you take European Mandrake with Diphenhydramine, Pseudoephedrine?
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 Diphenhydramine, Pseudoephedrine?
Diphenhydramine, Pseudoephedrine 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 Diphenhydramine, Pseudoephedrine 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.