Drug & supplement interaction

Scopolia + Diphenhydramine

Diphenhydramine brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, and others.

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

Scopolia has a major interaction with Diphenhydramine. The alkaloid constituents of scopolia, including hyoscyamine, scopolamine, and atropine, could potentiate the effects and adverse effects of anticholinergic drugs.

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

Scopolia and Diphenhydramine

Here is the interaction we found between these two, with the evidence behind it.

Major

ANTICHOLINERGIC DRUGS

Why this applies to Diphenhydramine

Diphenhydramine falls under ANTICHOLINERGIC DRUGS — the group Scopolia interacts with.

The alkaloid constituents of scopolia, including hyoscyamine, scopolamine, and atropine, could potentiate the effects and adverse effects of anticholinergic drugs.
Severity Major 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 simple version: diphenhydramine (Benadryl) is itself a strong anticholinergic. That means it already blocks acetylcholine in your body, which is exactly what gives you that drowsy, dry-mouth feeling. Scopolia contains powerful anticholinergic alkaloids (atropine, scopolamine, hyoscyamine) that do the very same thing. Stack the two together and you're basically doubling up on the same effect.

That can mean a much drier mouth, blurry vision, constipation, trouble urinating, a racing heartbeat, confusion, and in older folks especially, agitation or dangerous overheating. This concern is based on how these compounds work rather than hard studies, but the math is straightforward and the plant itself is toxic. Please don't combine them without talking to 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

Scopolia Also Interacts With Other Medications

Scopolia has 199 major, known drug interactions in our database — the Diphenhydramine one above is one of them. If you take anything else, check it against the full list below.

Major 199 No known interaction 2,631 (incl. Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Scopolia

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

From our Q&A

Questions About Scopolia or 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 Scopolia or 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 Diphenhydramine

This page covers Scopolia only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine page lists 147 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), Gamma-hydroxybutyrate (ghb) (major) and Henbane (major).

By severity: 9 major · 119 moderate · 19 minor.

From our pharmacist’s overview on the Diphenhydramine page

“Diphenhydramine (Benadryl, Simply Sleep) is sedating by design, and most of the 147 supplements and herbal ingredients on this list lean into that. Seventy-eight are sedating substances themselves, alcohol and kava the standouts, and stacking them can slow breathing and reflexes well beyond ordinary drowsiness.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine interaction page

How much people look this up

Where Scopolia and 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 Scopolia
Top half

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

29 days ago today
Medication Diphenhydramine
Top half

#738 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 Scopolia

What is Scopolia?

Scopolia
  • Stomach and intestinal cramps
  • Motion sickness
  • Spasms and colic
  • Excess saliva or secretions
  • Pain relief (traditional)

Scopolia is a poisonous plant in the nightshade family that contains powerful anticholinergic alkaloids like atropine, hyoscyamine, and scopolamine. While these compounds are used in carefully measured prescription medicines, the raw plant is dangerous for self-treatment and should never be used without a doctor's supervision.

Read the full Scopolia monograph & all interactions
Medication

About Diphenhydramine

What Is Diphenhydramine Used For?

Brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, Simply Sleep, Sominex, Diphenhydramine, Compoz, Sleep Aid, Benadryl cream, Benadryl spray, Dermamycin cream, Ziradryl, Nytol

Diphenhydramine temporarily relieves symptoms of hay fever, other upper respiratory allergies, and the common cold — including runny nose, sneezing, itchy or watery eyes, and itching of the nose or throat.

After Bite Xtra gel is formulated for topical use and is approved to temporarily relieve pain and itching from minor burns, minor cuts and scrapes, insect bites, minor skin irritations, and rashes from poison ivy, poison oak, and poison sumac.

See full Diphenhydramine drug information
Keep checking

Other Drugs & Scopolia

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

199Major
0Moderate
0Minor
2,630No known interaction
199 Major 2,630 No interaction
Major

199 interactions

Showing 60 of 199 major interactions — see all 199 on the Scopolia page.

No interaction 2,630 drugs checked — show the list

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

Showing the 60 most looked-up of 2,630 medications checked with no known interaction — see the full Scopolia list.

See the full Scopolia interactions page
See every supplement checked against 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
Scopolia monograph › Uses, safety, and every drug interaction in one place Diphenhydramine supplement interactions › Every supplement checked against Diphenhydramine, ranked by severity Diphenhydramine drug information › The full plain-English guide to this medication 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 Scopolia and Diphenhydramine Together: Common Questions

Can you take Scopolia with Diphenhydramine?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Scopolia and Diphenhydramine interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Diphenhydramine and Scopolia?

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.