Drug & supplement interaction

Clubmoss + Diphenhydramine

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

Moderate Interaction
The bottom line Moderate

Clubmoss has a moderate interaction with Diphenhydramine. Evidence from in vitro research suggests that clubmoss extract can inhibit acetylcholinesterase activity.

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

Clubmoss and Diphenhydramine

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

Moderate

ANTICHOLINERGIC DRUGS

Why this applies to Diphenhydramine

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

Evidence from in vitro research suggests that clubmoss extract can inhibit acetylcholinesterase activity. Theoretically, concurrent use of anticholinergic drugs and clubmoss might decrease the effectiveness of club moss or the anticholinergic agent. Some anticholinergic drugs include atropine, benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and trihexyphenidyl (Artane).
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 simple version. Diphenhydramine (Benadryl) works partly by blocking acetylcholine, a messenger in your body. That's why it can dry you out, make you drowsy, and cause things like a dry mouth, blurry vision, or constipation. Clubmoss seems to do the opposite in lab dishes: it appears to raise acetylcholine levels by slowing the enzyme that breaks it down. So in theory, the two could work against each other and blunt what each one is trying to do.

I want to be honest though, this is only test-tube and animal evidence, so it's more of a theoretical concern than something proven in people. Still, clubmoss carries its own toxic alkaloids, so I'd skip it and check with your pharmacist before mixing the two.

References
  1. Orhan, I., Terzioglu, S., and Sener, B. Alpha-onocerin: an acetylcholinesterase inhibitor from Lycopodium clavatum. Planta Med. 2003;69(3):265-267.

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

Clubmoss Also Interacts With Other Medications

Clubmoss has 218 moderate 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.

Taking anything else?

Check Another of Your Medications Against Clubmoss

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

From our Q&A

Questions About Clubmoss 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 Clubmoss 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 Clubmoss 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 Clubmoss 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 Clubmoss
Steady interest

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

29 days ago today
Medication Diphenhydramine
Top half

#764 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 Clubmoss

What is Clubmoss?

Clubmoss
  • Bladder and kidney complaints
  • Digestive upset
  • Skin irritation and chafing
  • Respiratory problems
  • Used in homeopathy

Clubmoss (Lycopodium clavatum) is a primitive plant with a long history in folk medicine and homeopathy, but there is very little reliable human research to show it works for any health condition. It contains potentially toxic alkaloids, so it should be used with great caution, and people who are pregnant or breastfeeding should avoid it. Talk with a pharmacist or doctor before trying it.

Read the full Clubmoss 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 & Clubmoss

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

0Major
218Moderate
0Minor
2,611No known interaction
Moderate

218 interactions

Showing 60 of 218 moderate interactions — see all 218 on the Clubmoss page.

No interaction 2,611 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Clubmoss and Diphenhydramine Together: Common Questions

Can you take Clubmoss with 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.
How serious is the Clubmoss and 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.