Drug & supplement interaction

Calamus + Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine brand name: Actifed Allergy.

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

Diphenhydramine, Pseudoephedrine falls into 2 drug categories that Calamus can interact with; the most serious is rated moderate. Theoretically, concurrent use of CNS depressants and calamus might have an additive effect and increase the risk of sedative effects.

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

Calamus and Diphenhydramine, Pseudoephedrine

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

Why Are There 2 Interactions?

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

Diphenhydramine, Pseudoephedrine falls under CNS DEPRESSANTS — the group Calamus interacts with.

Theoretically, concurrent use of CNS depressants and calamus might have an additive effect and increase the risk of sedative effects.
Animal research shows that calamus is a CNS depressant and increases gamma-aminobutyric acid levels.
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 Actifed Allergy: one half of it, diphenhydramine, is a sedating antihistamine that already makes a lot of people drowsy and foggy. Calamus appears to have its own calming, sedative-like effect on the brain (in animal studies it raised GABA, a chemical that quiets nerve signals). Put the two together and the worry is simply that the sleepiness could stack up, leaving you more drowsy, dizzy, or slow to react than you'd expect.

I'll be honest, this is a theoretical concern based on lab and animal work, not strong human studies, so I don't want to alarm you. But calamus has real safety problems of its own (the FDA banned it from foods), so I'd avoid it and check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Koo, B. S., Park, K. S., Ha, J. H., Park, J. H., Lim, J. C., and Lee, D. U. Inhibitory effects of the fragrance inhalation of essential oil from Acorus gramineus on central nervous system. Biol Pharm.Bull. 2003;26(7):978-982. PubMed
  3. Panchal, G. M., Venkatakrishna-Bhatt, H., Doctor, R. B., and Vajpayee, S. Pharmacology of Acorus calamus L. Indian J Exp.Biol 1989;27(6):561-567.
Moderate

ANTICHOLINERGIC DRUGS

2 of 2

Diphenhydramine, Pseudoephedrine also falls under ANTICHOLINERGIC DRUGS.

Theoretically, concurrent use of anticholinergic drugs and calamus might decrease the effectiveness of the anticholinergic drug.
In vitro evidence shows that calamus can inhibit acetylcholinesterase (AChE).
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 basic idea with Actifed Allergy. The diphenhydramine part works partly by blocking acetylcholine, one of your body's signaling chemicals. In lab tests, calamus does the opposite, it slows down the enzyme that breaks acetylcholine down, so more of it sticks around. In theory, that extra acetylcholine could push back against the diphenhydramine and make it work a little less for your allergy or sleep symptoms.

I want to be honest though, this is only seen in test-tube and animal studies, not in real people, so it's quite theoretical. Calamus carries its own safety baggage (it was banned from foods in the U.S.), which is the bigger reason I'd steer clear of it. If you're considering it, please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Oh, M. H., Houghton, P. J., Whang, W. K., and Cho, J. H. Screening of Korean herbal medicines used to improve cognitive function for anti-cholinesterase activity. Phytomedicine 2004;11(6):544-548. PubMed

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

Calamus Also Interacts With Other Medications

Calamus has 1,097 moderate, 19 minor 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 1,097 Minor 19 No known interaction 1,714 (incl. Diphenhydramine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Calamus

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine, Pseudoephedrine

This page covers Calamus 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

One more smart check

Taking Calamus as Part of a Dietary Supplement Product? Check It for Interactions

We hold 71 real supplement products containing Calamus, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Calamus. Your product may carry other ingredients that interact with Diphenhydramine, Pseudoephedrine too, on top of Calamus — 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 Calamus 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 Calamus
Top half

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

29 days ago today
Medication Diphenhydramine, Pseudoephedrine
Steady interest

#1,738 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 Calamus

What is Calamus?

Calamus
  • Digestive upset and gas
  • Loss of appetite
  • Memory and focus (traditional)
  • Coughs and colds
  • Calming or sedative effect (traditional)

Calamus is a swamp plant with a long history in Ayurvedic and traditional Chinese medicine, mostly for digestive and nervous-system complaints. However, it contains beta-asarone, a compound linked to cancer and other toxic effects in animal studies, which is why the U.S. FDA banned it from foods. Because of these safety concerns and a lack of solid human evidence, it is generally best avoided.

Read the full Calamus monograph & all interactions
Keep checking

Other Drugs & Calamus

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

0Major
1,097Moderate
19Minor
1,713No known interaction
1,097 Moderate 19 Minor 1,713 No interaction
Moderate

1,097 interactions

Showing 60 of 1,097 moderate interactions — see all 1,097 on the Calamus page.

Minor

19 interactions

No interaction 1,713 drugs checked — show the list

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

Showing the 60 most looked-up of 1,713 medications checked with no known interaction — see the full Calamus list.

See the full Calamus 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
Calamus 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 Calamus and Diphenhydramine, Pseudoephedrine Together: Common Questions

Can you take Calamus 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 Calamus and Diphenhydramine, Pseudoephedrine?
Diphenhydramine, Pseudoephedrine belongs to more than one drug category, and Calamus 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 Calamus 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.