Drug & supplement interaction

Calea Zacatechichi + Diphenhydramine

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

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

Calea Zacatechichi has a minor interaction with Diphenhydramine. Theoretically, Calea zacatechichi might increase the sedative effects of CNS depressants.

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

Calea Zacatechichi and Diphenhydramine

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

Minor

CNS DEPRESSANTS

Why this applies to Diphenhydramine

Diphenhydramine falls under CNS DEPRESSANTS — the group Calea Zacatechichi interacts with.

Theoretically, Calea zacatechichi might increase the sedative effects of CNS depressants.
Calea zacatechichi can cause CNS depression in animals and humans.
Severity Minor 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) already makes most people drowsy, since calming the brain is part of how it works. The dream herb, Calea zacatechichi, has shown its own mild brain-slowing effect in both animals and people. Stack the two together and you may feel sleepier than you bargained for, with more grogginess, dizziness, dry mouth, or a foggy, slowed-down feeling the next morning.

I'll be honest with you: this concern is theoretical, based on how each one acts rather than solid studies, and it's rated as a minor interaction. Still, if you take diphenhydramine for sleep or allergies, it's worth a quick chat with your pharmacist or doctor before adding the herb, and don't drive until you know how the combo hits you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mayagoitia, L., Diaz, J. L., Contreras, C. M. Psychopharmacologic analysis of an alleged oneirogenic plant: Calea zacatechichi. J Ethnopharmacol. 1986;18:229-243. 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

Calea Zacatechichi Also Interacts With Other Medications

Calea Zacatechichi has 333 minor 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.

Minor 333 No known interaction 2,497 (incl. Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Calea Zacatechichi

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

From our Q&A

Questions About Calea Zacatechichi 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 Calea Zacatechichi 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 Calea Zacatechichi 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

One more smart check

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

We hold 21 real supplement products containing Calea Zacatechichi, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Calea Zacatechichi. Your product may carry other ingredients that interact with Diphenhydramine too, on top of Calea Zacatechichi — 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 Calea Zacatechichi 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 Calea Zacatechichi
Steady interest

#1,264 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Diphenhydramine
Top half

#756 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 Calea Zacatechichi

What is Calea Zacatechichi?

  • Promoting vivid or lucid dreams
  • Sleep and relaxation
  • Digestive upset
  • Fever
  • Traditional ritual use

Calea zacatechichi, often called 'dream herb,' is a Mexican plant traditionally used to encourage vivid dreams and to treat digestive complaints and fever. Human research is very limited, so its benefits are not well proven, and its safety has not been carefully studied. It tastes very bitter, can cause nausea, and should be avoided during pregnancy and breastfeeding.

Read the full Calea Zacatechichi 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 & Calea Zacatechichi

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

0Major
0Moderate
333Minor
2,496No known interaction
333 Minor 2,496 No interaction
Minor

333 interactions

Showing 60 of 333 minor interactions — see all 333 on the Calea Zacatechichi page.

No interaction 2,496 drugs checked — show the list

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

Showing the 60 most looked-up of 2,496 medications checked with no known interaction — see the full Calea Zacatechichi list.

See the full Calea Zacatechichi 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
Calea Zacatechichi 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 Calea Zacatechichi and Diphenhydramine Together: Common Questions

Can you take Calea Zacatechichi with Diphenhydramine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Calea Zacatechichi and Diphenhydramine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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

Still Have a Question About Diphenhydramine and Calea Zacatechichi?

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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.