Drug & supplement interaction

Yohimbe + diphenhydramine, calamine

diphenhydramine, calamine brand names: Caladryl cream, Caladryl lotion.

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

Yohimbe has a moderate interaction with diphenhydramine, calamine. CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.

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

Yohimbe and diphenhydramine, calamine

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

Moderate

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

Why this applies to diphenhydramine, calamine

diphenhydramine, calamine falls under CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS — the group Yohimbe interacts with.

CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes. Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine and reduces the clearance of yohimbine compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers..
Severity Moderate Likelihood Probable Evidence B

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 gist: yohimbine (the active part of yohimbe) is cleared from your body by a liver enzyme called CYP2D6. Diphenhydramine, the active ingredient in Caladryl, can mildly block that same enzyme. So when the two are combined, your body may clear yohimbine more slowly, letting it build up and push its effects harder. With yohimbine, that can mean a faster heartbeat, jitteriness, anxiety, and higher blood pressure.

The good news for Caladryl specifically: it's a cream or lotion you put on your skin for itching and rashes, so very little diphenhydramine actually reaches your bloodstream. A real interaction is unlikely from topical use. Oral diphenhydramine (like Benadryl pills) would matter more. If you take yohimbe at all, check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  2. Mueller-Schoell A, Michelet R, Weinelt F, Kloft C, Mikus G. CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications. Arch Toxicol. 2021. PubMed
  3. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
  4. Vay M, Meyer MJ, Blank A, et al. Oral yohimbine as a new probe drug to predict CYP2D6 activity: results of a fixed-sequence phase I trial. Clin Pharmacokinet. 2020;59(7):927-939. 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

Yohimbe Also Interacts With Other Medications

Yohimbe has 9 major, 679 moderate, 436 minor known drug interactions in our database — the diphenhydramine, calamine one above is one of them. If you take anything else, check it against the full list below.

Major 9 Moderate 679 Minor 436 No known interaction 1,706 (incl. diphenhydramine, calamine)
Taking anything else?

Check Another of Your Medications Against Yohimbe

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

Everything else you take

See Every Supplement That Interacts With diphenhydramine, calamine

This page covers Yohimbe only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the diphenhydramine, calamine page lists 6 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Dimethylsulfoxide (dmso) (moderate), Fever Bark (moderate), Iboga (moderate), Turpentine Oil (moderate) and Alchemilla (minor).

By severity: 5 moderate · 1 minor.

From our pharmacist’s overview on the diphenhydramine, calamine page

“Yohimbe is the entry I would read first. Diphenhydramine, the itch-relieving antihistamine in Caladryl cream and lotion, blocks a liver enzyme called CYP2D6, and yohimbine, the active compound in yohimbe bark, needs that enzyme to leave the body, so its levels and side effects can climb.”

Reviewed by 2 · Jul 18, 2026

Open the diphenhydramine, calamine interaction page

One more smart check

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

We hold 1,054 real supplement products containing Yohimbe, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yohimbe. Your product may carry other ingredients that interact with diphenhydramine, calamine too, on top of Yohimbe — 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 Yohimbe and diphenhydramine, calamine 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 Yohimbe
Top 25%

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

29 days ago today
Medication diphenhydramine, calamine
Top half

#803 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 Yohimbe

What is Yohimbe?

Yohimbe
  • Erectile dysfunction
  • Low sex drive
  • Sexual performance
  • Weight loss
  • Athletic performance

Yohimbe is a West African tree bark that contains yohimbine, a compound mainly promoted for erectile dysfunction and as an aphrodisiac. A prescription form of yohimbine has some evidence for erectile dysfunction, but over-the-counter yohimbe supplements vary widely in content and can cause serious side effects like high blood pressure and fast heart rate. Because of these safety concerns, talk to your pharmacist or doctor before using it.

Read the full Yohimbe monograph & all interactions
Keep checking

Other Drugs & Yohimbe

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

9Major
679Moderate
436Minor
1,705No known interaction
9 Major 679 Moderate 436 Minor 1,705 No interaction
Major

9 interactions

Moderate

679 interactions

Showing 60 of 679 moderate interactions — see all 679 on the Yohimbe page.

Minor

436 interactions

Showing 60 of 436 minor interactions — see all 436 on the Yohimbe page.

No interaction 1,705 drugs checked — show the list

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

Showing the 60 most looked-up of 1,705 medications checked with no known interaction — see the full Yohimbe list.

See the full Yohimbe interactions page
See every supplement checked against diphenhydramine, calamine, 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
Yohimbe monograph › Uses, safety, and every drug interaction in one place diphenhydramine, calamine supplement interactions › Every supplement checked against diphenhydramine, calamine, 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 Yohimbe and diphenhydramine, calamine Together: Common Questions

Can you take Yohimbe with diphenhydramine, calamine?
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 Yohimbe and diphenhydramine, calamine 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

Still Have a Question About diphenhydramine, calamine and Yohimbe?

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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.