Drug & supplement interaction

Mace + Diphenhydramine Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium brand name: Aleve PM.

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

Diphenhydramine Hydrochloride, Naproxen Sodium falls into 2 drug categories that Mace can interact with; the most serious is rated moderate. Several volatile oils in mace, such as methyleugenol, isoeugenol, safrole, myristicin, 1,8-cineole, and geranyl acetate, seem to have sedative effects.

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

Mace and Diphenhydramine Hydrochloride, Naproxen Sodium

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

Why Are There 2 Interactions?

Mace interacts with whole categories of medication. Diphenhydramine Hydrochloride, Naproxen Sodium falls into 2 of those categories, so it can interact with Mace 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 Hydrochloride, Naproxen Sodium

Diphenhydramine Hydrochloride, Naproxen Sodium falls under CNS DEPRESSANTS — the group Mace interacts with.

Several volatile oils in mace, such as methyleugenol, isoeugenol, safrole, myristicin, 1,8-cineole, and geranyl acetate, seem to have sedative effects. Evidence from animal research suggests that methyleugenol can induce anesthesia for a similar duration as pentobarbital. Due to the sedative effects of certain mace constituents, taking medicinal amounts of mace in combination with other CNS depressants may have additive effects. However, evidence from other animal research suggests that myristicin can reduce sleeping time in rats pretreated with phenobarbital. Until more is known, use medicinal amounts of mace cautiously in combination with CNS depressants. Some CNS depressants include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien), and others.
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

The product you're asking about, Aleve PM, pairs naproxen (a pain reliever) with diphenhydramine, an antihistamine that already makes most people drowsy. That sleepy effect is actually the point of the 'PM' version, since it's meant to help you rest. Here's the catch: some of the aromatic oils in mace, like myristicin and eugenol, seem to have mild sedative effects of their own. So if you take concentrated mace as a supplement on top of this, the two could potentially add up and leave you more groggy, dizzy, or foggy than expected.

To be fair, this is mostly theory drawn from animal studies, and the everyday pinch of mace in your cooking is very unlikely to matter. It's really only larger, medicinal doses worth watching. If you're considering mace supplements alongside Aleve PM, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sangalli BC, Chiang W. Toxicology of nutmeg abuse. Clin Toxicol 2000;38:671-8. PubMed
  2. Hallstrom H, Thuvander A. Toxicological evaluation of myristicin. Nat Toxins 1997;5:186-92. DOI
  3. Jeong HG, Yun CH. Induction of rat hepatic cytochrome P450 enzymes by myristicin. Biochem Biophys Res Commun 1995;217:966-71. PubMed
  4. Sell AB, Carlini EA. Anesthetic action of methyleugenol and other eugenol derivatives. Pharmacology. 1976;14(4):367-77. PubMed
  5. Fundarò A, Cassone MC. [Action of essential oils of chamomile, cinnamon, absinthium, mace and origanum on operant conditioning behavior of the rat]. Boll Soc Ital Biol Sper. 1980;56(22):2375-80.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Diphenhydramine Hydrochloride, Naproxen Sodium also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Animal research suggests that intraperitoneal injections of myristicin, a constituent of mace, can induce cytochrome P450 1A2 (CYP1A2) enzyme system. Theoretically, concomitant use of mace with drugs metabolized by CYP1A2 may increase the clearance of these drugs and reduce their effects. Some substrates of CYP1A2 include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), and others.
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 short version on combining mace with Aleve PM (which pairs naproxen, an anti-inflammatory pain reliever, with diphenhydramine, a sedating antihistamine). The concern on file is that a compound in mace called myristicin might speed up a liver enzyme (CYP1A2). In theory, revving up that enzyme could clear certain drugs a little faster and make them work less well.

Honestly, this is very weak evidence, based only on animal studies using injected myristicin, not people eating mace. Neither naproxen nor diphenhydramine relies mainly on CYP1A2, so a real-world effect is unlikely, especially at normal cooking amounts. I wouldn't worry about a pinch in your food. If you're considering concentrated mace supplements, just run it by your pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Jeong HG, Yun CH. Induction of rat hepatic cytochrome P450 enzymes by myristicin. Biochem Biophys Res Commun 1995;217:966-71. 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

Mace Also Interacts With Other Medications

Mace has 499 moderate known drug interactions in our database — the Diphenhydramine Hydrochloride, Naproxen Sodium one above is among them. If you take anything else, check it against the full list below.

Moderate 499 No known interaction 2,331 (incl. Diphenhydramine Hydrochloride, Naproxen Sodium)
Taking anything else?

Check Another of Your Medications Against Mace

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine Hydrochloride, Naproxen Sodium

This page covers Mace only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine Hydrochloride, Naproxen Sodium page lists 378 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), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 13 major · 320 moderate · 45 minor.

From our pharmacist’s overview on the Diphenhydramine Hydrochloride, Naproxen Sodium page

“Aleve PM combines naproxen, an NSAID, with the sedating antihistamine diphenhydramine, and its supplement list earns genuine care rather than a quick skim. Thirteen of the 378 ingredients on file rate major, and the two largest themes track the pill's two halves.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine Hydrochloride, Naproxen Sodium interaction page

One more smart check

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

We hold 38 real supplement products containing Mace, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Mace. Your product may carry other ingredients that interact with Diphenhydramine Hydrochloride, Naproxen Sodium too, on top of Mace — 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 Mace and Diphenhydramine Hydrochloride, Naproxen Sodium 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 Mace
Steady interest

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

29 days ago today
Medication Diphenhydramine Hydrochloride, Naproxen Sodium
Top 10%

#192 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 Mace

What is Mace?

  • Digestive upset and gas
  • Flavoring and culinary spice
  • Nausea
  • Appetite stimulation
  • Traditional pain or muscle relief

Mace is the lacy red covering of the nutmeg seed and comes from the same tree as nutmeg. It is mostly used as a cooking spice and in traditional medicine for digestion, but there is little solid human research to support its health uses. In normal food amounts it is generally safe, but large doses can be toxic, so use it as a spice and check with your pharmacist before taking concentrated supplements.

Read the full Mace monograph & all interactions
Keep checking

Other Drugs & Mace

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

0Major
499Moderate
0Minor
2,330No known interaction
499 Moderate 2,330 No interaction
Moderate

499 interactions

Showing 60 of 499 moderate interactions — see all 499 on the Mace page.

No interaction 2,330 drugs checked — show the list

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

Showing the 60 most looked-up of 2,330 medications checked with no known interaction — see the full Mace list.

See the full Mace interactions page
See every supplement checked against Diphenhydramine Hydrochloride, Naproxen Sodium, 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
Mace monograph › Uses, safety, and every drug interaction in one place Diphenhydramine Hydrochloride, Naproxen Sodium supplement interactions › Every supplement checked against Diphenhydramine Hydrochloride, Naproxen Sodium, 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 Mace and Diphenhydramine Hydrochloride, Naproxen Sodium Together: Common Questions

Can you take Mace with Diphenhydramine Hydrochloride, Naproxen Sodium?
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 Mace and Diphenhydramine Hydrochloride, Naproxen Sodium?
Diphenhydramine Hydrochloride, Naproxen Sodium belongs to more than one drug category, and Mace 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 Mace and Diphenhydramine Hydrochloride, Naproxen Sodium 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.