Drug & supplement interaction

Nutmeg + Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine brand names: Tylenol PM, Tylenol PM Ex Strength.

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

Acetaminophen, Diphenhydramine falls into 3 drug categories that Nutmeg can interact with; the most serious is rated moderate. Theoretically, nutmeg might increase the risk of additive sedation when taken with CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Nutmeg and Acetaminophen, Diphenhydramine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Nutmeg interacts with whole categories of medication. Acetaminophen, Diphenhydramine falls into 3 of those categories, so it can interact with Nutmeg in 3 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 3

Why this applies to Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine falls under CNS DEPRESSANTS — the group Nutmeg interacts with.

Theoretically, nutmeg might increase the risk of additive sedation when taken with CNS depressants.
Animal studies suggest that nutmeg extracts and several volatile oils in nutmeg, such as methyleugenol, isoeugenol, safrole, myristicin, trimyristin, 1,8-cineole, and geranyl acetate, have sedative effects. One animal study shows that petroleum ether extracts of nutmeg can potentiate the effects of pentobarbital or phenobarbital. However, evidence from other animal research suggests that the nutmeg constituent myristicin can actually reduce sleeping time in rats pretreated with phenobarbital.
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 about Tylenol PM: it already contains diphenhydramine, the same drowsy-making ingredient found in Benadryl. That's what helps you fall asleep. Nutmeg comes into the picture because, in animal and lab studies, some of its compounds (like myristicin) have shown a mild sedative or calming effect. So in theory, piling nutmeg on top of a product that's designed to make you sleepy could add up to extra grogginess, deeper drowsiness, or feeling foggy and slow the next morning.

I want to be honest, though: this is a theoretical concern based only on animal research, and normal cooking amounts of nutmeg in your food almost certainly won't matter. Concentrated nutmeg supplements are a different story and aren't recommended anyway. If you're using one, just check with your pharmacist 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.
  6. Grover JK, Khandkar S, Vats V, Dhunnoo Y, Das D. Pharmacological studies on Myristica fragrans--antidiarrheal, hypnotic, analgesic and hemodynamic (blood pressure) parameters. Methods Find Exp Clin Pharmacol. 2002;24(10):675-80. PubMed
  7. Sherry CJ, Ray LE, Herron RE. The pharmacological effects of the ligroin extract of nutmeg (Myristica fragrans). J Ethnopharmacol. 1982;6(1):61-6.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Acetaminophen, Diphenhydramine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, nutmeg might decrease levels of drugs metabolized by CYP1A2.
Animal research suggests that intraperitoneal injections of myristicin, a constituent of nutmeg, can induce CYP1A2.
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 situation with your Tylenol PM, which pairs acetaminophen (a pain and fever reducer) with diphenhydramine (the Benadryl-type antihistamine that makes you sleepy). The concern on file is theoretical: a compound in nutmeg called myristicin may speed up an enzyme (CYP1A2) that helps process certain drugs. If that happened, your body could clear these medicines a little faster, possibly making them slightly less effective.

Honestly, this is very weak evidence, coming only from animal studies using injected nutmeg, not from people eating it. Normal cooking amounts of nutmeg are very unlikely to matter here. If you regularly take large medicinal nutmeg doses (which can be toxic anyway), chat with 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
Moderate

ANTICHOLINERGIC DRUGS

3 of 3

Acetaminophen, Diphenhydramine also falls under ANTICHOLINERGIC DRUGS.

Theoretically, concomitant use of nutmeg and anticholinergic drugs might decrease the effectiveness of either agent.
Animal research suggests that nutmeg extract can inhibit acetylcholinesterase and might increase acetylcholine 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 gist for your Tylenol PM. The diphenhydramine in it is an antihistamine that works partly by blocking acetylcholine, a signaling chemical in the body. That's what gives it the sleepy, dry-mouth, drowsy effect. In lab and animal studies, nutmeg seems to do the opposite, nudging acetylcholine levels up. So in theory, large amounts of nutmeg could slightly blunt how well the diphenhydramine works, meaning it might not make you as drowsy as expected.

Honestly, this is very weak, theoretical evidence, and the acetaminophen (the pain/fever part) isn't really involved here. A sprinkle of nutmeg on your food won't matter. Only big, risky medicinal doses are a concern, and those aren't safe anyway. If you're curious, just run it by your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mukherjee PK, Kumar V, Houghton PJ. Screening of Indian medicinal plants for acetylcholinesterase inhibitory activity. Phytother Res. 2007;21(12):1142-5. 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

Nutmeg Also Interacts With Other Medications

Nutmeg has 527 moderate known drug interactions in our database — the Acetaminophen, Diphenhydramine one above is among them. If you take anything else, check it against the full list below.

Moderate 527 No known interaction 2,303 (incl. Acetaminophen, Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Nutmeg

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Diphenhydramine

This page covers Nutmeg only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine page lists 254 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 Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 204 moderate · 39 minor.

Open the Acetaminophen, Diphenhydramine interaction page

One more smart check

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

We hold 182 real supplement products containing Nutmeg, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Nutmeg. Your product may carry other ingredients that interact with Acetaminophen, Diphenhydramine too, on top of Nutmeg — 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 Nutmeg and Acetaminophen, 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 Nutmeg
Top half

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

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 10%

#225 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 Nutmeg

What is Nutmeg?

Nutmeg
  • Digestive upset
  • Diarrhea
  • Sleep and relaxation
  • Pain and inflammation
  • Flavoring spice

Nutmeg is a popular cooking spice that has long been used in traditional medicine for digestion and other complaints, but there is little solid human research to support its medicinal use. In normal cooking amounts it is generally safe, but larger "medicinal" doses can cause serious poisoning, so it should never be taken in high amounts.

Read the full Nutmeg monograph & all interactions
Keep checking

Other Drugs & Nutmeg

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

0Major
527Moderate
0Minor
2,302No known interaction
527 Moderate 2,302 No interaction
Moderate

527 interactions

Showing 60 of 527 moderate interactions — see all 527 on the Nutmeg page.

No interaction 2,302 drugs checked — show the list

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

Showing the 60 most looked-up of 2,302 medications checked with no known interaction — see the full Nutmeg list.

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

Can you take Nutmeg with Acetaminophen, 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.
Why are there 3 interactions listed for Nutmeg and Acetaminophen, Diphenhydramine?
Acetaminophen, Diphenhydramine belongs to more than one drug category, and Nutmeg 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 Nutmeg and Acetaminophen, 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.