Drug & supplement interaction

Mace + Hyoscyamine, Phenobarbital

Hyoscyamine, Phenobarbital brand names: Levsin Pb, Levsinex Pb Timecaps.

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

Hyoscyamine, Phenobarbital 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 Hyoscyamine, Phenobarbital

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. Hyoscyamine, Phenobarbital 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

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Why this applies to Hyoscyamine, Phenobarbital

Hyoscyamine, Phenobarbital 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 combination you're asking about already contains phenobarbital, which is a barbiturate that slows down the central nervous system. The concern here is pretty straightforward: some of the aromatic oils in mace (like myristicin and methyleugenol) appear to have mild sedative effects of their own. In theory, stacking those on top of phenobarbital could add up to extra drowsiness, dizziness, slowed breathing, or feeling foggy and uncoordinated.

I want to be honest with you though, this is based on animal and lab studies, not solid human research, and the evidence is mixed (one study even suggested mace shortened phenobarbital's effect). Normal cooking amounts of mace are very unlikely to matter. Concentrated mace supplements are a different story, so check with your pharmacist or doctor before combining them.

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

PHENOBARBITAL (Luminal)

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Evidence from animal research suggests that myristicin, a constituent of mace, can reduce sleeping time in rats pretreated with phenobarbital. Theoretically, concomitant use may decrease the therapeutic effects of phenobarbital.
Severity Moderate Likelihood Probable Evidence D

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

Your medicine pairs hyoscyamine with phenobarbital, a barbiturate that calms the nervous system and is often used to settle stomach cramping. The interaction we have on file is really about the phenobarbital part. In animal studies, a compound in mace called myristicin appeared to shorten how long phenobarbital kept rats asleep, which suggests mace might speed up how the body clears it. In theory, that could make the phenobarbital work a little less well.

Keep this in perspective. This is a theoretical concern based on animal data, not human studies, and a sprinkle of mace as a cooking spice is very unlikely to matter. Concentrated mace supplements are a different story. Since phenobarbital needs steady, reliable levels, check with your pharmacist or doctor before using any mace supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hallstrom H, Thuvander A. Toxicological evaluation of myristicin. Nat Toxins 1997;5:186-92. DOI
  2. 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 Hyoscyamine, Phenobarbital 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. Hyoscyamine, Phenobarbital)
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 Hyoscyamine, Phenobarbital

This page covers Mace only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hyoscyamine, Phenobarbital page lists 164 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: 10 major · 134 moderate · 20 minor.

From our pharmacist’s overview on the Hyoscyamine, Phenobarbital page

“The person taking Levsin PB (hyoscyamine with phenobarbital) for gut spasms is often the same person browsing calming herbs and sleep aids, and with this medicine that habit calls for real vigilance. Ten of the 164 supplements on record rate major, and the largest group, 78 ingredients, shares one danger.”

Reviewed by 2 · Jul 18, 2026

Open the Hyoscyamine, Phenobarbital 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 Hyoscyamine, Phenobarbital 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 Hyoscyamine, Phenobarbital 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

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

29 days ago today
Medication Hyoscyamine, Phenobarbital
Steady interest

#1,527 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 Hyoscyamine, Phenobarbital, 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 Hyoscyamine, Phenobarbital supplement interactions › Every supplement checked against Hyoscyamine, Phenobarbital, 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 Hyoscyamine, Phenobarbital Together: Common Questions

Can you take Mace with Hyoscyamine, Phenobarbital?
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 Hyoscyamine, Phenobarbital?
Hyoscyamine, Phenobarbital 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 Hyoscyamine, Phenobarbital 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.