Drug & supplement interaction

Black Pepper + Belladonna, Caffeine, Ergotamine, Pentobarbital

Belladonna, Caffeine, Ergotamine, Pentobarbital brand name: Micomp PB.

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

Belladonna, Caffeine, Ergotamine, Pentobarbital falls into 3 drug categories that Black Pepper can interact with; the most serious is rated moderate. Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.

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

Black Pepper and Belladonna, Caffeine, Ergotamine, Pentobarbital

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

Why Are There 3 Interactions?

Black Pepper interacts with whole categories of medication. Belladonna, Caffeine, Ergotamine, Pentobarbital falls into 3 of those categories, so it can interact with Black Pepper in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 3

Why this applies to Belladonna, Caffeine, Ergotamine, Pentobarbital

Belladonna, Caffeine, Ergotamine, Pentobarbital falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Black Pepper interacts with.

Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.
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

This combination medicine (Micomp PB) is sometimes used for headaches and contains ergotamine, which your liver clears using an enzyme called CYP3A4. Lab and computer studies hint that piperine, the active part of black pepper, may slow that enzyme down. In theory, that could let a little more ergotamine linger in your body, nudging up side effects like nausea, tingling or coldness in the fingers and toes, leg cramping, or stronger caffeine-like jitteriness.

Here is the honest part: this has only been seen in test tubes and simulations, never confirmed in real people, and ergotamine is one of those drugs where small changes can matter. The sprinkle of pepper on your dinner is no concern. If you take concentrated piperine supplements, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  2. Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. PubMed
  3. Lin F, Hu Y, Zhang Y, Zhao L, Zhong D, Liu J. Predicting Food-Drug Interactions between Piperine and CYP3A4 Substrate Drugs Using PBPK Modeling. Int J Mol Sci 2024;25(20):10955. PubMed
Moderate

PENTOBARBITAL (Nembutal)

2 of 3
Theoretically, black pepper might increase the sedative effects of pentobarbital.
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time.
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

This combination product contains a barbiturate called pentobarbital, and that's the piece we're watching here. Piperine, the active compound in black pepper, can slow down some of the liver enzymes that clear pentobarbital out of your body. If that happens, more of the sedative can hang around longer than expected, which could leave you feeling extra drowsy, groggy, foggy, or unsteady on your feet.

I want to be upfront though: this concern comes from animal studies where piperine lengthened sleeping time, so it's mostly theoretical in people. A sprinkle of pepper on dinner is very unlikely to matter. Concentrated piperine supplements (often paired with turmeric/curcumin) are where I'd be more cautious. Please run any pepper-based supplement past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L., and Naik, S. R. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp.Biol. 1990;28(5):486-487.
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 3

Belladonna, Caffeine, Ergotamine, Pentobarbital also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in 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

This combo product (Micomp PB) contains caffeine, which your liver clears using an enzyme called CYP1A2. In lab and animal studies, piperine from black pepper appears to speed up that enzyme. If that held true in people, your body might clear caffeine a little faster, so you could notice slightly less of its effect. The belladonna, ergotamine, and pentobarbital pieces aren't really driven by this same pathway.

Here's the reassuring part: this is only a theoretical, minor interaction that has never been shown in humans, and food-amounts of pepper are very unlikely to matter. Concentrated piperine supplements are where I'd be a bit more cautious. If you take these together regularly, just mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Black Pepper Also Interacts With Other Medications

Black Pepper has 976 moderate, 43 minor known drug interactions in our database — the Belladonna, Caffeine, Ergotamine, Pentobarbital one above is among them. If you take anything else, check it against the full list below.

Moderate 976 Minor 43 No known interaction 1,811 (incl. Belladonna, Caffeine, Ergotamine, Pentobarbital)
Taking anything else?

Check Another of Your Medications Against Black Pepper

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

From our Q&A

Questions About Black Pepper or Belladonna, Caffeine, Ergotamine, Pentobarbital

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Black Pepper or Belladonna, Caffeine, Ergotamine, Pentobarbital, 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 Belladonna, Caffeine, Ergotamine, Pentobarbital

This page covers Black Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Belladonna, Caffeine, Ergotamine, Pentobarbital page lists 290 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), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 15 major · 227 moderate · 48 minor.

From our pharmacist’s overview on the Belladonna, Caffeine, Ergotamine, Pentobarbital page

“People who take Micomp PB for migraines are often the same people reaching for an herbal sleep aid or a caffeinated energy product during a rough stretch, and with four drugs in one tablet (belladonna, caffeine, ergotamine, pentobarbital) nearly everything clashes with something. The 290 supplement ingredients on file here earn genuine…”

Reviewed by 2 · Jul 18, 2026

Open the Belladonna, Caffeine, Ergotamine, Pentobarbital interaction page

One more smart check

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

We hold 5,528 real supplement products containing Black Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Pepper. Your product may carry other ingredients that interact with Belladonna, Caffeine, Ergotamine, Pentobarbital too, on top of Black Pepper — 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 Black Pepper and Belladonna, Caffeine, Ergotamine, Pentobarbital 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 Black Pepper
Top 5%

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

29 days ago today
Medication Belladonna, Caffeine, Ergotamine, Pentobarbital
Top 5%

#104 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 Black Pepper

What is Black Pepper?

Black Pepper
  • Flavoring and culinary use
  • Digestive complaints like bloating and indigestion
  • Boosting absorption of other supplements
  • Antioxidant and anti-inflammatory support
  • Cold and congestion remedies

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (like curcumin from turmeric). Strong human evidence for black pepper treating specific health conditions is limited, so use supplement-strength products with care and check with your pharmacist.

Read the full Black Pepper monograph & all interactions
Keep checking

Other Drugs & Black Pepper

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

0Major
976Moderate
43Minor
1,810No known interaction
976 Moderate 43 Minor 1,810 No interaction
Moderate

976 interactions

Showing 60 of 976 moderate interactions — see all 976 on the Black Pepper page.

Minor

43 interactions

No interaction 1,810 drugs checked — show the list

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

Showing the 60 most looked-up of 1,810 medications checked with no known interaction — see the full Black Pepper list.

See the full Black Pepper interactions page
See every supplement checked against Belladonna, Caffeine, Ergotamine, Pentobarbital, 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
Black Pepper monograph › Uses, safety, and every drug interaction in one place Belladonna, Caffeine, Ergotamine, Pentobarbital supplement interactions › Every supplement checked against Belladonna, Caffeine, Ergotamine, Pentobarbital, 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 Black Pepper and Belladonna, Caffeine, Ergotamine, Pentobarbital Together: Common Questions

Can you take Black Pepper with Belladonna, Caffeine, Ergotamine, Pentobarbital?
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 Black Pepper and Belladonna, Caffeine, Ergotamine, Pentobarbital?
Belladonna, Caffeine, Ergotamine, Pentobarbital belongs to more than one drug category, and Black Pepper 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 Black Pepper and Belladonna, Caffeine, Ergotamine, Pentobarbital 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.