Drug & supplement interaction

Black Pepper + Maprotiline

Maprotiline brand name: Ludiomil.

Moderate Interaction
The bottom line Moderate

Black Pepper has a moderate interaction with Maprotiline. Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.

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

Black Pepper and Maprotiline

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

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Why this applies to Maprotiline

Maprotiline falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Black Pepper interacts with.

Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. 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

Here's the simple version: your body uses a liver enzyme called CYP2D6 to help clear maprotiline out of your system. Piperine, the active part of black pepper, may slow that enzyme down a bit. If it does, more maprotiline could linger in your blood, which could nudge up its usual side effects like drowsiness, dry mouth, constipation, blurry vision, or feeling lightheaded when you stand up.

The reassuring part: this concern comes only from lab (test tube) studies, not from real people, so it's theoretical. Normal cooking amounts of pepper on your food are very unlikely to cause trouble. Concentrated piperine supplements are the bigger question mark. If you're taking one, just run it by your pharmacist or doctor before mixing.

References
  1. Subehan, Usia, T., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum. Planta Med 2006;72(6):527-532.
  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. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. 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 975 moderate, 43 minor known drug interactions in our database — the Maprotiline one above is one of them. If you take anything else, check it against the full list below.

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 Maprotiline

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 Maprotiline, 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 Maprotiline

This page covers Black Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Maprotiline page lists 116 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Lithium (major), 1,3-dmaa (moderate), 5-htp (moderate) and Acacia Rigidula (moderate).

By severity: 2 major · 90 moderate · 24 minor.

From our pharmacist’s overview on the Maprotiline page

“The riskiest pairing on this page belongs to lithium. Taken alongside a serotonergic antidepressant like maprotiline (Ludiomil), it can both mask and raise the odds of serotonin syndrome, a dangerous buildup of serotonin activity, and it earns one of the list's two major ratings for that reason.”

Reviewed by 2 · Jul 18, 2026

Open the Maprotiline 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 Maprotiline 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 Maprotiline 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%

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

29 days ago today
Medication Maprotiline
Steady interest

#1,912 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
Medication

About Maprotiline

What Is Maprotiline Used For?

Brand name: Ludiomil

  • Maprotiline is used to treat depression, bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods), and anxiety. Maprotiline is in a class of medications called tetracyclic antidepressants. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.

See full Maprotiline drug information
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
975Moderate
43Minor
1,811No known interaction
Moderate

975 interactions

Showing 60 of 975 moderate interactions — see all 975 on the Black Pepper page.

Minor

43 interactions

No interaction 1,811 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Black Pepper and Maprotiline Together: Common Questions

Can you take Black Pepper with Maprotiline?
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 Black Pepper and Maprotiline 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 Maprotiline and Black Pepper?

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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.