Drug & supplement interaction

Indian Long Pepper + Methadone

Methadone brand name: Dolophine.

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

Indian Long Pepper has a moderate interaction with Methadone. Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.

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

Indian Long Pepper and Methadone

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Methadone

Methadone falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Indian Long Pepper interacts with.

Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP3A4.
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

Your body relies on a liver enzyme called CYP3A4 to help break down methadone. Piperine, the active compound in Indian long pepper, has been shown in lab studies to slow that same enzyme down. In theory, that could let methadone build up a bit more than usual, which might mean stronger effects and a higher chance of side effects like drowsiness, slowed breathing, constipation, or feeling foggy.

Now, the honest part: this is based on test-tube research, not real people, so we can't say for sure it actually happens at the amounts you'd eat or take. Still, because methadone is a drug where small shifts can matter, it's worth mentioning. Please don't change your dose on your own. Just let your pharmacist or doctor know you're using this spice so they can keep an eye on things.

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

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

Indian Long Pepper Also Interacts With Other Medications

Indian Long Pepper has 892 moderate, 3 minor known drug interactions in our database — the Methadone one above is one of them. If you take anything else, check it against the full list below.

Moderate 892 Minor 3 No known interaction 1,935 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against Indian Long Pepper

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

From our Q&A

Questions About Indian Long Pepper or Methadone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Indian Long Pepper or Methadone, 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 Methadone

This page covers Indian Long Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methadone page lists 223 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 Grapefruit (major).

By severity: 10 major · 174 moderate · 39 minor.

From our pharmacist’s overview on the Methadone page

“If you take methadone, choose your supplements with genuine care. Of the 223 ingredients on this page, most either add to methadone's sedating effect or change how fast your body clears it, which can push its blood level up or down.”

Reviewed by 2 · Jul 18, 2026

Open the Methadone interaction page

One more smart check

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

We hold 597 real supplement products containing Indian Long Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Long Pepper. Your product may carry other ingredients that interact with Methadone too, on top of Indian Long 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 Indian Long Pepper and Methadone 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 Indian Long Pepper
Top 25%

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

29 days ago today
Medication Methadone
Top half

#807 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 Indian Long Pepper

What is Indian Long Pepper?

Indian Long Pepper
  • Digestive upset
  • Respiratory and cough complaints
  • Boosting absorption of other supplements
  • Pain and inflammation
  • General wellness in Ayurveda

Indian long pepper (pippali) is a spice long used in Ayurvedic medicine and is best known for its piperine content, which may increase how well the body absorbs certain other substances. Modern human research on its health benefits is limited, so use it cautiously and let your pharmacist or doctor know if you take it regularly.

Read the full Indian Long Pepper monograph & all interactions
Medication

About Methadone

What Is Methadone Used For?

Brand name: Dolophine

Methadone treats severe and persistent pain that requires daily, around-the-clock, long-term opioid treatment and cannot be managed adequately with other options. It is available in several forms for this use, including oral solution, oral tablets, oral concentrate, and injectable forms (intravenous, intramuscular, and subcutaneous). Injectable methadone is not approved for outpatient pain treatment — it is reserved for hospitalized patients unable to take oral medication.

Methadone is also used for the detoxification and maintenance treatment of opioid addiction (dependence on heroin or other morphine-like drugs). Oral forms — including tablets, dispersible tablets (such as Methadose Dispersible and DISKETS), and oral concentrates (such as Methadone Hydrochloride Intensol™, Methadose, and others) — are approved for this use. By law, methadone for opioid addiction treatment must be dispensed only by certified opioid treatment programs. Injectable methadone is not approved for outpatient addiction treatment.

See full Methadone drug information
Keep checking

Other Drugs & Indian Long Pepper

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

0Major
892Moderate
3Minor
1,934No known interaction
892 Moderate 3 Minor 1,934 No interaction
Moderate

892 interactions

Showing 60 of 892 moderate interactions — see all 892 on the Indian Long Pepper page.

Minor

3 interactions

No interaction 1,934 drugs checked — show the list

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

Showing the 60 most looked-up of 1,934 medications checked with no known interaction — see the full Indian Long Pepper list.

See the full Indian Long Pepper interactions page
See every supplement checked against Methadone, 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
Indian Long Pepper monograph › Uses, safety, and every drug interaction in one place Methadone supplement interactions › Every supplement checked against Methadone, ranked by severity Methadone drug information › The full plain-English guide to this medication 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 Indian Long Pepper and Methadone Together: Common Questions

Can you take Indian Long Pepper with Methadone?
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 Indian Long Pepper and Methadone 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 Methadone and Indian Long 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.