Drug & supplement interaction

N,n-dmpea + Methadone

Methadone brand name: Dolophine.

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

N,n-dmpea has a moderate interaction with Methadone. In vitro research shows that N,N-DMPEA strongly inhibits cytochrome P450 2D6 (CYP2D6).

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

N,n-dmpea and Methadone

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

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Why this applies to Methadone

Methadone falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group N,n-dmpea interacts with.

In vitro research shows that N,N-DMPEA strongly inhibits cytochrome P450 2D6 (CYP2D6). Theoretically, concomitant use with drugs metabolized by CYP2D6 might increase the risk for adverse effects from these drugs.
Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), 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

Here's the gist for methadone. Lab tests suggest N,N-DMPEA may block an enzyme called CYP2D6, which is one of the pathways your body uses to clear methadone. If that pathway slows down, methadone could build up a bit more than usual, and that can mean stronger opioid effects like heavy drowsiness, slowed or shallow breathing, and constipation.

I want to be honest about how shaky this evidence is: it comes only from test-tube studies, not real people, so we can't say how big the effect would be in you. But methadone is a powerful, long-acting opioid where even small changes matter, and these stimulant-type supplements are poorly studied. Please loop in your doctor or pharmacist before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. 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

N,n-dmpea Also Interacts With Other Medications

N,n-dmpea has 192 moderate 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 192 No known interaction 2,638 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against N,n-dmpea

Covers the 2,830 medications we’ve checked against N,n-dmpea. Pick one to open its full report.

From our Q&A

Questions About N,n-dmpea 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 N,n-dmpea 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 N,n-dmpea 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

How much people look this up

Where N,n-dmpea 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 N,n-dmpea
Steady interest

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

29 days ago today
Medication Methadone
Top 25%

#563 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 N,n-dmpea

What is N,n-dmpea?

  • Mood or energy support
  • Pre-workout or stimulant effect
  • Cognitive or focus support

N,N-DMPEA (N,N-dimethylphenethylamine) is a synthetic relative of phenethylamine sometimes marketed in stimulant or pre-workout supplements. There is very little reliable human research on its effects or safety, and it is not a well-established dietary ingredient, so it should be approached with real caution.

Read the full N,n-dmpea monograph & all interactions
Medication

About Methadone

What Is Methadone Used For?

Brand name: Dolophine

Methadone treats two main problems. Some products are used for severe, persistent pain that needs daily, around-the-clock opioid treatment when other options are not adequate. Some products are used for opioid addiction (heroin or other morphine-like drugs), as detoxification or as maintenance treatment along with social and medical services.

Not every product is approved for every use. Methadone tablets, oral solution and oral concentrate (Intensol) list both pain and opioid addiction. Diskets, Methadose Dispersible tablets and the Methadose and Methadone Hydrocloride oral concentrates are labeled only for opioid addiction. Methadone injection is for severe pain, and for short-term treatment of opioid dependence in people who cannot take medicine by mouth, such as hospitalized patients. It is not approved for outpatient opioid dependence treatment. Methadone is not meant to be used as an as-needed pain reliever.

See full Methadone drug information
Keep checking

Other Drugs & N,n-dmpea

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

0Major
192Moderate
0Minor
2,637No known interaction
192 Moderate 2,637 No interaction
Moderate

192 interactions

Showing 60 of 192 moderate interactions — see all 192 on the N,n-dmpea page.

No interaction 2,637 drugs checked — show the list

We also checked N,n-dmpea against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,637 medications checked with no known interaction — see the full N,n-dmpea list.

See the full N,n-dmpea 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
N,n-dmpea 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 N,n-dmpea and Methadone Together: Common Questions

Can you take N,n-dmpea 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 N,n-dmpea 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 N,n-dmpea?

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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.