Drug & supplement interaction

Hordenine + Methadone

Methadone brand name: Dolophine.

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

Hordenine has a minor interaction with Methadone. Hordenine weakly inhibits cytochrome P450 2D6 (CYP2D6) enzymes in vitro.

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

Hordenine and Methadone

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

Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Why this applies to Methadone

Methadone falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Hordenine interacts with.

Hordenine weakly inhibits cytochrome P450 2D6 (CYP2D6) enzymes in vitro. Theoretically, hordenine might increase the levels of CYP2D6 substrates.
Some of drugs that are CYP2D6 substrates 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 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

Here's the gist with hordenine and methadone: in test-tube studies, hordenine weakly blocks a liver enzyme called CYP2D6, which is one of the helpers your body uses to break down methadone. If that breakdown slows, methadone could build up a bit, which in theory means more of its effects, like extra drowsiness, slowed breathing, constipation, or confusion. Methadone is one of those drugs where even small shifts deserve respect, since its effects on breathing can be serious.

That said, this is only laboratory evidence and the blocking effect looks weak, so the real-world risk for most people is likely small. Still, because methadone is so potent, I'd run any hordenine product by your prescriber or pharmacist first.

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

Hordenine Also Interacts With Other Medications

Hordenine has 180 moderate, 148 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 180 Minor 148 No known interaction 2,502 (incl. Methadone)
Taking anything else?

Check Another of Your Medications Against Hordenine

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

From our Q&A

Questions About Hordenine 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 Hordenine 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 Hordenine 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 Hordenine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 339 real supplement products containing Hordenine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Hordenine. Your product may carry other ingredients that interact with Methadone too, on top of Hordenine — 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 Hordenine 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 Hordenine
Top 25%

#271 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 Hordenine

What is Hordenine?

Hordenine
  • Energy and stimulation
  • Athletic and workout performance
  • Weight loss/fat burning
  • Focus and mood
  • Appetite control

Hordenine is a natural alkaloid found in barley and some cacti that is marketed as a stimulant for energy, focus, and fat loss, but solid human evidence for these benefits is lacking. Its safety in people has not been well studied, so caution is warranted, and it should be avoided in pregnancy, breastfeeding, and by people with heart conditions.

Read the full Hordenine 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 & Hordenine

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

0Major
180Moderate
148Minor
2,501No known interaction
180 Moderate 148 Minor 2,501 No interaction
Moderate

180 interactions

Showing 60 of 180 moderate interactions — see all 180 on the Hordenine page.

Minor

148 interactions

Showing 60 of 148 minor interactions — see all 148 on the Hordenine page.

No interaction 2,501 drugs checked — show the list

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

Showing the 60 most looked-up of 2,501 medications checked with no known interaction — see the full Hordenine list.

See the full Hordenine 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
Hordenine 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 Hordenine and Methadone Together: Common Questions

Can you take Hordenine with Methadone?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Hordenine and Methadone interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Methadone and Hordenine?

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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.