Drug & supplement interaction

Hordenine + Hydrocodone

Hydrocodone brand names: Hydrocodone, Zohydro ER.

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

Hordenine has a minor interaction with Hydrocodone. 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 Hydrocodone

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

Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Why this applies to Hydrocodone

Hydrocodone 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 something worth knowing about this pairing. Hydrocodone is actually a prodrug for pain relief. Your body uses an enzyme called CYP2D6 to turn it into hydromorphone, which is the part that does most of the heavy lifting against pain. Hordenine has been shown in lab dishes (not in people) to weakly block that same enzyme.

So in theory, if hordenine slows CYP2D6, your body might make a little less of that active painkiller, meaning hydrocodone could feel less effective at controlling your pain. The flip side is that the parent drug may linger, so the picture isn't fully clear. Honestly, this is only test-tube evidence and rated minor, so it's likely small. Still, since you rely on hydrocodone for severe pain, please run this by your pharmacist or doctor before adding hordenine.

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 Hydrocodone 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. Hydrocodone)
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 Hydrocodone

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 Hydrocodone, 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 Hydrocodone

This page covers Hordenine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrocodone page lists 212 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: 9 major · 164 moderate · 39 minor.

From our pharmacist’s overview on the Hydrocodone page

“Most people taking hydrocodone (Zohydro ER) are treating real pain, and pain wrecks sleep, so sedating supplements look tempting. They are the worst pairing on this page: 78 of the 212 interacting ingredients add to hydrocodone's sedation, which with an opioid can mean dangerously slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Hydrocodone 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 Hydrocodone 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 Hydrocodone 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%

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

29 days ago today
Medication Hydrocodone
Steady interest

#1,532 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 Hydrocodone

What Is Hydrocodone Used For?

Brand names: Hydrocodone, Zohydro ER

Hydrocodone extended-release products are used to manage severe and persistent pain that requires daily, long-term treatment with an opioid and cannot be adequately controlled with other options, including immediate-release opioids.

These products are not intended for use on an as-needed basis. They are reserved for patients whose pain cannot be managed with non-opioid medicines or shorter-acting opioid products.

See full Hydrocodone 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 Hydrocodone, 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 Hydrocodone supplement interactions › Every supplement checked against Hydrocodone, ranked by severity Hydrocodone 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 Hydrocodone Together: Common Questions

Can you take Hordenine with Hydrocodone?
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 Hydrocodone 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 Hydrocodone and Hordenine?

Our pharmacists answer your medication & supplement questions — free.

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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.