Drug & supplement interaction

Sage + Tramadol

Tramadol brand names: Ultram, Zytram XL, Qdolo.

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

Tramadol falls into 3 drug categories that Sage can interact with; the most serious is rated moderate. Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sage and Tramadol

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Sage interacts with whole categories of medication. Tramadol falls into 3 of those categories, so it can interact with Sage in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 3

Why this applies to Tramadol

Tramadol falls under CNS DEPRESSANTS — the group Sage interacts with.

Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.
Some constituents of sage have CNS depressant activity.
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 with sage and tramadol: some compounds in sage seem to have a mild calming effect on the brain, at least in lab studies. Tramadol already slows down the nervous system to ease pain, so the worry is that the two together could add up. That could mean feeling extra drowsy, foggy, dizzy, or more sedated than usual.

I want to be honest about the strength here. This is a theoretical concern based on test-tube and animal research, not real patient cases, and a little sage in your cooking is very unlikely to do anything. Concentrated sage extracts or the essential oil are where I'd be more cautious. If you take tramadol daily, just run any sage supplement past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Perry NS, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 2003;75:651-9.. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

Tramadol also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2D6. So far, this interaction 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 wrinkle with tramadol: it's actually a prodrug. Your body uses an enzyme called CYP2D6 to turn it into its stronger active form, which does most of the pain relieving. Lab studies hint that concentrated sage extracts might slow down CYP2D6. If that happened, you could end up with less of the active painkiller, so tramadol might not control your pain as well.

I want to be honest about how soft this evidence is. It comes only from test-tube studies, and no real cases have ever been reported in people. A little sage in your cooking is very unlikely to matter. If you're taking strong sage extracts or the essential oil regularly, just mention it to your pharmacist or doctor so they can keep an eye on your pain control.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  2. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007 Nov;101:350-8.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Tramadol also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4. So far, this interaction 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 gist with sage and your tramadol. Sage may slow down an enzyme in your liver called CYP3A4, which is one of the pathways that helps clear tramadol. If that pathway slows, a bit more tramadol could hang around in your body. In theory that might mean stronger effects, like extra drowsiness, dizziness, nausea, or constipation. It could also nudge up the small risk of dangerous side effects with opioids, especially if you take other sedating medicines.

That said, this is based only on lab testing, not real people, so it may not amount to much, and ordinary cooking amounts of sage are very unlikely to matter. Concentrated sage extracts or oil are the bigger question mark. Please check with your pharmacist or doctor before adding a sage supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  2. Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.

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

Sage Also Interacts With Other Medications

Sage has 1,295 moderate known drug interactions in our database — the Tramadol one above is among them. If you take anything else, check it against the full list below.

Moderate 1,295 No known interaction 1,535 (incl. Tramadol)
Taking anything else?

Check Another of Your Medications Against Sage

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

From our Q&A

Questions About Sage or Tramadol

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

This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol 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 Tramadol page

“Tramadol (Ultram, Qdolo) is an opioid, and its supplement interactions worry me more than most because the worst of them compound the drug's most dangerous effects. Alcohol and dozens of calming herbs deepen its sedation, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Tramadol interaction page

One more smart check

Taking Sage as Part of a Dietary Supplement Product? Check It for Interactions

We hold 718 real supplement products containing Sage, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sage. Your product may carry other ingredients that interact with Tramadol too, on top of Sage — 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 Sage and Tramadol 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 Sage
Top 25%

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

29 days ago today
Medication Tramadol
Top 25%

#416 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 Sage

What is Sage?

Sage
  • Sore throat and mouth irritation
  • Digestive upset
  • Excessive sweating
  • Memory and thinking
  • Menopause symptoms (hot flashes)
  • General antioxidant support

Sage is a common kitchen herb that is generally safe in food amounts and is traditionally used for sore throats, digestion, sweating, and memory. Some early research is encouraging for sore throat and menopausal hot flashes, but most uses are not well proven. Concentrated extracts and the essential oil should be used carefully because high doses contain a compound called thujone, which can be harmful.

Read the full Sage monograph & all interactions
Medication

About Tramadol

What Is Tramadol Used For?

Brand names: Ultram, Zytram XL, Qdolo

Tramadol is used in adults for pain that is severe enough to need an opioid-strength medication and where non-opioid treatments haven't been enough. It's typically reserved for situations where milder options have failed or aren't expected to work.

It is not meant for everyday or long-term use unless the pain remains severe and alternatives continue to fall short. Prescribers carefully weigh the benefits against the real risks before starting tramadol.

See full Tramadol drug information
Keep checking

Other Drugs & Sage

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

0Major
1,295Moderate
0Minor
1,534No known interaction
1,295 Moderate 1,534 No interaction
Moderate

1,295 interactions

Showing 60 of 1,295 moderate interactions — see all 1,295 on the Sage page.

No interaction 1,534 drugs checked — show the list

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

Showing the 60 most looked-up of 1,534 medications checked with no known interaction — see the full Sage list.

See the full Sage interactions page
See every supplement checked against Tramadol, 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
Sage monograph › Uses, safety, and every drug interaction in one place Tramadol supplement interactions › Every supplement checked against Tramadol, ranked by severity Tramadol 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 Sage and Tramadol Together: Common Questions

Can you take Sage with Tramadol?
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.
Why are there 3 interactions listed for Sage and Tramadol?
Tramadol belongs to more than one drug category, and Sage interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Sage and Tramadol 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 Tramadol and Sage?

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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.