Drug & supplement interaction

Same + Tramadol

Tramadol brand names: Ultram, Zytram XL, Qdolo.

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

Same has a moderate interaction with Tramadol. Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.

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

Same and Tramadol

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

Moderate

SEROTONERGIC DRUGS

Why this applies to Tramadol

Tramadol falls under SEROTONERGIC DRUGS — the group Same interacts with.

Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.
SAMe has serotonergic effects. Theoretically, combining serotonergic drugs with SAMe might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. In one case report, SAMe 100 mg intramuscularly was given daily with clomipramine (Anafranil) 25 mg per day. When the clomipramine dose was increased to 75 mg per day the patient experienced serotonin syndrome about 48-72 hours later, requiring hospitalization.
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 thing to know about pairing SAM-e with tramadol: both can raise serotonin activity in your body. Tramadol is a bit unusual for a pain reliever because, on top of its opioid effect, it also boosts serotonin and norepinephrine. SAM-e is thought to have its own serotonin-related effects, so stacking the two could, in theory, push serotonin too high.

That overlap can lead to what we call serotonin syndrome. Watch for agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused. To be fair, the evidence here is mostly anecdotal (a single case report with a different drug), so this isn't common. Still, it's worth a quick chat with your pharmacist or doctor before combining them, especially if you take other antidepressants.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522. PubMed
  2. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Res 1992;44:257-62. PubMed
  3. Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432-6. PubMed
  4. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. PubMed
  5. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. 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

Same Also Interacts With Other Medications

Same has 188 moderate known drug interactions in our database — the Tramadol one above is one of them. If you take anything else, check it against the full list below.

Moderate 188 No known interaction 2,642 (incl. Tramadol)
Taking anything else?

Check Another of Your Medications Against Same

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

From our Q&A

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

We hold 9 real supplement products containing Same, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Same. Your product may carry other ingredients that interact with Tramadol too, on top of Same — 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 Same 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 Same
Top half

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

29 days ago today
Medication Tramadol
Top 25%

#538 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 Same

What is Same?

Same
  • Depression
  • Osteoarthritis joint pain
  • Liver conditions
  • Fibromyalgia

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it may help with these conditions, but the quality of evidence is mixed and more study is needed. Talk with your pharmacist or doctor before trying it, especially if you take other medicines or have bipolar disorder.

Read the full Same monograph & all interactions
Medication

About Tramadol

What Is Tramadol Used For?

Brand names: Ultram, Zytram XL, Qdolo

Tramadol treats pain that is severe enough to need an opioid pain medicine when other treatments are not enough. Other options, such as non-opioid pain relievers, should have failed, not been tolerated, or be unlikely to work.

The use depends on the form. Tramadol tablets and oral solution are for adults with pain severe enough to need an opioid. Extended-release tablets and capsules are for severe, persistent pain that needs around-the-clock, long-term opioid treatment. They are not for pain taken only as needed.

See full Tramadol drug information
Keep checking

Other Drugs & Same

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

0Major
188Moderate
0Minor
2,641No known interaction
188 Moderate 2,641 No interaction
Moderate

188 interactions

Showing 60 of 188 moderate interactions — see all 188 on the Same page.

No interaction 2,641 drugs checked — show the list

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

Showing the 60 most looked-up of 2,641 medications checked with no known interaction — see the full Same list.

See the full Same 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
Same 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 Same and Tramadol Together: Common Questions

Can you take Same 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.
How serious is the Same 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 Same?

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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.