Drug & supplement interaction

Phenethylamine (pea) + Tramadol

Tramadol brand names: Ultram, Zytram XL, Qdolo.

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

Phenethylamine (pea) has a moderate interaction with Tramadol. Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of serotonergic adverse effects.

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

Phenethylamine (pea) 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 Phenethylamine (pea) interacts with.

Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of serotonergic adverse effects.
Animal research shows that phenethylamine increases levels of serotonin, norepinephrine, and dopamine. Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of additive serotonergic adverse effects, including serotonin syndrome and cerebral vasoconstrictive disorders. However, low-quality clinical research has used phenethylamine with selegiline, a monoamine oxidase inhibitor (MAOI), with apparent safety.
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 about tramadol: besides easing pain, it also raises serotonin levels in your brain. Phenethylamine (PEA) may nudge serotonin, norepinephrine, and dopamine upward too. Stacking the two could, in theory, add up and increase the small risk of serotonin syndrome, which can show up as agitation, a racing heart, sweating, shivering, muscle twitching, or confusion. PEA may also bump up blood pressure and heart rate on its own.

I'll be honest, this concern is mostly theoretical and based on animal data, not strong human studies, so it isn't a reason to panic. Still, since both touch serotonin, please run this combo by your pharmacist or doctor before pairing them, especially if you have heart or blood pressure issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  2. Sabelli H, Fink P, Fawcett J, et al. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996;8(2):168-71.
  3. Xie Z, Miller G. Beta-phenylehtylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther. 2008;325(2):617-28.
  4. Nakamura M, Ishii A, Nakahara D. Characterization of beta-phenyltheylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study. Eur J Pharmacol. 1998;349(2-3):163-9.
  5. Bailey B, Philips S, Boulton A. In vivo release of endogenous dopamine, 5-hydroxytryptamine and some of their metabolites from rat caudate nucleus by phenylethylamine. Neurochem Res. 1987;12(2):173-8. 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

Phenethylamine (pea) Also Interacts With Other Medications

Phenethylamine (pea) has 186 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 186 No known interaction 2,644 (incl. Tramadol)
Taking anything else?

Check Another of Your Medications Against Phenethylamine (pea)

Covers the 2,830 medications we’ve checked against Phenethylamine (pea). Pick one to open its full report.

From our Q&A

Questions About Phenethylamine (pea) 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 Phenethylamine (pea) 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 Phenethylamine (pea) 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 Phenethylamine (pea) as Part of a Dietary Supplement Product? Check It for Interactions

We hold 208 real supplement products containing Phenethylamine (pea), each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phenethylamine (pea). Your product may carry other ingredients that interact with Tramadol too, on top of Phenethylamine (pea) — 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 Phenethylamine (pea) 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 Phenethylamine (pea)
Top half

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

29 days ago today
Medication Tramadol
Top 10%

#284 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 Phenethylamine (pea)

What is Phenethylamine (pea)?

Phenethylamine (pea)
  • Mood support
  • Focus and concentration
  • Energy and pre-workout boost
  • Feeling of well-being
  • Athletic performance

Phenethylamine (PEA) is a natural compound made in the body and found in foods like chocolate; supplements are marketed for mood, focus, and energy. Reliable human research on the supplement is very limited, and it may raise blood pressure or heart rate, so people with heart or blood pressure problems should be cautious and check with a pharmacist or doctor first.

Read the full Phenethylamine (pea) 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 & Phenethylamine (pea)

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

0Major
186Moderate
0Minor
2,643No known interaction
186 Moderate 2,643 No interaction
Moderate

186 interactions

Showing 60 of 186 moderate interactions — see all 186 on the Phenethylamine (pea) page.

No interaction 2,643 drugs checked — show the list

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

Showing the 60 most looked-up of 2,643 medications checked with no known interaction — see the full Phenethylamine (pea) list.

See the full Phenethylamine (pea) 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
Phenethylamine (pea) 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 Phenethylamine (pea) and Tramadol Together: Common Questions

Can you take Phenethylamine (pea) 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 Phenethylamine (pea) 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 Phenethylamine (pea)?

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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.