Drug & supplement interaction

Phenethylamine (pea) + Safinamide Mesylate

Safinamide Mesylate brand name: Xadago.

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

Safinamide Mesylate falls into 2 drug categories that Phenethylamine (pea) can interact with; the most serious is rated moderate. Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of serotonergic adverse effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Phenethylamine (pea) and Safinamide Mesylate

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Phenethylamine (pea) interacts with whole categories of medication. Safinamide Mesylate falls into 2 of those categories, so it can interact with Phenethylamine (pea) in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

SEROTONERGIC DRUGS

1 of 2

Why this applies to Safinamide Mesylate

Safinamide Mesylate 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 key thing about Xadago (safinamide): it's an MAO-B inhibitor, which means it slows down one of the very enzymes that normally clears phenethylamine (PEA) out of your system. PEA also nudges up brain chemicals like serotonin, norepinephrine, and dopamine. So when you put the two together, PEA can build up and its stimulant-like effects can be amplified. On top of that, both can push serotonin in the same direction.

In theory that raises the risk of serotonin syndrome (agitation, sweating, fast heartbeat, tremor, high blood pressure) or blood vessel tightening. I'll be honest: this concern is based mostly on animal data, and PEA has been used with a related drug fairly safely. Still, with an MAO-B inhibitor I'd play it safe. Please check with your doctor or pharmacist before combining them.

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
Moderate

MONOAMINE OXIDASE INHIBITORS (MAOIs)

2 of 2

Safinamide Mesylate also falls under MONOAMINE OXIDASE INHIBITORS (MAOIs).

Theoretically, taking phenethylamine concomitantly with MAOIs may increase adverse effects.
In humans, phenethylamine is oxidized by MAO-B to form the inactive metabolite phenylacetic acid. Animal research shows that administering an MAOI prior to phenethylamine increases the amphetamine-like effects of phenethylamine. However, low-quality clinical research has used phenethylamine with selegiline, an 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 simple version: your Parkinson's medicine Xadago (safinamide) is an MAO-B inhibitor, which means it slows down the very enzyme that normally clears PEA out of your body. PEA leans hard on MAO-B for its breakdown, so if that pathway is blocked, PEA can hang around longer and build up. In theory, that could exaggerate its stimulant-like effects, things like a faster heartbeat, jitteriness, or a bump in blood pressure.

I want to be honest about the evidence here. This concern comes mostly from animal and lab work, and some low-quality human studies with a similar drug didn't show problems. Still, since PEA can nudge blood pressure on its own, I'd play it safe and talk with your doctor or pharmacist before pairing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sabelli H, Fink P, Fawcett J, et al. Sustained antidepressant effect of PEA replacement. J Neuropsychiatry Clin Neurosci. 1996;8(2):168-71.
  2. Mantegazza P, Riva M. Amphetamine-like activity of beta-phenethylamine after a monoamine oxidase inhibitor in vivo. Journal of Pharmacy and Pharmacology. 1963;151(1):472-8.
  3. Grimsby J, Toth M, Chen K, et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet. 1997;17(2):206-10.
  4. Lindemann L, Hoener MC. A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol Sci. 2005;26(5):274-81. 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 Safinamide Mesylate one above is among them. If you take anything else, check it against the full list below.

Moderate 186 No known interaction 2,644 (incl. Safinamide Mesylate)
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.

Everything else you take

See Every Supplement That Interacts With Safinamide Mesylate

This page covers Phenethylamine (pea) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Safinamide Mesylate page lists 81 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Bitter Orange (major), Brewer's Yeast (major) and Cowhage (major).

By severity: 14 major · 56 moderate · 11 minor.

Open the Safinamide Mesylate 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 Safinamide Mesylate 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 Safinamide Mesylate 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

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

29 days ago today
Medication Safinamide Mesylate
Top 25%

#559 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 Safinamide

What Is Safinamide Used For?

Brand name: Xadago

Safinamide (brand name Xadago) is used as an add-on treatment to levodopa/carbidopa in people with Parkinson’s disease who have “off” episodes. “Off” episodes are times when Parkinson’s symptoms return or get worse between doses of your usual medicine.

Xadago has been shown to work only when taken together with levodopa/carbidopa.

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

Can you take Phenethylamine (pea) with Safinamide Mesylate?
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 2 interactions listed for Phenethylamine (pea) and Safinamide Mesylate?
Safinamide Mesylate belongs to more than one drug category, and Phenethylamine (pea) 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 Phenethylamine (pea) and Safinamide Mesylate 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 Safinamide Mesylate 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.