Drug & supplement interaction

Phenethylamine (pea) + Selegiline

Selegiline brand names: Carbex, Eldepryl, Emsam, Zelapar.

Moderate Interaction
The bottom line Moderate

Selegiline 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 Selegiline

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. Selegiline 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 Selegiline

Selegiline 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 important piece with selegiline: it's an MAO-B inhibitor, and your body normally relies on MAO-B to quickly break down phenethylamine (PEA). So while selegiline is on board, PEA can hang around longer and build up instead of clearing fast. On top of that, animal studies suggest PEA can nudge up serotonin, norepinephrine, and dopamine, the same messengers selegiline already boosts.

Stacked together, the theoretical concern is too much of these signals at once, which could mean things like a spike in blood pressure, a racing or pounding heart, headache, agitation, or sweating. To be fair, some low-quality research actually used PEA with selegiline without obvious trouble, so this is more caution than alarm. Still, please don't add a PEA supplement without checking with your pharmacist or doctor first.

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

Selegiline 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 thing with this pairing: your body normally clears PEA very quickly using an enzyme called MAO-B. Selegiline's whole job is to block MAO-B, so when you add a PEA supplement on top of it, that PEA can't be broken down as fast and may pile up. That could amplify PEA's stimulant-like effects, with concerns like a faster heartbeat, jitteriness, or a bump in blood pressure.

I want to be honest about the evidence, though. This is mostly theoretical and based on animal studies, and some low-quality human research actually used the two together without obvious problems. Small food amounts of PEA (like chocolate) aren't the worry here; concentrated supplements are. Before combining them, please run it by your pharmacist or doctor first.

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 Selegiline one above is among them. If you take anything else, check it against the full list below.

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 Selegiline

This page covers Phenethylamine (pea) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Selegiline page lists 102 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 · 75 moderate · 13 minor.

Open the Selegiline 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 Selegiline 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 Selegiline 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

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

29 days ago today
Medication Selegiline
Steady interest

#2,183 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 Selegiline

What Is Selegiline Used For?

Brand names: Carbex, Eldepryl, Emsam, Zelapar

Selegiline is used as an add-on treatment for people with Parkinson's disease who are already taking levodopa/carbidopa but are finding that the medication's effects are wearing off or becoming less reliable. It is not used alone — it only works as part of a combination approach.

In clinical studies, adding selegiline helped reduce the amount of daily levodopa needed, cut down on "off" time (periods when symptoms break through), and improved things like tremor, speech, movement, and overall daily function.

See full Selegiline 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
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
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

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Pharmacist Counseling Corner

Taking Phenethylamine (pea) and Selegiline Together: Common Questions

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

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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.