Drug & supplement interaction

Phenethylamine (pea) + Cyclobenzaprine

Cyclobenzaprine brand names: Cyclobenzaprine, Flexeril, Cycloprine.

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

Phenethylamine (pea) has a moderate interaction with Cyclobenzaprine. 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 Cyclobenzaprine

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

Moderate

SEROTONERGIC DRUGS

Why this applies to Cyclobenzaprine

Cyclobenzaprine 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 gist for cyclobenzaprine (Flexeril): it has mild serotonin-related activity, and PEA can nudge up your brain's serotonin, norepinephrine, and dopamine. Stacking the two could, in theory, add up and raise the small chance of too much serotonin activity. Signs to watch for would be things like agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused. Cyclobenzaprine on its own already tends to cause drowsiness and dry mouth.

I want to be honest about the strength of this: it's theoretical, built on animal and lab data, not solid human studies. For most people the risk is low, especially since PEA breaks down fast in the body. Still, please run it by your pharmacist or doctor before combining them, particularly if you have heart or blood pressure concerns.

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 Cyclobenzaprine 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. Cyclobenzaprine)
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 Cyclobenzaprine

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 Cyclobenzaprine, 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 Cyclobenzaprine

This page covers Phenethylamine (pea) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclobenzaprine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lithium (major), Procaine (major) and St. John's Wort (major).

By severity: 5 major · 146 moderate · 46 minor.

Open the Cyclobenzaprine 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 Cyclobenzaprine 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 Cyclobenzaprine 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

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

29 days ago today
Medication Cyclobenzaprine
Top 25%

#301 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 Cyclobenzaprine

What Is Cyclobenzaprine Used For?

Brand names: Cyclobenzaprine, Flexeril, Cycloprine

Cyclobenzaprine tablets and extended-release capsules are used alongside rest and physical therapy to relieve muscle spasm caused by acute, painful musculoskeletal conditions — easing pain, tenderness, and limited movement. This use is intended for short-term treatment only (up to 2–3 weeks).

Tonmya, the sublingual (under-the-tongue) form of cyclobenzaprine, is separately indicated for the treatment of fibromyalgia in adults. It is not the same as the oral tablet or capsule formulations.

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

Can you take Phenethylamine (pea) with Cyclobenzaprine?
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 Cyclobenzaprine 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 Cyclobenzaprine and Phenethylamine (pea)?

Our pharmacists answer your medication & supplement questions — free.

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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.