Drug & supplement interaction

Phenethylamine (pea) + Hydrocodone/Chlorpheniramine

Hydrocodone/Chlorpheniramine brand name: Tussionex.

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

Phenethylamine (pea) has a moderate interaction with Hydrocodone/Chlorpheniramine. 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 Hydrocodone/Chlorpheniramine

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

Moderate

SEROTONERGIC DRUGS

Why this applies to Hydrocodone/Chlorpheniramine

Hydrocodone/Chlorpheniramine 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 with Tussionex (hydrocodone with chlorpheniramine). This combo isn't a classic serotonin drug, but hydrocodone (like many opioids) can nudge serotonin levels a bit, and PEA supplements are thought to raise serotonin, norepinephrine, and dopamine too. So in theory, stacking them could add up and slightly raise the chance of serotonin-related effects such as agitation, fast heartbeat, sweating, shivering, or tremor.

I want to be honest about the strength here: this is theoretical, based mostly on animal data, and real human cases with this pairing are basically nonexistent. PEA is also broken down very quickly in the body. Still, both can affect heart rate and blood pressure, so if you take Tussionex regularly or have heart concerns, run the PEA supplement past your pharmacist or doctor 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

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 Hydrocodone/Chlorpheniramine 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. Hydrocodone/Chlorpheniramine)
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 Hydrocodone/Chlorpheniramine

This page covers Phenethylamine (pea) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrocodone/Chlorpheniramine page lists 258 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: 12 major · 204 moderate · 42 minor.

From our pharmacist’s overview on the Hydrocodone/Chlorpheniramine page

“Tussionex (hydrocodone with chlorpheniramine) pairs an opioid with a sedating antihistamine, so anything that deepens drowsiness or slows breathing is a genuine hazard, and 78 of the 258 supplements on file do exactly that. Alcohol in any form tops that group, and kava carries a major rating for the same reason.”

Reviewed by 2 · Jul 18, 2026

Open the Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine 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

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

29 days ago today
Medication Hydrocodone/Chlorpheniramine
Steady interest

#1,715 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
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 Hydrocodone/Chlorpheniramine, 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 Hydrocodone/Chlorpheniramine supplement interactions › Every supplement checked against Hydrocodone/Chlorpheniramine, ranked by severity 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 Hydrocodone/Chlorpheniramine Together: Common Questions

Can you take Phenethylamine (pea) with Hydrocodone/Chlorpheniramine?
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 Hydrocodone/Chlorpheniramine 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 Hydrocodone/Chlorpheniramine 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.