Drug & supplement interaction

L-tryptophan + acetaminophen, dextromethorphan, doxylamine

acetaminophen, dextromethorphan, doxylamine brand name: NyQuil.

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

L-tryptophan has a major interaction with acetaminophen, dextromethorphan, doxylamine. Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

L-tryptophan and acetaminophen, dextromethorphan, doxylamine

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

Major

CNS DEPRESSANTS

Why this applies to acetaminophen, dextromethorphan, doxylamine

acetaminophen, dextromethorphan, doxylamine falls under CNS DEPRESSANTS — the group L-tryptophan interacts with.

Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.
Clinical research shows that L-tryptophan can cause fatigue and drowsiness.
Severity Major Likelihood Probable Evidence B

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to keep in mind: NyQuil already contains two ingredients that can make you sleepy, dextromethorphan (the cough suppressant) and doxylamine (a sedating antihistamine). Adding L-tryptophan, which on its own tends to cause drowsiness and fatigue, can stack on top of that. The result may be feeling more groggy, slow, or foggy than you'd expect from NyQuil alone.

There's also a small extra wrinkle: both dextromethorphan and tryptophan nudge serotonin upward, so in theory combining them isn't ideal. In real life, the bigger and more likely concern is simply too much sedation. I'd avoid driving or anything that needs full alertness, and check with your pharmacist before pairing them, especially if you take other sleep aids.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lieberman HR, Corkin S, Spring BJ. The effects of dietary neurotransmitter precursors on human behavior. Am J Clin Nutr 1985;42:366-70. 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

L-tryptophan Also Interacts With Other Medications

L-tryptophan has 247 major, 146 moderate known drug interactions in our database — the acetaminophen, dextromethorphan, doxylamine one above is one of them. If you take anything else, check it against the full list below.

Major 247 Moderate 146 No known interaction 2,437 (incl. acetaminophen, dextromethorphan, doxylamine)
Taking anything else?

Check Another of Your Medications Against L-tryptophan

Covers the 2,830 medications we’ve checked against L-tryptophan. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With acetaminophen, dextromethorphan, doxylamine

This page covers L-tryptophan only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the acetaminophen, dextromethorphan, doxylamine page lists 106 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: 8 major · 78 moderate · 20 minor.

From our pharmacist’s overview on the acetaminophen, dextromethorphan, doxylamine page

“NyQuil (acetaminophen, dextromethorphan, doxylamine) is designed to make you drowsy, and that is exactly where most of its supplement interactions live. Seventy-eight of the 106 ingredients on this list add to its sedation, and the eight rated major, alcohol and kava among them, can push a nighttime cold remedy toward serious depressio…”

Reviewed by 2 · Jul 18, 2026

Open the acetaminophen, dextromethorphan, doxylamine interaction page

One more smart check

Taking L-tryptophan as Part of a Dietary Supplement Product? Check It for Interactions

We hold 5 real supplement products containing L-tryptophan, each one broken down to its full ingredient list — and combination products often carry several ingredients besides L-tryptophan. Your product may carry other ingredients that interact with acetaminophen, dextromethorphan, doxylamine too, on top of L-tryptophan — 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 L-tryptophan and acetaminophen, dextromethorphan, doxylamine 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 L-tryptophan
Steady interest

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

29 days ago today
Medication acetaminophen, dextromethorphan, doxylamine
Top 5%

#65 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 L-tryptophan

What is L-tryptophan?

L-tryptophan
  • Sleep problems
  • Low mood and depression
  • Anxiety
  • Premenstrual symptoms
  • Appetite and food cravings

L-tryptophan is an essential amino acid the body uses to make serotonin and melatonin, and people take it to support sleep and mood. The evidence for supplement use is limited and mixed, and there are real safety concerns, so talk to a pharmacist or doctor before trying it.

Read the full L-tryptophan monograph & all interactions
Keep checking

Other Drugs & L-tryptophan

Browse every other medication we’ve checked against L-tryptophan — both the ones with a known interaction and the ones without. Select any drug for the full detail.

247Major
146Moderate
0Minor
2,436No known interaction
247 Major 146 Moderate 2,436 No interaction
Major

247 interactions

Showing 60 of 247 major interactions — see all 247 on the L-tryptophan page.

Moderate

146 interactions

Showing 60 of 146 moderate interactions — see all 146 on the L-tryptophan page.

No interaction 2,436 drugs checked — show the list

We also checked L-tryptophan against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,436 medications checked with no known interaction — see the full L-tryptophan list.

See the full L-tryptophan interactions page
See every supplement checked against acetaminophen, dextromethorphan, doxylamine, 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
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Pharmacist Counseling Corner

Taking L-tryptophan and acetaminophen, dextromethorphan, doxylamine Together: Common Questions

Can you take L-tryptophan with acetaminophen, dextromethorphan, doxylamine?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the L-tryptophan and acetaminophen, dextromethorphan, doxylamine interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About acetaminophen, dextromethorphan, doxylamine and L-tryptophan?

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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.