Drug & supplement interaction

L-tryptophan + Phenobarbital

Phenobarbital brand names: Phenobarbital, Solfoton, Luminal.

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

L-tryptophan has a major interaction with Phenobarbital. 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 Phenobarbital

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

Major

CNS DEPRESSANTS

Why this applies to Phenobarbital

Phenobarbital 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: phenobarbital already works by calming down activity in your brain, which is why it can make you feel sleepy, slow, or foggy. L-tryptophan can add to that drowsiness because your body turns it into serotonin and melatonin, which also nudge you toward sleep. Put the two together and the sedation can stack up.

So you might feel more tired than usual, have a harder time concentrating, or feel unsteady on your feet. This isn't about phenobarbital building up in your blood; it's simply two sleepy effects landing at the same time. The concern is reasonable, not just theoretical. Before adding tryptophan, please check with your pharmacist or doctor first.

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 Phenobarbital 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. Phenobarbital)
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.

From our Q&A

Questions About L-tryptophan or Phenobarbital

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers L-tryptophan or Phenobarbital, 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 Phenobarbital

This page covers L-tryptophan only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital page lists 174 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 Henbane (major).

By severity: 10 major · 143 moderate · 21 minor.

Open the Phenobarbital 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 Phenobarbital 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 Phenobarbital 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

#1,025 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Phenobarbital
Top half

#1,135 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
Medication

About Phenobarbital

What Is Phenobarbital Used For?

Brand names: Phenobarbital, Solfoton, Luminal

Phenobarbital tablets and oral solutions are used to treat generalized and partial seizures and as a sedative. Phenobarbital Sodium injection is used as a long-term anticonvulsant for generalized tonic-clonic and focal seizures, for emergency control of acute convulsive episodes (including status epilepticus), for sedation, short-term treatment of insomnia, and as a preanesthetic. It is also used in pediatric patients as an anticonvulsant and sedative, including before and after surgery.

Sezaby (phenobarbital injection, intravenous) is specifically indicated for the treatment of neonatal seizures in term and preterm infants. It is not approved for use in adolescents or adults.

See full Phenobarbital drug information
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 Phenobarbital, 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
L-tryptophan monograph › Uses, safety, and every drug interaction in one place Phenobarbital supplement interactions › Every supplement checked against Phenobarbital, ranked by severity Phenobarbital 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 L-tryptophan and Phenobarbital Together: Common Questions

Can you take L-tryptophan with Phenobarbital?
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 Phenobarbital 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 Phenobarbital and L-tryptophan?

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.