Drug & supplement interaction

L-tryptophan + Phenelzine Sulfate

Phenelzine Sulfate brand name: Nardil.

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

Phenelzine Sulfate falls into 2 drug categories that L-tryptophan can interact with; the most serious is rated major. Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

L-tryptophan and Phenelzine Sulfate

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

L-tryptophan interacts with whole categories of medication. Phenelzine Sulfate falls into 2 of those categories, so it can interact with L-tryptophan in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 2

Why this applies to Phenelzine Sulfate

Phenelzine Sulfate 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 where I want to slow down with you. Phenelzine (Nardil) is an MAO inhibitor, and that's actually a bigger deal than the simple drowsiness note on file. MAOIs block the enzyme that breaks down serotonin, so serotonin levels are already running high. L-tryptophan is a building block your body turns into more serotonin. Stacking these together can push serotonin too far and trigger a dangerous reaction called serotonin syndrome, with symptoms like agitation, sweating, a racing heart, muscle twitching, high fever, and confusion.

On top of that, tryptophan can add to the sedation, so you may feel extra tired or foggy. Please don't combine these on your own. Talk with your doctor or pharmacist first, since this is a combination that genuinely needs caution.

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
Moderate

SEROTONERGIC DRUGS

2 of 2

Phenelzine Sulfate also falls under SEROTONERGIC DRUGS.

Theoretically, combining L-tryptophan with serotonergic drugs might cause additive serotonergic effects.
L-tryptophan is a precursor to serotonin. Theoretically, combining serotonergic drugs with L-tryptophan might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders.
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 key thing about phenelzine (Nardil): it's an MAOI, which means it blocks the enzyme that normally breaks serotonin back down. So your brain already holds onto more serotonin than usual. Now add L-tryptophan, which your body turns into 5-HTP and then into serotonin, and you've got more serotonin being made and less being cleared away. Those two pile on top of each other.

That combo can push serotonin too high, raising the risk of serotonin syndrome (agitation, fast heartbeat, sweating, shaking, high blood pressure, confusion). This warning is based on how the drugs work rather than lots of case reports, but with an MAOI I'd treat it seriously. Please check with your doctor or pharmacist before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol 1993;31:603-30. PubMed
  2. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. 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 Phenelzine Sulfate one above is among them. If you take anything else, check it against the full list below.

Major 247 Moderate 146 No known interaction 2,437 (incl. Phenelzine Sulfate)
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 Phenelzine Sulfate

This page covers L-tryptophan only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenelzine Sulfate page lists 144 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), Bitter Orange (major) and Brewer's Yeast (major).

By severity: 18 major · 111 moderate · 15 minor.

From our pharmacist’s overview on the Phenelzine Sulfate page

“Few medications demand as much dietary and supplement care as phenelzine sulfate (Nardil), an older MAOI antidepressant, and this list backs that up, with 18 of its 144 recorded interactions rated major. The two dominant themes are sedation and blood pressure.”

Reviewed by 2 · Jul 18, 2026

Open the Phenelzine Sulfate 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 Phenelzine Sulfate 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 Phenelzine Sulfate 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

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

29 days ago today
Medication Phenelzine Sulfate
Top half

#1,120 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 Phenelzine

What Is Phenelzine Used For?

Brand name: Nardil

Phenelzine is used to treat depression — specifically the types described as atypical, nonendogenous, or neurotic depression. This often includes people who have a mix of anxiety and depression, or who have phobic or hypochondriacal features (strong fears about illness or physical symptoms).

It is generally not the first antidepressant a doctor will try. It is best suited for patients who have already tried other antidepressants without enough relief. There is less evidence supporting its use in severe depression with classic biological features (called endogenous depression).

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

Can you take L-tryptophan with Phenelzine Sulfate?
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.
Why are there 2 interactions listed for L-tryptophan and Phenelzine Sulfate?
Phenelzine Sulfate belongs to more than one drug category, and L-tryptophan 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 L-tryptophan and Phenelzine Sulfate 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 Phenelzine Sulfate 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.