NutriStack
L-Tryptophan and Tramadol, contraindicated.
Tramadol has serotonergic activity in addition to its opioid effect, and L-Tryptophan is a serotonin precursor. Combining them can increase serotonin signaling and raise the risk of serotonin syndrome, which can cause agitation, tremor, sweating, diarrhea, fever, muscle rigidity, seizures, and rarely death. Risk is higher if you also take antidepressants, migraine triptans, linezolid, MDMA, or St. John's Wort.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- L-Tryptophan and Tramadol
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. Tramadol has serotonergic activity in addition to its opioid effect, and L-Tryptophan is a serotonin precursor. Combining them can increase serotonin signaling and raise the risk of serotonin syndrome, which can cause agitation, tremor, sweating, diarrhea, fever, muscle rigidity, seizures, and rarely death. Risk is higher if you also take antidepressants, migraine triptans, linezolid, MDMA, or St. John's Wort.
Mechanism. Tramadol inhibits serotonin reuptake and can trigger serotonin toxicity, especially with other serotonergic agents. L-Tryptophan can increase serotonin synthesis, adding a separate mechanism that increases serotonergic tone.
Recommendation. Avoid L-Tryptophan while taking tramadol. Do not try to manage the risk by separating doses; the concern is overlapping serotonergic effects over time. Seek urgent care for clonus, high fever, severe agitation, confusion, or seizure.
Sources (2)
- Beakley BD, Kaye AM, Kaye AD. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review. Pain Physician. 2015;18(4):395-400. PMID 26218943
- Ambarapu S, Tilwe K, Pandit RA, Gaikwad BV, Meshram HM, Choudhary J, et al. Serotonin Syndrome Masquerading as Status Epilepticus following Ingestion of Tranylcypromine and Clomipramine and L-Tryptophan: A Case Report. Ann Indian Acad Neurol. 2022;25(5):960-962. PMID 36561019
Stack Score
How this pair moves the number.
Effect on the composite score
If both L-Tryptophan and Tramadol are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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