Supplements and Tramadol hydrochloride.
Tramadol hydrochloride, sold under the brand names Zydol, Zamadol, Maxitram SR, Tramquel SR, Tramulief SR, Ultram, is an opioid analgesic.
Tramadol hydrochloride is an opioid analgesic. The class binds primarily to mu receptors, producing analgesia, sedation, respiratory depression at high doses, and a documented dependence profile. UK primary care prescribing has shifted substantially since the early 2010s away from chronic opioid use for non-cancer pain. The shift follows Faculty of Pain Medicine and NHS England stewardship guidance. The supplement surface includes three patterns. Additive CNS depression (alcohol, benzodiazepines, kava, valerian at higher doses, magnesium glycinate at high doses at bedtime). Constipation amplification (almost universal with chronic opioid use). And serotonergic concerns for the more serotonergic opioids when combined with SSRIs, SNRIs, MAOIs, 5-HTP, or rhodiola. Tramadol is the textbook example for the serotonergic concern, with pethidine to a lesser extent. The BNF and MHRA flag the combination.
Below are the 6 documented pairs we have explicitly assessed against Tramadol hydrochloride in the Distil database: 6 amber. The pairs cluster around 1 mechanism: Additive serotonergic activity. Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not on this list is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by supplement, and the missing-item form at the bottom of the page routes any uncatalogued supplement into our next curation pass.
Documented interactions
Last reviewed 9 June 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
Additive serotonergic activity
Amber Does 5-HTP interact with ?
5-HTP is the building block your body uses to make serotonin, and tramadol raises serotonin as part of how it works. Combining them may increase the risk of serotonin syndrome (agitation, sweating, tremor, shivering, a racing heart). Do not stack them without your prescriber's involvement, and be especially careful if your tramadol dose has recently increased.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does L-Tryptophan interact with ?
Tryptophan is the building block your body turns into serotonin, and tramadol raises serotonin as part of how it relieves pain. Taking them together may increase the risk of serotonin syndrome (agitation, sweating, tremor, shivering, muscle twitching, a racing heart). Do not stack them without your prescriber's involvement, especially around a dose change.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Rhodiola Rosea interact with ?
Rhodiola has mild effects on serotonin pathways, and tramadol raises serotonin as part of how it relieves pain. Taking them together may increase the risk of serotonin syndrome. Most people tolerate the combination, but watch for restlessness, sweating, tremor, or a racing heart, and talk to your prescriber before stacking them, especially if your tramadol dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does SAMe interact with ?
SAMe has its own antidepressant, serotonin-related activity, and tramadol raises serotonin as part of how it works. Taking them together may increase the risk of serotonin syndrome. Most people tolerate the combination, but watch for restlessness, sweating, tremor, shivering, or a racing heart, and tell your prescriber before stacking them, especially if your tramadol dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Saffron Extract interact with ?
Saffron has antidepressant, serotonin-related activity of its own, and tramadol raises serotonin as part of how it works. Taking them together may add to that serotonin effect. Most people tolerate the combination, but discuss it with your prescriber before stacking them, especially if your tramadol dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does St John's Wort interact with ?
Tramadol raises serotonin as part of how it relieves pain, and St John's Wort raises serotonin too. Taking them together may increase the risk of serotonin syndrome (agitation, sweating, tremor, shivering, a racing heart, confusion). This is not a strict do-not-combine like St John's Wort plus an SSRI, but it is one to avoid stacking without your prescriber's involvement, especially if your tramadol dose has recently gone up.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
What this list does not say. Pairs not flagged here are not implicitly safe. They are either not yet in our database, or fall outside our inclusion scope (food-supplement interactions only; for drug-drug interactions, the BNF is authoritative). Use the checker below to surface any supplement, and submit a missing item if you take something we have not catalogued.
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How we grade severity, choose what's in scope, and what we exclude.
Every call on this page is reasoned. We publish the full rubric for severity tiers, the medication inclusion logic, the evidence grades we accept, and what we deliberately leave out. About three thousand words. Worth reading once if you use this tool more than occasionally.
Read the full methodologyA full supplement review, built around you, not a generic stack.
The free checker answers one interaction question at a time. A Distil report reviews the bigger picture: your goals, diet, medications, current supplements and any blood results you provide, then shows what appears worth keeping, changing, adding or leaving out.
- what your diet already covers, so you are not adding a capsule for something food is already handling
- which evidence-graded compounds are worth considering for your goals, and which were considered but left out
- what to keep, change or stop from what you already take, plus the order to introduce anything new
- how your medications and complete supplement stack fit together, with daily timing and a clear point for reassessment
The interaction check is one section of the full report. You also get the reasoning behind each recommendation and the evidence references used.
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