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Medication · opioid

Supplements and Tramadol hydrochloride.

Every documented pair, every citation. Below: 6 documented pairs grouped by mechanism.

Tramadol hydrochloride, sold under the brand names Zydol, Zamadol, Maxitram SR, Tramquel SR, Tramulief SR, 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, or 5-HTP. 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

Additive serotonergic activity

Amber 5-HTP

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.

Reviewer-flagged: awaiting clinical-reviewer sign-off.

Amber L-Tryptophan

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.

Reviewer-flagged: awaiting clinical-reviewer sign-off.

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.

Reviewer-flagged: awaiting clinical-reviewer sign-off.

Amber SAMe

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.

Reviewer-flagged: awaiting clinical-reviewer sign-off.

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.

Reviewer-flagged: awaiting clinical-reviewer sign-off.

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.

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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For adults over 18. This tool gives evidence-graded information, not medical advice. Always discuss changes with your GP, especially if you take any medication, are pregnant, breastfeeding, or have a serious health condition.
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How we decide

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.

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Distil's interactions database is reviewed and updated every quarter. We grade evidence transparently and publish our methodology, including every database change, at /about/methodology. This tool is information, not a substitute for clinical judgement. If you take medication and supplements together, your GP or pharmacist can review your full regimen against your medical history. If you want a full personalised stack reasoned against this same database, the Distil report is the next step up.