Syrian Rue + Tramadol, Acetaminophen
Tramadol, Acetaminophen brand name: Tramacet.
Tramadol, Acetaminophen falls into 4 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, Syrian rue might increase the risk of serotonergic adverse effects, including serotonin syndrome, when taken with serotonergic drugs.
Read the full interaction reportSyrian Rue and Tramadol, Acetaminophen
These two interact in 4 distinct ways. Each one is explained separately below.
Why Are There 4 Interactions?
Syrian Rue interacts with whole categories of medication. Tramadol, Acetaminophen falls into 4 of those categories, so it can interact with Syrian Rue in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
SEROTONERGIC DRUGS
1 of 4Why this applies to Tramadol, Acetaminophen
Tramadol, Acetaminophen falls under SEROTONERGIC DRUGS — the group Syrian Rue interacts with.
Syrian rue contains harmaline and harmine, which have demonstrated strong, reversible inhibition of monoamine oxidase (MAO) A and weak inhibition of MAO B in animal and in vitro research. This may increase the risk for adverse effects with serotonergic drugs.
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.
Here's the concern with Tramacet, which combines tramadol and acetaminophen. The tramadol part doesn't just block pain, it also raises serotonin levels in your brain. Syrian Rue contains harmala alkaloids that act as MAO inhibitors, meaning they slow down an enzyme that normally clears extra serotonin. Put them together and serotonin can stack up too high, raising the risk of a reaction called serotonin syndrome. That can show up as agitation, a racing heart, sweating, shivering, muscle twitching, or confusion.
To be fair, this is mostly based on lab and animal research, so it's theoretical rather than proven in people. Still, because the consequences can be serious, I'd play it safe. Please check with your pharmacist or doctor before combining these.
- Kawanishi, K., Hashimoto, Y., Fujiwara, M., Kataoka, Y., and Ueki, S. Pharmacological characteristics of abnormal behavior induced by harmine with special reference to tremor in mice. J Pharmacobiodyn 1981;4(7):520-527. PubMed
- Herraiz, T., Gonzalez, D., Ancin-Azpilicueta, C., Aran, V. J., and Guillen, H. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol 2010;48(3):839-845. PubMed
- Fuller, R. W., Wong, C. J., and Hemrick-Luecke, S. K. MD 240928 and harmaline: opposite selectivity in antagonism of the inactivation of types A and B monoamine oxidase by pargyline in mice. Life Sci 1986;38(5):409-412. PubMed
- Abdel-Fattah, A. F., Matsumoto, K., Murakami, Y., Adel-Khalek, Gammaz H., Mohamed, M. F., and Watanabe, H. Central serotonin level-dependent changes in body temperature following administration of tryptophan to pargyline- and harmaline-pretreated rats. Ge PubMed
- Bergstrom, M., Westerberg, G., and Langstrom, B. 11C-harmine as a tracer for monoamine oxidase A (MAO-A): in vitro and in vivo studies. Nucl Med Biol 1997;24(4):287-293. PubMed
- Gerardy, J. Effect of moclobemide on rat brain monoamine oxidase A and B: comparison with harmaline and clorgyline. Prog Neuropsychopharmacol Biol Psychiatry 1994;18(4):793-802.
- Sacher, J., Houle, S., Parkes, J., Rusjan, P., Sagrati, S., Wilson, A. A., and Meyer, J. H. Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: an [11C]-harmine PET study. J Psychiatry
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
2 of 4Tramadol, Acetaminophen also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.
Syrian rue contains beta-carboline alkaloids, including harmine, harmaline, harmalol, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids can inhibit CYP2D6 enzymes.
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..
Here's the wrinkle with Tramacet. The tramadol part actually needs your CYP2D6 enzyme to be turned into its stronger painkilling form, so tramadol is partly a prodrug. Syrian Rue's harmala alkaloids can block that same enzyme (this is based on lab research, so it's theoretical rather than proven in people). That blocking could mean less of the active pain reliever is made, so you might get weaker pain relief. At the same time, parent tramadol can build up, which may raise the chance of nausea, dizziness, or feeling sedated.
There's a bigger worry too: Syrian Rue acts like an MAO inhibitor, and tramadol raises serotonin, so combining them can risk serotonin overload. Please check with your pharmacist or doctor before mixing these.
- Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.
HEPATOTOXIC DRUGS
3 of 4Tramadol, Acetaminophen also falls under HEPATOTOXIC DRUGS.
Cases of hepatotoxicity and hepatic failure have been reported in patients who ingested a large quantity (up to 100 grams) of Syrian rue seeds.
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.
Here's the gist with Tramacet (tramadol with acetaminophen). The acetaminophen part of this combo is processed by your liver, and in large amounts it can stress the liver. Syrian Rue's concern is similar: people who swallowed very large quantities of the seeds (up to about 100 grams) have had liver injury reported. So stacking two things that can both burden the liver is the worry here.
To be fair, this is a theoretical caution based on how these work, not strong human proof, and the liver cases involved huge seed amounts. Still, watch for signs like yellowing skin or eyes, dark urine, belly pain, or unusual tiredness. Before mixing these, please check with your pharmacist or doctor first.
- Yuruktumen, A., Karaduman, S., Bengi, F., and Fowler, J. Syrian rue tea: a recipe for disaster. Clin Toxicol (Phila) 2008;46(8):749-752. PubMed
- Berdai MA, Labib S, Harandou M. Peganum harmala L. Intoxication in a Pregnant Woman. Case Rep Emerg Med 2014;2014:783236.
- Ghizlane EA, Manal M, Ines HA, et al. Fatal poisoning of pregnant women by peganum harmala L.: a case reports. Ann Med Surg (Lond) 2021;68:102649. PubMed
- Durmaz Çelik N, Ger Akarsu F, Ozkan S, Özdemir AÖ, Aykac Ö, Memmedova F. Herbal teas can be harmful: a case of Peganum harmala induced coma in a patient with Parkinson's disease. Neurocase 2021;27(2):117-119.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
4 of 4Tramadol, Acetaminophen also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
Syrian rue contains beta-carboline alkaloids, including harmine, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids competitively inhibit CYP3A4 enzymes.
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.
Here's the thing with Tramacet, which combines tramadol and acetaminophen. Lab studies suggest the harmala alkaloids in Syrian Rue can block CYP3A4, one of the liver enzymes that helps break down tramadol. If that pathway slows, tramadol could build up, possibly leading to more drowsiness, dizziness, nausea, or even trouble breathing in higher amounts.
But there's a bigger concern I want to flag. Syrian Rue acts like an MAO inhibitor, and tramadol already raises serotonin. Combining them could push serotonin too high, causing agitation, sweating, a racing heart, or shaking. This warning is mostly theoretical, based on lab work, not human studies, but the serotonin risk makes me cautious. Please check with your pharmacist or doctor before mixing these.
- Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Syrian Rue Also Interacts With Other Medications
Syrian Rue has 1,121 moderate known drug interactions in our database — the Tramadol, Acetaminophen one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Syrian Rue
We haven’t checked that one against Syrian Rue yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Syrian Rue. Pick one to open its full report.
See Every Supplement That Interacts With Tramadol, Acetaminophen
This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol, Acetaminophen page lists 280 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).
By severity: 12 major · 224 moderate · 44 minor.
From our pharmacist’s overview on the Tramadol, Acetaminophen page
“The combinations I worry about most with tramadol and acetaminophen (Tramacet) involve anything that deepens drowsiness or strains the liver. Tramadol is an opioid, so sedating supplements like kava, along with alcohol in any form, can slow breathing on top of adding sleepiness, which is why this list deserves genuine care rather than…”
Reviewed by 2 · Jul 18, 2026
Where Syrian Rue and Tramadol, Acetaminophen 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.
#1,058 of 1,452 supplements looked up here in the last 7 days
#385 of 2,830 medications looked up here in the last 7 days
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.
About Syrian Rue
What is Syrian Rue?
- Traditional remedy for digestive complaints
- Used as a sedative or for mood
- Antimicrobial and antiparasitic folk use
- Used as a dye and incense
- Recreational psychoactive use
Syrian Rue (Peganum harmala) is a traditional plant whose seeds contain potent compounds called harmala alkaloids, including MAO-inhibiting harmine and harmaline. There is little reliable human evidence that it safely treats any condition, and it carries real risks of toxicity, so it is not recommended for self-treatment. Talk to a pharmacist or doctor before considering it.
Other Drugs & Syrian Rue
Browse every other medication we’ve checked against Syrian Rue — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
1,121 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Diphenhydramine ›
- Hydrocortisone ›
- Methylphenidate ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Amoxicillin ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Fenofibrate ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Glyburide ›
- Glycopyrrolate ›
- Methyltestosterone ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Allopurinol ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Ipratropium ›
- Miconazole ›
- Morphine Sulfate ›
- Phenylephrine ›
- Procainamide ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Dimenhydrinate ›
- Everolimus ›
Showing 60 of 1,121 moderate interactions — see all 1,121 on the Syrian Rue page.
No interaction 1,708 drugs checked — show the list
We also checked Syrian Rue against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Aspirin ›
- Ivermectin ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Ibuprofen ›
- Semaglutide ›
- Tirzepatide ›
- Bupropion ›
- Metformin ›
- Acyclovir ›
- Lisinopril ›
- Bendamustine ›
- Lamotrigine ›
- Gabapentin ›
- Pregabalin ›
- Azithromycin ›
- Isotretinoin ›
- Naproxen ›
- Levothyroxine, Liothyronine ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Roxithromycin ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Valsartan ›
- Levothyroxine Sodium ›
- Levetiracetam ›
- Spironolactone ›
- Factor 7a ›
- Thyroid Hormone ›
- Minoxidil ›
- Mitomycin ›
- Ezetimibe ›
- Cefaclor ›
- Phentermine, Topiramate ›
- Vancomycin ›
- Hethylphenidate Hcl ›
- Dirithromycin ›
- Bentoquatam ›
- Pentobarbitone ›
- Tenecteplase ›
- Hydroxychloroquine ›
- Digoxin ›
- Azelaic Acid ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Tocainide ›
- Acetylsalicylic Acid ›
- Pizotifen ›
- Hydrochlorothiazide ›
- Rocuronium ›
- Telmisartan ›
- Succimer ›
Showing the 60 most looked-up of 1,708 medications checked with no known interaction — see the full Syrian Rue list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Tramadol, Acetaminophen Is Linked to Lower Levels of One Nutrient
Natural Medicines records Tramadol, Acetaminophen as a medicine that can lower these. This is not an interaction with Syrian Rue — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Tramadol, Acetaminophen nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Syrian Rue and Tramadol, Acetaminophen Together: Common Questions
Can you take Syrian Rue with Tramadol, Acetaminophen?
Why are there 4 interactions listed for Syrian Rue and Tramadol, Acetaminophen?
How serious is the Syrian Rue and Tramadol, Acetaminophen interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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