Syrian Rue + Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.
Acetaminophen, Aspirin, Caffeine falls into 3 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with hepatotoxic drugs.
Read the full interaction reportSyrian Rue and Acetaminophen, Aspirin, Caffeine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Syrian Rue interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 3 of those categories, so it can interact with Syrian Rue in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
HEPATOTOXIC DRUGS
1 of 3Why this applies to Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine falls under HEPATOTOXIC DRUGS — the group Syrian Rue interacts with.
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 concern with combining Syrian rue and a product like Excedrin Migraine. The acetaminophen piece is the one that can be hard on your liver, especially in higher doses or with regular use. Syrian rue, particularly in large amounts, has been linked to liver injury too. So the worry is simply that stacking two things that stress the liver could add up and raise your risk of harm.
I want to be honest about how solid this is: it's theoretical, based mostly on reports of people swallowing very large amounts of Syrian rue seeds (up to 100 grams). Small culinary exposures are unlikely to matter. Still, because acetaminophen and your liver don't mix well in excess, please check with your pharmacist or doctor before combining them.
- 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
2 of 3Acetaminophen, Aspirin, Caffeine 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.
Let's talk about combining Syrian Rue with Excedrin-type products that mix acetaminophen, aspirin, and caffeine. The concern on file is that compounds in Syrian Rue may slow down a liver enzyme called CYP3A4. If that enzyme is blocked, drugs that rely on it can build up a bit. For this combo, caffeine is the piece most worth watching, so you might feel jittery, anxious, have a racing heart, or trouble sleeping if its levels climb.
Honestly, this is a theoretical interaction based on lab research, not real human cases, so I wouldn't lose sleep over it. Still, Syrian Rue carries its own toxicity risks, so please check with your pharmacist or doctor before using it with anything.
- 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.
CAFFEINE
3 of 3Acetaminophen, Aspirin, Caffeine also falls under CAFFEINE.
Syrian rue contains the constituent harmaline. Animal research suggests that a combination of caffeine and harmaline increases the intensity and duration of harmaline-induced tremors.
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 deal with Excedrin: the part that interacts with Syrian Rue is the caffeine, not the acetaminophen or aspirin. Syrian Rue contains harmaline, and animal studies suggest that pairing it with caffeine can make harmaline-related tremors (shakiness) stronger and longer-lasting. On top of that, caffeine on its own can already cause jitteriness, a racing heart, and trouble sleeping, so combining the two could amplify that wired, shaky feeling.
I'll be honest, this is a theoretical concern based mostly on lab and animal research, not solid human studies, so I don't want to alarm you. Still, Syrian Rue carries real toxicity risks of its own. Please check with your pharmacist or doctor before combining them.
- Al-Deeb, S., Al-Moutaery, K., Arshaduddin, M., Biary, N., and Tariq, M. Effect of acute caffeine on severity of harmaline induced tremor in rats. Neurosci Lett 2002;325(3):216-218. PubMed
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 Acetaminophen, Aspirin, Caffeine 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 Acetaminophen, Aspirin, Caffeine
This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 supplements it has a documented interaction with, worst first, each one explained.
The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Ephedra (major).
By severity: 13 major · 312 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Aspirin, Caffeine page
“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”
Reviewed by 2 · Jul 18, 2026
Where Syrian Rue and Acetaminophen, Aspirin, Caffeine 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.
#1,003 of 1,452 supplements looked up here in the last 7 days
#64 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 ›
- Ivermectin ›
- Aspirin ›
- Docusate ›
- Tirzepatide ›
- Ibuprofen ›
- Hydroxyurea ›
- Valacyclovir ›
- Semaglutide ›
- Metformin ›
- Lisinopril ›
- Bupropion ›
- Bendamustine ›
- Isotretinoin ›
- Acyclovir ›
- Pregabalin ›
- Lamotrigine ›
- Azithromycin ›
- Gabapentin ›
- Naproxen ›
- Levothyroxine, Liothyronine ›
- Candesartan Cilexetil ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Cyclopentolate ›
- Cephalexin ›
- Mannitol ›
- Roxithromycin ›
- Levetiracetam ›
- Ezetimibe ›
- Levothyroxine Sodium ›
- Phentermine, Topiramate ›
- Pegunigalsidase Alfa-iwxj ›
- Spironolactone ›
- Thyroid Hormone ›
- Daptomycin ›
- Valsartan ›
- Acetylsalicylic Acid ›
- Mitomycin ›
- Hexobarbitone ›
- Factor 7a ›
- Cefaclor ›
- Minoxidil ›
- Bentoquatam ›
- Hethylphenidate Hcl ›
- Azelaic Acid ›
- Pizotifen ›
- Hydroxychloroquine ›
- Rocuronium ›
- Salbutamol Sulfate ›
- Insulin Degludec, Liraglutide ›
- Alglucosidase Alpha ›
- Flutemetamol F-18 ›
- Ribavirin Aerosol ›
- Insulin Human, Sodium Chloride ›
- Sacubitril, Valsartan ›
- Canagliflozin, Metformin ›
- Vancomycin ›
- Digoxin ›
- Casanthranol, Docusate ›
- Hydrochlorothiazide, Lisinopril ›
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
Acetaminophen, Aspirin, Caffeine Is Linked to Lower Levels of 5 Nutrients
Natural Medicines records Acetaminophen, Aspirin, Caffeine 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 Acetaminophen, Aspirin, Caffeine 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 Acetaminophen, Aspirin, Caffeine Together: Common Questions
Can you take Syrian Rue with Acetaminophen, Aspirin, Caffeine?
Why are there 3 interactions listed for Syrian Rue and Acetaminophen, Aspirin, Caffeine?
How serious is the Syrian Rue and Acetaminophen, Aspirin, Caffeine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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