Syrian Rue + Acetaminophen, Caffeine, Codeine
Acetaminophen, Caffeine, Codeine brand names: Gesic C8, Gesic C15, Lenoltec 2, Gesic C30, Lenoltec 3, and others.
Acetaminophen, Caffeine, Codeine falls into 4 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP2D6.
Read the full interaction reportSyrian Rue and Acetaminophen, Caffeine, Codeine
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. Acetaminophen, Caffeine, Codeine 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).
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
1 of 4Why this applies to Acetaminophen, Caffeine, Codeine
Acetaminophen, Caffeine, Codeine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Syrian Rue interacts with.
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 this combination: the codeine part of your pill is a prodrug. Your body has to convert it into morphine using a liver enzyme called CYP2D6 before it can relieve pain. Syrian Rue's harmala compounds may block that same enzyme, at least based on lab studies. So in theory, less of your codeine would turn into active morphine, meaning you might get weaker pain relief rather than more side effects.
I'll be honest, this is theoretical and comes from test-tube data, not human studies, so I wouldn't panic. But Syrian Rue carries its own real toxicity risks and acts as an MAO inhibitor, which raises other safety concerns. Please check with your pharmacist or doctor before pairing 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
2 of 4Acetaminophen, Caffeine, Codeine 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 thing to know about combining Syrian Rue with this pill: the concern is really about your liver. The acetaminophen part of this combo (the Tylenol component) is processed by your liver, and in large amounts it can stress that organ. Syrian Rue seeds, especially in big concentrated doses, have been linked to liver injury too. So the worry is two liver stressors stacking up.
I'll be honest, this is a theoretical concern based on how these things work, not solid human studies, and the reported liver problems came from people eating huge quantities of seeds (around 100 grams). Still, since acetaminophen already has a liver ceiling, it's wise not to add another liver burden. Please check with your pharmacist or doctor before mixing the two.
- 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
3 of 4Acetaminophen, Caffeine, Codeine 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 gist for this combo pill. The harmala compounds in Syrian Rue can slow down a liver enzyme called CYP3A4 in lab studies, and that enzyme helps process several medicines. For the codeine piece, this is where it gets tricky: codeine is a prodrug, meaning your body has to convert it (mostly through a different enzyme, CYP2D6) into morphine to relieve pain. Syrian Rue is also a strong MAO inhibitor, and mixing MAO inhibitors with opioids like codeine is the bigger worry, since it can lead to serious reactions and heavy sedation.
The CYP3A4 part here is only theoretical, based on test-tube data, so I wouldn't panic. Still, given the MAOI overlap, please check with your pharmacist or doctor before using these together.
- 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
4 of 4Acetaminophen, Caffeine, Codeine 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.
This combo pill mixes acetaminophen for pain, a little caffeine, and codeine. The piece that overlaps with Syrian Rue here is the caffeine. Syrian Rue contains harmala alkaloids (like harmaline), and in animal studies, pairing those with caffeine seemed to make tremors (shakiness) stronger and last longer. So in theory, taking the two together could leave you feeling jittery, shaky, or wired, with a racing heart.
I'll be honest: this is a theoretical concern based on lab and animal work, not solid human proof, so I don't want to alarm you. Still, Syrian Rue carries real toxicity risks on its own. Please run it by your pharmacist or doctor before combining anything with this medication.
- 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 1,123 moderate known drug interactions in our database — the Acetaminophen, Caffeine, Codeine 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, Caffeine, Codeine
This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Codeine page lists 303 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 Ephedra (major).
By severity: 15 major · 244 moderate · 44 minor.
Where Syrian Rue and Acetaminophen, Caffeine, Codeine 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.
#826 of 1,452 supplements looked up here in the last 7 days
#221 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 “”.
1,123 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 1,123 moderate interactions — see all 1,123 on the Syrian Rue page.
No interaction 1,706 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 ›
- Isotretinoin ›
- Tirzepatide ›
- Ibuprofen ›
- Levothyroxine, Liothyronine ›
- Docusate ›
- Metformin ›
- Semaglutide ›
- Hydroxyurea ›
- Valacyclovir ›
- Lisinopril ›
- Bupropion ›
- Azithromycin ›
- Pregabalin ›
- Gabapentin ›
- Lamotrigine ›
- Naproxen ›
- Bendamustine ›
- Acyclovir ›
- Candesartan Cilexetil ›
- Acetylsalicylic Acid ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Insulin Degludec, Liraglutide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Aminophylline, Amobarbital, Ephedrine ›
- Aspirin, Butalbital ›
- Atenolol, Chlorthalidone ›
- Enalapril Maleate ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Ephedrine, Phenobarbital, Theophylline ›
- Bismuth Subcarbonate, Calcium Carbonate, Opium ›
- Ezetimibe ›
- Cephalexin ›
- Sacubitril, Valsartan ›
- Aspirin, Ethoheptazine, Meprobamate ›
- Levetiracetam ›
- Cyclopentolate ›
- Insulin Aspart, Insulin Degludec ›
- Canagliflozin, Metformin ›
- Candesartan Cilexetil, Hydrochlorothiazide ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Saxagliptin, Metformin Xr ›
- Sodium Bicarbonate (otc Drug) ›
- Efgartigimod Alfa-fcab ›
- Amobarbital, Ephedrine Sulfate ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Alginic Acid, Aluminum Hydroxide ›
- Measles, Mumps, Rubella Virus Live ›
- Cytomegalovirus Immune Globulin ›
- Thyroid Hormone ›
- Fosinopril, Hydrochlorothiazide ›
- Mannitol ›
- Famotidine, Ibuprofen ›
- Peginterferon Alfa-2a, Ribavirin ›
- Aminolevulinic Acid Hydrochloride ›
- Sulfadiazine, Trimethoprim ›
- Valsartan ›
- Bupivacaine, Meloxicam ›
Showing the 60 most looked-up of 1,706 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, Caffeine, Codeine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Codeine 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, Caffeine, Codeine 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, Caffeine, Codeine Together: Common Questions
Can you take Syrian Rue with Acetaminophen, Caffeine, Codeine?
Why are there 4 interactions listed for Syrian Rue and Acetaminophen, Caffeine, Codeine?
How serious is the Syrian Rue and Acetaminophen, Caffeine, Codeine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Caffeine, Codeine and Syrian Rue?
Our pharmacists answer your medication & supplement questions — free.
This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.