Syrian Rue + Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine
Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine brand names: Tylenol Cold Ex Strength, Children's Tylenol Cold Plus Cough.
Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine falls into 5 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 Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine
These two interact in 5 distinct ways. Each one is explained separately below.
Why Are There 5 Interactions?
Syrian Rue interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine falls into 5 of those categories, so it can interact with Syrian Rue in 5 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
SEROTONERGIC DRUGS
1 of 5Why this applies to Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine
Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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.
This cold and cough combo includes dextromethorphan, the cough suppressant, which gently raises serotonin activity in the brain. Syrian Rue acts like a natural MAO inhibitor, and MAO is one of the enzymes that helps clear serotonin. Put them together and you could, in theory, push serotonin too high. That can cause what's called serotonin syndrome: agitation, a racing heart, sweating, shivering, muscle twitching, or feeling confused.
I'll be honest with you, this concern comes mostly from lab and animal studies, not from solid human cases, so the real-world risk isn't well proven. Still, because Syrian Rue is potent and unpredictable, I'd run this by your pharmacist or doctor before combining the two rather than guessing.
- 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 5Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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..
This is a multi-ingredient cold medicine, and the piece that matters most here is the dextromethorphan (the cough suppressant). Your body relies on an enzyme called CYP2D6 to clear it. Syrian Rue's harmala alkaloids can block that enzyme, so dextromethorphan may build up. That could mean more dizziness, drowsiness, or feeling foggy.
There's a second, bigger concern. Syrian Rue acts like an MAO inhibitor, and combining MAOIs with dextromethorphan (and the pseudoephedrine in this product) can raise the risk of serotonin syndrome and blood pressure spikes. The CYP2D6 part is theoretical, based on lab studies, but the MAOI risk is well known and serious. Please don't pair these without checking with your pharmacist or doctor first.
- 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 5Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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.
This combination cold product includes acetaminophen (Tylenol), which your liver has to process. On its own, acetaminophen is hard on the liver at high doses. Syrian rue has its own concern here: large amounts of the seeds (people have swallowed up to about 100 grams) have been linked to liver injury and even liver failure. Put two things that can stress the liver together, and at least in theory you could raise the risk of harm to that organ.
I want to be honest that this is a theoretical worry based on how these substances behave, not something proven in careful studies, and normal cold-medicine dosing is the bigger factor. Still, watch for yellowing skin or eyes, dark urine, belly pain, or nausea, and never exceed the acetaminophen label. Please run this by 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 5Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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.
This cold and cough combo packs a few ingredients, and one of them, dextromethorphan (the cough suppressant), is partly broken down by an enzyme called CYP3A4. On paper, Syrian Rue may slow that enzyme down, which could let dextromethorphan build up a bit and lead to more drowsiness, dizziness, or feeling foggy. Keep in mind this is only a theoretical concern based on lab studies, not real patient reports.
The bigger worry is actually a separate one: Syrian Rue acts like an MAO inhibitor, and dextromethorphan plus pseudoephedrine can react badly with MAOIs, raising the risk of dangerously high blood pressure or serotonin problems. Please check with your pharmacist or doctor before combining 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.
ANTICHOLINERGIC DRUGS
5 of 5Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine also falls under ANTICHOLINERGIC DRUGS.
Syrian rue contains harmine. Animal research suggests that intravenous administration of harmine potentiates the effects of acetylcholine or increases acetylcholine levels.
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 combination cold product includes chlorpheniramine, an antihistamine with drying (anticholinergic) effects that help dry up a runny nose. The idea here is that Syrian Rue may raise levels of acetylcholine in the body, which could work against that drying action. In plain terms, the chlorpheniramine piece might feel a little less effective. I want to stress this is purely theoretical and comes from animal studies using injected compounds, not real-world human data, so I would not lose sleep over it.
The other ingredients (acetaminophen, dextromethorphan, pseudoephedrine) are not really affected by this particular mechanism. That said, Syrian Rue acts like an MAO inhibitor, and mixing MAOIs with dextromethorphan and pseudoephedrine can be genuinely risky on its own. Please check with your pharmacist or doctor before combining these.
- Slotkin, T. A. and DiStefano, V. Cardiovascular and respiratory effects of harmine. Proc Soc Exp Biol Med 1970;133(2):662-664. PubMed
- Javoy, F., Euvrard, C., Herbet, A., Bockaert, J., Enjalbert, A., Agid, Y., and Glowinski, J. Lack of involvement of dopaminergic and GABA neurones in the inhbitory effect of harmaline on the activity of striatal cholinergic neurones in the rat. Naunyn Sch
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, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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, Chlorpheniramine, Dextromethorphan, Pseudoephedrine
This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine page lists 301 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), Ephedra (major) and Grapefruit (major).
By severity: 14 major · 242 moderate · 45 minor.
From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine page
“Because Tylenol Cold Extra Strength packs four drugs into one dose (acetaminophen, chlorpheniramine, dextromethorphan, and pseudoephedrine), its supplement list runs to 301 ingredients, and 14 carry a major rating, so I'd approach this one with real care. The biggest hazards mirror the drugs themselves.”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine interaction page
Where Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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.
#822 of 1,452 supplements looked up here in the last 7 days
#74 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 ›
- Tirzepatide ›
- Ibuprofen ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Isotretinoin ›
- Semaglutide ›
- Metformin ›
- Lisinopril ›
- Bupropion ›
- Bendamustine ›
- Pregabalin ›
- Lamotrigine ›
- Acyclovir ›
- Azithromycin ›
- Gabapentin ›
- Levothyroxine, Liothyronine ›
- Naproxen ›
- Candesartan Cilexetil ›
- Cyclopentolate ›
- Acetylsalicylic Acid ›
- Cephalexin ›
- Ezetimibe ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Levetiracetam ›
- Thyroid Hormone ›
- Mannitol ›
- Roxithromycin ›
- Spironolactone ›
- Valsartan ›
- Phentermine, Topiramate ›
- Insulin Degludec, Liraglutide ›
- Levothyroxine Sodium ›
- Atenolol ›
- Mitomycin ›
- Canagliflozin, Metformin ›
- Minoxidil ›
- Amobarbital, Ephedrine Sulfate ›
- Alginic Acid, Aluminum Hydroxide ›
- Magnesium Hydroxide (otc Drug) ›
- Daptomycin ›
- Abrocitinib ›
- Acenocoumarol ›
- Cefaclor ›
- Hydroxychloroquine ›
- Pegunigalsidase Alfa-iwxj ›
- Hydrochlorothiazide ›
- Sacubitril, Valsartan ›
- Insulin Human, Sodium Chloride ›
- Digoxin ›
- Bupivacaine, Meloxicam ›
- Factor 7a ›
- Hexobarbitone ›
- Bentoquatam ›
- Hydrochlorothiazide, Valsartan ›
- Flutemetamol F-18 ›
- Irbesartan, Hydrochlorothiazide ›
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, Chlorpheniramine, Dextromethorphan, Pseudoephedrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine 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:
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, Chlorpheniramine, Dextromethorphan, Pseudoephedrine Together: Common Questions
Can you take Syrian Rue with Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine?
Why are there 5 interactions listed for Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine?
How serious is the Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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