Syrian Rue + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine brand name: Colrex.
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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, Codeine, Phenylephrine
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, Codeine, Phenylephrine 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, Codeine, Phenylephrine
Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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 Colrex combo has a few moving parts, and two of them matter here. Codeine and phenylephrine both nudge serotonin and other brain and blood-pressure chemicals. Syrian Rue acts like an MAO inhibitor, which slows the breakdown of those same chemicals. Stacking them could, in theory, push serotonin too high (a problem called serotonin syndrome) with symptoms like agitation, sweating, a racing heart, shivering, or confusion. Phenylephrine plus an MAOI can also spike blood pressure.
To be fair, this concern is theoretical and based on lab and animal studies, not real-world cases. Still, because Syrian Rue itself can be toxic, please check with your pharmacist or doctor before combining them.
- 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, Codeine, Phenylephrine 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 combination cold product has a wrinkle worth knowing about. The codeine in it is a prodrug, meaning your body has to convert it into morphine (the part that actually relieves pain and cough) using an enzyme called CYP2D6. Syrian Rue appears to block that very enzyme, at least in lab studies. So in theory, less of your codeine would turn into morphine, and you might get weaker pain or cough relief from it.
I want to be honest that this is theoretical, based on how the compounds behave in a test tube, not proven in people. Still, Syrian Rue carries real toxicity risks of its own, and it can clash with antidepressants too. 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
3 of 5Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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.
The piece of this combo product I'd watch here is the acetaminophen (the Tylenol part). Your liver does the heavy lifting of breaking it down, and large amounts of Syrian Rue seeds have been linked to liver injury and even liver failure in people who swallowed a lot of them. Stack a liver-stressing supplement on top of acetaminophen and, in theory, you could add to that strain.
To be fair, this is a theoretical concern based on how these substances behave, not strong human proof, and it really points at concentrated seed doses, not tiny amounts. Still, since acetaminophen already carries its own liver warnings, it's worth a quick chat with your pharmacist or doctor before mixing the two. Don't change either one on your own.
- 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, Codeine, Phenylephrine 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 combo product is a mix of four ingredients, and the one I'd watch most with Syrian Rue is the codeine. Lab studies suggest the harmala alkaloids in Syrian Rue can gently block CYP3A4, an enzyme that helps process codeine and acetaminophen. If that pathway slows down, more of the drug can hang around, which could mean extra drowsiness, dizziness, constipation, or slowed breathing from the codeine.
There's an added wrinkle here: Syrian Rue also acts like an MAO inhibitor, and pairing an MAOI with codeine and chlorpheniramine can raise the risk of serious reactions on its own. Honestly, this is mostly theoretical and based on test-tube work, but given those overlapping risks, please check with your pharmacist or doctor before combining them.
- 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, Codeine, Phenylephrine 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 product (Colrex) includes chlorpheniramine, an antihistamine with anticholinergic activity. The idea here is that Syrian Rue may raise levels of acetylcholine in the body, which could push back against the drying, calming part of chlorpheniramine's effect. In plain terms, the antihistamine's relief from a runny nose or sneezing might feel a bit weaker. Keep in mind this is only a theoretical concern based on animal studies, not real human data, so it may not amount to much at all.
I'd be more cautious about Syrian Rue's bigger issue: it acts like an MAO inhibitor, and the codeine and phenylephrine in this product can interact with MAOIs in ways that matter. Please check with your pharmacist or doctor before combining them.
- 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, Codeine, Phenylephrine 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, Codeine, Phenylephrine
This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page lists 338 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: 18 major · 275 moderate · 45 minor.
From our pharmacist’s overview on the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine page
“Someone taking Colrex is usually fighting a miserable cold, and cold season is also when people reach for herbal sleep aids and energy boosters, which is exactly where this list bites hardest. Colrex combines acetaminophen, chlorpheniramine, codeine, and phenylephrine, and 18 of its 338 supplement interactions rate major, enough to war…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction page
Where Syrian Rue and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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.
#857 of 1,452 supplements looked up here in the last 7 days
#305 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 ›
- Isotretinoin ›
- Tirzepatide ›
- Ibuprofen ›
- Docusate ›
- Valacyclovir ›
- Hydroxyurea ›
- Metformin ›
- Semaglutide ›
- Lisinopril ›
- Levothyroxine, Liothyronine ›
- Bupropion ›
- Bendamustine ›
- Azithromycin ›
- Pregabalin ›
- Lamotrigine ›
- Gabapentin ›
- Acyclovir ›
- Naproxen ›
- Candesartan Cilexetil ›
- Acetylsalicylic Acid ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Insulin Degludec, Liraglutide ›
- Ezetimibe ›
- Cyclopentolate ›
- Cephalexin ›
- Thyroid Hormone ›
- Mannitol ›
- Levetiracetam ›
- Roxithromycin ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Atenolol, Chlorthalidone ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Avatrombopag Maleate ›
- Valsartan ›
- Sacubitril, Valsartan ›
- Magnesium Hydroxide (otc Drug) ›
- Spironolactone ›
- Bupivacaine, Meloxicam ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Mitomycin ›
- Alginic Acid, Aluminum Hydroxide ›
- Atenolol ›
- Flutemetamol F-18 ›
- Amobarbital, Ephedrine Sulfate ›
- Canagliflozin, Metformin ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Enalapril Maleate ›
- Levothyroxine Sodium ›
- Aspirin, Butalbital ›
- Charcoal (otc Drug) ›
- Irbesartan, Hydrochlorothiazide ›
- Minoxidil ›
- Abrocitinib ›
- Articaine, Epinephrine ›
- Ephedrine, Phenobarbital, Theophylline ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Peginterferon Alfa-2a, Ribavirin ›
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, Codeine, Phenylephrine Is Linked to Lower Levels of One Nutrient
Natural Medicines records Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine 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, Chlorpheniramine, Codeine, Phenylephrine 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, Chlorpheniramine, Codeine, Phenylephrine Together: Common Questions
Can you take Syrian Rue with Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
Why are there 5 interactions listed for Syrian Rue and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine?
How serious is the Syrian Rue and Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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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.