Syrian Rue + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine brand name: Hycomine Compound.
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine falls into 5 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, Chlorpheniramine, Hydrocodone, 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, Caffeine, Chlorpheniramine, Hydrocodone, 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).
CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES
1 of 5Why this applies to Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 worth knowing about this combination product. One of its ingredients, hydrocodone, is a prodrug that your liver enzyme CYP2D6 converts into a stronger painkiller called hydromorphone. Syrian Rue's harmala alkaloids can block CYP2D6 in lab studies, so in theory less hydrocodone gets activated, which could mean weaker pain relief than expected.
For the other pieces, like chlorpheniramine, slowed breakdown could nudge up drowsiness or dry mouth. Honestly though, this is theoretical, based on test-tube data, not real patient outcomes. There's a bigger concern: Syrian Rue acts like an MAO inhibitor, and mixing MAOIs with opioids and decongestants can be genuinely risky. 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.
HEPATOTOXIC DRUGS
2 of 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 combination product I want to focus on is the acetaminophen (Tylenol), since that's the ingredient that can stress the liver. On its own, acetaminophen is processed by the liver and is hard on it in high amounts. Syrian Rue carries its own concern here too: people who swallowed very large quantities of the seeds (think tens of grams) have had reports of liver injury.
So the worry is mostly additive strain on the liver. Honestly, this is a theoretical concern based on how these things behave, not strong human proof, and culinary or tiny amounts are unlikely to matter. Still, with liver issues, warning signs like yellowing skin, dark urine, belly pain, or unusual tiredness deserve attention. Please check with your pharmacist or doctor before mixing these.
- 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 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 combination product (Hycomine Compound) contains hydrocodone, the ingredient I'd watch most closely here. Lab studies suggest the harmala alkaloids in Syrian Rue can gently block CYP3A4, one of the enzymes that helps your body clear hydrocodone. If that enzyme is slowed, hydrocodone could build up a bit, which may mean stronger or longer-lasting effects like extra drowsiness, dizziness, constipation, or slowed breathing. The chlorpheniramine and the opioid together already cause sedation, so anything that adds to it deserves caution.
Keep in mind this is theoretical, based on test-tube data rather than real patient reports, so I don't want to alarm you. Still, Syrian Rue is risky on its own. Please check with your pharmacist or doctor before mixing the two.
- 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
4 of 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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 (Hycomine Compound) includes chlorpheniramine, an antihistamine with anticholinergic action, meaning it works partly by quieting the chemical messenger acetylcholine. That's what gives it some of its drying and sedating effects. Syrian Rue contains harmine, and in animal studies harmine seemed to nudge acetylcholine levels up. In theory, that could push back against chlorpheniramine and slightly dampen its effect.
I want to be honest that this is a theoretical concern based on lab and animal data, not real cases in people, so I wouldn't lose sleep over it. The bigger worry is Syrian Rue itself, which acts as an MAO inhibitor and can be genuinely toxic, a real problem alongside the hydrocodone and caffeine here. Please run this by 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
CAFFEINE
5 of 5Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine 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 is a combination product, and the piece that matters here is the caffeine. Your Hycomine Compound has caffeine added to it, and that's the ingredient Syrian Rue may butt heads with. The concern is mostly theoretical and comes from animal studies, not solid human data, so I don't want you to panic.
Here's the idea: harmaline, one of the compounds in Syrian Rue, can trigger tremors, and adding caffeine seemed to make those tremors stronger and longer-lasting in animals. So in real life you might notice more shakiness, jitteriness, a racing heart, or trouble sleeping. Keep in mind there are other active ingredients here too (hydrocodone, chlorpheniramine), and Syrian Rue itself carries real toxicity risks. Please check with your pharmacist or doctor before mixing the two.
- 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, Caffeine, Chlorpheniramine, Hydrocodone, 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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine
This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page lists 339 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: 17 major · 276 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine page
“If you've been prescribed Hycomine Compound (acetaminophen, caffeine, chlorpheniramine, hydrocodone, and phenylephrine) for a hard cough or cold, this list deserves real attention, since 17 of the 339 flagged supplements are rated major and most of those magnify what the medicine already does. Anything sedating, alcohol included, stack…”
Reviewed by 2 · Jul 18, 2026
Open the Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction page
Where Syrian Rue and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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.
#999 of 1,452 supplements looked up here in the last 7 days
#167 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 ›
- Lamotrigine ›
- Pregabalin ›
- 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 ›
- Mitomycin ›
- Acetylsalicylic Acid ›
- Hexobarbitone ›
- Factor 7a ›
- Cefaclor ›
- Minoxidil ›
- Hethylphenidate Hcl ›
- Bentoquatam ›
- Azelaic Acid ›
- Pizotifen ›
- Hydroxychloroquine ›
- Rocuronium ›
- Ribavirin Aerosol ›
- Salbutamol Sulfate ›
- Alglucosidase Alpha ›
- Insulin Degludec, Liraglutide ›
- Flutemetamol F-18 ›
- Vancomycin ›
- Insulin Human, Sodium Chloride ›
- Digoxin ›
- Canagliflozin, Metformin ›
- Sacubitril, Valsartan ›
- Hydrochlorothiazide, Lisinopril ›
- Triptorelin ›
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, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine Is Linked to Lower Levels of 2 Nutrients
Natural Medicines records Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, 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:
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, Chlorpheniramine, Hydrocodone, Phenylephrine Together: Common Questions
Can you take Syrian Rue with Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
Why are there 5 interactions listed for Syrian Rue and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine?
How serious is the Syrian Rue and Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine and Syrian Rue?
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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.