Drug & supplement interaction

Syrian Rue + Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine brand name: Multi Symptom Cold Relief.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine 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 report
SeverityModerate
LikelihoodPossible
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Interaction report

Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

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, Phenylpropanolamine 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).

Moderate

SEROTONERGIC DRUGS

1 of 5

Why this applies to Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine falls under SEROTONERGIC DRUGS — the group Syrian Rue interacts with.

Theoretically, Syrian rue might increase the risk of serotonergic adverse effects, including serotonin syndrome, when taken with serotonergic drugs.
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.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the piece to focus on in this combo cold product: the dextromethorphan (the cough suppressant). It nudges serotonin activity in the brain. Syrian Rue acts like an MAO inhibitor, which slows the breakdown of serotonin. Put the two together and serotonin can climb higher than your body wants. That raises the theoretical risk of serotonin syndrome, with symptoms like agitation, a racing heart, sweating, shivering, muscle twitching, or confusion.

Honestly, this concern is based on lab and animal data, not solid human studies, so I don't want to scare you. But Syrian Rue's MAOI effect is potent, and the phenylpropanolamine in this product can also push blood pressure up. Please check with your pharmacist or doctor before mixing them.

References
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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.
  7. 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
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 5

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP2D6.
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.
Severity Moderate Likelihood Probable Evidence D

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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Let's focus on the dextromethorphan piece of this cold combo, since that's the cough suppressant in the mix. Your body relies on an enzyme called CYP2D6 to break it down. Syrian Rue's harmala alkaloids appear (in lab studies) to slow that enzyme down, so dextromethorphan could pile up higher than usual. That might mean more drowsiness, dizziness, or feeling foggy, and at higher levels even agitation or restlessness.

There's an extra wrinkle: Syrian Rue acts like an MAO inhibitor, and mixing MAOIs with dextromethorphan can rarely trigger serotonin overload. Honestly, this is mostly theory rather than proven harm, but it's a combo I'd steer clear of. Please check with your pharmacist or doctor first.

References
  1. 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.
Moderate

HEPATOTOXIC DRUGS

3 of 5

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine also falls under HEPATOTOXIC DRUGS.

Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with 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.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combination cold product contains acetaminophen, the same pain and fever reliever found in Tylenol. Acetaminophen is already known to stress the liver if you take too much, which is why staying under the daily limit matters. Syrian rue carries its own liver concern: in reports where people swallowed very large amounts of the seeds (up to around 100 grams), liver injury and even liver failure have shown up.

The worry here is mostly theoretical and based on how these two might add up, not on solid human studies pairing them. Still, doubling up on things that can tax the liver isn't wise. Watch for yellowing skin or eyes, dark urine, belly pain, or unusual tiredness, and check with your pharmacist or doctor before mixing these.

References
  1. 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
  2. Berdai MA, Labib S, Harandou M. Peganum harmala L. Intoxication in a Pregnant Woman. Case Rep Emerg Med 2014;2014:783236.
  3. 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
  4. 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.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 5

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP3A4.
Syrian rue contains beta-carboline alkaloids, including harmine, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids competitively inhibit CYP3A4 enzymes.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combo cold product carries several ingredients, and one of them, dextromethorphan (the cough suppressant), is partly broken down by the CYP3A4 enzyme. In lab studies, compounds in Syrian Rue appear to slow that enzyme down. In theory, that could let dextromethorphan build up a bit, leading to more drowsiness, dizziness, or feeling foggy.

There's a bigger concern here, though. Syrian Rue acts like an MAO inhibitor, and mixing that with dextromethorphan can raise the risk of serotonin-related problems (agitation, racing heart, confusion). Keep in mind this CYP3A4 link is theoretical, based only on test-tube data. Still, please check with your pharmacist or doctor before pairing these two.

References
  1. 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.
Moderate

ANTICHOLINERGIC DRUGS

5 of 5

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine also falls under ANTICHOLINERGIC DRUGS.

Theoretically, Syrian rue might decrease the effects of anticholinergic drugs.
Syrian rue contains harmine. Animal research suggests that intravenous administration of harmine potentiates the effects of acetylcholine or increases acetylcholine levels.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combo cold product has a few ingredients, but the one that matters here is chlorpheniramine, an antihistamine that works partly by blocking acetylcholine in the body (an anticholinergic action). Syrian Rue contains harmine, which animal studies suggest can do the opposite and raise acetylcholine levels. So in theory, Syrian Rue could blunt some of the chlorpheniramine's effects, meaning a bit less drying and possibly less drowsiness.

I want to be clear that this is theoretical, based only on lab and animal data, so the real-world impact is uncertain. Honestly, the bigger concern is that Syrian Rue acts like an MAO inhibitor, which can interact dangerously with the dextromethorphan and decongestant in this product. Please check with your pharmacist or doctor before mixing them.

References
  1. Slotkin, T. A. and DiStefano, V. Cardiovascular and respiratory effects of harmine. Proc Soc Exp Biol Med 1970;133(2):662-664. PubMed
  2. 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.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • 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.
Evidence the quality of the studies behind the rating (graded A–D)
  • 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.

Keep it in perspective

Syrian Rue Also Interacts With Other Medications

Syrian Rue has 1,123 moderate known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Syrian Rue

Covers the 2,830 medications we’ve checked against Syrian Rue. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine page lists 300 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 · 241 moderate · 45 minor.

Open the Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine interaction page

How much people look this up

Where Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine 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.

Supplement Syrian Rue
Steady interest

#790 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine
Top 5%

#67 of 2,830 medications looked up here in the last 7 days

29 days ago today

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.

Supplement

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.

Read the full Syrian Rue monograph & all interactions
Keep checking

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.

0Major
1,123Moderate
0Minor
1,706No known interaction
Moderate

1,123 interactions

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.

Showing the 60 most looked-up of 1,706 medications checked with no known interaction — see the full Syrian Rue list.

Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

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

Keep exploring
Pharmacist Counseling Corner

Taking Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine Together: Common Questions

Can you take Syrian Rue with Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 5 interactions listed for Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine?
Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine belongs to more than one drug category, and Syrian Rue interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Syrian Rue and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine and Syrian Rue?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.