Drug & supplement interaction

Syrian Rue + Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine

Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine brand name: Vicks NyQuil.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Dextromethorphan, Doxylamine, 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 report
SeverityModerate
LikelihoodPossible
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Syrian Rue and Acetaminophen, Dextromethorphan, Doxylamine, 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, Dextromethorphan, Doxylamine, 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).

Moderate

SEROTONERGIC DRUGS

1 of 5

Why this applies to Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine

Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine 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 of NyQuil that matters most with Syrian Rue: the dextromethorphan (the cough suppressant). Dextromethorphan raises serotonin activity in the brain, and Syrian Rue acts like a natural MAO inhibitor, which slows the breakdown of serotonin. Stacking the two together could push serotonin too high and, in theory, trigger serotonin syndrome, with symptoms like agitation, a racing heart, sweating, shivering, muscle twitching, or confusion.

To be fair, this warning is based on lab and animal research, not solid human studies, so the real-world risk isn't well proven. Still, combining an MAOI-type product with dextromethorphan is a pairing pharmacists genuinely try to avoid. Please check with your pharmacist or doctor before taking these together.

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, Dextromethorphan, Doxylamine, Pseudoephedrine 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

Here's the piece that matters with NyQuil: one of its ingredients, dextromethorphan (the cough suppressant), is cleared by a liver enzyme called CYP2D6. Lab studies suggest the harmala alkaloids in Syrian Rue can block that enzyme. If it's blocked, dextromethorphan can build up and hit you harder, which may mean extra drowsiness, dizziness, confusion, or in larger amounts a spaced-out, restless feeling.

There's a bigger concern, though. Syrian Rue acts like an MAO inhibitor, and mixing MAOIs with dextromethorphan can rarely trigger serotonin-related problems. This is mostly theoretical here, but I'd play it safe. Please check with your pharmacist or doctor before combining the 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

HEPATOTOXIC DRUGS

3 of 5

Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine 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

NyQuil contains acetaminophen, which is the part that matters most here. Acetaminophen is one of the most common causes of liver injury when it builds up, especially at high doses or with anything else that stresses the liver. In large amounts, Syrian Rue seeds have been linked to liver damage and even liver failure. So the worry is a possible added burden on the liver when you combine the two.

To be clear, this concern is mostly theoretical and based on how each one behaves, not on solid human studies of the pair. It also seems tied to very large quantities of Syrian Rue. Still, since acetaminophen already has a narrow safety margin for the liver, I'd check with your pharmacist or doctor before mixing them, and watch for signs like belly pain, yellowing skin or unusual fatigue.

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, Dextromethorphan, Doxylamine, Pseudoephedrine 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

NyQuil packs four ingredients, and a couple of them lean on the liver enzyme CYP3A4 to be cleared, with dextromethorphan (the cough suppressant) being the main one. Lab studies hint that the harmala alkaloids in Syrian rue can slow that enzyme down. If that happened in real life, the dextromethorphan could build up a bit and leave you feeling more drowsy, dizzy, or foggy than usual.

The bigger worry here is separate from CYP3A4: Syrian rue acts like an MAO inhibitor, and mixing MAOIs with dextromethorphan and the decongestant pseudoephedrine can be genuinely risky (think dangerous blood pressure spikes or serotonin problems). This enzyme part is only theoretical, but please loop in your pharmacist before combining these.

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, Dextromethorphan, Doxylamine, Pseudoephedrine 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

Here's the piece of NyQuil that matters most for this question: the doxylamine. Doxylamine is an antihistamine that works partly by blocking acetylcholine, which is why it causes that classic drowsiness, dry mouth, and grogginess. Syrian Rue's harmala alkaloids may push acetylcholine levels in the other direction, so in theory they could blunt some of doxylamine's effects.

I want to be honest that this is theoretical, based only on animal research, not human studies. The bigger concern is Syrian Rue acting as an MAO inhibitor alongside the dextromethorphan and pseudoephedrine in NyQuil, which is a more serious mix. I'd really steer clear of combining these and check with your pharmacist or doctor first.

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 1,121 moderate known drug interactions in our database — the Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine 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, Dextromethorphan, Doxylamine, Pseudoephedrine

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine page lists 286 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 · 227 moderate · 45 minor.

Open the Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine interaction page

How much people look this up

Where Syrian Rue and Acetaminophen, Dextromethorphan, Doxylamine, 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.

Supplement Syrian Rue
Steady interest

#1,032 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine
Steady interest

#1,926 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
1,121Moderate
0Minor
1,708No known interaction
Moderate

1,121 interactions

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
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

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Pharmacist Counseling Corner

Taking Syrian Rue and Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine Together: Common Questions

Can you take Syrian Rue with Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine?
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, Dextromethorphan, Doxylamine, Pseudoephedrine?
Acetaminophen, Dextromethorphan, Doxylamine, Pseudoephedrine 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, Dextromethorphan, Doxylamine, Pseudoephedrine 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

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