Drug & supplement interaction

Syrian Rue + Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate brand name: Anacin w/ Codeine.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Aspirin, Caffeine, Codeine Phosphate falls into 3 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 report
SeverityModerate
LikelihoodProbable
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Syrian Rue and Aspirin, Caffeine, Codeine Phosphate

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Syrian Rue interacts with whole categories of medication. Aspirin, Caffeine, Codeine Phosphate falls into 3 of those categories, so it can interact with Syrian Rue in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Syrian Rue interacts with.

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 wrinkle with this combo. The codeine part of your Anacin w/ Codeine is a prodrug, which means it doesn't do much until your body converts it into morphine using an enzyme called CYP2D6. Syrian Rue's harmala alkaloids appear to block that very enzyme. So instead of building codeine up, blocking CYP2D6 would likely make less morphine, meaning weaker pain relief for you.

I'll be honest though, this is theoretical and comes from lab testing, not real patients, so the real-world effect is uncertain. The bigger concern with Syrian Rue is its MAO-inhibiting toxicity on its own. Please run this by your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Aspirin, Caffeine, Codeine Phosphate 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 pill mixes aspirin, caffeine, and codeine. The piece to watch here is the caffeine, which your body partly clears using the CYP3A4 enzyme. In lab studies, the harmala compounds in Syrian Rue can slow that enzyme down, so caffeine could linger longer and feel stronger. That might mean a jittery, racing heart, trouble sleeping, or feeling wound up.

I want to be honest that this is a theoretical concern based on test-tube data, not real patient reports, so don't panic. That said, Syrian Rue also acts as an MAO inhibitor, which raises bigger safety questions when mixed with codeine and caffeine. Please check with your pharmacist or doctor before combining the two.

Contact Dr. Brian directly if you have additional questions on this interaction
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

CAFFEINE

3 of 3

Aspirin, Caffeine, Codeine Phosphate also falls under CAFFEINE.

Theoretically, taking Syrian rue with caffeine might increase the risk of adverse effects, including tremors.
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.
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 product has three parts (aspirin, caffeine, and codeine), but the concern here is the caffeine. Syrian rue contains harmaline, and in animal studies pairing harmaline with caffeine made tremors stronger and longer-lasting. So the worry is that taking the two together could leave you feeling jittery, shaky, or anxious, with a racing heart or trouble sleeping.

I'll be honest: this is a theoretical interaction based mostly on lab and animal work, not solid human evidence, so don't panic if you've taken them once. Still, Syrian rue isn't something I'd recommend self-treating with given its own toxicity risks. If you're thinking about using it, please check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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.

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 Aspirin, Caffeine, Codeine Phosphate one above is among them. If you take anything else, check it against the full list below.

Moderate 1,121 No known interaction 1,709 (incl. Aspirin, Caffeine, Codeine Phosphate)
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 Aspirin, Caffeine, Codeine Phosphate

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Codeine Phosphate page lists 398 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 Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Caffeine, Codeine Phosphate page

“Anacin with Codeine combines aspirin, caffeine, and codeine, and each of the three picks up its own supplement problems, so this is a list worth real caution. Just over half of the 398 ingredients here, 202 of them, can add to aspirin's blood-thinning action and raise bleeding risk.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Codeine Phosphate interaction page

How much people look this up

Where Syrian Rue and Aspirin, Caffeine, Codeine Phosphate 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

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

29 days ago today
Medication Aspirin, Caffeine, Codeine Phosphate
Top half

#709 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
1,121 Moderate 1,708 No 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

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 1,708 medications checked with no known interaction — see the full Syrian Rue list.

See the full Syrian Rue interactions page
See every supplement checked against Aspirin, Caffeine, Codeine Phosphate, ranked by severity
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
Syrian Rue monograph › Uses, safety, and every drug interaction in one place Aspirin, Caffeine, Codeine Phosphate supplement interactions › Every supplement checked against Aspirin, Caffeine, Codeine Phosphate, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Syrian Rue and Aspirin, Caffeine, Codeine Phosphate Together: Common Questions

Can you take Syrian Rue with Aspirin, Caffeine, Codeine Phosphate?
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 3 interactions listed for Syrian Rue and Aspirin, Caffeine, Codeine Phosphate?
Aspirin, Caffeine, Codeine Phosphate 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 Aspirin, Caffeine, Codeine Phosphate 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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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.