Drug & supplement interaction

Syrian Rue + Codeine, Papaverine

Codeine, Papaverine brand name: Copavin.

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

Syrian Rue has a moderate interaction with Codeine, Papaverine. Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodProbable
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Syrian Rue and Codeine, Papaverine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Why this applies to Codeine, Papaverine

Codeine, Papaverine 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. Codeine is what we call a prodrug, meaning it's fairly weak until your body converts it into morphine, and the enzyme that does that conversion is CYP2D6. Syrian Rue's harmala alkaloids can block CYP2D6 in lab studies, so in theory they could slow that switch from codeine to morphine. The likely result is less pain relief, not more, since you'd make less of the active morphine.

I'll be honest, this is based on test-tube data, not real patient studies, so the size of the effect is uncertain. But Syrian Rue is also a strong MAO inhibitor and carries genuine toxicity risks on its own, so please don't pair it with codeine without first checking with your pharmacist or doctor.

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.

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 Codeine, Papaverine one above is one of them. If you take anything else, check it against the full list below.

Moderate 1,123 No known interaction 1,707 (incl. Codeine, Papaverine)
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 Codeine, Papaverine

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Codeine, Papaverine page lists 145 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), American Mistletoe (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 8 major · 114 moderate · 23 minor.

From our pharmacist’s overview on the Codeine, Papaverine page

“Codeine combined with papaverine (Copavin) is an opioid product, and I read its supplement list as one that calls for genuine care. More than half of the 145 entries pile sedation on top of the drug's own, and the standouts are everyday alcohol (beer and wine each carry a major rating, well documented in people) and kava, combinations…”

Reviewed by 2 · Jul 18, 2026

Open the Codeine, Papaverine interaction page

How much people look this up

Where Syrian Rue and Codeine, Papaverine 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

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

29 days ago today
Medication Codeine, Papaverine
Top 25%

#497 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
1,123 Moderate 1,706 No 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.

See the full Syrian Rue interactions page
See every supplement checked against Codeine, Papaverine, 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 Codeine, Papaverine supplement interactions › Every supplement checked against Codeine, Papaverine, 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 Codeine, Papaverine Together: Common Questions

Can you take Syrian Rue with Codeine, Papaverine?
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.
How serious is the Syrian Rue and Codeine, Papaverine 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 Codeine, Papaverine 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.