Drug & supplement interaction

Syrian Rue + Meperidine, Promethazine

Meperidine, Promethazine brand names: Meprozine, Mepergan.

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

Meperidine, Promethazine falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Syrian Rue and Meperidine, Promethazine

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. Meperidine, Promethazine 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

SEROTONERGIC DRUGS

1 of 3

Why this applies to Meperidine, Promethazine

Meperidine, Promethazine 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

This combo product pairs meperidine (a pain medicine also known as Demerol) with promethazine. Meperidine stands out because, on top of pain relief, it nudges up serotonin in the body. Syrian Rue acts like a natural MAO inhibitor, meaning it slows down an enzyme that normally clears extra serotonin. Put them together and serotonin can climb too high, which is why pairing meperidine with MAO inhibitors is a well-known concern.

If that happens, you could feel agitated, sweaty, or shaky, with a racing heart, high fever, or muscle stiffness. That reaction (serotonin syndrome) can turn serious. The evidence here is mostly lab and animal based, but with meperidine the caution is real. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
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 3

Meperidine, Promethazine 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 bigger concern with this combo. Meperidine (the opioid in Meprozine/Mepergan) should never be paired with a strong MAO inhibitor, and Syrian Rue acts like one. Together they can trigger a dangerous reaction called serotonin syndrome, with high fever, agitation, muscle stiffness, racing heart, and dangerously high or low blood pressure. This is a well-known, serious problem with meperidine specifically.

On top of that, the harmala compounds in Syrian Rue may slow the CYP2D6 enzyme that helps clear both meperidine and promethazine. In theory that could let these drugs build up, meaning more drowsiness, dizziness, and slowed breathing. This part is theoretical, but the MAOI risk is real. Please don't combine them without talking to your doctor or pharmacist first.

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

ANTICHOLINERGIC DRUGS

3 of 3

Meperidine, Promethazine 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

Let's talk about Meprozine, which is a combo of meperidine (a pain reliever) and promethazine. The promethazine part has anticholinergic activity, meaning it blocks a brain and body chemical called acetylcholine. That's part of how it calms nausea and adds sedation.

Now here's the theory: Syrian Rue contains harmine, and in animal studies it seemed to raise acetylcholine levels. If that holds true in people, it could push back against promethazine's effect and slightly weaken it. Honestly though, this is theoretical and based only on lab and animal data, so it's not a strong concern.

The bigger worry is something different: meperidine plus an MAO-inhibiting plant like Syrian Rue can be a dangerous mix. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Meperidine, Promethazine 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. Meperidine, Promethazine)
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 Meperidine, Promethazine

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Meperidine, Promethazine page lists 207 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Henbane (major).

By severity: 10 major · 160 moderate · 37 minor.

From our pharmacist’s overview on the Meperidine, Promethazine page

“Meprozine combines meperidine, an opioid painkiller, with promethazine, a sedating antihistamine, so it already slows the brain on two fronts. I would read this list of 207 supplements and herbal ingredients with genuine care, starting with the 10 rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Meperidine, Promethazine interaction page

How much people look this up

Where Syrian Rue and Meperidine, Promethazine 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

#1,021 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Meperidine, Promethazine
Top 10%

#273 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 Meperidine, Promethazine, 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 Meperidine, Promethazine supplement interactions › Every supplement checked against Meperidine, Promethazine, 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 Meperidine, Promethazine Together: Common Questions

Can you take Syrian Rue with Meperidine, Promethazine?
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 Meperidine, Promethazine?
Meperidine, Promethazine 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 Meperidine, Promethazine 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.