Drug & supplement interaction

Syrian Rue + Caffeine , Sodium Benzoate

Caffeine , Sodium Benzoate brand name: Caffeine and Sodium Benzoate.

Moderate Interaction
The bottom line Moderate

Caffeine , Sodium Benzoate falls into 2 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 CYP3A4.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Interaction report

Syrian Rue and Caffeine , Sodium Benzoate

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Syrian Rue interacts with whole categories of medication. Caffeine , Sodium Benzoate falls into 2 of those categories, so it can interact with Syrian Rue in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Caffeine , Sodium Benzoate

Caffeine , Sodium Benzoate falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Syrian Rue interacts with.

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

Here's the situation with caffeine and sodium benzoate (the injectable caffeine sometimes given to newborns or used for certain headaches) and Syrian Rue. The compounds in Syrian Rue can slow down a liver enzyme called CYP3A4, which is one of the pathways that helps clear caffeine from your body. If that enzyme gets blocked, caffeine may hang around longer and build up.

In plain terms, that could mean stronger caffeine effects than expected: a racing or pounding heart, jitteriness, anxiety, trouble sleeping, or an upset stomach. Keep in mind this is a theoretical concern based on lab studies, not real-world cases, so it may never cause a problem. Still, Syrian Rue carries its own toxicity risks, so please check with your pharmacist or doctor before combining them.

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

2 of 2
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

Here's the short version: caffeine and sodium benzoate is basically a strong dose of caffeine (often used in hospitals for things like newborn breathing issues or certain headaches). On its own, caffeine can already cause jitteriness, a racing heart, and shaky hands. Syrian Rue contains harmaline, and animal studies suggest that mixing it with caffeine can make tremors more intense and last longer.

I want to be upfront that this is a theoretical concern based mostly on lab and animal research, not solid human studies, so I don't want to alarm you. Still, both substances stir up the nervous system, so combining them could leave you feeling extra shaky, wired, or anxious. Since Syrian Rue isn't recommended for self-treatment anyway, please check with your pharmacist or doctor before pairing them.

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 Caffeine , Sodium Benzoate 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 Caffeine , Sodium Benzoate

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Caffeine , Sodium Benzoate page lists 208 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Peyote (major) and Rauvolfia Vomitoria (major).

By severity: 7 major · 155 moderate · 46 minor.

From our pharmacist’s overview on the Caffeine , Sodium Benzoate page

“Caffeine and sodium benzoate is itself a stimulant medication, so the supplements most likely to cause trouble are the ones doing the same job. Seven of the 208 ingredients on file rate major, several of them stimulant herbs such as ephedra that can pile extra blood pressure and heart strain onto a drug already revving the nervous system.”

Reviewed by 2 · Jul 18, 2026

Open the Caffeine , Sodium Benzoate interaction page

How much people look this up

Where Syrian Rue and Caffeine , Sodium Benzoate 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

#1,056 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Caffeine , Sodium Benzoate
Top 25%

#462 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

Keep exploring
Pharmacist Counseling Corner

Taking Syrian Rue and Caffeine , Sodium Benzoate Together: Common Questions

Can you take Syrian Rue with Caffeine , Sodium Benzoate?
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 2 interactions listed for Syrian Rue and Caffeine , Sodium Benzoate?
Caffeine , Sodium Benzoate 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 Caffeine , Sodium Benzoate 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 Caffeine , Sodium Benzoate 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.