Drug & supplement interaction

Syrian Rue + Clomipramine

Clomipramine brand names: Anafranil, Anafranil SR.

Moderate Interaction
The bottom line Moderate

Clomipramine 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 Clomipramine

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. Clomipramine 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 Clomipramine

Clomipramine 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 thing with Syrian Rue and your Clomipramine. The harmala compounds in those seeds can block an enzyme called CYP2D6, which is one of the main ways your body clears clomipramine. Slow down that clearance and the drug can build up in your system, meaning stronger effects and more side effects like dry mouth, constipation, drowsiness, a racing heartbeat, or feeling dizzy when you stand. At higher levels, heart rhythm changes become a real worry too.

On top of that, Syrian Rue acts like an MAO inhibitor, and combining that with a serotonin-boosting medicine like clomipramine raises the risk of serotonin syndrome, which can be dangerous. This is based on lab and pharmacology reasoning, not big human studies, but it's a combination I'd steer clear of. Please check with your doctor or pharmacist first.

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

Clomipramine 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

Here's the situation with these two together. Your body clears clomipramine in part through a liver enzyme called CYP3A4. Lab studies suggest the harmala alkaloids in Syrian Rue can slow that enzyme down, so in theory clomipramine could build up in your system more than expected. Since clomipramine is an active drug (not a prodrug), more of it sticking around means a stronger effect, which could show up as extra drowsiness, dry mouth, constipation, blurry vision, dizziness, or a faster heartbeat.

There's a bigger worry too. Both Syrian Rue (an MAO inhibitor) and clomipramine raise serotonin, and combining them can push serotonin too high. This is theoretical for the enzyme part, but please don't pair these on your own. Check with your doctor or pharmacist first.

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

Clomipramine 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 is the gist for your clomipramine (Anafranil). Part of how this antidepressant works is by blocking acetylcholine, which is also why it can cause dry mouth, blurry vision, constipation, and trouble urinating. Syrian Rue may push in the opposite direction by raising acetylcholine levels, so in theory it could blunt some of clomipramine's anticholinergic effects.

That said, this is a theoretical concern drawn from animal studies, not real human evidence, so I would not lose sleep over the acetylcholine angle alone. The bigger worry is that Syrian Rue acts as an MAO inhibitor, and combining MAOIs with a serotonin drug like clomipramine can be dangerous. Please check with your doctor or pharmacist before mixing these.

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 Clomipramine 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.

From our Q&A

Questions About Syrian Rue or Clomipramine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Syrian Rue or Clomipramine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Clomipramine

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Clomipramine page lists 236 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Henbane (major), Scopolia (major) and St. John's Wort (major).

By severity: 5 major · 179 moderate · 52 minor.

From our pharmacist’s overview on the Clomipramine page

“A tricyclic antidepressant used mostly for OCD, clomipramine (Anafranil) is unforgiving of shifts in its blood level, which is why its 236 supplement interactions deserve genuine wariness. Most of the list involves metabolism: herbs that speed up or slow down the liver enzymes handling clomipramine can drag its level too low or push it…”

Reviewed by 2 · Jul 18, 2026

Open the Clomipramine interaction page

How much people look this up

Where Syrian Rue and Clomipramine 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

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

29 days ago today
Medication Clomipramine
Top half

#1,186 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
Medication

About Clomipramine

What Is Clomipramine Used For?

Brand names: Anafranil, Anafranil SR

Clomipramine — sold as Anafranil and under the generic name Clomipramine Hydrochloride — is approved to treat obsessions and compulsions in people with Obsessive-Compulsive Disorder (OCD). This includes adults and children/adolescents ages 10 to 17.

To qualify for treatment, the obsessions or compulsions must cause significant distress, take up a lot of time, or noticeably interfere with work, school, or social life.

See full Clomipramine drug information
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 Clomipramine Together: Common Questions

Can you take Syrian Rue with Clomipramine?
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 Clomipramine?
Clomipramine 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 Clomipramine 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.