Drug & supplement interaction

Syrian Rue + Imipramine

Imipramine brand names: Tofranil, Tofranil PM.

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

Imipramine falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Syrian Rue and Imipramine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Syrian Rue interacts with whole categories of medication. Imipramine falls into 4 of those categories, so it can interact with Syrian Rue in 4 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 4

Why this applies to Imipramine

Imipramine 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

Here's the concern with pairing Syrian Rue and imipramine (Tofranil). Syrian Rue's seeds contain harmala alkaloids that act like an MAO inhibitor, meaning they slow down an enzyme that normally clears certain brain chemicals like serotonin. Imipramine, a tricyclic antidepressant, already raises serotonin and norepinephrine. Stacking these two ways of boosting the same chemicals can push levels too high.

The worry is serotonin syndrome, which can show up as agitation, sweating, a racing heart, shivering, muscle twitching, or confusion. Mixing an MAOI with a tricyclic is a classic combination doctors try to avoid. Honestly, the human evidence here is thin (mostly lab and animal data), but given the real risk, I'd steer clear and check with your doctor or pharmacist first.

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 4

Imipramine 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 situation with imipramine and Syrian Rue. Your body relies on a liver enzyme called CYP2D6 to clear imipramine out of your system. Lab studies suggest the harmala alkaloids in Syrian Rue can slow that enzyme down. If that happens, imipramine could pile up higher than expected, which may mean more of its usual side effects: dry mouth, constipation, drowsiness, dizziness on standing, blurred vision, and a faster or irregular heartbeat.

There's a second concern worth flagging. Syrian Rue acts like an MAO inhibitor, and combining MAOIs with tricyclic antidepressants can be risky. For now this is mostly theory and test-tube data, not proven in people, so I wouldn't panic. But please check with 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

3 of 4

Imipramine 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 short version: your body uses a liver enzyme called CYP3A4 to help clear imipramine (Tofranil). Lab studies suggest the harmala alkaloids in Syrian Rue can slow that enzyme down. If that happens in real life, imipramine could build up a bit more than expected, which may mean stronger side effects like dry mouth, constipation, blurry vision, drowsiness, dizziness on standing, or a faster heartbeat.

I want to be honest that this is theoretical, based on test-tube data rather than people, so we don't know how big a deal it really is. But there's a bigger concern: Syrian Rue acts like an MAO inhibitor, and combining that with an antidepressant like imipramine can be genuinely risky. Please don't pair these 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

4 of 4

Imipramine 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's the gist of this pairing. Imipramine has noticeable anticholinergic activity, which is why it can cause dry mouth, blurry vision, constipation, and trouble urinating. Syrian Rue contains harmine, and in animal studies (given by IV, not by mouth) it seemed to nudge acetylcholine levels up, which works in the opposite direction from imipramine's drying effects. In theory, that could blunt some of imipramine's anticholinergic action.

I want to be honest about how thin this evidence is. It is based on lab and animal data, not real people taking these two together, so the practical effect in humans is unknown. The bigger concern with Syrian Rue is that it acts like an MAO inhibitor, and combining MAOIs with antidepressants like imipramine can be genuinely dangerous. Please check with your doctor or pharmacist before mixing 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 Imipramine 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. Imipramine)
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 Imipramine

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 Imipramine, 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 Imipramine

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Imipramine page lists 254 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 11 major · 190 moderate · 53 minor.

From our pharmacist’s overview on the Imipramine page

“Imipramine (Tofranil) is an older tricyclic antidepressant, and the supplements on this page deserve real scrutiny before you add one. Most of the list acts on the liver enzymes that process the drug, so an ingredient can quietly raise or lower imipramine levels: grapefruit pushes them up, while St.”

Reviewed by 2 · Jul 18, 2026

Open the Imipramine interaction page

How much people look this up

Where Syrian Rue and Imipramine 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

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

29 days ago today
Medication Imipramine
Steady interest

#1,627 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 Imipramine

What Is Imipramine Used For?

Brand names: Tofranil, Tofranil PM

Imipramine is used to relieve symptoms of depression. Both Imipramine Hydrochloride tablets and Imipramine Pamoate capsules are approved for this use. Endogenous depression — the kind that seems to arise from within rather than a clear outside cause — tends to respond especially well. It may take one to three weeks before you notice the full benefit.

Imipramine Hydrochloride tablets are also approved as a short-term, add-on treatment to help reduce nighttime bedwetting (nocturnal enuresis) in children aged 6 and older, after a doctor has ruled out physical causes.

See full Imipramine 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
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 Imipramine, 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 Imipramine supplement interactions › Every supplement checked against Imipramine, ranked by severity Imipramine drug information › The full plain-English guide to this medication 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 Imipramine Together: Common Questions

Can you take Syrian Rue with Imipramine?
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 4 interactions listed for Syrian Rue and Imipramine?
Imipramine 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 Imipramine 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 Imipramine 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.