Drug & supplement interaction

Licorice + 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 Licorice can interact with; the most serious is rated moderate. Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Licorice and Imipramine

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

Why Are There 4 Interactions?

Licorice interacts with whole categories of medication. Imipramine falls into 4 of those categories, so it can interact with Licorice in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

1 of 4

Why this applies to Imipramine

Imipramine falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES — the group Licorice interacts with.

Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.
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 for imipramine (Tofranil). Your liver uses an enzyme called CYP2C19 to help clear this antidepressant out of your system. Licorice, at least in lab dish studies, can slow that enzyme down. If it did the same thing in your body, imipramine could build up a bit higher than expected and lead to stronger side effects like dry mouth, constipation, drowsiness, blurry vision, dizziness on standing, or a faster heartbeat.

The honest part: this is only seen in test-tube research, not in real people, so it's theoretical. Imipramine is not a prodrug, so the direction (more drug, not less) makes sense. Still, occasional culinary licorice is unlikely to be the issue; regular DGL or glycyrrhizin supplements are the bigger question. Check with your pharmacist before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 4

Imipramine also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes. However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity. Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.
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 honest picture with licorice and imipramine. Your liver uses several enzymes to clear imipramine, and one of them is called CYP2C9. Lab tests hint that licorice might slow that enzyme, while an animal study suggests it could actually speed it up. So the direction isn't settled, and all of this is theoretical at this point.

If licorice slowed the enzyme, more imipramine could linger and you might notice extra dry mouth, constipation, drowsiness, dizziness, or a faster heartbeat. If it sped things up, the medicine could work less well. There's a separate worry too: licorice (the real glycyrrhizin kind, not DGL) can raise blood pressure and lower potassium, which isn't ideal alongside a heart-sensitive drug like this. Please check with your pharmacist or doctor before adding it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30:709-15.. PubMed
  2. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  3. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

Imipramine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity. Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity. However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species. Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
Severity Moderate Likelihood Possible Evidence B

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 imipramine and licorice. Your body partly relies on a liver enzyme called CYP3A4 to clear imipramine, and licorice can nudge that enzyme in either direction depending on the species and product. Some licorice may speed up that enzyme (which could lower imipramine levels and make it work less well), while other types may slow it (which could raise levels and bring on more side effects like drowsiness, dry mouth, constipation, blurry vision, or a faster heartbeat).

Honestly, the evidence here is on the weaker, more theoretical side, so I wouldn't panic. Occasional culinary amounts are unlikely to matter much, but regular licorice supplements are worth a quick chat with your pharmacist or doctor before combining.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30:709-15.. PubMed
  2. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  3. Tu, J. H., He, Y. J., Chen, Y., Fan, L., Zhang, W., Tan, Z. R., Huang, Y. F., Guo, D., Hu, D. L., Wang, D., and Hong-Hao Zhou. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol 2010;66(8):805-810. PubMed
  4. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

4 of 4

Imipramine also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, licorice might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that licorice induces CYP1A2 enzymes.
Severity Minor 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 for imipramine: your liver uses an enzyme called CYP1A2 to help clear it out. Lab studies (in test tubes, not people) hint that licorice may speed that enzyme up a bit. If that happened in the body, it could nudge imipramine levels down, which in theory might make it work a little less well, so your depression symptoms (or a child's bedwetting) could creep back.

I want to be honest though: this is rated minor and rests on weak, theoretical evidence, so it's not something I'd lose sleep over. Occasional culinary licorice is unlikely to matter. If you're using concentrated licorice supplements regularly, just mention it to your pharmacist or doctor so they can keep an eye on how well your medicine is working.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Licorice Also Interacts With Other Medications

Licorice has 976 moderate, 63 minor 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 976 Minor 63 No known interaction 1,791 (incl. Imipramine)
Taking anything else?

Check Another of Your Medications Against Licorice

Covers the 2,830 medications we’ve checked against Licorice. Pick one to open its full report.

From our Q&A

Questions About Licorice 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 Licorice 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 Licorice 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

One more smart check

Taking Licorice as Part of a Dietary Supplement Product? Check It for Interactions

We hold 4,721 real supplement products containing Licorice, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Licorice. Your product may carry other ingredients that interact with Imipramine too, on top of Licorice — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Licorice 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 Licorice
Top 5%

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

29 days ago today
Medication Imipramine
Steady interest

#2,015 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 Licorice

What is Licorice?

Licorice
  • Sore throat and cough
  • Heartburn and stomach upset
  • Mouth ulcers and digestive complaints
  • Inflammation
  • Traditional tonic/adrenal support

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regular licorice contains glycyrrhizin, which can raise blood pressure and lower potassium when taken in large amounts or for a long time, so deglycyrrhizinated (DGL) products are often preferred. Talk to your pharmacist or doctor before using it, especially if you have high blood pressure, heart, or kidney problems.

Read the full Licorice 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 & Licorice

Browse every other medication we’ve checked against Licorice — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
976Moderate
63Minor
1,790No known interaction
976 Moderate 63 Minor 1,790 No interaction
Moderate

976 interactions

Showing 60 of 976 moderate interactions — see all 976 on the Licorice page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Licorice page.

No interaction 1,790 drugs checked — show the list

We also checked Licorice against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,790 medications checked with no known interaction — see the full Licorice list.

See the full Licorice 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
Licorice 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 Licorice and Imipramine Together: Common Questions

Can you take Licorice 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 Licorice and Imipramine?
Imipramine belongs to more than one drug category, and Licorice 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 Licorice 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 Licorice?

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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.