Drug & supplement interaction

Kava + Imipramine

Imipramine brand names: Tofranil, Tofranil PM.

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

Imipramine falls into 5 drug categories that Kava can interact with; the most serious is rated moderate. Theoretically, kava might increase levels of CYP2C19 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions5
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Imipramine

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Kava interacts with whole categories of medication. Imipramine falls into 5 of those categories, so it can interact with Kava in 5 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 5

Why this applies to Imipramine

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

Theoretically, kava might increase levels of CYP2C19 substrates.
In vitro research shows that kava significantly inhibits CYP2C19 enzymes. This effect 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 as one of the ways it helps break this medicine down. In test tube studies, kava appears to slow that enzyme. If that same effect happened in people, imipramine could clear a bit more slowly and build up in your system. Since imipramine is an active drug (not a prodrug that needs switching on), higher levels usually mean stronger effects and more side effects, such as drowsiness, dry mouth, constipation, blurry vision, dizziness on standing, or a faster heartbeat.

I want to be honest about the evidence: this is only a lab finding, not something proven in humans, so it may not amount to much. Still, two things make me cautious. Kava has been tied to rare liver injury, and feeling extra sleepy from both together can stack up. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 5

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

Theoretically, kava might increase levels of CYP2C9 substrates.
In vitro research shows that kava significantly inhibits CYP2C9 enzymes. This effect 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 situation with kava and your imipramine. Your body uses a liver enzyme called CYP2C9 (among others) to help clear imipramine out of your system. In lab studies, kava appears to slow that enzyme down. If that happened in real life, imipramine could build up a bit more than usual, which might lead to stronger side effects like drowsiness, dry mouth, constipation, blurry vision, dizziness when standing, or a faster heartbeat.

I want to be honest about the strength of this: it's only been seen in test-tube research, not in actual people, so it's more of a theoretical caution than a proven problem. Still, both kava and imipramine can make you sleepy and both can stress the liver, so please loop in your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 5

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

It is unclear if kava inhibits CYP1A2; research is conflicting.
Although in vitro research and a case report suggest that kava inhibits CYP1A2, more robust clinical evidence shows that kava has no effect on CYP1A2. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP1A2 activity.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version on combining kava with imipramine (Tofranil). On paper, there was a worry that kava might slow down a liver enzyme called CYP1A2, which is one of the pathways your body uses to clear imipramine. If that happened, more drug could linger, which in theory could mean stronger side effects like drowsiness, dry mouth, constipation, or feeling lightheaded when you stand.

The good news is that the better-quality human research found kava had no real effect on this enzyme, so this interaction is rated minor and unlikely. My bigger concern is overlap: both kava and imipramine can be calming, so together they may make you extra sleepy. Kava can also stress the liver. Please run this past your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Toohey TP, Lu BY, Wada C. Toxic effects of psychotropics related to possible p450 enzyme inhibition by kava:report of 2 cases. Prim Care Companion CNS Disord 2013;15(5). PubMed
  5. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

4 of 5

Imipramine also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

It is unclear if kava inhibits CYP1A2; research is conflicting.
In vitro research shows that kava extract significantly inhibits CYP2D6. However, clinical research shows that kava does not affect the metabolism of CYP2D6 substrates in humans.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version on combining kava with imipramine. Your liver uses an enzyme called CYP2D6 to help clear imipramine from your body. In a test tube, kava looked like it could slow that enzyme down, which in theory might let imipramine build up and bring on more of its usual side effects like drowsiness, dry mouth, constipation, blurry vision, or a faster heartbeat. But here's the reassuring part: when this was actually studied in real people, kava did not meaningfully change how the body handles CYP2D6 medications.

So this is a minor, unlikely concern based on weak evidence. The bigger thing I'd flag is that both kava and imipramine can be sedating, and kava has been tied to rare liver problems. Please loop in your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
  5. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

5 of 5

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

It is unclear if kava inhibits CYP3AA; research is conflicting.
Although in vitro research suggests that kava inhibits CYP3A4, more robust clinical evidence shows that kava has no effect on CYP3A4. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP3A4 activity.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for combining kava with imipramine (Tofranil). On paper, kava was once thought to slow down CYP3A4, one of the liver enzymes that helps break down imipramine. If that were true, your imipramine levels could creep up and bring more of its usual effects, things like drowsiness, dry mouth, constipation, or a faster heartbeat. But the better human research tells a calmer story: a study where people took kava for 28 days showed no real effect on CYP3A4. So this particular interaction is rated minor and unlikely.

My bigger concern is overlap, not metabolism. Both kava and imipramine can make you sleepy or foggy, and both can stress the liver. Please check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.

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

Kava Also Interacts With Other Medications

Kava has 248 major, 576 moderate, 341 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.

Major 248 Moderate 576 Minor 341 No known interaction 1,665 (incl. Imipramine)
Taking anything else?

Check Another of Your Medications Against Kava

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

From our Q&A

Questions About Kava 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 Kava 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 Kava 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 Kava as Part of a Dietary Supplement Product? Check It for Interactions

We hold 403 real supplement products containing Kava, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kava. Your product may carry other ingredients that interact with Imipramine too, on top of Kava — 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 Kava 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 Kava
Top 25%

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

29 days ago today
Medication Imipramine
Steady interest

#1,991 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 Kava

What is Kava?

Kava
  • Anxiety and stress
  • Restlessness
  • Trouble sleeping
  • Relaxation in social or cultural settings
  • Menopausal symptoms

Kava is a Pacific Island plant traditionally used to promote relaxation and ease anxiety, and some studies suggest it may help mild anxiety. However, kava has been linked to rare but serious liver damage, so it should be used with caution, avoided by people with liver problems, and only used after talking with your pharmacist or doctor.

Read the full Kava 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 & Kava

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

248Major
576Moderate
341Minor
1,664No known interaction
248 Major 576 Moderate 341 Minor 1,664 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the Kava page.

Moderate

576 interactions

Showing 60 of 576 moderate interactions — see all 576 on the Kava page.

Minor

341 interactions

Showing 60 of 341 minor interactions — see all 341 on the Kava page.

No interaction 1,664 drugs checked — show the list

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

Showing the 60 most looked-up of 1,664 medications checked with no known interaction — see the full Kava list.

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

Can you take Kava 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 5 interactions listed for Kava and Imipramine?
Imipramine belongs to more than one drug category, and Kava 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 Kava 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 Kava?

Our pharmacists answer your medication & supplement questions — free.

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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.