Drug & supplement interaction

Kava + Cyclobenzaprine

Cyclobenzaprine brand names: Cyclobenzaprine, Flexeril, Cycloprine.

Minor Interaction
Medically reviewed by · Updated October 2026
The bottom line Minor

Cyclobenzaprine falls into 3 drug categories that Kava can interact with; the most serious is rated minor. It is unclear if kava inhibits CYP1A2; research is conflicting.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Cyclobenzaprine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Kava interacts with whole categories of medication. Cyclobenzaprine falls into 3 of those categories, so it can interact with Kava in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Cyclobenzaprine

Cyclobenzaprine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Kava interacts with.

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 situation with kava and cyclobenzaprine. Your body partly clears cyclobenzaprine using a liver enzyme called CYP1A2. The theory is that kava might slow that enzyme down, which could let cyclobenzaprine build up a little and make its usual effects (drowsiness, dry mouth, dizziness, and a foggy or sluggish feeling) more noticeable.

The good news is that this concern is mostly on paper. A well-run study in healthy people found kava did not change CYP1A2 activity, so a real-world problem here is unlikely. That said, both kava and cyclobenzaprine can be calming and both can stress the liver, so combining them may leave you extra sleepy. 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. 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

2 of 3

Cyclobenzaprine 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 practical picture with kava and cyclobenzaprine (Flexeril). In a test tube, kava looked like it might slow down CYP2D6, one of the liver enzymes that helps clear cyclobenzaprine. If that were true in real life, the drug could build up and you'd feel more of its usual effects, like extra drowsiness, dizziness, dry mouth, or grogginess. The good news is that human studies didn't show kava actually changing how the body handles CYP2D6 medicines, so this interaction is rated minor and unlikely.

The bigger thing I'd flag isn't the enzyme at all. Both kava and cyclobenzaprine can make you sleepy and relaxed, so stacking them may leave you more sedated than you expect. Kava has also been tied to rare liver injury. 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
  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

3 of 3

Cyclobenzaprine 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 bottom line on pairing kava with cyclobenzaprine (Flexeril). On paper, kava was once thought to slow down a liver enzyme called CYP3A4, which is one of the pathways your body uses to clear cyclobenzaprine. If that were true, the drug could build up and cause more drowsiness or grogginess. But the better human research tells a calmer story: a study in healthy volunteers found kava didn't actually change CYP3A4 activity. So this particular concern is unlikely and rated minor.

The bigger thing I'd flag isn't the enzyme at all. Both kava and cyclobenzaprine are calming, so together they may stack up sleepiness, dizziness, or fuzzy thinking. 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
  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, 581 moderate, 337 minor known drug interactions in our database — the Cyclobenzaprine one above is among them. If you take anything else, check it against the full list below.

Major 248 Moderate 581 Minor 337 No known interaction 1,664 (incl. Cyclobenzaprine)
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 Cyclobenzaprine

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 Cyclobenzaprine, 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 Cyclobenzaprine

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclobenzaprine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 5 major · 146 moderate · 46 minor.

Open the Cyclobenzaprine 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 Cyclobenzaprine 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 Cyclobenzaprine 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%

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

29 days ago today
Medication Cyclobenzaprine
Top half

#896 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 Cyclobenzaprine

What Is Cyclobenzaprine Used For?

Brand names: Cyclobenzaprine, Flexeril, Cycloprine

Cyclobenzaprine tablets and extended-release capsules (including Fexmid and Amrix) are used along with rest and physical therapy. They relieve muscle spasm from acute, painful muscle and joint conditions. That means easing pain, tenderness and limited movement.

Tonmya, a sublingual (under-the-tongue) tablet, is used to treat fibromyalgia in adults. Cyclobenzaprine has not been found effective for spasticity from brain or spinal cord disease, or in children with cerebral palsy.

See full Cyclobenzaprine 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
581Moderate
337Minor
1,663No known interaction
248 Major 581 Moderate 337 Minor 1,663 No interaction
Major

248 interactions

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

Moderate

581 interactions

Showing 60 of 581 moderate interactions — see all 581 on the Kava page.

Minor

337 interactions

Showing 60 of 337 minor interactions — see all 337 on the Kava page.

No interaction 1,663 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 1,663 medications checked with no known interaction — see the full Kava list.

See the full Kava interactions page
See every supplement checked against Cyclobenzaprine, 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 Cyclobenzaprine supplement interactions › Every supplement checked against Cyclobenzaprine, ranked by severity Cyclobenzaprine 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 Cyclobenzaprine Together: Common Questions

Can you take Kava with Cyclobenzaprine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Kava and Cyclobenzaprine?
Cyclobenzaprine 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 Cyclobenzaprine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Cyclobenzaprine 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.