Drug & supplement interaction

Kava + Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate brand name: Anacin w/ Codeine.

Major Interaction
The bottom line Major

Aspirin, Caffeine, Codeine Phosphate falls into 4 drug categories that Kava can interact with; the most serious is rated major. Combining kava with CNS depressants can have additive sedative effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions4
EvidenceA
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Aspirin, Caffeine, Codeine Phosphate

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

Why Are There 4 Interactions?

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

Major

CNS DEPRESSANTS

1 of 4

Why this applies to Aspirin, Caffeine, Codeine Phosphate

Aspirin, Caffeine, Codeine Phosphate falls under CNS DEPRESSANTS — the group Kava interacts with.

Combining kava with CNS depressants can have additive sedative effects.
Kava has CNS depressant effects. Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression. Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that CNS depressants, including alcohol and benzodiazepines, not be used with kava.
Severity Major Likelihood Probable Evidence A

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

The piece of this combo product that matters most here is the codeine. Codeine is a narcotic that calms the brain and can make you sleepy. Kava works in a similar calming direction on the nervous system. When you put the two together, those effects can stack up, leaving you more drowsy, foggy, or unsteady than you'd expect, with slower reflexes and, in heavier cases, slowed breathing.

This isn't a guess. The research and expert guidelines are solid enough that they actively advise against mixing kava with brain-calming medicines. There's also a separate worry: both kava and aspirin can be hard on the body (kava on the liver, aspirin on the stomach). Please don't start or stop anything on your own. Check with your pharmacist or doctor first.

References
  1. Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 2000;20:84-9. PubMed
  2. Munte TF, Heinze HJ, Matzke M, Steitz J. Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task. Neuropsychobiology 1993;27:46-53.
  3. Cairney S, Maruff P, Clough AR, et al. Saccade and cognitive impairment associated with kava intoxication. Hum Psychopharmacol 2003;18:525-33. PubMed
  4. Sarris J, Kavanagh DJ, Byrne G, et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology 2009;205:399-407. PubMed
  5. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 4

Aspirin, Caffeine, Codeine Phosphate 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

This combination product contains three ingredients, but the one that connects to kava here is caffeine, which your body clears using a liver enzyme called CYP1A2. The theory is that kava might slow that enzyme, letting caffeine linger longer and possibly causing jitteriness, a racing heart, or trouble sleeping. In reality, a clinical study showed kava had no meaningful effect on CYP1A2, so this concern is mostly based on lab tests and a single case report. I'd rate this as a low-priority interaction.

My bigger note is unrelated to this enzyme: both kava and the codeine here can make you drowsy, and kava carries a rare risk of liver harm. Since this product already includes liver-processed ingredients, please check with your pharmacist or doctor before pairing them.

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

3 of 4

Aspirin, Caffeine, Codeine Phosphate 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 piece that matters: the codeine in this combo is actually a prodrug. Your body has to flip it into morphine using a liver enzyme called CYP2D6, and that's what gives you the pain relief. In test-tube studies, kava looked like it might block CYP2D6, which in theory could mean less morphine forms and weaker pain control. But here's the reassuring part: when researchers actually tested this in people, kava did not meaningfully change how CYP2D6 handles its targets.

So this interaction is rated minor and unlikely. The aspirin and caffeine parts aren't really involved here. My bigger caution with kava is its rare link to liver damage, so it's still worth a quick chat with your pharmacist or doctor before combining them.

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

4 of 4

Aspirin, Caffeine, Codeine Phosphate 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

This combination pairs kava with a pain reliever that contains aspirin, caffeine, and codeine. The interaction on file focuses on whether kava blocks a liver enzyme called CYP3A4. Here's the good news: while early test-tube studies hinted kava might slow that enzyme, better human research showed kava had no real effect on it. So in practice, kava is unlikely to meaningfully change how this medicine is broken down.

The bigger thing I'd watch is overlap in drowsiness. Codeine already makes many people sleepy, and kava is calming too, so together they may leave you more groggy or foggy than expected. Kava can also stress the liver, and aspirin shares some liver concerns. Please check with your pharmacist or doctor before combining them.

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 247 major, 577 moderate, 341 minor known drug interactions in our database — the Aspirin, Caffeine, Codeine Phosphate 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 Kava

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Codeine Phosphate

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Codeine Phosphate page lists 398 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Caffeine, Codeine Phosphate page

“Anacin with Codeine combines aspirin, caffeine, and codeine, and each of the three picks up its own supplement problems, so this is a list worth real caution. Just over half of the 398 ingredients here, 202 of them, can add to aspirin's blood-thinning action and raise bleeding risk.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Codeine Phosphate 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 Aspirin, Caffeine, Codeine Phosphate 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 Aspirin, Caffeine, Codeine Phosphate 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%

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

29 days ago today
Medication Aspirin, Caffeine, Codeine Phosphate
Steady interest

#1,491 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
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.

247Major
577Moderate
341Minor
1,664No known interaction
Major

247 interactions

Showing 60 of 247 major interactions — see all 247 on the Kava page.

Moderate

577 interactions

Showing 60 of 577 moderate interactions — see all 577 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
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 Kava and Aspirin, Caffeine, Codeine Phosphate Together: Common Questions

Can you take Kava with Aspirin, Caffeine, Codeine Phosphate?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 4 interactions listed for Kava and Aspirin, Caffeine, Codeine Phosphate?
Aspirin, Caffeine, Codeine Phosphate 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 Aspirin, Caffeine, Codeine Phosphate interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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.