Drug & supplement interaction

Kratom + nefazodone

nefazodone brand name: Serzone.

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

nefazodone falls into 3 drug categories that Kratom can interact with; the most serious is rated moderate. Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kratom and nefazodone

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

Why Are There 3 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 3

Why this applies to nefazodone

nefazodone falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Kratom interacts with.

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that kratom extract inhibits CYP3A4 enzyme activity. A pharmacokinetic study in adults shows that taking kratom tea 2 grams modestly increases the plasma concentration time-curve (AUC) and maximum concentration (Cmax) of CYP3A4 probe midazolam by 40-50% and its CYP3A4-mediated metabolites 18-27%. However, a lack of change in the half-life of midazolam and a simulation of the kratom-midazolam interaction suggest that kratom inhibits CYP3A4 enzymes in the small intestine but not the liver. Additionally, there is one case report of a 27-year-old male who died from neuroleptic malignant-like symptoms after concomitant use of kratom and quetiapine, a CYP3A4 substrate. Although it did not appear that the patient had consumed large quantities of quetiapine, postmortem plasma levels were in the lethal range, indicating possible inhibition of CYP3A4 by kratom. In another case report, a 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It is hypothesized that CYP3A4 inhibition by kratom reduced metabolism of desvenlafaxine, trazodone, and ziprasidone and consequently increased systemic exposure to serotonin.
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 nefazodone: your liver clears it using an enzyme called CYP3A4, and kratom appears to slow that same enzyme down. Nefazodone is an active drug (not a prodrug needing activation), so blocking its breakdown could let more of it build up in your system. That may mean stronger effects and more side effects, like drowsiness, dizziness, lightheadedness when you stand up, dry mouth, or feeling foggy. Because both kratom and nefazodone affect mood and serotonin, there's also a theoretical concern for too much serotonin.

To be fair, this warning is based mostly on lab work and a few case reports, so it isn't proven. Still, kratom carries real risks on its own. Please run this by your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356. PubMed
  2. Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019 Mar;15(1):110-113. PubMed
  3. Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
  4. Tanna RS, Nguyen JT, Hadi DL, et al. Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom. Clin Pharmacol Ther 2023;113(6):1315-1325. PubMed
Moderate

SEROTONERGIC DRUGS

2 of 3

nefazodone also falls under SEROTONERGIC DRUGS.

Theoretically, taking kratom in combination with serotonergic drugs may increase levels of serotonin, increasing the risk of serotonin syndrome.
A 63-year-old male presented with possible serotonin syndrome after taking an unknown dose of kratom for up to 3 months along with serotonergic prescription medications bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone. It was hypothesized that kratom inhibited the cytochrome P450 3A4-, 2C9-, 2D6-, and 1A2-mediated metabolism of several of these serotonergic medications, consequently increasing systemic exposure to serotonin.
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 thing with nefazodone (Serzone): it's a serotonin modulator, meaning it nudges up serotonin in your brain to help with depression. Kratom also touches the serotonin system. Stacking the two together could push serotonin too high, which raises the risk of something called serotonin syndrome. That can show up as agitation, a racing heart, sweating, shivering, muscle twitching, or confusion. There's also a second concern: kratom may slow the liver enzymes (like CYP3A4) that clear nefazodone, so more of the drug could build up and add to side effects like drowsiness or dizziness.

I'll be honest, this is based mostly on a single case report and theory, not strong studies, so it's a possibility, not a certainty. Still, please don't combine these without checking with your doctor or pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

3 of 3

nefazodone also falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS.

CYP3A4 inhibitors might increase the concentrations and clinical effects of kratom's primary active alkaloid mitragynine.
A pharmacokinetic study in healthy adults suggests that CYP3A4 inhibition with itraconazole increases the peak plasma concentration (Cmax) of mitragynine by about 1.5-fold. However, CYP3A4 inhibition reduces the Cmax and area under the plasma concentration time curve (AUC) over 72 hours of 7-hydroxymitragynine, one of kratom's active constituents, by about 3-fold, possibly by decreasing the metabolism of mitragynine to 7-hydroxymitragynin.
Animal research suggests that CYP3A4 inhibition with ketoconazole reduces the metabolism and clearance of kratom, increasing the Cmax of the active metabolite mitragynine by 130%, time to reach maximum plasma concentration (Tmax) from 1 to 2.6 hours, and AUC by 120%. Additionally, CYP3A4-mediated conversion of mitragynine into 7-hydroxymitragynine increases systematic exposure by 130%. However, other CYP isoforms are likely involved in this conversion. CYP3A4 inhibition could lead to increased adverse effects and mu-opioid-receptor-mediated behavioral effects associated with kratom and its metabolites.
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 key thing about nefazodone (Serzone): it's one of the stronger blockers of a liver enzyme called CYP3A4. Your body uses that same enzyme to handle kratom's main active compound, mitragynine. So when you take nefazodone, it can slow that breakdown and let more mitragynine build up in your blood. In practice, that means kratom's opioid-like effects, things like heavy sedation, slowed breathing, dizziness, low blood pressure, and constipation, could hit harder than you'd expect.

This is based on small human and animal studies, so it's a real but moderate concern rather than a sure thing. Nefazodone also carries its own serious liver warning, and kratom can be hard on the liver too, which makes the combination more worrying. Please talk with your pharmacist or doctor before mixing these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kamble SH, Obeng S, León F, et al. Pharmacokinetic and Pharmacodynamic Consequences of Cytochrome P450 3A Inhibition on Mitragynine Metabolism in Rats. J Pharmacol Exp Ther 2023;385(3):180-192. PubMed
  2. Mongar P, Jaisi A, Inkviya T, Wungsintaweekul J, Wiwattanawongsa K. Effects of Itraconazole on Pharmacokinetics of Mitragynine and 7-Hydroxymitragynine in Healthy Volunteers. ACS Pharmacol Transl Sci 2024;7(3):823-833. 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

Kratom Also Interacts With Other Medications

Kratom has 982 moderate, 12 minor known drug interactions in our database — the nefazodone one above is among them. If you take anything else, check it against the full list below.

Moderate 982 Minor 12 No known interaction 1,836 (incl. nefazodone)
Taking anything else?

Check Another of Your Medications Against Kratom

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

From our Q&A

Questions About Kratom or nefazodone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Kratom or nefazodone, 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 nefazodone

This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the nefazodone page lists 159 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), St. John's Wort (major) and 5-htp (moderate).

By severity: 4 major · 114 moderate · 41 minor.

From our pharmacist’s overview on the nefazodone page

“Nefazodone (Serzone) treats depression by working on serotonin, and it also strongly blocks a liver enzyme called CYP3A4, which is exactly why this list deserves your close attention. The largest group, 121 ingredients, are ones nefazodone can push to higher levels because it slows their breakdown.”

Reviewed by 2 · Jul 18, 2026

Open the nefazodone interaction page

One more smart check

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

We hold 8 real supplement products containing Kratom, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kratom. Your product may carry other ingredients that interact with nefazodone too, on top of Kratom — 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 Kratom and nefazodone 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 Kratom
Top 25%

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

29 days ago today
Medication nefazodone
Steady interest

#2,634 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 Kratom

What is Kratom?

Kratom
  • Pain relief
  • Opioid withdrawal symptoms
  • Anxiety and stress
  • Low energy or fatigue
  • Mood enhancement

Kratom is a Southeast Asian plant whose leaves act on the brain's opioid receptors and can produce both stimulant-like and opioid-like effects. It is not approved or proven safe by health regulators, carries real risks of dependence and serious harm, and its legal status varies widely. Talk to a pharmacist or doctor before considering it.

Read the full Kratom monograph & all interactions
Medication

About Nefazodone

What Is Nefazodone Used For?

Brand name: Serzone

Nefazodone Hydrochloride tablets are approved to treat depression, specifically major depressive disorder (MDD). Clinical trials established its effectiveness over 6 to 8 weeks in outpatients and 6 weeks in hospitalized patients with depression.

Nefazodone has also been shown to help prevent depression from coming back in patients who responded well to initial treatment. Because of a serious risk of liver failure, prescribers are advised to consider other antidepressants before turning to nefazodone.

See full Nefazodone drug information
Keep checking

Other Drugs & Kratom

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

0Major
982Moderate
12Minor
1,835No known interaction
982 Moderate 12 Minor 1,835 No interaction
Moderate

982 interactions

Showing 60 of 982 moderate interactions — see all 982 on the Kratom page.

Minor

12 interactions

No interaction 1,835 drugs checked — show the list

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

Showing the 60 most looked-up of 1,835 medications checked with no known interaction — see the full Kratom list.

See the full Kratom interactions page
See every supplement checked against nefazodone, 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
Kratom monograph › Uses, safety, and every drug interaction in one place nefazodone supplement interactions › Every supplement checked against nefazodone, ranked by severity Nefazodone 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 Kratom and nefazodone Together: Common Questions

Can you take Kratom with nefazodone?
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 3 interactions listed for Kratom and nefazodone?
nefazodone belongs to more than one drug category, and Kratom 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 Kratom and nefazodone 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 nefazodone and Kratom?

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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.