Drug & supplement interaction

Kratom + Venlafaxine

Venlafaxine brand names: Effexor XR, Effexor.

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

Venlafaxine falls into 3 drug categories that Kratom can interact with; the most serious is rated moderate. Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.

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

Kratom and Venlafaxine

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. Venlafaxine 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 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Venlafaxine

Venlafaxine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Kratom interacts with.

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.
In vitro research suggests that kratom extract inhibits CYP2D6 enzyme activity. However, human research shows that a single low dose of kratom tea 2 grams does not inhibit CYP2D6 activity. However, this kratom dose is lower than what is normally taken for psychoactive effects. In one 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 was hypothesized that kratom inhibited CYP2D6-mediated metabolism of buspirone and consequently increased systemic exposure to serotonin. In another case, a 37-year-old male stable for 15 years on amitriptyline presented with anticholinergic symptoms including xerostomia, dry eyes, and constipation, along with mildly elevated bilirubin and liver enzymes after taking progressively higher doses of up to 14 grams of kratom daily for 12 weeks. It was hypothesized that the adverse effects of amitriptyline were precipitated by CYP2D6 inhibition by kratom.
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 with venlafaxine (Effexor) and kratom. Your body clears venlafaxine partly through an enzyme called CYP2D6. Lab studies suggest kratom can slow that enzyme down, which could let venlafaxine build up in your system. Venlafaxine is an active drug (not a prodrug), so more of it means stronger effects, things like nausea, high blood pressure, fast heartbeat, sweating, jitteriness, or trouble sleeping.

There's a bigger worry too. Kratom acts on the brain and venlafaxine raises serotonin, so combining them may raise the risk of serotonin syndrome (agitation, shivering, rapid heartbeat, confusion). The hard evidence here is mostly theoretical and from a few case reports, so I'm not trying to alarm you. Still, please run this by your pharmacist or doctor before mixing the two.

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. 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
  3. 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
  4. Vanani NB, Stevanovic SG, Stevanovic N. Adverse Drug Interaction Between Kratom and Amitriptyline With Gastrointestinal and Mild Hepatic Effects. Cureus 2023;15(1):e33809. PubMed
Moderate

VENLAFAXINE (Effexor)

2 of 3
Theoretically, taking kratom in combination with venlafaxine may increase levels and clinical effects of venlafaxine.
A 36-year-old male presented to the emergency department with serotonin syndrome and QT interval prolongation after concomitant use of venlafaxine, quetiapine, and kratom. It is hypothesized that kratom may have inhibited the cytochrome P450 (CYP) metabolism of both venlafaxine and quetiapine.
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 concern with mixing kratom and venlafaxine. Your body uses liver enzymes (the CYP450 family) to clear venlafaxine. Kratom appears to slow some of those enzymes down. When that happens, venlafaxine can build up in your system, and a higher level means stronger effects and a bigger chance of side effects like nausea, jitteriness, fast heartbeat, sweating, high blood pressure, or trouble sleeping.

There's a second worry too. Both kratom and venlafaxine raise serotonin activity, so combining them can push you toward serotonin syndrome (agitation, shivering, muscle twitching, racing heart). This warning leans on a single case report, so it's not strong proof, but it's real enough to take seriously. Please talk with your pharmacist or doctor before pairing these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brogdon HD, McPhee MM, Paine MF, Cox EJ, Burns AG. A Case of Potential Pharmacokinetic Kratom-drug Interactions Resulting in Toxicity and Subsequent Treatment of Kratom Use Disorder With Buprenorphine/Naloxone. J Addict Med 2022. PubMed
Moderate

SEROTONERGIC DRUGS

3 of 3

Venlafaxine 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 to keep in mind if you take venlafaxine (Effexor) and are curious about kratom. Venlafaxine already raises serotonin in your brain, and kratom can nudge serotonin upward too. Stacking the two could, in theory, push serotonin too high and trigger something called serotonin syndrome. Watch for agitation, a racing heart, sweating, shivering, muscle twitching, or confusion.

There's also a possibility that kratom slows the enzymes (like CYP2D6) that clear venlafaxine, letting more of it build up. That could mean stronger side effects such as nausea, dizziness, high blood pressure, or trouble sleeping. This is based mostly on a single case report and theory, not strong proof, so don't panic. Still, please check with your pharmacist or doctor before combining them.

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

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 Venlafaxine 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. Venlafaxine)
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 Venlafaxine

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 Venlafaxine, 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 Venlafaxine

This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Venlafaxine page lists 110 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: 8 major · 82 moderate · 20 minor.

From our pharmacist’s overview on the Venlafaxine page

“Venlafaxine (Effexor, Effexor XR) is an antidepressant that raises serotonin, which is exactly where part of the danger on this page sits, and its 110 interactions deserve genuine respect. Eight carry a major rating, most tied to heart rhythm: several ingredients, grapefruit among them, can stretch the QT interval and add to a strain v…”

Reviewed by 2 · Jul 18, 2026

Open the Venlafaxine 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 Venlafaxine 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 Venlafaxine 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 half

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

29 days ago today
Medication Venlafaxine
Top 5%

#98 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 Venlafaxine

What Is Venlafaxine Used For?

Brand names: Effexor XR, Effexor

Venlafaxine is used to treat major depressive disorder (MDD) across all available formulations. Extended-release capsules (including Effexor XR) are also approved for generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD).

Extended-release tablets are approved for major depressive disorder and social anxiety disorder. Immediate-release venlafaxine tablets are indicated for major depressive disorder only.

See full Venlafaxine 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 Venlafaxine, 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 Venlafaxine supplement interactions › Every supplement checked against Venlafaxine, ranked by severity Venlafaxine 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 Venlafaxine Together: Common Questions

Can you take Kratom with Venlafaxine?
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 Venlafaxine?
Venlafaxine 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 Venlafaxine 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 Venlafaxine 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.