Herb & supplement monograph

Kratom Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by ·Updated July 2026
What is this page for?

First and foremost: how Kratom interacts with medications. The heart of this page is the interaction list — every drug Kratom is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Kratom is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

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On this page

Kratom Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Because nearly all documented Kratom drug interactions are rated moderate, we consider the overall risk of a clinically significant interaction to be moderate, especially with sedating or mood-related medications. None of the listed interactions are rated major, but almost all carry a moderate rating, based mainly on lab findings and individual case reports.

Interactions deserving the most attention

CNS depressants such as opioids and sedatives deserve the most caution, since kratom acts on the same brain receptors and deaths have been reported when it was combined with these drugs. Serotonergic drugs, including many antidepressants, are also a concern, with case reports describing serotonin syndrome. One fatal case involved quetiapine, where kratom may have slowed the drug's breakdown and raised it to a dangerous level.

What the rest of the list means

Most of the remaining interactions reflect kratom's possible effect on enzymes the body uses to clear many medications. That concern comes largely from lab research, and in one human study kratom tea only modestly raised levels of a test drug. So many of these predicted interactions remain theoretical, though they could matter more for medicines with a narrow safety margin.

Check your medications against Kratom

Based on HelloPharmacist’s Kratom interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with Kratom

995 medications have a known interaction with Kratom, graded by severity. Select any drug for the full evidence-based detail.

2,830 drugs
Ado-trastuzumab EmtansineKadcyla
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Ado-trastuzumab Emtansine interaction Ado-trastuzumab Emtansine drug page: uses, dosage & side effects
AbametapirXeglyze
Moderate Cytochrome P450 3a4 (cyp3a4) Inhibitors

CYP3A4 inhibitors might increase the concentrations and clinical effects of kratom's primary active alkaloid mitragynine.

Read the full Kratom + Abametapir interaction
AbemaciclibVerzenio
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Abemaciclib interaction Abemaciclib drug page: uses, dosage & side effects
Abiraterone
Moderate Cytochrome P450 3a4 (cyp3a4) Inhibitors

CYP3A4 inhibitors might increase the concentrations and clinical effects of kratom's primary active alkaloid mitragynine.

Read the full Kratom + Abiraterone interaction Abiraterone drug page: uses, dosage & side effects
Abiraterone AcetateYonsa, Zytiga
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Abiraterone Acetate interaction Abiraterone Acetate drug page: uses, dosage & side effects
AcalabrutinibCalquence
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Acalabrutinib interaction Acalabrutinib drug page: uses, dosage & side effects
AcepromazineAtravet
Moderate Cns Depressants

Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.

Read the full Kratom + Acepromazine interaction
AcetaminophenChildren's Tylenol, Children's Tylenol Meltaways, Tylenol, Tylenol Ex Strength
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen interaction Acetaminophen drug page: uses, dosage & side effects
Acetaminophen, AspirinGemnisyn
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Aspirin interaction
Acetaminophen, Aspirin, CaffeineExcedrin, Excedrin Extra Strength, Excedrin Migraine
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Aspirin, Caffeine interaction
Acetaminophen, Brompheniramine, PhenylpropanolamineDimetapp Cold and Flu
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Brompheniramine, Phenylpropanolamine interaction
Acetaminophen, ButalbitalAxocet, Bancap, Bucet, Butex Forte, Esgic CF, Orbivan CF +5 more
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Butalbital interaction
Acetaminophen, Butalbital, CaffeineEsgic, Esgic Plus, Fiogesic, Fioricet, Repan, Tecnal +1 more
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Butalbital, Caffeine interaction Acetaminophen, Butalbital, Caffeine drug page: uses, dosage & side effects
Acetaminophen, Butalbital, Caffeine, CodeineEsgic with Codeine, Fioricet w/ Codeine
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Butalbital, Caffeine, Codeine interaction
Acetaminophen, Butalbital, CodeineBancap w/ Codeine
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Butalbital, Codeine interaction
Acetaminophen, Butalbital, Codeine PhosphatePhrenilin #3
Moderate Cns Depressants

Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.

Read the full Kratom + Acetaminophen, Butalbital, Codeine Phosphate interaction
Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, PhenylephrineHycomine Compound
Moderate Cytochrome P450 2d6 (cyp2d6) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.

Read the full Kratom + Acetaminophen, Caffeine, Chlorpheniramine, Hydrocodone, Phenylephrine interaction
Acetaminophen, Caffeine, CodeineGesic C15, Gesic C30, Gesic C8, Lenoltec 1, Lenoltec 2, Lenoltec 3 +1 more
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Caffeine, Codeine interaction
Acetaminophen, Caffeine, Codeine, SalicylamideCodalan No.1, Codalan No.2, Codalan No.3
Moderate Cns Depressants

Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.

Read the full Kratom + Acetaminophen, Caffeine, Codeine, Salicylamide interaction
Acetaminophen, Caffeine, DihydrocodeineDHC Plus, Panlor DC, Panlor SS
Moderate Cns Depressants

Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.

Read the full Kratom + Acetaminophen, Caffeine, Dihydrocodeine interaction
Acetaminophen, Caffeine, IsomethepteneMigralam
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Acetaminophen, Caffeine, Isometheptene interaction
Acetaminophen, Caffeine, PyrilamineMidol Max Strength Menstrual
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Caffeine, Pyrilamine interaction
Acetaminophen, Chlorpheniramine Maleate, Dextromethorphan HbrVicks Formula 44M Cough, Cold & Flu Relief
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Acetaminophen, Chlorpheniramine Maleate, Dextromethorphan Hbr interaction
Acetaminophen, Chlorpheniramine, Codeine, PhenylephrineColrex
Moderate Cytochrome P450 2d6 (cyp2d6) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.

Read the full Kratom + Acetaminophen, Chlorpheniramine, Codeine, Phenylephrine interaction
Acetaminophen, Chlorpheniramine, DextromethorphanCoricidin II Extra Strength Cold and Flu
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Acetaminophen, Chlorpheniramine, Dextromethorphan interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan HydrobromideCoricidin HBP Maximum Strength Flu
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Chlorpheniramine, Dextromethorphan Hydrobromide interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan, PhenylpropanolamineMulti Symptom Cold Relief
Moderate Cytochrome P450 3a4 (cyp3a4) Substrates

Kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Read the full Kratom + Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine interaction
Acetaminophen, Chlorpheniramine, Dextromethorphan, PseudoephedrineChildren's Tylenol Cold Plus Cough, Tylenol Cold Ex Strength
Moderate Serotonergic Drugs

Theoretically, taking kratom in combination with serotonergic drugs may increase levels of serotonin, increasing the risk of serotonin syndrome.

Read the full Kratom + Acetaminophen, Chlorpheniramine, Dextromethorphan, Pseudoephedrine interaction
Acetaminophen, Chlorpheniramine, Guaifenesin, Phenylephrine, SalicylamideRhinogesic GG
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Chlorpheniramine, Guaifenesin, Phenylephrine, Salicylamide interaction
Acetaminophen, Chlorpheniramine, PhenylephrineAlka-Seltzer PLUS, Histex SR, Protid
Moderate Cytochrome P450 1a2 (cyp1a2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full Kratom + Acetaminophen, Chlorpheniramine, Phenylephrine interaction
Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

  • Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
  • Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
  • Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
  • No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

  • Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
  • Probable. 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.
  • Possible. 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
  • Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

  • Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
  • Each drug listed above links to the full report for that exact Kratom combination — clinical detail, likelihood, evidence level, and citations.
  • Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
The big picture

The kinds of drugs Kratom affects

Every type of medication (drug category) Kratom is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 11 drug categories Kratom interacts with
Cns DepressantsCytochrome P450 1a2 (cyp1a2) SubstratesCytochrome P450 2d6 (cyp2d6) SubstratesCytochrome P450 3a4 (cyp3a4) InhibitorsCytochrome P450 3a4 (cyp3a4) SubstratesModafinil (provigil)Naltrexone (vivitrol)Quetiapine (seroquel)Serotonergic DrugsVenlafaxine (effexor)Cytochrome P450 2c19 (cyp2c19) Substrates
Cns Depressants

Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.
Kratom contains mitragynine, a mu-receptor agonist that may cause respiratory depression. Although results from animal research suggest that mitragynine causes less respiratory depression than the CNS depressant codeine, fatalities have been reported for patients who ingested a combination of kratom and O-desmethyltramadol, another mu-receptor agonist. Additionally, observational research suggests that adverse effects such as drowsiness and coma are more likely to occur in individuals taking kratom in combination with agents such as opioids and sedatives. Theoretically, ingesting kratom along with other CNS depressants can increase the risk of adverse effects, including drowsiness, coma, and/or severe or fatal respiratory depression.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that kratom extract inhibits the activity of CYP1A2. 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 CYP1A2-mediaed metabolism of ziprasidone which consequently increased systemic exposure to serotonin.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

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.

Likelihood Possible Evidence D
Modafinil (Provigil)

Theoretically, taking kratom in combination with modafinil may increase the risk of seizures.
A 43-year-old male patient experienced generalized tonic-clonic seizures after adding modafinil 100 mg to his chronic ingestion of kratom tea four times daily to further improve alertness and as a self-treatment for opioid withdrawal. The exact mechanism by which this interaction may occur is unknown.

Likelihood Possible Evidence D
Naltrexone (Vivitrol)

Taking kratom in combination with naltrexone might precipitate withdrawal.
Animal research shows that, while naltrexone does not antagonize the primary kratom alkaloid mitragynine, it does inhibit the behavioral effects of the metabolite 7-hyroxymitragynine by antagonizing its binding at the mu-opioid receptor. In humans, taking naltrexone has precipitated withdrawal from kratom. In one case, a patient chronically consuming kratom developed agitation, hallucinations, and delirium within about 2 hours of beginning oral naltrexone therapy. In another case, a 38-year-old male who was admitted to a residential rehabilitation treatment program for polysubstance abuse experienced opioid withdrawal after administration of intramuscular naltrexone. Although the patient reported discontinuing kratom, continued use was confirmed through positive urine mitragynine tests. Manufacturer guidance states that patients should be opioid-free for a minimum of 7-10 days prior to initiating treatment with naltrexone; this case report suggests that kratom use should be given similar consideration.

Likelihood Possible Evidence D
Quetiapine (Seroquel)

Theoretically, taking kratom in combination with quetiapine may increase levels and adverse effects of quetiapine.
A 27-year-old male was found deceased due to neuroleptic malignant-like symptoms after concomitant consumption of quetiapine and kratom. Although it did not appear that he had consumed large quantities of the medication, he was found to have a lethal plasma level of quetiapine. It is hypothesized that kratom inhibited cytochrome P450 (CYP) 3A4, the primary metabolic pathway for quetiapine. Also, a 36-year-old male presented to the emergency department with serotonin syndrome and QT interval prolongation after concomitant use of quetiapine, venlafaxine, and kratom. It is hypothesized that kratom may have inhibited the metabolism of both venlafaxine and quetiapine.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
Venlafaxine (Effexor)

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.

Likelihood Possible Evidence D
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, kratom might increase the levels of drugs metabolized by CYP2C19.
In vitro research shows that kratom extract weakly inhibits CYP2C19 enzyme activity.

Likelihood Possible Evidence D
Monograph

Kratom: Uses, Safety & Side Effects

Medically reviewed by · Reviewed July 2026 ·
The bottom line

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.

Kratom
Scientific name
Mitragyna speciosa
Family
Rubiaceae
Part used
Leaves
Common forms
Dried leaf powder, capsules, tablets, brewed tea, liquid extracts, and concentrated gummies
People commonly use it for
  • Pain relief
  • Opioid withdrawal symptoms
  • Anxiety and stress
  • Low energy or fatigue
  • Mood enhancement

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance
OverallBest avoided

Kratom carries risks of dependence, serious side effects, and contaminated products, and is not regulated as a safe supplement.

PregnancyPossibly Unsafe

When used orally. There have been multiple case reports of neonatal abstinence syndrome in the infants of those who used kratom during pregnancy. Anim...

Read the full pregnancy detail
BreastfeedingInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Jump to a section

Overview

Kratom comes from the leaves of a tropical tree called Mitragyna speciosa, which grows in Southeast Asia in countries like Thailand, Malaysia, and Indonesia. For many years, workers in this region chewed the fresh leaves or brewed them into tea to fight tiredness and ease pain.

Today kratom is sold in many countries as a powder, capsule, tablet, tea, liquid extract, or concentrated gummy. People often take it for pain, low energy, anxiety, or to help with opioid withdrawal. Interestingly, it can act like a stimulant at lower amounts and more like an opioid sedative at higher amounts.

It is important to know that kratom is not approved as a medicine in the United States, and the U.S. Food and Drug Administration (FDA) has warned about its risks. Product quality varies a lot, and some products have been found to be contaminated.

How it works

Kratom leaves contain natural compounds called alkaloids. The two studied most are mitragynine and 7-hydroxymitragynine. These compounds interact with the brain's opioid receptors, which is why kratom can produce pain relief, relaxation, and a feeling of well-being.

At lower amounts, kratom tends to act more like a stimulant, giving a sense of energy and alertness. At higher amounts, it tends to act more like an opioid, causing sedation and stronger pain relief. Because it touches the same brain pathways as opioids, it can also lead to tolerance, dependence, and withdrawal.

Much of this understanding is based on laboratory and animal research, so the full picture of how kratom works in people is still not completely clear.

Effectiveness

Does Kratom work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by .

Evidence overview · 12 uses evaluated
12 Insufficient evidence
How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.
2Likely EffectiveGood evidence, though not yet conclusive.
3Possibly EffectiveSome evidence suggests a benefit.
4Possibly IneffectiveSome evidence it may not help.
5Likely IneffectiveFairly strong evidence it doesn’t help.
6IneffectiveStrong evidence it doesn’t work.
7Insufficient Reliable Evidence to RateToo little research to say either way.

For Kratom, current evidence isn’t strong enough to rate any specific use. The conditions it has been studied for are listed below.

Also studied for 12 conditions — evidence insufficient to rate
Insufficient Reliable Evidence To Rate Anxiety
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for anxiety, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Athletic performance
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for athletic performance, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Cough
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for cough, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Depression
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for depression, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Diabetes
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for diabetes, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Diarrhea
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for diarrhea, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Erectile dysfunction (ED)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral kratom is beneficial for ED.

Insufficient Reliable Evidence To Rate Fatigue
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for fatigue, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Hypertension
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for hypertension, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Opioid withdrawal
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for opioid withdrawal, there is insufficient reliable information about the clinical effects of kratom for this condition.

Insufficient Reliable Evidence To Rate Pain (acute)
Rating & evidence shown verbatim from Natural Medicines

It is unclear if oral kratom is beneficial for acute pain.

Insufficient Reliable Evidence To Rate Sexual dysfunction
Rating & evidence shown verbatim from Natural Medicines

Although there has been interest in using oral kratom for sexual dysfunction, there is insufficient reliable information about the clinical effects of kratom for this condition.

Source & disclaimer. Effectiveness ratings and evidence summaries are provided by Natural Medicines (Therapeutic Research Center) and shown as licensed. Where Natural Medicines hasn’t rated a use, HelloPharmacist’s pharmacists may add their own reviewed rating and evidence (each such entry is labeled). This is educational information, not medical advice — talk with your pharmacist or doctor before starting, stopping, or changing a supplement.

Safety & precautions

Kratom is not considered a safe supplement by major health authorities. The FDA has not approved it for any use and has raised concerns about its risks. It can cause dependence and withdrawal symptoms similar to opioids, especially with regular or heavy use.

People with heart problems, liver disease, mental health conditions, or a history of substance use should be especially cautious. Because kratom products are not tightly regulated, they may contain contaminants such as heavy metals or bacteria, or be mixed with other substances.

Pregnancy and breastfeeding: Kratom should be avoided. Use during pregnancy has been linked to withdrawal symptoms in newborns, and its compounds may pass into breast milk. Anyone who is pregnant, planning to become pregnant, or nursing should not use kratom.

Always talk with a pharmacist or doctor before using kratom, particularly if you take other medicines or have ongoing health conditions.

Side effects

Common side effects include nausea, vomiting, constipation, dry mouth, itching, sweating, dizziness, and drowsiness. Some people also feel restless, anxious, or irritable, and frequent use can lead to dependence.

More serious harms have been reported, including liver injury, seizures, high blood pressure, fast heartbeat, confusion, and trouble breathing. In rare cases, kratom has been linked to deaths, often when combined with other drugs or in contaminated products.

Stopping kratom after regular use can cause withdrawal symptoms such as muscle aches, irritability, runny nose, trouble sleeping, and mood changes. Seek medical help right away for severe symptoms like difficulty breathing, chest pain, or seizures.

Kratom: Reported Adverse Effects

Documented safety reports on Kratom from the evidence-graded Natural Medicines (TRC Healthcare) database, shown word-for-word from the licensed record.

Orally, kratom is possibly unsafe. Topically, no adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.

Most Common Adverse Effects:

Orally: Constipation, dependence (chronic use), dry mouth, frequent urination, nausea, tongue numbness, and vomiting.

Serious Adverse Effects (Rare):

Orally: Cardiac arrest, death, encephalopathy syndrome, hallucinations, hypertension, hypothyroidism, insomnia, liver damage, rhabdomyolysis, respiratory depression, seizures, serotonin syndrome, and tachycardia. However, a definite causal link between kratom and most of these serious adverse effects has not yet been confirmed.

Reports by condition
Acute respiratory distress syndrome (ARDS) Pulmonary/Respiratory

Orally, kratom has been linked to respiratory depression, particularly when used in combination with other mu-opioid agonists. In one case report, a 36-year-old male with a history of substance abuse and smoking was diagnosed with kratom-induced acute respiratory distress syndrome (ARDS) after presenting with progressive respiratory failure, hypoxemia, and bilateral lung infiltrates. The patient was treated with mechanical ventilation, intravenous methylprednisolone, and supplemental oxygen. Additionally, a 32-year-old male with a history of substance abuse, depression, and obesity presented after collapsing due to seizure with acute mitragynine intoxication. The patient was found to have pulmonary edema along with cardiomegaly with left ventricular hypertrophy, hepatomegaly, and cerebral edema. Postmortem toxicology analysis of blood, organs, and gastric contents were negative for all illicit and prescription drugs except for the kratom components mitragynine and 7-hydroxymitragynine.

  1. Backstrom BG, Classon G, Lowenhielm P, Thelander G. [Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden]. Lakartidningen 2010;107(50):3196-3197.
  2. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol 2011;35(4):242-247.
  3. US Food and Drug Administration (2014). SNI National is Voluntarily recalling Kratom XL 4 Pack, Maeng Da Kratom 10 Pack, Max Kratom 20 Pack, and Bali Kratom 40 pack Due to Undeclared Drug Ingredients [Press Release].
  4. Davidson C, Cao D, King T, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abuse. 2020:1-10.
  5. Graves JM, Dilley JA, Terpak L, et al. Kratom exposures among older adults reported to U.S. poison centers, 2014-2019. J Am Geriatr Soc 2021;69(8):2176-2184.
  6. Peran D, Stern M, Cernohorsky P, Sykora R, Popela S, Duska F. Mitragyna speciosa (Kratom) poisoning: Findings from ten cases. Toxicon 2023;225:107054.
  7. Ahmed S, Tran QV, McLean M. The Great Imitator: A Case of Accidental Kratom Overdose. Cureus 2023;15(8):e43144.
  8. Chinnappan J, Navari Y, Casini D, Palanisamy N, Parikh N, Seedahmed E. Kratom-Induced Acute Respiratory Distress Syndrome (ARDS). Eur J Case Rep Intern Med 2023;10(4):003835.
  9. Mata DC, Chang HH. Postmortem Mitragynine Distribution in a Single Drug Fatality Case. Acad Forensic Pathol 2023;13(1):34-40.
Alcohol-related liver disease Neurologic/CNS

In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 75% of cases reported neurologic effects, including agitation, coma, confusion, dizziness, drowsiness, hallucinations, seizures, and tremor. Other reports of calls to poison control centers related to kratom use and data from the US Food and Drug Administration (FDA) Adverse Events Reporting System show that 5% to 25% of cases included reports of seizures, coma, headache, or confusion.

Multiple cases of kratom-induced new-onset or recurrent generalized tonic-clonic seizures have been reported in regular users of kratom. One case series describes two patients with prior epilepsy who developed breakthrough seizures associated with kratom use and one patient who developed a diagnosis of epilepsy after continued use of kratom. Seizures generally occurred within 1 month of initiation of kratom and ceased with discontinuation of kratom and continuation of an effective antiepileptic drug regimen.

Most case reports of seizure often involve use of multiple active agents, including diphenhydramine, methamphetamine, and other medications not normally associated with seizures. A case of seizure and coma has been reported for a 64-year-old habitual kratom user who had ingested a tea containing an undetermined quantity of kratom and jimson weed 30 minutes prior to the event. This patient had also been taking amitriptyline and oxycodone chronically, although neither of these drugs is typically associated with increased seizure risk. Additionally, a case of generalized tonic-clonic seizures has been reported for a 43-year-old male patient who added modafinil 100 mg to his chronic ingestion of kratom tea four times daily as self-treatment for opioid withdrawal. Modafinil is not generally associated with increased seizures; however, it is speculated that the combination of modafinil with kratom may have contributed to the adverse event. Finally, there is a case report of a 22-year-old male who presented to the emergency room with severe headache, confusion, hypertension, and visual disturbances due to posterior reversible encephalopathy syndrome (PRES) after taking an undisclosed amount of dextroamphetamine and kratom. It is believed that the combination with kratom resulted in increased blood pressure and neurotoxicity that caused PRES.

Orally, kratom has been linked to respiratory depression, particularly when used in combination with other mu-opioid agonists. In reviews of kratom-associated adverse events reported to the National Poison Data System, up to 12% of cases experienced respiratory effects, including respiratory depression. There were 9 reports of deaths most likely due to respiratory depression in patients who ingested a combination product (Krypton) containing kratom and O-desmethyltramadol, another mu-receptor agonist. Serum concentrations of O-desmethyltramadol ranged from 0.4 to 4.3 mcg/gram. Tramadol concentrations >1 mcg/gram are considered toxic, and O-desmethyltramadol is considered to be a more potent metabolite of tramadol. Therefore, it is believed that O-desmethyltramadol probably contributed to the toxicity, but kratom possibly had an additive effect. Nearly all of these patients had brain edema and lung edema or congestion and some also had liver steatosis during autopsy. Many of these patients had a history of drug abuse and also had detectable serum concentrations of antidepressants, benzodiazepines, alcohol, amphetamines, zopiclone, alimemazine, or other drugs.

Kratom was implicated in a case of serotonin syndrome in a patient taking multiple serotonergic prescription medications. In the case report, a 63-year-old male was stable for 2 years on bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone when he started taking kratom 3 times daily for 3 months. The patient presented with aphasia, spontaneous clonus, confusion, diaphoresis, dysarthria, facial droop, fever, flushing, hyperreflexia, and tremors with elevated creatine phosphokinase and lactic acid. Symptoms improved after discontinuing kratom and supportive care with cyproheptadine, lorazepam, intravenous fluids, and cooling blankets.

Observational research has found that habitual intake of kratom is associated with withdrawal symptoms, including hot flashes and fever.

  1. Graves JM, Dilley JA, Terpak L, et al. Kratom exposures among older adults reported to U.S. poison centers, 2014-2019. J Am Geriatr Soc 2021;69(8):2176-2184.
  2. Cumpston KL, Carter M, Wills BK. Clinical outcomes after Kratom exposures: A poison center case series. Am J Emerg Med. 2018;36(1):166-168.
  3. Eggleston W, Stoppacher R, Suen K, Marraffa JM, Nelson LS. Kratom Use and Toxicities in the United States. Pharmacotherapy. 2019 Jul;39(7):775-777. doi: 10.1002/phar.2280. Epub 2019 Jun 13.
  4. Davidson C, Cao D, King T, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abuse. 2020:1-10.
  5. Peran D, Stern M, Cernohorsky P, Sykora R, Popela S, Duska F. Mitragyna speciosa (Kratom) poisoning: Findings from ten cases. Toxicon 2023;225:107054.
  6. Afzal H, Esang M, Rahman S. A case of kratom-induced seizures. Cureus. 2020;12(1):e6588.
  7. Halim SA, Low JH, Chee YC, Alias MR. Seizures among young adults consuming kratom beverages in Malaysia: A case series. Epilepsy Behav 2021;121(Pt A):108057.
  8. Mata DC, Chang HH. Postmortem Mitragynine Distribution in a Single Drug Fatality Case. Acad Forensic Pathol 2023;13(1):34-40.
  9. Burke DJ, Mahonski SG, Van Cott AC. Breakthrough Seizure Associated With Kratom Use in Patients With Epilepsy. Neurol Clin Pract 2021;11(1):78-84.
  10. Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM. Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure. J Med Toxicol 2010;6(4):424-426.
  11. Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction 2008;103(6):1048-1050.
  12. Castillo A, Payne JD, Nugent K. Posterior reversible leukoencephalopathy syndrome after kratom ingestion. Proc (Bayl Univ Med Cent). 2017;30(3):355-357.
  13. Backstrom BG, Classon G, Lowenhielm P, Thelander G. [Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden]. Lakartidningen 2010;107(50):3196-3197.
  14. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol 2011;35(4):242-247.
  15. US Food and Drug Administration (2014). SNI National is Voluntarily recalling Kratom XL 4 Pack, Maeng Da Kratom 10 Pack, Max Kratom 20 Pack, and Bali Kratom 40 pack Due to Undeclared Drug Ingredients [Press Release].
  16. Reich N, Salvo G, Leong D, Wan V, Kosatsky T. Kratom exposures managed by the British Columbia poison centre, 2012-2019: a descriptive analysis. CMAJ Open 2022;10(3):E755-E761.
  17. Ahmed S, Tran QV, McLean M. The Great Imitator: A Case of Accidental Kratom Overdose. Cureus 2023;15(8):e43144.
  18. Eudaley ST, Brooks SP, Hamilton LA. Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents. J Pharm Pract 2022.
  19. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend 2014 Jun 1;139:132-7.
Alcohol-related liver disease Hepatic

Orally, kratom has been associated with cases of liver damage. Between 2003 and 2019, there were 11 cases of liver injury reported in the Drug-Induced Liver Injury Network (DILIN) with definite, highly likely, or probable causality attributed to kratom. Of these cases, 8 were reported between 2017 and 2019. The median time from kratom use to the onset of symptoms was 14 days. Just over half of the patients had evidence of mixed liver injury, including both hepatocellular and cholestatic injury. In addition, published case reports, the FDA adverse event databases, DILIN, and the British Columbia poison control center identified 72 reports of kratom-induced liver injury, although it's possible some duplication of reporting occurred across the databases.

Multiple detailed case reports of liver injury have been published. One case of intrahepatic cholestasis has been reported for a 25-year-old healthy male who consumed kratom powder, starting at 1-2 teaspoons (2.3-7 grams) daily and increasing to 4-6 teaspoons (9-21 grams) daily over 2 weeks. In another case report, a 40-year-old female presented with symptoms of mixed cholestatic and hepatocellular liver injury after consuming kratom once weekly for the past month. Her symptoms resolved upon discontinuation of kratom. Cases of transaminitis, with or without bilirubin elevation, also have been described. In one such case, a 60-year-old patient presented with elevated transaminases and bilirubin after ingesting kratom one teaspoon three times daily for one month. The liver enzymes normalized after discontinuing kratom and receiving supportive treatment with N-acetylcysteine. In another case, a patient with a several-year history of kratom use and a history of hepatic steatosis, choledocholithiasis, and cholecystectomy presented with worsening jaundice, scleral icterus, ascites, and pitting edema. The patient was found to have cholestatic hepatitis consistent with drug-induced liver injury, as well as steatohepatitis with marked fibrosis and scarring. A third case also reported a mixed cholestatic and hepatocellular liver injury in a 23-year-old male who had consumed a cocktail containing kratom leaves, caffeinated soda, and diphenhydramine syrup daily for 2 weeks. Liver function tests normalized after supportive care and discontinuation of the kratom-containing product. In one case of chronic kratom abuse, an adult presented with acute liver failure with hyperbilirubinemia and acute kidney injury. The patient recovered after plasma exchange treatment daily for 4 days in addition to supportive care.

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  8. Botejue M, Walia G, Shahin O, Sharma J, Zackria R. Kratom-Induced Liver Injury: A Case Series and Clinical Implications. Cureus 2021;13(4):e14679.
  9. Roma K, Mohammed S, Sieck B, Naik K, Wahid S. Kratom-induced acute liver injury: A case study and the importance of herbal supplement regulation. J Hepatol 2023.
  10. Thewjitcharoen Y, Krittiyawong S, Nakasatien S, Himathongkam T. Kratom-Associated Mixed Cholestatic-Hepatocellular Liver Injury in a Patient With Long COVID: A case Report. Clin Med Insights Case Rep 2022;15:11795476221132824.
  11. Smith KE, Feldman JD, Dunn KE, et al. Examining the paradoxical effects of kratom: a narrative inquiry. Front Pharmacol 2023;14:1174139.
  12. Vanani NB, Stevanovic SG, Stevanovic N. Adverse Drug Interaction Between Kratom and Amitriptyline With Gastrointestinal and Mild Hepatic Effects. Cureus 2023;15(1):e33809.
  13. Dasgupta A, Ye Z. Severe jaundice with life-threatening liver failure after Kratom use: Reversed by plasma exchange. Transfus Apher Sci 2024.
Anxiety Psychiatric

Orally, kratom has been associated with aggression, agitation, altered mental status, anxiety, delusions, depression, hallucinations, insomnia, irritability, paranoia, restlessness, sedation, and suicidal ideation, in case reports and case series. In a review of kratom-associated adverse events reported to the National Poison Data System, 18.6% of users reported agitation, 13.6% reported drowsiness, 8.1% reported confusion, and 4.8% reported hallucinations. In an analysis of kratom abuse cases in Thailand and the United States from 2010-2017, agitation/irritability, drowsiness/lethargy, confusion, and hallucinations were reported in approximately 26%, 21%, 16%, and 7%, respectively. Additionally, data from the US Food and Drug Administration (FDA) Adverse Event Reporting System from 2004 to 2021 shows that kratom use was linked to dependence, anxiety, withdrawal syndrome, and drug abuse in 11%, 6%, 5%, and 5% of total adverse events reported.

A cross-sectional study in approximately 400 adults with regular kratom use suggests that kratom dose and frequency of use are positively associated with symptoms of kratom use disorder and withdrawal. Additionally, multiple case reports of patients who habitually ingest kratom at high doses report physical tolerance, dependence, and subsequent withdrawal upon discontinuation that is consistent with DSM-5 diagnostic criteria for kratom use disorder. Some cases of dependence and/or withdrawal have been successfully treated with buprenorphine/naloxone. One case of acute withdrawal symptoms was managed with intravenous lorazepam and dexmedetomidine. Additionally, in a case of acute mania due to kratom withdrawal, aripiprazole was used to manage symptoms.

There have been multiple case reports of neonatal abstinence syndrome (NAS) occurring in the infants of patients who used kratom throughout pregnancy. Daily kratom doses in these cases ranged from 15-60 grams daily; self-directed attempts to discontinue use during pregnancy failed due to symptoms of withdrawal. The affected infants were successfully treated with standard NAS monitoring and care. The absence of kratom identification by standard urine toxicology tests can make detection of kratom use challenging. However, specialized umbilical cord testing can identify kratom analytes mitragynine and speciociliatine as biomarkers for in-utero kratom exposure. In some patients, prenatal screening with questionnaires specifically inquiring about kratom use has led to early detection and successful transition to buprenorphine for the remainder of the pregnancy.

  1. US Food and Drug Administration (2014). SNI National is Voluntarily recalling Kratom XL 4 Pack, Maeng Da Kratom 10 Pack, Max Kratom 20 Pack, and Bali Kratom 40 pack Due to Undeclared Drug Ingredients [Press Release].
  2. Cumpston KL, Carter M, Wills BK. Clinical outcomes after Kratom exposures: A poison center case series. Am J Emerg Med. 2018;36(1):166-168.
  3. Li X, Ndungu P, Taneja SB, et al. An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021. Clin Transl Sci 2023.
  4. Peran D, Stern M, Cernohorsky P, Sykora R, Popela S, Duska F. Mitragyna speciosa (Kratom) poisoning: Findings from ten cases. Toxicon 2023;225:107054.
  5. Settle AG, Yang C. A Case of Severe Kratom Addiction Contributing to a Suicide Attempt. Cureus 2022;14(9):e29698.
  6. Smith KE, Feldman JD, Dunn KE, et al. Examining the paradoxical effects of kratom: a narrative inquiry. Front Pharmacol 2023;14:1174139.
  7. Ahmed S, Tran QV, McLean M. The Great Imitator: A Case of Accidental Kratom Overdose. Cureus 2023;15(8):e43144.
  8. Awad M, Burke HH, Oakman SA. Kratom-Induced Psychiatric Decompensation and Paranoid Delusions. Cureus 2024;16(2):e54626.
  9. Eggleston W, Stoppacher R, Suen K, Marraffa JM, Nelson LS. Kratom Use and Toxicities in the United States. Pharmacotherapy. 2019 Jul;39(7):775-777. doi: 10.1002/phar.2280. Epub 2019 Jun 13.
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  14. Hong S, Zimmerman PE, Rao V, Markwalter DW. Buprenorphine-Naloxone in the Setting of Kratom Withdrawal, Opioid Use Disorder, and Stage IV Lung Adenocarcinoma. J Palliat Med 2023;26(5):734-736.
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Arrhythmia Cardiovascular

Orally, kratom can cause tachycardia and changes in blood pressure, especially when used in doses of 8 grams or more. In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 45% of cases reported cardiovascular effects. Patients who have called poison control centers in the United States, Thailand, and British Columbia report stimulant effects including tachycardia and hypertension after chronic and acute kratom use.

Additionally, a large analysis of adverse effect reporting databases suggests that mitragynine, a constituent of kratom, is associated with an increased risk of ventricular arrhythmias and cardiac arrest, but not QTc prolongation. The validity of this study is limited by voluntary reports and potential for multiple co-ingestions or co-exposures in individual reports.

One observational study reported that regular kratom use, with an estimated daily intake of mitragynine 7.06 mg/kg/day, was associated with at least an 8-fold increase in the odds of presenting with sinus tachycardia when compared with non-kratom users. However, there was no difference in the odds of having other ECG abnormalities. In this study, kratom use was associated with an increased odds of borderline QTc intervals, but not prolonged QTc intervals. The highest odds occurred in those who started using kratom after age 18, had used kratom for more than 6 years, or those who had used kratom within 3 hours of the ECG. In regular kratom users, a case series conducted to analyze serum mitragynine levels with respect to cardiovascular functioning found that higher serum mitragynine levels (i.e., at least 9.6 mg/L) were associated with prolongation of the QT interval and such effects were found to be dose-dependent.

In one case report, an otherwise healthy, 35-year-old male with a history of opioid use disorder presented with cardiac arrest after recently consuming kratom tea multiple times per day. No other substance use was identified on toxicology screening or via patient report.

Another case of cardiac arrest with ventricular fibrillation has been reported in a 24-year-old male who reported long-term use of kratom (dose and frequency unknown). While the patient had a history of polysubstance abuse, his serum and urine drug screens were negative for opiates, benzodiazepines, amphetamines, and cocaine. Similarly, cardiac arrest with ventricular fibrillation was reported in an 18-year-old male during football training following the consumption of 2 grams of kratom and an energy drink. Blood tests were positive for kratom and caffeine. It is unclear if the cardiac event was related to kratom, caffeine, exercise, or other factors. A 32-year-old male with a history of substance abuse, depression, and obesity presented after collapsing due to seizure with acute mitragynine intoxication. The patient also presented with cardiomegaly with left ventricular hypertrophy, hepatomegaly, cerebral edema, and pulmonary edema. Postmortem toxicology analysis of blood, organs, and gastric contents were negative for all illicit and prescription drugs except for the kratom components mitragynine and 7-hydroxymitragynine.

There have been two case reports of 54-year-old adults using kratom regularly for one year who developed stimulatory effects and a large hemorrhagic stroke. In both cases, the development of these adverse effects occurred immediately after the transition to a different kratom product. In one case, the product was found to be adulterated with phenethylamine (PEA), an amphetamine-like chemical, which was considered the likely cause of these effects.

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Constipation Gastrointestinal

Kratom ingestion has been associated with nausea, vomiting, dry mouth, tongue numbness, increased appetite, and constipation. In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 25% of cases reported gastrointestinal effects. Observational research, data from the British Columbia poison control center, and a report from the US Food and Drug Administration (FDA) Adverse Event Reporting System have found that habitual intake of kratom is associated with withdrawal symptoms, including decreased appetite and diarrhea.

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  3. Castillo A, Payne JD, Nugent K. Posterior reversible leukoencephalopathy syndrome after kratom ingestion. Proc (Bayl Univ Med Cent). 2017;30(3):355-357.
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  5. Davidson C, Cao D, King T, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abuse. 2020:1-10.
  6. Li X, Ndungu P, Taneja SB, et al. An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021. Clin Transl Sci 2023.
  7. Smith KE, Feldman JD, Dunn KE, et al. Examining the paradoxical effects of kratom: a narrative inquiry. Front Pharmacol 2023;14:1174139.
  8. 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.
  9. Graves JM, Dilley JA, Terpak L, et al. Kratom exposures among older adults reported to U.S. poison centers, 2014-2019. J Am Geriatr Soc 2021;69(8):2176-2184.
  10. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend 2014 Jun 1;139:132-7.
  11. Reich N, Salvo G, Leong D, Wan V, Kosatsky T. Kratom exposures managed by the British Columbia poison centre, 2012-2019: a descriptive analysis. CMAJ Open 2022;10(3):E755-E761.
Epilepsy Musculoskeletal

Observational research has found that habitual intake of kratom is associated with withdrawal symptoms, including arthralgias, lower extremity hyperreflexia, muscle pain, rigidity, spasms, and tremors.

In a case report, a 45-year-old adult who had used kratom intermittently for 10 months experienced mild rhabdomyolysis and generalized seizures. Several cases of severe rhabdomyolysis and associated kidney injury necessitating hemodialysis have been described.

In another case report, a 39-year-old adult experienced transient paralysis, with full awareness but an inability to move or speak, within 1 hour of using kratom. The patient reported a recent history of kratom use over the past few months, but that the paralysis occurred immediately after the use of a different kratom product.

  1. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend 2014 Jun 1;139:132-7.
  2. Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol 1988;23(1):115-119.
  3. Davidson C, Cao D, King T, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abuse. 2020:1-10.
  4. Hong S, Zimmerman PE, Rao V, Markwalter DW. Buprenorphine-Naloxone in the Setting of Kratom Withdrawal, Opioid Use Disorder, and Stage IV Lung Adenocarcinoma. J Palliat Med 2023;26(5):734-736.
  5. Smith KE, Feldman JD, Dunn KE, et al. Examining the paradoxical effects of kratom: a narrative inquiry. Front Pharmacol 2023;14:1174139.
  6. Cumpston KL, Carter M, Wills BK. Clinical outcomes after Kratom exposures: A poison center case series. Am J Emerg Med. 2018;36(1):166-168.
  7. Sangani V, Sunnoqrot N, Gargis K, Ranabhotu A, Mubasher A, Pokal M. Unusual Presentation of Kratom Overdose With Rhabdomyolysis, Transient Hearing Loss, and Heart Failure. J Investig Med High Impact Case Rep 2021;9:23247096211005069.
  8. Patel P, Aknouk M, Keating S, et al. Cheating Death: A Rare Case Presentation of Kratom Toxicity. Cureus 2021;13(7):e16582.
  9. Matos-Casano HA, Nanduri S. Transient Paralysis: A Novel Expression of Kratom Toxicity in Humans. Neurol Clin Pract 2021;11(1):e28-e29.
Epilepsy Other

Data from the US Food and Drug Administration (FDA) Adverse Event Reporting System shows that from 2004 to 2021, out of 489 kratom-related adverse reaction reports, 102 deaths and 34 accidental deaths were reported, accounting for 21% and 7% of total adverse events reported. However, only 45% of reported adverse events listed kratom as the only drug ingested. In February 2018, the FDA reported at least 44 deaths associated with kratom use. This number was based on information from academic research, poison control centers, medical examiner reports, social science research, and adverse event reports. The exact cause of death was not determined in most cases. More recently, the Centers for Disease Control and Prevention (CDC) analyzed data from the State Unintentional Drug Overdose Reporting System (SUDORS) to determine what percentage of kratom-positive deaths reported between July 2016 and December 2017 were caused by kratom. Of 27,338 overdose deaths reported, 152 of the decedents tested positive for kratom in a postmortem analysis. Of these cases in which the decedents were kratom-positive, 91 of the deaths were considered to be kratom-involved. In one Poison Control Center report of 3484 exposures to kratom, the majority of which involved oral single-substance exposures, 8 deaths occurred in cases where kratom was the only substance involved. Adverse effects prior to kratom-related death have included pulmonary edema and congestion, pulmonary embolism, encephalopathy, cardiorespiratory arrest, cardiomegaly, hemorrhagic stroke, and seizures.

In almost all cases, kratom was used along with other drugs, so it is unclear if kratom was the primary causal agent or a contributing factor. Furthermore, in an analysis of deaths attributed to kratom in Colorado, re-testing of residual blood from decedents found that all cases of kratom-related death involved other drugs, including those that were initially reported as not involving other drugs. Concomitant drugs included fentanyl, benzodiazepines, opioids, stimulants, antidepressants, antihistamines, antitussives, sedatives, antihypertensives, antidiarrheals, anticonvulsants, and other medications. Additionally, samples of commercially available kratom products may contain high levels of lead which pose significant health risks to consumers, especially at high doses. There is significant overlap in adverse effects in the central nervous system, liver, gastrointestinal tract, and cardiovascular system between kratom and lead toxicity, which raises the possibility that toxic effects attributed to kratom may actually be due to lead contaminants in kratom products.

Long-term, heavy kratom intake does not appear to be associated with abnormalities in standard hematological and clinical chemistry blood tests.

  1. Li X, Ndungu P, Taneja SB, et al. An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021. Clin Transl Sci 2023.
  2. FDA Adverse Event Reporting System: Kratom Deaths. February 6, 2018. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/CDERFOIAElectronicReadingRoom/UCM595575.pdf. Accessed March 6, 2018.
  3. Olsen EO, O'Donnell J, Mattson CL, Schier JG, Wilson N. Notes from the field: Unintentional drug overdose deaths with kratom detected - 27 States, July 2016-December 2017. MMWR Morb Mortal Wkly Rep. 2019;68(14):326-327.
  4. Graves JM, Dilley JA, Terpak L, et al. Kratom exposures among older adults reported to U.S. poison centers, 2014-2019. J Am Geriatr Soc 2021;69(8):2176-2184.
  5. Mata DC, Chang HH. Postmortem Mitragynine Distribution in a Single Drug Fatality Case. Acad Forensic Pathol 2023;13(1):34-40.
  6. Gershman K, Timm K, Frank M, et al. Deaths in Colorado Attributed to Kratom. N Engl J Med. 2019 Jan 3;380(1):97-98.
  7. Matson M, Schenk N. Fatality of 33-year-old man involving kratom toxicity. J Forensic Sci. 2019;64(6):1933-5.
  8. Prozialeck W, Fowler A, Edwards J. Public Health Implications and Possible Sources of Lead (Pb) as a Contaminant of Poorly Regulated Kratom Products in the United States. Toxics 2022;10(7):398.
  9. Singh D, Murugaiyah V, Hamid SBS, et al. Assessment of gonadotropins and testosterone hormone levels in regular Mitragyna speciosa (Korth.) users. J Ethnopharmacol 2018;221:30-6. doi: 10.1016/j.jep.2018.04.005.
  10. Singh D, Müller CP, Murugaiyah V, et al. Evaluating the hematological and clinical-chemistry parameters of kratom (Mitragyna speciosa) users in Malaysia. J Ethnopharmacol 2018;214:197-206. doi: 10.1016/j.jep.2017.12.017.
Hypothyroidism Endocrine

A case of primary hypothyroidism has been reported for an individual who regularly consumed kratom. However, a causal link between kratom use and thyroid dysfunction has not yet been determined.

  1. Sheleg SV, Collins GB. A coincidence of addiction to "Kratom" and severe primary hypothyroidism. J Addict Med 2011;5(4):300-301.
Nausea and vomiting Renal

Orally, kratom has been associated with frequent urination, electrolyte abnormalities, and renal insufficiency,. In one case report, a 61-year-old male with no significant past medical history experienced persistent asymptomatic hyperkalemia after 4 months of regular, nearly daily use of kratom. Potassium levels normalized upon discontinuation of kratom. In another case, a 62-year-old male with severe hyponatremia presented with altered mental status, restlessness, and minimal fluid intake after consuming large doses of kratom. The hyponatremia was treated with fluids and discontinuation of kratom.

In another case report, a 21-year-old female was diagnosed with acute renal insufficiency after presenting with nausea, vomiting, left flank pain, elevated serum creatinine, proteinuria, and bilateral enlarged kidneys after consuming kratom tea. Testing of the kratom leaf sample revealed the presence of hydrocodone, morphine, and mitragynine which all contributed to acute renal insufficiency. The symptoms resolved following discontinuation of the kratom product and supportive care with intravenous fluids. It is unclear whether the renal insufficiency was due to kratom or the other adulterants in the tested sample.

  1. Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol 1988;23(1):115-119.
  2. US Food and Drug Administration (2014). SNI National is Voluntarily recalling Kratom XL 4 Pack, Maeng Da Kratom 10 Pack, Max Kratom 20 Pack, and Bali Kratom 40 pack Due to Undeclared Drug Ingredients [Press Release].
  3. Castillo A, Payne JD, Nugent K. Posterior reversible leukoencephalopathy syndrome after kratom ingestion. Proc (Bayl Univ Med Cent). 2017;30(3):355-357.
  4. Torres-Ortiz A, Al Zein S, Alqudsi M. A Case of Hyperkalemia Induced by Kratom (Mitragyna speciosa). Cureus 2022;14(4):e24036.
  5. LeSaint KT, Yin S, Sharma A, Avery BA, McCurdy CR, Waksman JC. Acute Renal Insufficiency Associated With Consumption of Hydrocodone- and Morphine-Adulterated Kratom (Mitragyna Speciosa). J Emerg Med 2022;63(1):e28-e30.
  6. Martin G, Collins DP, Valenzuela H. Life-Threatening Hyponatremia Secondary to Chronic Kratom Use: A Case Presentation. Cureus 2022;14(9):e29073.
DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

Adverse-effects data: Natural Medicines, Therapeutic Research Center

Dosing

There is no established safe or standardized dose for kratom. The strength of products varies widely, and the amount of active compounds can differ greatly from one batch to another, even within the same brand.

Because of these unknowns and the real risks of dependence and harm, we cannot recommend a specific amount. If you are considering kratom despite the risks, follow the product label and speak with a pharmacist or doctor first. Avoid mixing it with alcohol, opioids, sedatives, or other substances.

Pregnancy & Breastfeeding

Kratom & Pregnancy

Possibly Unsafe

When used orally. There have been multiple case reports of neonatal abstinence syndrome in the infants of those who used kratom during pregnancy. Animal research suggests that kratom crosses the placenta.

  1. Mackay L, Abrahams R. Novel case of maternal and neonatal kratom dependence and withdrawal. Can Fam Physician. 2018 Feb;64(2):121-122.
  2. Davidson L, Rawat M, Stojanovski S, Chandrasekharan P. Natural drugs, not so natural effects: Neonatal abstinence syndrome secondary to 'kratom'. J Neonatal Perinatal Med. 2019;12(1):109-112.
  3. Muhammad BY, Abdullahi AD, Kadir, SS, Abdul Razak TB, Ahmed QU. In-utero effects of the crude ethanolic extract of the leaves of Mitragyna speciose on neural tube formation in rats. Asian J Exp Biol Sci. 2010;1(2):404-408.

Kratom & Breastfeeding

Insufficient reliable information

Insufficient reliable information available; avoid using.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

© 2026 Therapeutic Research Center

Pregnancy & lactation ratings: Natural Medicines, Therapeutic Research Center

References & further reading

The 77 references that drive our Kratom monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend 2014 Jun 1;139:132-7. PubMed
  2. Backstrom BG, Classon G, Lowenhielm P, Thelander G. [Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden]. Lakartidningen 2010;107(50):3196-3197.
  3. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol 2011;35(4):242-247. PubMed
  4. Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction 2008;103(6):1048-1050.
  5. Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol 1988;23(1):115-119. PubMed
  6. Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM. Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure. J Med Toxicol 2010;6(4):424-426. PubMed
  7. Sheleg SV, Collins GB. A coincidence of addiction to "Kratom" and severe primary hypothyroidism. J Addict Med 2011;5(4):300-301. PubMed
  8. Kapp FG, Maurer HH, Auwarter V, Winkelmann M, Hermanns-Clausen M. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J Med Toxicol 2011;7(3):227-231. PubMed
  9. 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
  10. US Food and Drug Administration (2014). SNI National is Voluntarily recalling Kratom XL 4 Pack, Maeng Da Kratom 10 Pack, Max Kratom 20 Pack, and Bali Kratom 40 pack Due to Undeclared Drug Ingredients [Press Release].
  11. Castillo A, Payne JD, Nugent K. Posterior reversible leukoencephalopathy syndrome after kratom ingestion. Proc (Bayl Univ Med Cent). 2017;30(3):355-357. PubMed
  12. Cumpston KL, Carter M, Wills BK. Clinical outcomes after Kratom exposures: A poison center case series. Am J Emerg Med. 2018;36(1):166-168. PubMed
  13. FDA Adverse Event Reporting System: Kratom Deaths. February 6, 2018. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/CDERFOIAElectronicReadingRoom/UCM595575.pdf. Accessed March 6, 2018.
  14. Trakulsrichai S, Sathirakul K, Auparakkitanon S, et al. Pharmacokinetics of mitragynine in man. Drug Des Devel Ther. 2015;9:2421-9. PubMed
  15. Kruegel AC, Grundmann O. The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse.Neuropharmacology. 2017. pii: S0028-3908(17)30393-3. PubMed
Keep reading

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.

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

Kratom: Common Questions

What is Kratom used for, and does it work?
People use Kratom for a range of reasons, but according to the Natural Medicines database the current clinical evidence is insufficient to confirm it works for the specific conditions it has been studied for. See the graded list on this page, and talk to your pharmacist or doctor before relying on it for any condition.
Does Kratom interact with prescription medications?
Yes. We list 995 medications with a known interaction with Kratom. Use the checker above to see how Kratom interacts with a specific drug.
How are Kratom interactions rated?
Each interaction is graded major, moderate, or minor based on how clinically significant it is and the strength of the evidence behind it. Major interactions are the most serious and are best avoided, or used only under close professional supervision.
Is it safe to take Kratom with my medications?
It depends on the specific medication. Some combinations are fine, while others call for monitoring, timing changes, or should be avoided. Check your exact drug above and confirm with your pharmacist or doctor before starting, stopping, or changing anything.
Where does this Kratom interaction information come from?
Our interaction data is built on the Natural Medicines database — an evidence-graded reference for vitamins, herbs, and supplements — and is reviewed by licensed HelloPharmacist pharmacists, who may add clinical context.
Is Kratom legal?
Kratom's legal status varies. It is banned or restricted in some U.S. states and many countries, while it remains available in others. Check your local laws before buying or using it.
Can Kratom be addictive?
Yes. Because Kratom acts on the brain's opioid receptors, regular use can lead to tolerance, dependence, and withdrawal symptoms when you stop.
Is Kratom safe to use during pregnancy or breastfeeding?
No. Kratom should be avoided during pregnancy and breastfeeding. It has been linked to withdrawal symptoms in newborns, and its compounds may pass into breast milk.
Is Kratom a proven treatment for opioid withdrawal?
No. Although some people use it for this reason, Kratom is not an approved or proven treatment. Safe, FDA-approved medicines are available, so speak with a healthcare provider about your options.

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

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