Kratom + Caffeine (prescription drug)
Caffeine (prescription drug) brand names: Dextrophin, Caffeine.
Caffeine (prescription drug) falls into 2 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 CYP1A2.
Read the full interaction reportKratom and Caffeine (prescription drug)
These two interact in 2 distinct ways. Each one is explained separately below.
Why Are There 2 Interactions?
Kratom interacts with whole categories of medication. Caffeine (prescription drug) falls into 2 of those categories, so it can interact with Kratom in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
1 of 2Why this applies to Caffeine (prescription drug)
Caffeine (prescription drug) falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Kratom interacts with.
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.
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.
Here's the short version: your body relies on a liver enzyme called CYP1A2 to clear caffeine out of your system. Lab studies suggest kratom may slow that same enzyme down. If that happens, caffeine could linger longer and build up, which means a normal dose might hit harder than usual.
In real life, that could feel like a jittery, wired feeling, a racing or pounding heart, trouble sleeping, anxiety, or an upset stomach. I want to be honest, though, this is based on test-tube research and pharmacology, not solid human studies, so it's more of a theoretical concern than a proven one. Still, kratom carries its own real risks, so please loop in your pharmacist or doctor before combining the two.
- 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
- 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
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 2Caffeine (prescription drug) also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
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.
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.
Here's the gist for prescription caffeine: kratom can mildly slow down a liver and gut enzyme called CYP3A4, which is one of the pathways your body uses to break this drug down. If that pathway runs slower, a bit more caffeine can hang around than usual, so you might feel the stimulant effects more strongly. Think jitteriness, a racing or pounding heart, trouble sleeping, restlessness, or an upset stomach.
I'll be honest with you though, this one is theoretical and mostly based on lab data, not strong human studies, so the real-world effect is probably modest. Still, since both kratom and caffeine work on your body and mind, please check with your pharmacist or doctor before combining them rather than guessing.
- 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
- Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019 Mar;15(1):110-113. PubMed
- 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
- 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
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Kratom Also Interacts With Other Medications
Kratom has 982 moderate, 12 minor known drug interactions in our database — the Caffeine (prescription drug) one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Kratom
We haven’t checked that one against Kratom yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Kratom. Pick one to open its full report.
Questions About Kratom or Caffeine (prescription drug)
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 Caffeine (prescription drug), 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.
See Every Supplement That Interacts With Caffeine (prescription drug)
This page covers Kratom only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Caffeine (prescription drug) page lists 208 supplements it has a documented interaction with, worst first, each one explained.
The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Peyote (major) and Rauvolfia Vomitoria (major).
By severity: 7 major · 155 moderate · 46 minor.
From our pharmacist’s overview on the Caffeine (prescription drug) page
“Prescription caffeine is itself a stimulant, which is exactly why this list calls for genuine care rather than a quick skim. Seven of the 208 ingredients on file are rated major, and those deserve attention first.”
Reviewed by 2 · Jul 18, 2026
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 Caffeine (prescription drug) 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:
Where Kratom and Caffeine (prescription drug) 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.
#411 of 1,452 supplements looked up here in the last 7 days
#360 of 2,830 medications looked up here in the last 7 days
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.
About Kratom
What is 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.
About Caffeine
What Is Caffeine Used For?
Brand names: Dextrophin, Caffeine
Caffeine citrate injection and caffeine citrate oral solution are indicated for the short-term treatment of apnea of prematurity (breathing pauses in premature babies) in infants between 28 and 33 weeks gestational age. These are prescription, hospital-administered products.
Over-the-counter caffeine tablets (such as Diurex) are used by adults to temporarily reduce fatigue and drowsiness. The Earthmed Uplift Chewable products are chewable caffeine gels for adults 18 and older. Children under 12 should not use caffeine products as a substitute for sleep.
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.
No drugs match “”.
982 interactions
- Diltiazem ›
- Theophylline ›
- Nifedipine ›
- Metronidazole ›
- Diphenhydramine ›
- Hydrocortisone ›
- Methylphenidate ›
- Naproxen ›
- Erythromycin ›
- Estradiol ›
- Propranolol ›
- Lidocaine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Phenylephrine ›
- Trimipramine ›
- Acetaminophen ›
- Amphetamine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Meprobamate ›
- Nortriptyline ›
- Oxymorphone ›
- Propoxyphene ›
- Rifampin ›
- Selegiline ›
Showing 60 of 982 moderate interactions — see all 982 on the Kratom page.
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.
- Levothyroxine ›
- Ivermectin ›
- Aspirin ›
- Rosuvastatin ›
- Isotretinoin ›
- Tirzepatide ›
- Ibuprofen ›
- Docusate ›
- Hydroxyurea ›
- Valacyclovir ›
- Metformin ›
- Semaglutide ›
- Levothyroxine, Liothyronine ›
- Methotrexate ›
- Amoxicillin ›
- Lisinopril ›
- Bupropion ›
- Azithromycin ›
- Doxycycline ›
- Acyclovir ›
- Candesartan Cilexetil ›
- Amoxicillin, Clavulanate Potassium ›
- Acetylsalicylic Acid ›
- Insulin Degludec, Liraglutide ›
- Calcium Oxybate, Magnesium Oxybate, Potassium Oxybate, Sodium Oxybate ›
- Aluminum Hydroxide, Aspirin, Magnesium Hydroxide ›
- Ezetimibe ›
- Cyclopentolate ›
- Cephalexin ›
- Avatrombopag Maleate ›
- Atenolol, Chlorthalidone ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Bendroflumethiazide, Rauwolfia Serpentina ›
- Mannitol ›
- Levodopa ›
- Sacubitril, Valsartan ›
- Canagliflozin, Metformin ›
- Valsartan ›
- Aspirin, Butalbital ›
- Enalapril Maleate ›
- Sulfamethoxazole, Trimethoprim ›
- Acarbose ›
- Ceftolozane Sulfate, Tazobactam Sodium ›
- Bupivacaine, Meloxicam ›
- Spironolactone ›
- Alginic Acid, Aluminum Hydroxide ›
- Mitomycin ›
- Atenolol ›
- Flutemetamol F-18 ›
- Hydrocortisone, Clioquinol, Pramoxine ›
- Charcoal (otc Drug) ›
- Rosiglitazone Maleate ›
- Efgartigimod Alfa-fcab ›
- Magnesium Hydroxide (otc Drug) ›
- Irbesartan, Hydrochlorothiazide ›
- Atropine Methyl Nitrate, Digestive Enzymes ›
- Levothyroxine Sodium ›
- Daunorubicin, Cytarabine ›
- Peginterferon Alfa-2a, Ribavirin ›
Showing the 60 most looked-up of 1,835 medications checked with no known interaction — see the full Kratom list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Caffeine (prescription drug) Is Linked to Lower Levels of One Nutrient
Natural Medicines records Caffeine (prescription drug) as a medicine that can lower these. This is not an interaction with Kratom — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Caffeine (prescription drug) nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Kratom and Caffeine (prescription drug) Together: Common Questions
Can you take Kratom with Caffeine (prescription drug)?
Why are there 2 interactions listed for Kratom and Caffeine (prescription drug)?
How serious is the Kratom and Caffeine (prescription drug) interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Caffeine (prescription drug) 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.