Kratom Guides

Kratom Drug Interactions

Any substance or herb with a strong impact on the body brings increased risks for side effects and interactions with other substances. This is not something that’s unique to kratom. 

People are always looking for herbs or medications that can alleviate symptoms without bringing any added risk — this is simply not possible. The very nature of having a substance with a strong effect means it will also bring the potential of having too much effect. 

Kratom will interact negatively with many different types of medications — some combinations can be very dangerous, others are manageable as long as you’re careful with the dose. 

In all cases, if you’re using prescription medications for any reason, it’s wise to speak to your doctor about your desire to use kratom first. 

Last updated 6 days ago by Dr. Devin Carlson

Kratom Drug Interactions

Types of Drug Interactions with Kratom

Kratom will interact differently with every medication class — but we can summarize each type of interaction in three ways:

1. Increased Effect (Agonistic Interaction)

The effects of some medications overlap with the effects of kratom. When this happens, the effect becomes extra strong — which could lead to increased risk of side effects or overdose — both of which you’ll want to avoid. 

In lower doses, kratom has a stimulating effect. If combined with other stimulant medications, like Adderall or Modafinil, the stimulating effects could become too strong — leading to increased risk of damage to the heart, stroke, digestive discomfort, or insomnia.

In higher doses, kratom is a sedative. If combined with other sedative medications, it could lead to much stronger sedative action — potentially leading to feelings of sedation and grogginess. This could be dangerous if the user needs to drive or is responsible for small children or pets. 

2. Decreased Effect (Antagonistic Interaction)

This interaction happens when kratom has the opposite effect to the medications one is using. If kratom cancels out or inhibits the effects of a medication, it could reduce the effectiveness of that medicine for treating a health condition. 

When medications become less effective, symptoms of the underlying condition may present. In some cases, this effect could be dangerous. 

3. Slowed Elimination (Metabolic Competitor)

All drugs are metabolized by enzymes in the liver called the cytochrome P450 enzymes. There are many different kinds, each one specialized for breaking down different types of compounds. 

The vast majority of drugs (70%) are metabolized by CYP3A4, CYP2D6, CYP1A2, CYP2C9, and CYP2C19 [1].

Kratom contains over a dozen active ingredients, most of which are classified as alkaloids. These compounds have varying affinities for CYP enzymes, but most are metabolized by the CYP2D6, CYP2C9, and CYP3A4 enzymes [2].

When you take a medication and kratom that both require the same route of metabolism, they’re going to compete with each other and both will have a slower rate of elimination than normal. 

This could mean both kratom and the medication last longer and remain in higher doses in the bloodstream. 

For single doses, this usually isn’t a huge problem. This competitive interaction becomes a real problem for medications that are used on a daily basis. Gradually, levels of the medication could begin to build up in the bloodstream if it isn’t being cleared fast enough. Eventually, this could lead to toxic levels — thus increasing the chance for both side effects and overdose. 

Summary: What CYP Enzymes Does Kratom Affect?

  • High inhibitory effect — CYP2D6
  • Moderate inhibitory effect — CYP2C9 and CYP3A4

Kratom-Drug Interactions Chart

Drug ClassIncreased EffectDecreased EffectSlowed MetabolismLevel of Risk
ACE InhibitorsHigh
Alcohol ✅ High
Alpha-BlockersHigh
Anti-Epileptics Moderate
Antibiotics Moderate
AntihistaminesModerate
Barbiturates✅ High
BenzodiazepinesHigh
Beta-blockers✅ Moderate
Blood Thinners High
BiguanidesHigh
Calcium Channel BlockersModerate
DiureticsModerate
EugeroicsHigh
HIV antivirals Moderate
InsulinMild
Immunosuppressants Moderate
MAO Inhibitors  Moderate
NSAIDsModerate
Opiates High
PDE5 InhibitorsModerate
Peripheral Adrenergic InhibitorsHigh
Proton Pump InhibitorsMild
SARIsModerate
SNRIs  Moderate
SSRIs  Moderate
StatinsModerate
StimulantsHigh
Tricyclic Antidepressants  Moderate
5-ARIsModerate

References 

  1. Arimoto, R. (2006). Computational models for predicting interactions with cytochrome p450 enzyme. Current topics in medicinal chemistry, 6(15), 1609-1618.
  2. Hanapi, N. A., Ismail, S., & Mansor, S. M. (2013). Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities. Pharmacognosy research, 5(4), 241.