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 .
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 .
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 Class||Increased Effect||Decreased Effect||Slowed Metabolism||Level of Risk|
|Calcium Channel Blockers||✅||✅||Moderate|
|Peripheral Adrenergic Inhibitors||✅||✅||High|
|Proton Pump Inhibitors||✅||Mild|
- Arimoto, R. (2006). Computational models for predicting interactions with cytochrome p450 enzyme. Current topics in medicinal chemistry, 6(15), 1609-1618.
- Hanapi, N. A., Ismail, S., & Mansor, S. M. (2013). Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities. Pharmacognosy research, 5(4), 241.