Kratom's psychoactive properties are largely due to its alkaloids, mitragynine and 7-hydroxymitragynine, which act on mu-opioid receptors. However, these compounds also influence other systems in the body, leading to a wide array of potential drug-drug interactions. The combination of kratom with other substances is particularly hazardous because it can lead to synergistic or additive effects that are greater than the sum of their individual risks. The FDA has issued multiple warnings about kratom's potential for serious adverse events, especially when used with other drugs.
Combining Kratom with Central Nervous System Depressants
One of the most dangerous drug interactions involving kratom is with other central nervous system (CNS) depressants. This is because both substances can slow down essential bodily functions, especially breathing. The risk of respiratory depression, coma, and fatal overdose increases exponentially with this combination.
Opioids and Benzodiazepines
Kratom's opioid-like effects mean that mixing it with prescription opioids (e.g., hydrocodone, fentanyl) or benzodiazepines (e.g., Xanax, Valium) creates a high risk for serious, potentially fatal outcomes.
- Synergistic Sedation: The combined sedative effects can lead to extreme drowsiness and loss of consciousness.
- Respiratory Failure: Both kratom and opioids can cause a dangerously slow heart rate and breathing, leading to oxygen deprivation.
- Polysubstance Overdoses: A significant number of deaths associated with kratom use have involved other drugs like benzodiazepines.
Alcohol
Since alcohol is also a CNS depressant, combining it with kratom can lead to similarly dangerous effects. The interaction can cause significant impairment and organ damage.
- Amplified Effects: The sedative effects of both substances are heightened, increasing the risk of impaired judgment, poor coordination, and accidents.
- Organ Strain: The liver must work to metabolize both substances, increasing the risk of liver damage or failure.
- Increased Overdose Risk: The conflicting signals to the body can lead to a dangerously irregular heart rate and a heightened risk of overdose.
Kratom and Medications Affecting the Liver
Kratom alkaloids, particularly mitragynine, are known to inhibit specific cytochrome P450 (CYP) enzymes in the liver, such as CYP3A4 and CYP2D6. These enzymes are responsible for metabolizing a vast number of prescription medications. By inhibiting these enzymes, kratom can cause other drugs to build up to toxic levels in the body.
Impact on Specific Medications
- Anticoagulants (e.g., Warfarin): Kratom can increase the blood-thinning effects of warfarin, significantly raising the risk of bleeding.
- Antidepressants: Increased levels of certain antidepressants can increase the risk of side effects or lead to serotonin syndrome, as discussed below.
- Heart Medications: Kratom can interfere with the metabolism of antiarrhythmics, calcium channel blockers, and beta-blockers, leading to cardiovascular issues like irregular heartbeat.
Other Notable Kratom Interactions
Beyond CNS depressants and liver enzyme inhibitors, kratom has other specific and dangerous interactions.
Antidepressants and Serotonin Syndrome
Some kratom alkaloids interact with serotonin receptors, meaning that combining kratom with serotonergic drugs (like SSRIs) can create a state of excessive serotonin activity known as serotonin syndrome. This condition can cause severe symptoms, including hyperthermia, seizures, and death.
Naltrexone and Precipitated Withdrawal
Naltrexone is a medication used to treat opioid and alcohol use disorders by blocking opioid receptors. Since kratom's alkaloids act on these same receptors, taking naltrexone while using kratom can trigger an immediate and severe precipitated withdrawal. This can be an extremely unpleasant and dangerous experience.
Stimulants and Seizures
Case reports have shown that combining kratom with stimulants like modafinil can increase the risk of seizures. This interaction highlights the unpredictable nature of kratom's effects when combined with other psychoactive substances.
Comparison of Drug Interactions with Kratom
| Drug Class | Mechanism of Interaction | Potential Risk | Example Drugs |
|---|---|---|---|
| CNS Depressants | Additive/synergistic CNS depression | Respiratory depression, coma, fatal overdose | Opioids, Benzodiazepines, Alcohol |
| Serotonergic Drugs | Inhibition of metabolism, increased serotonin | Serotonin syndrome, seizures, cardiac problems | SSRIs (e.g., Sertraline), MAOIs |
| Liver Enzyme Substrates | Inhibition of CYP enzymes (CYP3A4, 2D6) | Increased concentration, toxicity of the other drug | Warfarin, Antidepressants, Heart medications |
| Stimulants | Unknown, possibly neurological pathway disruption | Increased seizure risk | Modafinil |
| Opioid Antagonists | Competitive blocking of mu-opioid receptors | Precipitated withdrawal | Naltrexone |
The Unregulated Nature of Kratom
One of the most significant compounding factors in kratom's drug interactions is its lack of regulation. Since it is sold as an herbal supplement, there is no government oversight to ensure product purity, potency, or consistent dosage.
- Contamination: Kratom products have been found to be contaminated with other drugs, heavy metals, and pathogens like salmonella.
- Variable Potency: The concentration of active alkaloids can vary dramatically between products, making consistent dosing and risk assessment nearly impossible.
Conclusion
The question of what drugs does kratom interact with reveals a serious lack of understanding surrounding this unregulated substance. Interactions with CNS depressants, antidepressants, liver enzyme substrates, and other substances pose significant, potentially fatal risks. Due to the unpredictable nature of kratom products, including variable potency and contamination risks, medical professionals universally advise against its use, particularly when combined with other medications. The safest course of action is to avoid kratom entirely, especially if you are taking prescription or over-the-counter medications.
For more information, the FDA provides detailed warnings regarding the use of kratom.
A note of caution
This information is for educational purposes only and is not a substitute for professional medical advice. Always consult a healthcare provider before using any new herbal supplement or combining it with other medications.
