Kratom is a tropical tree native to Southeast Asia, with leaves that contain compounds that have psychotropic (mind-altering) effects. Kratom is not currently an illegal substance in the United States and is sold as an herbal supplement. Many people take kratom to self-treat pain, anxiety, depression, and opioid withdrawal symptoms.
How kratom works in the body?
The key psychoactive compounds in kratom are mitragynine and 7-hydroxy mitragynine. These substances bind to and activate opioid receptors in the brain, causing analgesic (pain-relieving) and euphoric effects like feelings of pleasure, relaxation, and emotional uplift. At higher doses, kratom also has sedative effects.
Mitragynine and 7-hydroxy mitragynine interact with opioid receptors somewhat differently than classic opioid agonists like morphine. They are partial rather than full agonists, meaning they activate the receptors but with less intense effects. This may explain why kratom tends to have a milder opioid-like effect than prescription painkillers.
Metabolism and excretion
When kratom is ingested, mitragynine and 7-hydroxy mitragynine are metabolized in the liver. The metabolites that result are then excreted primarily through the kidneys. Mitragynine and 7-hydroxy mitragynine, as well as their metabolites, may be detectable in urine for up to 9 days after kratom use. The main enzyme responsible for metabolizing mitragynine and 7-hydroxy mitragynine is CYP3A4. Anything that inhibits or induces the CYP3A4 enzyme potentially impacts the metabolism of these compounds, causing them to be broken down faster or slower.
Risks of combining kratom with other substances
Due to kratom’s opioid-like effects, combining it with other substances that act on opioid receptors increases the risk of adverse effects. Some potentially dangerous combinations include:
- Opioid pain medications like morphine, oxycodone, and fentanyl – These drugs have similar effects to kratom but are often more potent. Combining them with kratom significantly raises the risk of overdose and respiratory depression.
- Benzodiazepines like Xanax, Klonopin, and Valium – These anti-anxiety medications depress the central nervous system. Mixed with kratom’s sedative effects, benzodiazepines slow breathing to dangerous levels.
- Alcohol – Both kratom and alcohol depress the central nervous system. Together, the sedation and respiratory depression are severe. There are multiple reports of deaths involving kratom mixed with alcohol or benzodiazepines.
- Stimulants like cocaine and methamphetamine – While stimulants and opioids have opposite effects, combining them stresses the cardiovascular system and increases the risk of heart attack or stroke.
- Medications metabolized by CYP3A4 – Drugs like the blood thinner warfarin, the antidepressant sertraline, and the heart medication amlodipine are all metabolized by the CYP3A4 enzyme. If taken with kratom, levels of these medications in the bloodstream could rise to unsafe levels.
- Medications that prolong the QT interval – Drugs like methadone, celexa, and amitriptyline disrupt the heart’s electrical activity when combined with kratom, increasing the risk of arrhythmia.
Anyone currently taking opioid medications, benzodiazepines, alcohol, or other central nervous system depressants should avoid kratom entirely due to the high risk of oversedation or respiratory depression. Even over-the-counter medications and supplements should be carefully reviewed before use or buy kratom.
Always discuss kratom and any supplements with your healthcare provider. In certain individuals or circumstances, the safest option may be avoiding kratom altogether.
