Kratom, derived from the leaves of the Southeast Asian tree Mitragyna speciosa, is an herbal substance consumed for its pain-relieving and stimulating properties. Its active compounds, primarily alkaloids, are increasingly used worldwide, often for self-management of opioid withdrawal symptoms. The relationship between kratom consumption and the onset of seizures represents a significant safety concern.
Documented Prevalence and Incidence
Determining the exact frequency of kratom-related seizures is challenging due to the substance’s unregulated status and lack of standardized reporting. Most available data comes from retrospective reviews of adverse event reports and individual case studies, which inherently skew toward severe outcomes. Data from United States poison control centers indicate that seizures are reported in approximately 6.1% to 9.6% of single-substance kratom exposures.
In some international reports, the incidence has been documented as high as 17.5% of cases involving kratom ingestion. While these percentages suggest seizures are a consistent neurological complication, the absolute number of confirmed cases remains small in the medical literature.
A vast majority of documented seizure events (approximately 71% in some reviews) involved the co-ingestion of other substances, complicating the direct attribution to kratom alone. Despite this confounding factor, the consistent documentation of generalized tonic-clonic seizures following kratom use confirms that the substance carries a potential for neurotoxicity in susceptible individuals.
Neurobiological Mechanism of Action
The pathways by which kratom may induce seizures are complex, involving the actions of its primary alkaloids, mitragynine and 7-hydroxymitragynine. Mitragynine acts as a partial agonist at the mu-opioid receptor (MOR), which is the source of its pain-relieving and sedative effects. The alkaloid also displays significant affinity for the adrenergic-alpha2 and serotonin (5-HT) receptors in the central nervous system.
This interaction with non-opioid systems is thought to be the basis for lowering the seizure threshold, increasing the brain’s susceptibility to electrical over-activity. Mitragynine’s engagement with adrenergic-alpha2 and 5-HT receptors can disrupt the delicate balance between excitatory and inhibitory neurotransmission in the brain. The presence of two major alkaloids with competing effects further complicates the matter, as MOR activation is generally sedative, while the adrenergic and serotonergic modulation can be proconvulsant.
The metabolite 7-hydroxymitragynine, while a more potent MOR agonist, does not bind as strongly to the adrenergic or serotonergic systems. This divergence suggests that the overall seizure risk is tied to the full pharmacological profile of the raw kratom preparation.
Poly-Substance Use and Adulterants
The risk of seizure is significantly amplified when kratom is consumed alongside other psychoactive drugs, a phenomenon known as poly-substance use. In a large proportion of reported cases, individuals had co-ingested substances that independently lower the seizure threshold or interact metabolically with kratom’s alkaloids. Common co-ingestants include central nervous system depressants like benzodiazepines and alcohol, as well as stimulants such as amphetamines and modafinil.
These combinations create synergistic effects that destabilize the neuronal networks, making a seizure more probable than kratom use alone. The unregulated nature of the kratom market also poses the risk of product adulteration. Contaminated products may contain undisclosed synthetic opioids, illicit substances, or other compounds that are potent seizure-inducers.
The presence of these unknown adulterants complicates the assessment of causality, making it difficult to determine whether the seizure was caused by the kratom alkaloids or a toxic contaminant. Consumers should recognize that drug-drug interactions and product contamination are external variables that substantially increase the neurological risk associated with this substance.
Pre-existing Conditions and Dosage as Risk Modifiers
An individual’s physiology and consumption patterns are major factors that modify the risk of experiencing a kratom-associated seizure. Chronic, high-dose consumption is frequently noted in case reports, with daily intake often exceeding 20 grams, and sometimes even 100 grams, of raw material. This consistently high exposure increases the concentration of the active alkaloids, placing a greater strain on the body’s ability to maintain central nervous system stability.
Individual metabolic differences also play a role, particularly variations in the liver enzymes responsible for processing kratom’s alkaloids. Differences in metabolic rates can lead to unpredictable levels of mitragynine and its active metabolites in the bloodstream, increasing the risk of toxicity. A pre-existing medical history significantly predisposes a person to adverse events.
Individuals with a history of epilepsy, traumatic brain injury, or other neurological conditions have an inherently lower seizure threshold. For these vulnerable patients, kratom use, even at moderate doses, can trigger breakthrough seizures. The concurrent use of prescription medications, particularly those that affect the central nervous system, further modifies the individual risk profile by introducing complex drug interactions.