FDA has warned consumers not to use kratom because of the risk of serious adverse events, including liver toxicity, seizures, and substance use disorder (SUD). In rare cases, deaths have been associated with kratom use, as confirmed by a medical examiner or toxicology reports. However, in these cases, kratom was usually used in combination with other drugs, and the contribution of kratom in the deaths is unclear. Cases of kratom-related SUD have also been observed. In these cases, individuals met certain criteria for SUD, including using kratom for longer than intended, using more kratom than intended, having cravings for kratom, continuing to use kratom despite adverse consequences (either physically or in their personal life), increasing the amount of kratom used to produce the same effect (tolerance), and experiencing withdrawal symptoms when kratom use was stopped (physical dependence). FDA is also aware of cases involving neonatal abstinence syndrome, in which newborns experienced withdrawal signs such as jitteriness, irritability, and muscle stiffness following prolonged exposure to kratom prior to birth. FDA has warned the public when certain kratom products were contaminated with Salmonella and/or concerning levels of heavy metals. These contaminants can put people at risk and can result in numerous documented illnesses. There are no FDA-approved kratom drug products or over-the-counter drugs containing kratom that are legally on the market in the U.S. FDA continues to warn consumers not to use kratom because of the risk of serious adverse events, including liver toxicity, seizures, and substance use disorder (SUD). Consistent with its mission to protect the public’s health, FDA regularly exercises its authority to protect consumers from companies selling unapproved kratom drug products, making false or misleading claims about unproven benefits of kratom, and selling unlawfully marketed kratom dietary supplements and conventional foods. The agency has partnered with the U.S. Customs and Border Protection and with the Department of Justice to take numerous actions to limit the sale of unlawful kratom products in the U.S. The agency continues to work with its federal partners to warn the public about risks associated with use of kratom. Unapproved drug products are some of the most challenging products that FDA regulates, due to the complex and fragmented supply chain of distributors, wholesalers, retailers, and even individuals. These entities are not usually registered with FDA, may operate out of residences, and distribute kratom through sales made on the internet, social media, smoke/vape shops, other small stores, or by using the mail or other package delivery services. Kratom-containing drug products have been shipped through U.S. and international mail facilities and may falsely be declared as other items, such as potpourri or incense. FDA will continue to work with its federal partners to warn the public about the risks associated with the use of kratom and protect consumers from entities that are selling violative kratom products, including products with false or misleading labeling claims about unproven health benefits of kratom. Additionally, states may have their own regulations or prohibitions for kratom products. State health and law enforcement agencies are the best resource concerning applicable state laws. Research on Safety Issues While kratom contains over 50 alkaloids, most scientific research focuses on mitragynine and 7-OH, both of which bind to the same receptors in the brain (mu opioid receptors) as opioid drugs such as codeine. Mitragynine also has additional mechanisms of action on other chemical systems of the brain, including serotonin, dopamine, norepinephrine, and kappa opioid receptors. These compounds may produce classic opioid-related effects such as sedation, nausea/vomiting, constipation, physical dependence/withdrawal, and respiratory depression that may lead to death. However, as with all drugs, the ability of kratom to cause harmful responses will depend on how much of the drug is taken and under what conditions. One additional safety concern with kratom is that of abuse potential. There are epidemiological data suggesting that some individuals develop substance use disorder following kratom use. To date, a well-designed human abuse potential study has not been conducted that would show whether kratom, mitragynine, or 7-OH produce rewarding effects (such as feeling “high”) that might lead an individual to abuse kratom. This means that the abuse potential of kratom has yet to be fully understood. Research on Kratom by FDA Clinical Investigators To better understand kratom’s safety profile, FDA funded a single ascending dose study to evaluate the effects of botanical kratom ingestion in humans. FDA researchers have submitted a manuscript to a peer-reviewed journal and will make the results publicly available upon acceptance. Building on this preliminary study, FDA awarded a grant for a human abuse potential study on kratom in September 2024. While these studies will further FDA’s efforts to characterize kratom’s safety profile, results from these studies will need to be considered in relation to the many and varied kratom-related products available to consumers and other scientific research. Are There Possible Therapeutic Uses as a Drug? FDA recognizes that it is necessary to develop therapies for patients with unmet medical needs. The agency has numerous programs that help drug companies develop and obtain approval for new drug products. Drug companies that are interested in kratom-related drug development are encouraged to contact the relevant review division in the Center for Drug Evaluation and Research to answer questions related to their specific drug development program. While FDA continues to evaluate the available safety information about the effects of kratom, the agency encourages health care professionals and consumers to report any adverse reactions to the FDA’s MedWatch program or the Safety Reporting Portal.
