As kratom questions increase, many pharmacists and other health care professionals may remain unfamiliar it and the potential risks.
Kratom refers to extracts made from the leaves of Mitragyna speciosa (Korth), a tree native to Southeast Asia.1 Traditionally, people of the region have chewed on the leaves or used topical preparations to treat a variety of indications, including pain, fever, anxiety, and gastrointestinal disturbances. Kratom extracts have been shown to contain at least 54 different alkaloids, of which the most predominant is mitragynine. Research has repeatedly shown mitragynine to be a partial agonist at the µ- and κ-opioid receptors. A metabolite of mitragynine, 7-hydroxymitragynine (7-OH), is a minor component of extracts but has demonstrated potent activity at the µ-opioid receptor and moderate activity at κ- and δ-opioid receptors. Another major constituent of many extracts is speciofoline. Some kratom products have been found to have a higher concentration of speciofoline than mitragynine.
Pierce Bernard BS, and Hunter Roley, BS, are both 2027 PharmD candidates at the University of Wyoming School of Pharmacy in Laramie.
Tracy Mahvan, PharmD, MBA, BCGP, is a professor and the chair of the department of pharmacy practice at the University of Wyoming School of Pharmacy in Laramie.
In a metabolomics study published in 2020, speciofoline was found to have no appreciable affinity for any human opioid receptors.2 It was suspected that the differing concentrations of mitragynine and speciofoline could be responsible for the variety of effects and potency reported by users. Other alkaloids that have been investigated in vitro and in vivo, such as paynantheine and speciogynine, have exhibited high affinity for serotonin 5-HT1A and 5-HT2B receptors, supporting the previous hypothesis that some constituents of kratom extracts have nonopioid activity.3
Kratom products come in a variety of dosage forms, including powders and powder-filled capsules, liquid extracts and tinctures, candy, tea, and topicals. Consumers can purchase these products online or in person at a variety of stores, including smoke shops and gas stations. Product marketing statements can vary widely, with a focus ranging from claims that the product will boost focus and energy to those that promise relaxation and vitality.
The increasing prevalence of kratom use poses potential challenges for medical practitioners. Kratom use has been associated with several adverse effects (AEs), including respiratory depression, seizures, and sedation. In addition to these effects, kratom has been linked with CYP3A4 and CYP2D6 inhibition.4 There are numerous medications metabolized through these pathways, including several opioids, antidepressants, and β-blockers.
As it stands under the Controlled Substances Act, kratom is not classified as a controlled substance and therefore has no federal oversight via statute or regulation by the Drug Enforcement Administration (DEA).5 Additionally, the US FDA has not approved kratom for medicinal use and has concluded that there is not sufficient evidence to give reasonable assurance that kratom does not present a significant risk of illness or injury. Due to these concerns, kratom is currently not lawfully marketed in the US as a drug product, a dietary supplement, or a food additive in conventional food.6
Recently, the FDA has been focusing its attention on the more controversial active ingredient 7-OH. Taking a bold step, the agency issued a news release in which it announced steps would be made to restrict 7-OH opioid products it stated were treatening American consumers, urging the DEA to schedule 7-OH products under the Controlled Substances Act.7 At the time of writing, no federal action has been made.
Due to the lack of federal oversight, several states have, in some manner, taken action to regulate kratom use. As of January 2026, 30 states have established laws pertaining to kratom or its components, and these vary from state to state. In some cases, both mitragynine and 7-OH are considered Schedule I controlled substances meaning that all kratom products are banned in the state, whereas in others, it is as simple as implementing age restrictions.8 Verifying current federal and state laws and regulations before issuing guidance will be important as the regulatory landscape continues to evolve.
On Monday, September 21, 2026, 2 University of Mississippi students—aged 18 and 20 years and who were from Englewood, Colorado, and Atlanta, Georgia—were found dead at 2 separate locations where packaged kratom was present on scene. At the time, authorities had stated that there had been no definitive link made between kratom and the deaths, but it was noted that kratom was found at both scenes and that it was sold from a retail store.9 Toxicology results later disclosed in a court filing showed that both students had mitragynine and the synthetic kratom derivatives MGM-15 and MGPI present in their bloodstreams.10
Beyond recent news reports, published literature provides additional insight into the potential risks associated with kratom use. In a 2025 review published in Frontiers in Pharmacology11, the authors identified 95 published cases of acute adverse health effects associated with kratom. Of the 55 cases with toxicological confirmation of mitragynine, 35 patients died and 20 survived hospitalization. Additional reported AEs included seizures, altered mental status, liver injury, pulmonary complications, and cardiovascular effects; however, 32 of the 35 fatal cases involved additional substances, making it difficult to determine whether kratom alone contributed to these outcomes.11
Additional evidence comes from a 2026 report published by CDC12, which examined kratom-related exposure reports submitted to US poison centers between 2015 and 2025. During this period, 14,449 exposure reports and 233 associated deaths were documented, with 79% of the deaths involving multiple substances. Opioids, benzodiazepines, stimulants, and alcohol were among the substances identified. Although these findings raise concerns regarding kratom-related toxicity, the CDC noted that the data could not determine which substance was primarily responsible for the outcomes. Additionally, the report did not distinguish traditional kratom leaf products from concentrated formulations.12
Together, these findings highlight the need for continued research to better understand kratom toxicity, particularly with concurrent substance use.12
