BACKGROUND: The ketamine landscape in the USA is rapidly shifting, especially given recent increases in off-label prescribing of ketamine as a psychiatric treatment. Research is needed to determine the extent to which illicit ketamine is available, nonmedically used, and associated with morbidity and mortality in the USA.
METHODS: This observational study used eight unique annual repeated cross-sectional datasets to examine illicit ketamine availability (using seizure data as a proxy), use, and consequences of use, including self-reported nonmedical use among noninstitutionalized individuals aged >/=12 years (2006–2014, 2015–2019, and 2021–2023) and among 12th grade students (2000–2023). Further, it assessed reported ketamine-related poisonings (1991–2023) and mortalities (2020–2023), diversion of undispensed pharmaceutical ketamine (2008–2024), drug seizures testing positive for ketamine (2001–2024), and the number and total weight of ketamine seizures from two additional law enforcement agencies (2017–2024 and 2019–2024). Piecewise linear regression models were used to estimate annual trends.
FINDINGS: Nonmedical ketamine use among individuals aged =12 years increased between 2021 (0.19%) and 2023 (0.34%) (b [slope] = 0.08 [SE = 0.001], p = 0.0072). Regarding reported poisonings, there was initial increase from 1994 to 2000 (from 0.17 to 1.40 per 1,000,000 population; b = 0.20 [SE = 0.02], p < 0.0001), a decrease through 2003 (0.58 per 1,000,000 population; b = -0.34 [SE = 0.08, p = 0.0002) and an increase from 2017 through 2023 (from 0.76 to 1.54 per 1,000,000 population; b = 0.12 [SE = 0.03], p = 0.0002). The number of reported diversions increased from 2008 (n = 23) to 2017 (n = 202) (b = 18.72 [SE = 2.20], p < 0.0001) and again from 2021 (n = 183) to 2024 (n = 286) (b = 39.00 [SE = 12.04], p < 0.0001). Regarding seizures, there was an increase in ketamine reports to one agency from 2015 (n = 1448) through 2024 (n = 4008) (b = 201.41 [SE = 57.83], p = 0.0023). In another source, there was an increase in seizures from 2022 (n = 247) through 2024 (n = 502) (b = 127.50 [SE = 10.40], p = 0.0003). Rates of ketamine-involved deaths did not significantly shift between 2020 and 2023. Nonmedical use declined among 12th grade students, first from 2000 (2.49%) through 2005 (1.61%) (b = -0.19 [SE = 0.06], p = 0.0039] and then again from 2005 through 2023 (0.9%) (b = -0.04 [SE = 0.01], p = 0.0019).
INTERPRETATION: Ketamine poisonings, pharmaceutical diversion, and seizures have increased; trends in nonmedical ketamine use vary. Prevention and harm reduction are needed as use and morbidity are expected to continue to increase.
Trends in nonmedical ketamine use, poisonings, related deaths, pharmaceutical diversions, and law enforcement seizures: Results from annual population-based repeated cross-sectional studies
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