Summary
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.
Funding
National Institute on Drug Abuse at the National Institutes of Health.
Keywords: Ketamine, Nonmedical use, Poisonings, Drug seizures, Mortality
Research in context.
Evidence before this study
The ketamine landscape in the USA is rapidly shifting, especially given recent increases in off-label prescribing of ketamine as a psychiatric treatment since 2020. While there has been increased research focusing on increases and shifting patterns in off-label prescribing of ketamine, less epidemiologic research has focused on nonmedical use. To identify studies relevant to the epidemiology of illicit or nonmedical ketamine use, we searched PubMed using the following search term: ((ketamine specific deaths) OR (ketamine attributable deaths) OR (ketamine-attributable deaths) OR (ketamine attributable mortality) OR (ketamine-attributable mortality) OR (ketamine poisoning) OR (ketamine seizure) OR (ketamine law enforcement) OR (ketamine prevalence) OR (ketamine trend)). As of April 14, 2025, 2880 articles with these terms have been published. Most articles are about ketamine used during medical procedures or as a medical (e.g., psychiatric) treatment. Far fewer reports focused on illicit or nonmedical use and very few focused on trends in nonmedical use or consequences of use (e.g., poisonings) in the USA. Most of such studies focused on illicit use in convenience or targeted samples (e.g., online samples, high-risk populations). Most toxicology studies (focusing largely on exposures, wastewater, law enforcement seizures, poisonings, and mortality) have been conducted outside the USA, and survey studies have largely focused on correlates of reported use. Studies of high-risk populations such as nightclub and dance festival attendees have estimated increases in use through 2024. Some US studies have estimated increases in illicit ketamine use and poisonings in the US general population, and others have estimated increases in ketamine diversion and law enforcement seizures, but typically within relatively short time periods, and recent data are scant. The recency of data is a notable gap, as in recent years, both prescribed and illicit ketamine have become more available, and public concern has grown given links to a high-profile death (Friends star, Matthew Perry). A comprehensive analysis of long-term trends synthesizing epidemiologic sources and outcomes is needed to determine the extent to which illicit ketamine is available, used, and associated with morbidity and mortality.
Added value of this study
This observational study used eight unique annual repeated cross-sectional datasets to examine ketamine availability, 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 poisonings (1991–2023), mortalities linked to ketamine (2020–2023), diversion of undispensed pharmaceutical ketamine (2008–2024) and drug seizures testing positive for ketamine (1997–2024), and the number and total weight of seizures from two additional law enforcement agencies (2017–2024 and 2019–2024). We found evidence suggesting that while use has decreased among adolescents across two decades, use has recently begun to increase among the general US population. We found that reported poisonings involving ketamine use increased through 2023, although rates of ketamine-related deaths did not significantly shift. Analysis of two of three law enforcement drug seizure datasets suggested recent increases in illicit ketamine seizures (and increases in the total annual weight of ketamine seized), which indicates increased illicit availability of this drug. Results suggest that illicit ketamine is increasingly becoming a public health threat.
Implications of all the available evidence
Nonmedical ketamine use, ketamine-related poisonings, and pharmaceutical diversion and law enforcement seizures of ketamine have increased according to five national datasets. Prevention and harm reduction education are needed as use and morbidity are expected to continue to increase.
Introduction
Ketamine is an N-methyl-d-aspartate receptor antagonist which induces analgesic, anesthetic, and hallucinogenic effects, and has a long history of both medical and nonmedical use.1 This dissociative anesthetic, approved by the United States (US) Food and Drug Administration in 1970, has been used in humans for over a half century in field conditions and in prehospital settings, and it has a long history of use in veterinary medicine.1,2 Nonmedical (recreational) use began to appear as early as the 1970s, with this drug becoming a prevalent party drug (e.g., used at dance parties) by the 1990s.1,3 While typically distributed in liquid form, the drug is most commonly converted into white powder and sniffed, although injection and oral use also occur.4 In response to an increase in thefts from veterinary clinics and to a rise in recreational use, in 1999, the US Drug Enforcement Administration (DEA) classified ketamine as a Schedule III controlled substance.5 While nonmedical use in the USA was reported by ∼2% of adolescents through the early 2000s, prevalence of use thereafter decreased.6 In the 2000s, nonmedical use appeared to be particularly popular in the United Kingdom,7 leading ketamine to be classified as a Class C drug in 2005.4 However, past-year use among 16–24-year-olds in England and Wales recently increased from 0.8% in 2006/07 to a peak of 3.8% in 2022/23, with 2.9% having used in 2023/24.8 In Australia, among people aged ≥14 years, past-year use has also increased—from 0.3% in 2004 to 1.4% in 2022/23.9 Increased prevalence of nonmedical use is concerning because despite ketamine as a pharmaceutical drug having an established safety profile, acute effects may include dissociation, somnolence, hypoesthesia, anxiety, agitation, decreased attention, executive function, and verbal memory, as well as gastrointestinal toxicity and psychosis.7,10,11 Individuals experiencing dissociation are also at increased risk for trauma.7,12 Chronic use can lead to use disorder (resulting from tolerance and withdrawal), neurotoxicity, persisting psychosis, urological disorders such as “ketamine bladder” (e.g., urinary cystitis), gastric pain (“K-cramps”), kidney dysfunction, and both short- and long-term memory impairment.7,12, 13, 14, 15
There has been little focus on recent trends in nonmedical ketamine use in the USA (e.g., through the 2020s) and much focus has been on high-risk populations. For example, a recent study estimated that past-year use among nightclub attendees in New York City increased from 7.4% in 2017 to 14.3% in 2024.16 Although, prevalence is likely underestimated given that survey studies that incorporate biospecimen testing suggest that populations such as nightclub attendees are often unknowingly exposed to ketamine (e.g., as an adulterant in drugs like MDMA/ecstasy).17,18 Some studies have estimated increases in ketamine use, poisonings, and law enforcement seizures, but typically within short time periods19, 20, 21 and data on recent years are scant.19,22 Such data are important, as the ketamine landscape has become increasingly complex as direct-to-consumer advertising and off-label prescribing of ketamine for psychiatric disorders has been increasing, along with extensive media coverage which might help popularize both medical and nonmedical use.23,24 The potential for harmful effects of ketamine consumption in the USA has been covered extensively in the media since the death of Friends star, Matthew Perry, from the acute effects of ketamine in 2023.23 Estimates of the number of ketamine prescriptions in the USA vary with one figure estimating a 3-fold increase between 2015 and 2024 and another estimating a 5.5-fold increase between 2017 and 2022.23,25 It is unknown to what extent this increase is linked with illicit availability or nonmedical use, especially considering that illicitly-obtained ketamine tends to be cheaper than prescribed ketamine.24
While individual datasets and analyses of single outcomes provide valuable information on the ketamine landscape in the USA, a comprehensive understanding requires synthesizing evidence across multiple complementary sources. Indeed, information on ketamine in the USA is available through many sources. By integrating national survey data on prevalence of nonmedical use, poison center reports of adverse events, mortality statistics, pharmaceutical diversion records, and law enforcement seizure data, we can triangulate findings to identify consistent patterns and contradictions. This approach provides a more robust foundation for public health, capitalizing on various strengths across data sources. Additionally, examining long-term trends including recent data rather than focusing on shorter recent periods allows us to contextualize current shifts within historical patterns, distinguishing genuine emerging threats from cyclical fluctuations or reporting artifacts. As such, this study utilized national, repeated cross-sectional data from eight sources with data available through 2023/2024 to acquire better understanding regarding how illicit ketamine use and availability have been shifting, as well as ketamine-related poisonings and deaths.
The aim of this study was to determine the extent to which there have been shifts in illicit ketamine availability, nonmedical use, and associated morbidity and mortality in the USA. Specifically, this observational study used eight unique annual repeated cross-sectional datasets to examine illicit ketamine availability (using seizure data as a proxy19,22), 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).
Methods
Study design
This study focused on annual trends based on eight national data sources. It focused on two national drug surveys, reports from a national poison center, a database of reported drug-related mortality, a dataset of undistributed pharmaceutical diversions, and law enforcement seizure data from three sources. Both pharmaceutical diversion and law enforcement seizures were used as a proxy for illicit availability.19,22 We used all available data.
The National Survey on Drug Use and Health (NSDUH) is an annual cross-sectional, nationally representative survey of noninstitutionalized individuals ages ≥12 years in the USA using a multistage sampling design.26 The study is conducted in all 50 US states and the District of Columbia (DC). Between 2006 (the first year ketamine use was queried) and 2023 (with 2020 excluded due to different study methodology), the average interview response rate was 66.2% ± 10.7, ranging from 46.2% through 75.6%, and on average, 58,580 ± 5394 participants were surveyed each year (ranging from 55,160 to 71,369). Each year, within the hallucinogen section of the survey, participants were asked if they had ever used “ketamine, also called ‘Special K’ or ‘Super K’”. This analysis focused on self-reported past-12-month (past-year) use (focusing on an imputation-revised variable provided by NSDUH), estimated using sample weights provided by NSDUH to account for the complex survey design. Trends were estimated separately due to methodological changes in survey design,27 with trends estimated for 2006–2014, 2015–2019, and for 2021–2023. As sensitivity tests, we also repeated this trend analysis, stratified by two prespecified NSDUH age groups—ages 12–17 and ≥18 years.
Monitoring the Future (MTF), is an annual, cross-sectional survey of 12th graders (in both public and private high schools) in the USA.6 MTF uses a multistage random sampling procedure to select schools and students within schools in the 48 contiguous US states. Between 2000 and 2023, an average of 118.8 ± 21.4 schools ranging from 36 (in 2000) to 136 were included. Within this period, student response rates averaged 80.5% ± 3.7 with a minimum of 69% and a maximum of 85%. Students are randomly selected to complete one of six different survey forms. Ketamine was first queried on the survey in 2000 and included every year through 2023 on 2–3 survey forms—asking how many occasions in which students used “ketamine (‘Special K’, ‘Super K’)” in the past 12 months (which was dichotomized into any past-year reported use: yes/no). On average, 4575 ± 1650 students were asked about past-year ketamine use each year (with a minimum of 1086 in 2000 and maximum of 6824). There was an average missingness of 13.5% ± 2.5, ranging from 9.7% in 2007 to 18.0% in 2019. Similar to MTF national reports, missing data were not imputed.6 Past-year use was estimated for each year in which ketamine use was queried using sample weights provided by MTF to account for the complex survey design.
National poison center annual reports were analyzed and count data were extracted regarding the annual number of exposures (“poisonings”) reported involving ketamine or its analogs.28 Poison centers provide treatment advice to both the public and to healthcare professionals to treat suspected poisonings involving drugs, chemicals, and plants. Poison centers record exposure information as per the standards of America's Poison Centers. This analysis focused on counts of reported exposures from 1991 (the first year in which the count of reported ketamine exposures was noted) through 2023. While the catchment area of poison centers has expanded over time, annual reports provide population estimates for center coverage. As such, rates (per 1,000,000 catchment population) were computed.
Mortality data were publicly available from the US Centers for Disease Control and Prevention's State Unintentional Drug Overdose Reporting System (SUDORS).29 Data were available from 34 jurisdictions beginning in 2020 and this increased to 38 jurisdictions in 2023. As such, rates (per 100,000 population) were computed for each year. Ketamine-related deaths were cases in which toxicology reports noted detection of ketamine or its metabolites as a cause of death based on information from death certificates, medical examiner or coroner reports, and from postmortem toxicology reports.30
Data on undistributed pharmaceutical ketamine diversions were obtained from the US DEA via Freedom of Information Act requests. Since 2005, the US DEA requires purchasers and suppliers of controlled substances to rapidly report diversion of undistributed scheduled drugs.31 Annual count data on the number of reported ketamine diversions were obtained for 2008 (the first year of data the US DEA made available) through 2024.
The National Forensic Laboratory Information System (NFLIS) is a program overseen by the US DEA.32 It systematically collects drug identification results from drug-related cases submitted to laboratories throughout the USA that were secured during law enforcement operations. As of 2022, NFLIS has a laboratory response rate of over 98%, including laboratories from 50 state systems and 111 local/municipal laboratories or laboratory systems (totaling 284 individual laboratories).32 The NFLIS database contains data regarding the number of drug submissions that tested positive for ketamine.32 Data were examined beginning in 2001 as this is when NFLIS became a fully functioning information system.33 Data on the number of reports of drugs seized testing positive for ketamine use per year were accessed via the NFLIS public data query system.34
The High Intensity Drug Trafficking Areas (HIDTA) program assists federal, state, local, and tribal law enforcement agencies throughout the USA in areas determined to be critical drug trafficking regions.35 There are 33 HIDTAs that cover areas within all 50 US states and DC. Data on drug seizures by law enforcement agencies that participate are submitted quarterly. This analysis focused on the annual number of ketamine seizures reported by affiliated HIDTA organizations and the total weight in ketamine seized.
Finally, US Customs and Border Protection (CBP)36 seizure data were also obtained. Public data were available on seized ketamine reported to the CBP Office of Field Operations (OFO) 20 major field offices as well as CBP's preclearance sector which attempts to confiscate drugs about to enter the US from six countries.37 This analysis used publicly available data regarding the annual number and total weight of ketamine seizures.
Statistical analysis
Piecewise linear regression was used to model all annual trends across time, estimating the number of linear slopes that best fit the data, and the years in which the slopes significantly changed direction or magnitude. General linear models were modeled for each outcome, and the number and location of any breakpoints were selected using the Bayesian information criterion, as we have done in other work.20 Each final model was fit taking into consideration the piecewise linear relationship. R version 4.4.1 was used (R Foundation). All data in these analyses were exempt from review by the New York University Langone Medical Center institutional review board (IRB). This project was a secondary data analysis of deidentified data; therefore, per the guidelines of the New York University Langone Medical Center Institutional Review Board, IRB assessment was not necessary.
Role of the funding source
The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of this report.
Results
Table 1 presents the results of all trend analyses and Fig. 1 presents trends in estimated prevalence of past-year ketamine use in the general population and among 12th graders, trends in reported ketamine-related poisonings, and trends in rates of ketamine-related deaths. With respect to estimated prevalence of past-year use among noninstitutionalized individuals aged ≥12 years, significant shifts were not detected within the predesignated year fragments for 2006 (0.09%, SE = 0.02) through 2014 (0.08%, SE = 0.01) or 2015 (0.12%, SE = 0.02) through 2019 (0.18%, SE = 0.02), but a significant increase was detected between 2021 (0.19%, SE = 0.03) and 2023 (0.34%, SE = 0.05) (b [slope] = 0.08 [SE = 0.001], p = 0.0072). The sensitivity test focusing on adults aged ≥18 years yielded similar results with a significant increase detected between 2021 (0.20%, SE = 0.03) and 2023 (0.37%, SE = 0.05) (b = 0.08 [SE = 0.003], p = 0.0248) (Supplementary Table S1 and Supplementary Figure S1). However, among those aged 12–17 years, there was a significant decrease detected between 2010 (0.22%, SE = 0.05) and 2014 (0.10%, SE = 0.03) (b = −0.03 [SE = 0.01], p = 0.0096).
Table 1.
Trends in estimated prevalence of past-year ketamine use in the general population (2006–2014, 2015–2019, and 2021–2023) and among 12th graders (2000–2023), trends in reported ketamine-related poisonings (1991–2023), rates of ketamine-related deaths per 100,000 population (2020–2023), diversion of undistributed pharmaceutical ketamine (2008–2024), number of ketamine reports to NFLIS (2001–2024), and in the number of total weight of ketamine seizures by HIDTA (2017–2024) and by CBP OFO (2019–2024) in the USA.
| Past-year use | Trend yearsa | Trend beginning % (SE) | Trend end % (SE) | b (SE); p-value | Summary |
|---|---|---|---|---|---|
| Noninstitutionalized individuals aged ≥12 (NSDUH)b | 2006–2014 | 0.09 (0.02) | 0.08 (0.01) | 0.00 (0.003); p = 0.21 | Recent increase |
| 2015–2018 | 0.12 (0.02) | 0.11 (0.02) | 0.00 (0.006); p = 0.77 | ||
| 2018–2019 | 0.11 (0.02) | 0.18 (0.02) | 0.07 (0.01); p = 0.11 | ||
| 2021–2023 | 0.19 (0.03) | 0.34 (0.05) | 0.08 (0.001); p = 0.0072 | ||
| 12th graders (MTF) | 2000–2005 | 2.49 (0.35) | 1.61 (0.16) | −0.19 (0.06); p = 0.0039 | Decrease across time |
| 2005–2023 | 1.61 (0.16) | 0.88 (0.25) | −0.04 (0.01); p = 0.0019 |
| Exposures (Poisonings) | Trend yearsa | Trend beginning rate per 1,000,000 | Trend end rate per 1,000,000 | b (SE); p-value | Summary |
|---|---|---|---|---|---|
| Exposures reported to poison centers | 1991–1994 | 0.09 | 0.17 | 0.02 (0.08); p = 0.78 | Staggered |
| 1994–2000 | 0.17 | 1.40 | 0.20 (0.02); p < 0.0001 | increase across | |
| 2000–2003 | 1.40 | 0.58 | −0.34 (0.08); p = 0.0002 | time | |
| 2003–2008 | 0.58 | 0.37 | −0.06 (0.03); p = 0.10 | ||
| 2008–2013 | 0.37 | 0.97 | 0.14 (0.03); p = 0.0007 | ||
| 2013–2017 | 0.97 | 0.76 | −0.09 (0.05); p = 0.07 | ||
| 2017–2023 | 0.76 | 1.54 | 0.12 (0.03); p = 0.0002 |
| Mortality linked to use | Trend yearsa | Trend beginning rate per 100,000 | Trend end rate per 100,000 | b (SE); p-value | Summary |
|---|---|---|---|---|---|
| Ketamine-Positive Deaths (SUDORS) | 2020–2023 | 0.11 | 0.15 | 0.01 (0.01); p = 0.13 | No change |
| Undistributed pharmaceutical diversion | Trend yearsa | Trend beginning n | Trend end n | b (SE); p-value | Summary |
|---|---|---|---|---|---|
| Reported diversions (US DEA) | 2008–2017 | 23 | 202 | 18.72 (2.20); p < 0.0001 | Early and recent increases |
| 2017–2021 | 202 | 183 | −8.10 (5.39); p = 0.16 | ||
| 2021–2024 | 183 | 286 | 39.00 (12.04); p < 0.0001 |
| Seizures/Submissions | Trend yearsa | Trend beginning n/kg | Trend end n/kg | b (SE); p-value | Summary |
|---|---|---|---|---|---|
| NFLIS submissions (US DEA) | 2001–2015 | 1542 | 1448 | −3.67 (34.83); p = 0.92 | Recent increase |
| 2015–2024 | 1448 | 4008 | 201.41 (57.83); p = 0.0023 | ||
| HIDTA seizures | 2017–2022 | 55 | 247 | 34.80 (4.65); p = 0.0017 | Recent increase |
| 2022–2024 | 247 | 502 | 127.50 (10.40); p = 0.0003 | ||
| HIDTA total seizure weight | 2017–2019 | 57.8 kg | 145.7 kg | 43.96 (75.94); p = 0.59 | Recent increase |
| 2019–2024 | 145.7 kg | 1108.1 kg | 219.51 (33.96); p = 0.0030 | ||
| CBP OFO seizures | 2019–2024 | 1355 | 1079 | 19.23 (79.12); p = 0.82 | No change |
| CBP OFO total seizure weight | 2019–2022 | 432.1 kg | 6239.5 kg | 2244.10 (1012.50); p = 0.16 | No change |
| 2022–2024 | 6239.5 kg | 3294.4 kg | −1472.50 (1012.50); p = 0.28 |
Abbreviations: NSDUH, National Survey on Drug Use and Health; MTF, Monitoring the Future; SUDORS, State Unintentional Drug Overdose Reporting System; DEA, Drug Enforcement Administration; NFLIS, National Forensic Laboratory Information System; HIDTA, High Intensity Drug Trafficking Areas; CBP OFO, Customs and Border Protection Office of Field Operations.
When a single slope was detected, a single slope is reported for the full time period. When multiple slopes were detected, multiple slopes were reported. Slopes are interpreted as the average change in outcome prevalence for a one unit increase in the trend year.
NSDUH has changed their methods multiple times which led to “broken” trends that we are advised against directly comparing across time. Trends can be estimated with confidence in 2006–2014, 2015–2019, and in 2021–2023.
Fig. 1.
Trends in estimated prevalence of a) past-year ketamine use in the general population (2006–2014, 2015–2019, and 2021–2023) and b) among 12th graders (2000–2023), c) trends in reported ketamine-related poisonings (1991–2023), and d) trends in rates of ketamine-related deaths per 100,000 population (2020–2023) in the USA. Includes trends in prevalence and 95% CIs estimated by regression models with broken–line relationships. The best-fitting piecewise linear regression models estimating past-year ketamine use among noninstitutionalized individuals aged ≥12 years indicated one nonsignificant slope (with no breakpoints) between 2006 and 2014, one non-significant slope between 2015 and 2019, and a significant slope between 2021 and 2023 without breakpoints (b = 0.08, SE = 0.001, p = 0.0072). Among 12th grade students, we detected two significant negative slopes with estimated past-year use decreasing from 2000 to 2005 (with a detected breakpoint at 2005) (b = −0.19, SE = 0.06, p = 0.0039) and then a significant negative slope through 2023 (b = −0.04, SE = 0.01, p = 0.0019). With respect to reported ketamine-related poisonings, there was a staggered increase with six breakpoints. Specifically, we detected a positive slope between 1994 and 2000 (b = 0.20, SE = 0.02, p = 0.0021), followed by a negative slop through 2003 (b = −0.34, SE = 0.08, p = 0.0002). There was then a nonsignificant positive slope through 2008 followed by a significant positive slope through 2013 (b = 0.14, SE = 0.13, p = 0.0007). There was then a nonsignificant negative slope through 2017, followed by a positive slope through 2023 (b = 0.12, SE = 0.03, p = 0.0002). With regard to ketamine-related deaths, we detected a single non-significant slope. Observed values/estimates are depicted by black dots, fitted slopes are depicted by blue lines, and 95% CIs are depicted by the gray area surrounding slopes.
A total of 7570 exposures (poisonings) were reported to US poison centers between 1991 and 2023, and we detected a staggered increase across time (including six breakpoints). Specifically, reported poisonings initially increased from 1994 to 2000 (from 0.17 to 1.40 per 1,000,000 population; b = 0.20 [SE = 0.02], p < 0.0001), followed by a decrease through 2003 (to 0.58 per 1,000,000 population; b = −0.34 [SE = 0.08, p = 0.0002). There was then a nonsignificant decrease through 2008 (0.37 per 1,000,000 population) followed by a significant increase through 2013 (0.97 per 1,000,000 population; b = 0.14 [SE = 0.03], p = 0.0007). There was then a nonsignificant decrease through 2017 (0.76 per 1,000,000 population), followed by an increase through 2023 (to 1.54 per 1,000,000 population; b = 0.12 [SE = 0.03], p = 0.0002).
Fig. 2 presents trends in diversion of undistributed pharmaceutical ketamine, trends in number of ketamine reports to NFLIS, and trends in the number and total weight of ketamine seizures by HIDTA and by CBP OFO. There was a total of 2830 reported diversions of undistributed pharmaceutical ketamine between 2008 and 2024, and there was a significant increase between 2008 (n = 23) through 2017 (n = 202) (b = 18.72 [SE = 2.20], p < 0.0001). There was then a nonsignificant decrease through 2021 (n = 183) followed by a significant increase through 2024 (n = 286) (b = 39.00 [SE = 12.04], p < 0.0001).
Fig. 2.
Trends in a) diversion of undistributed pharmaceutical ketamine (2008–2024), b) trends in number of ketamine reports to NFLIS (2001–2024), and trends in c) the number and d) total weight of ketamine seizures by HIDTA (2017–2024) and e) the number and f) total weight of ketamine seizures by CBP OFO (2019–2024) in the USA. Includes trends in count data estimated by regression models with broken–line relationships. The best-fitting piecewise linear regression model estimating trends in diversions of undistributed pharmaceutical ketamine detected two breakpoints with results suggesting a significant positive slope between 2008 and 2017 (b = 18.72, SE = 2.20, p < 0.0001), followed by a nonsignificant slope through 2021, and another significant positive slope through 2024 (b = 39.00, SE = 12.04, p < 0.0001). With regard to drug submissions testing positive for ketamine submitted to NFLIS, one breakpoint was detected and while there was a nonsignificant slope from 2001 through 2015, we detected a significant positive slope through 2024 (b = 201.41, SE = 57.83, p = 0.0023). Regarding the number of HIDTA seizures, we detected one breakpoint in which there was a significant positive slope from 2017 through 2022 (b = 34.80, SE = 4.65, p = 0.0017) followed by a steeper slope through 2024 (b = 127.50, SE = 10.40, p = 0.0003). With respect to the total weight of HIDTA seizures, we also detected one breakpoint with a non-significant slope between 2017 and 2019, followed by a positive significant slope through 2024 (b = 219.51, SE = 33.96, p = 0.0030). Finally, with regard to both the number of seizures by CBP OFO and the total weight of seizures, we did not detect significant slopes. Observed values are depicted by black dots and fitted slopes are depicted by blue lines.
With regard to drug submissions testing positive for ketamine submitted to NFLIS, there were 42,232 drug reports between 2001 and 2024, and while there was a nonsignificant decrease from 2001 (n = 1542) through 2015 (n = 1448), there was then a significant increase through 2024 (n = 4008) (b = 201.41 [SE = 57.83], p = 0.0023). There were 1734 seizures identified as ketamine by HIDTA between 2017 and 2024, totaling 3995.3 kg. There was an increase in HIDTA seizures from 2017 (n = 55) through 2022 (n = 247) (b = 34.80 [SE = 4.65], p = 0.0017) and then a steeper increase through 2024 (n = 502) (b = 127.50 [SE = 10.40], p = 0.0003). There was an increase in total weight of ketamine seized by HIDTA between 2017 (57.8 kg) and 2019 (145.7 kg) which was not significant, but there was a significant increase from 2019 through 2024 (1108.1 kg) (b = 219.51 [SE = 33.96]. p = 0.0030). Finally, there were 6989 seizures by CBP OFO between 2019 and 2024, totaling 18,952.6 kg. The number of seizures remained stable (1355 in 2019 and 1079 in 2024, and the total weight seized also did not significantly shift across time.
With respect to deaths involving ketamine exposure, a total of 865 ketamine-positive deaths recorded by SUDORS in 2020–2023, and the increase from 175 (0.11 per 100,000 population) in 2020 to 320 (0.15 per 100,000 population) in 2023 was not significant.
Only among 12th grade students was there evidence of declining use. Among 12th graders, estimated past-year use decreased from 2000 (2.49%, SE = 0.35) through 2005 (1.61%, SE = 0.16) (b = −0.19 [SE = 0.06], p = 0.0039) and then decreased again from 2005 through 2023 (0.88%, SE = 0.25) (b = −0.04 [SE = 0.01], p = 0.0019).
Discussion
The present study estimated trends in ketamine outcomes across eight different national datasets. For five of the eight outcomes, there was evidence of recent increases. Specifically, estimated prevalence of past-year nonmedical use increased in the general population, poisonings increased, undistributed pharmaceutical ketamine diversions increased, and two law enforcement datasets further suggest that seizures have increased. For two outcomes, CBP OFO seizures and ketamine-related deaths, there were no observed changes in recent years, and among 12th grade students, there was evidence of sustained declines in the prevalence of estimated use. Adding to evidence for a decline among 12th graders, our sensitivity model estimating trends in use among the general population ages 12–17 confirmed a decrease in estimated prevalence of nonmedical use. In summary, triangulating across data sources indicates that the ketamine landscape in the USA has continued to become increasingly complex, with shifts in prevalence of nonmedical use, illicit availability, and ketamine-related morbidity. These shifts on top of increased off-label prescribing and increased media coverage suggest that both prescribed and illicit ketamine have become increasingly available with the potential to become more of a public health threat.
Trends in estimated nonmedical ketamine use indicate that while there have been increases in past-year use among the general population aged ≥12 years between 2021 and 2023 (with a similar pattern among adults ≥18 years), there was a sharp decrease among 12th graders from 2000 through 2005, and then a continued decrease through 2023. Indeed, in the early 2000s, ketamine was commonly used alongside other party drugs like MDMA/ecstasy among people in nightclub and rave scenes,7 and in the USA, prevalence of ecstasy use rapidly declined beginning in about 2002 alongside ketamine.6 While ecstasy/MDMA experienced periods of popularity in later years,6 ketamine use has not yet appeared to have regained popularity among adolescents (and those aged 26–34 and those with a college degree appear to be at particularly high risk for use38). Of note, use of illicit drugs other than cannabis reached an all-time low among adolescents in the USA in 2021.6 In fact, with recent drops in prevalence of common party drugs like cocaine and ecstasy/MDMA among 12th graders, the estimated prevalence of ketamine use is actually slightly higher.6 Increases in the general population but not among adolescents suggests that it may be older individuals who are more likely to engage in recreational use.
Importantly, estimated prevalence of ketamine use also still appears to be lower than in the UK, Australia, and China.8,9,39 There have also been recent increases in Switzerland, with ketamine seizures increasing in the European Union—with a particularly large portion of seizures occurring in The Netherlands and in Spain.39,40 In addition, ketamine is among the most commonly used psychoactive drugs in some Southeast Asian counties, and the drug also appears to be a leading drug of choice in China and in Taiwan.39 It should be noted, however, that percentages of people who use ketamine nonmedically across countries has different meaning in terms of absolute numbers of people affected depending on population size. For example, China has a population size over four-times greater than the USA, so a similar estimated percentage would equate to a greater number of people. As such, this may suggest an even greater possible burden (regarding the number of people affected) in China. Despite recent increases in use in the US general population, however, estimated prevalence is still below 1%, and ketamine use in the USA is estimated to be less prevalent than drugs such as cocaine, LSD, and methamphetamine.26 When focusing on adolescents (aged 12–17), prevalence was slightly higher than prevalence of adults over a decade ago, but prevalence among adolescents decreased between 2010 and 2014 and thereafter has remained lower than that of adults.
With respect to adverse events, while there were at least 865 deaths recorded in the USA in 2020–2023 in which decedents tested positive for ketamine exposure, we did not detect a significant increase over time. A recent analysis of deaths linked to ketamine use focusing on cases from the SUDORS dataset found that 59% involved co-detection of illicitly manufactured fentanyl (IMF), 82.4% involved co-detection of IMF and/or methamphetamine or cocaine, and that only 2.6% of deaths did not involve other drugs.30 As such, it appears that ketamine when not used in a polydrug context is less likely to be linked to mortality. We did, however, detect trends with respect to ketamine-related morbidity. Specifically, we detected a staggered increase in reported ketamine-related exposures (poisonings) between 1991 and 2023, most of which were nonfatal.28 The initial increase in the rate of poisoning cases appears to have coincided with the US DEA's ruling to schedule the drug in 1999,5 and the most recent increase (to the highest number of reported ketamine poisonings ever) began in 2017. Given that data were not available regarding reasons for use, type of ketamine use (e.g., medical vs. nonmedical use) and severity of outcomes, a greater focus on morbidity is needed. Relatedly, another limitation of US data is that the USA no longer has an emergency department drug exposure surveillance system that reports on drugs like ketamine. Of note, poisonings and hospitalizations likely represent more serious cases of exposure. More research is not only needed on poisonings or overdoses but on acute toxic effects and more long-term effects linked to both recreational use and chronic use with a particular focus on morbidity (including use disorder and urinary cystitis).
This analysis also focused on diversion and seizure data to indicate possible illicit availability of ketamine. We detected an increase in reported diversions of undispensed pharmaceutical ketamine between 2008 and 2017, and then a steeper increase from 2021 through 2024. This pattern appears to complement detected trends in illicit ketamine seizures. Seizure data trends show a nuanced and partially conflicting story regarding illicit ketamine availability, but we generally detected recent increases. Drug submissions testing positive for ketamine submitted to NFLIS increased from 2015 to 2024, and law enforcement seizures reported to HIDTA also increased between 2017 and 2024 with a particularly steep increase beginning in 2022. Similarly, the total annual weight of ketamine seized by HIDTA-affiliated agencies increased between 2019 and 2024. However, we did not detect a significant shift in count or total weight among seizures reported by CBP OFO. Regardless, between HIDTA and CBP OFO, assuming mutual exclusivity, 22,807 kg of ketamine were recorded as being confiscated between 2019 and 2024 (4402 kg in 2024 alone). The number of and total weight of ketamine seizures has also been increasing in Europe, with 2793 kg seized in 2022.41 It is unknown to what extent seizures indicate drug availability as compared to representing drugs removed from circulation.
More research, preferably at the state- or county-level, is needed to determine if and how such trends predict one another. For example, while trends in seizures and deaths have often been found to be closely related, such associations are less consistent for other drugs.42 More research is also needed to determine whether increases in off-label prescribing predict shifts in illicit use and associated poisonings.
This research is subject to limitations. We could not always differentiate between medical and nonmedical or illegally sourced ketamine, but it is assumed that most use was illicit as reported on drug surveys because illicit use was the main focus on both. Institutionalized and unhoused populations are underrepresented in NSDUH, and chronically absent students and dropouts are underrepresented in MTF. NSDUH has had multiple changes in methods over the past two decades so trends needed to be examined separately for years between methodological changes in a piecemeal manner.27 2020 NSDUH data could not be examined in trend analyses because of different methods conducted during the COVID-19 shutdown, and the 2020 MTF dataset was smaller than datasets from other years so caution is needed when considering 2020 data as part of trends. Also related to COVID-19, it is possible that delayed reporting occurred (e.g., regarding pharmaceutical diversion) and that seizures were affected due to lower levels of law enforcement activity in 2020.43 Underreporting also likely occurred as people who use drugs like ecstasy/MDMA may have been unknowingly exposed to ketamine as an adulterant.44 Relatedly, ketamine tends in be the main ingredient in an increasingly popular drug concoction called Tusi (also known as “pink cocaine”), and people who use may not know they are using ketamine.45 Reporting poisonings to poison centers is voluntary and not representative of all exposures, and drug testing was not always conducted during reporting. Ketamine-related mortality statistics were not available from all states and drug testing and reporting may vary. Ketamine diversions might be underreported, and diversion does not necessarily translate to black market availability or misuse. Finally, reports of drug seizures vary by agency. NFLIS reports depend on labs reporting detections to the US DEA, HIDTA-affiliated agencies likely do not test all drug samples for ketamine, and CBP data on seizures made at the US border were not publicly available.
This study contributes to the literature by demonstrating that the ketamine landscape in the USA has become increasingly complex and that illicit use and availability as well as related poisonings have increased. It is essential that clinicians and public health practitioners are aware that nonmedical ketamine availability and use are an increasing threat to public health. Clinicians who prescribe ketamine in an off-label manner for psychiatric reasons need to aware of ketamine's abuse potential and risk of diversion, and clinicians who treat substance use disorder need to be aware that nonmedical ketamine use is increasing. Results from a recent international survey of people with ketamine use disorder suggest that the majority of treatment services have little or only some awareness about this disorder.46 As such, a better understanding of illicit ketamine use and use disorder are needed among addiction specialists. With respect to policy, tighter regulation for off-label prescribing (e.g., regarding take-home use) may be needed. We are not aware of any interest in rescheduling of ketamine in the USA, but in the UK, the Home Office is now considering reclassifying ketamine from a Class B drug to a Class A drug.47 Regardless of legal status, continued monitoring is needed and health practitioners and people who are at risk for use require education to help prevent illicit use and to reduce and treat associated harm linked to use.
Contributors
JJP conceptualised the study and led the writing of the paper, and it was his decision to submit this manuscript for publication. JJP obtained and managed the data, and CR led the statistical analysis and helped draft sections of the methods and results and provided critical edits to other sections of the paper. KMK supervised the analysis, had access to and verified the underlying data, helped drafted sections of the paper, and provided critical edits to other sections of the paper.
Data sharing statement
All National Survey on Drug Use and Health data used for the present study are publicly available through the Substance Abuse and Mental Health Services Administration website (https://www.samhsa.gov/data/data-we-collect/nsduh-national-survey-drug-use-and-health/datafiles). All Monitoring the Future data used for the present study are publicly available through the Inter-university Consortium for Political and Social Research (https://www.icpsr.umich.edu/web/pages/). All poison center data used for the present study are available from published poison center annual reports (although journal subscription may be necessary). US Drug Enforcement Administration (DEA) prescription diversion data are not publicly available but can be available upon reasonable request to the authors (or through Freedom of Information Act request to the US DEA). All State Unintentional Drug Overdose Reporting System data used for the present study are publicly available through the US Centers for Disease Control and Prevention dashboard (https://www.cdc.gov/overdose-prevention/data-research/facts-stats/sudors-dashboard-fatal-overdose-data.html). All National Forensic Laboratory Information System drug report data used for the present study are publicly available through the US DEA's public data query system (https://www.nflis.deadiversion.usdoj.gov/home.xhtml). The High Intensity Drug Trafficking Areas (HIDTA) data used for the present study are available per request through the HIDTA performance management process website (https://www.hidta.org/resources/pmp-data-sharing/). All US Customs and Border Protection (CBP) Office of Field Operations data used for the present study are publicly available through the CBP website (https://www.cbp.gov/newsroom/stats/drug-seizure-statistics).
Declaration of interests
Dr Palamar reported receiving personal fees from the Washington–Baltimore High Intensity Drug Trafficking Areas program, Elsevier, Wiley, Rutgers University, Arizona State University, the University of Southern California, Queensland University, the National Network of Public Health Institutes, and Alta Mira Recovery programs, and nonfinancial support from NIH/NIDA, the University of Florida, Rx Summit, and the Reagan–Udall Foundation for the FDA during the conduct of the study. Dr Keyes and Miss Rutherford reported receiving personal fees from National Prescription Opioid Litigation for providing expert testimony outside the submitted work. No other disclosures were reported.
Acknowledgements
This research was supported by the National Institute on Drug Abuse of the National Institutes of Health under award numbers R01DA060207, R01DA057289, and U01DA051126. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Role of the funder/Sponsor: Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Numbers R01DA060207, R01DA057289, and U01DA051126. The National Institute on Drug Abuse of the National Institutes of Health had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Footnotes
Supplementary data related to this article can be found at https://doi.org/10.1016/j.lana.2025.101230.
Appendix A. Supplementary data
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