Faculty Bibliography

Recreational ketamine use and related adverse outcomes have been increasing; however, correct diagnostic classification of quantitative oral fluid test results remains challenging, considering the potential for unintentional exposure to ketamine as an adulterant in other drugs. We surveyed and collected oral fluid from 1819 adults entering nightclubs and compared detection results with past 24-h self-reported ketamine use. Other drug use (based on detection and on self-reported past 24-h use) was considered a risk factor for unintentional ketamine exposure as an adulterant. Oral fluid specimens were analyzed via liquid chromatography quadrupole time-of-flight mass spectrometry. 10.8% of participants reported past 24-h ketamine use, 23.7% tested positive for ketamine (≥ 1 ng/mL), and 10.9% tested positive for norketamine (≥ 1 ng/mL). 46.0% tested positive for drugs other than ketamine, primarily cocaine. Among those testing positive for ketamine (n = 431), 41.5% reported past 24-h use. Among these cases, the optimal ketamine concentration cut-point for predicting self-report was ≥ 18 ng/mL. In analyses using the full sample (n = 1819) and a subsample with data on past 48-h use (n = 795), optimal cut-points were ≥ 2 ng/mL and ≥ 5 ng/mL, respectively. However, norketamine detection was the strongest predictor of self-reported use across the full sample and subsamples examined. Using self-report as the comparison, norketamine detection most accurately classified reported use; however, relying solely on higher concentration thresholds of ketamine or norketamine detection alone may lead to underdetection in some cases. Findings indicate the importance of carefully selected biological markers and thresholds when interpreting oral fluid results in settings where adulterant exposure is common.

BACKGROUND:Ketamine is increasingly prescribed in an off-label manner to treat psychiatric disorders, raising concerns about direct-to-consumer advertising and the proliferation of clinics offering ketamine for at-home use without direct medical supervision. OBJECTIVES/OBJECTIVE:We aimed to identify and characterize clinics advertising ketamine for psychiatric conditions online in the New York metropolitan area (New York, New Jersey, and Connecticut), with attention to advertising suggesting ketamine is prescribed for at-home use. METHODS:In 2025, systematic web searches were conducted to identify clinics advertising prescription ketamine for psychiatric indications. Public-facing website content was reviewed to describe clinic characteristics: service delivery modality, clinician credentials, routes of administration, disorders treated, and advertising practices. A generalized linear model was used to delineate correlates of clinics advertising ketamine for at-home use. RESULTS:233 clinics were located; 36.5% prescribed ketamine for at-home use. 51.5% listed a medical doctor as part of their team and 42.9% advertised oral ketamine. Depression was the most commonly listed disorder treated (94.0%) and 21.9% advertised ketamine to treat substance use disorder. In the multivariable model, advertising ketamine for at-home use was more common among clinics advertising oral ketamine (aPR = 4.10, 95% CI: 2.20-7.60) and less common among clinics listing a medical doctor (aPR = 0.54, 95% CI: 0.30-0.99). CONCLUSIONS:Over a third of clinics advertised ketamine for at-home use. A limitation is that we only focused on public-facing websites. Advertising practices and clinician representation suggest clinics may be advertising in a more consumer-oriented manner, underscoring the need for monitoring and clearer guidance to mitigate potential safety risks.

AIMS/OBJECTIVE:To characterize decreases in overdose death rates in the United States (US) between 2023 and 2024 by race/ethnicity, and substance involvement. DESIGN/METHODS:Population-based study of national death records accessed via the Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER) platform using an underlying cause of death approach. SETTING/METHODS:US. PARTICIPANTS/CASES/METHODS:All individuals who died from drug overdose between January 1999 and December 2024. MEASUREMENTS/METHODS:Annual overdose deaths per 100 000 population. Year of occurrence of overdose death, substance involvement, race/ethnicity of decedents. FINDINGS/RESULTS:After many years of increases, the US overdose death rate dropped 24.4% between 2023 and 2024. Decreases reflected declining illicit fentanyl-involved deaths (with and without stimulant involvement). The fourth wave of the US overdose crisis-defined by deaths involving fentanyl together with stimulants-declined for the first time in 2024. Despite overall decreases, deaths involving stimulants without fentanyl and deaths involving xylazine continued to represent a growing fraction of overdose fatalities. Non-Hispanic Black and African Americans had the largest decrease in death rates in 2023-2024, falling by 29.3% but remaining elevated at 36.0 per 100 000, 1.51 times higher than the national average of 23.7 per 100 000. Non-Hispanic American Indian and Alaska Native individuals had the highest overdose death rates rate in 2024, at 50.8 per 100 000, 2.15 times the national average rate, and experienced a below-average relative decrease of 20.1%. CONCLUSIONS:All four previously defined waves of the US overdose crisis appear to be in decline, as deaths involving illicit fentanyl, with and without stimulants, dropped sharply between 2023 and 2024. Concurrently, the fraction of overdose deaths involving stimulants without fentanyl and those involving xylazine continued to increase. While racial disparities in drug overdose death rates narrowed slightly during this period, large gaps remain, with the highest overdose death rates among American Indian, Alaska Native, and Black individuals.

BACKGROUND:Between 1979 and 2016, US overdose death rates rose in a smooth fashion, described by Jalal and Burke using an exponential growth curve that fit observed data nearly perfectly. Fluctuations above this curve have subsequently been seen during shocks related to drug supply and the COVID-19 pandemic. However, large-magnitude dips below the curve have never been demonstrated. Given that overdose mortality began sharply falling during 2023-2024, we assess updated overdose trends against the Jalal-Burke curve. METHODS:We examined US overdose deaths from the National Vital Statistics System between 1979-2024. We recreated the Jalal-Burke curve, fitting an exponential growth curve to overdose rates from 1979 to 2016, projected through 2024, with 95% confidence intervals. We also examined trends by specific substance involvement. RESULTS:After precipitously surpassing exponential growth predictions in 2020-2023, overdose deaths decreased sharply from approximately 32 per 100,000 in 2021-2023 to 23.7 in 2024, falling below the lower bound of the Jalal-Burke curve (24.1 per 100,000) for the first time since 2001. These decreases reflected declining illicit fentanyl-involved deaths, which fell to 14.25 per 100,000 in 2024; however, deaths involving stimulants without fentanyl, and those involving xylazine, represent an increasing share of deaths, rising to 5.64 and 1.89 per 100,000, respectively, in 2024. CONCLUSIONS:Rather than simply representing a return to the Jalal-Burke exponential growth curve, recent decreases in overdose deaths represent the first significant, large-magnitude deviation below exponential growth projections. This represents a very positive development; however, shifting challenges in the US drug crisis require a tailored response.

PURPOSE OF REVIEW/OBJECTIVE:The U.S. drug landscape is rapidly shifting necessitating early warning surveillance of emerging drug threats. We describe one such surveillance effort from the United States: the National Drug Early Warning System (NDEWS). RECENT FINDINGS/RESULTS:NDEWS monitors drug indicators with a particular focus on trends in new psychoactive substances (NPS) and emerging adulterants. NDEWS has five major goals: develop a collaboration network, including people with lived experience, initiate methods that deliver the freshest data on drug trends, integrate data from sources to better understand signals, disseminate findings widely, and train the next generation of surveillance scientists. NDEWS collects primary data using venue-based methods (Rapid Street Reporting), Web Monitoring, and 911 (Emergency Medical Service) data, and utilizes secondary data on drug seizures and poisonings. Information is shared bidirectionally with our 16 Sentinel Sites, our Community-Based Health Expert network, and our informal networks which include medical examiners, toxicologists, funeral directors, reporters, and community overdose response workers. SUMMARY/CONCLUSIONS:Surveillance of emerging drug trends is increasingly important around the world as patterns of drug use continue to shift. With a focus on NPS and nonlagged data strategies, NDEWS warns communities at risk to prevent serious consequences and death.

BACKGROUND:In the US, 40 states and the District of Columbia (DC) have implemented medical cannabis legalization (MCL), while 24 states and DC have enacted some form of recreational cannabis legalization (RCL). We examined the association between cannabis legalization and law enforcement cannabis seizures to understand illegal drug market responses to increasing state cannabis legalization. METHODS:Data on law enforcement cannabis seizures came from the High Intensity Drug Trafficking Areas (HIDTA) program. We tested the association between state-level RCL and MCL adoption and annual changes in cannabis seizures aggregated by state-year from 2010 to 2023 using a series of Poisson regression models that controlled for time-varying state demographic and law enforcement variables in addition to state and year fixed effects. To account for potential lag time between MCL/RCL effective dates and policy impacts on seizures, we conducted additional analyses with 1-year MCL/RCL lags. RESULTS:Over the study period, there were 286,844 cannabis seizures by HIDTA-affiliated agencies, with 686 state-years of observation. In primary adjusted models, RCL adoption was associated with a significant decrease in cannabis seizures in MCL & RCL states versus MCL-only states, both immediately following RCL adoption (exp(β)=0.55, 95% CI: 0.54, 0.56) and one year after RCL went into effect (exp(β) for 1-year lag=0.62, 95% CI: 0.61, 0.64). CONCLUSIONS:The adoption of RCLs in US states, beyond only MCLs, may help to reduce the size of illegal cannabis markets, or there may be shifting law enforcement seizure priorities in those states.

OBJECTIVES/OBJECTIVE:Self-report and biospecimen testing to assess drug exposure have limitations. Surface testing of personal objects (e.g., mobile phones) may provide complementary information about drug exposure, particularly when there is discordance between biospecimen results and self-report. We examined whether mobile phone swab testing, alongside self-report and oral fluid data, could provide information regarding drug exposure among nightlife attendees-a population with high prevalence of party drug use. We also examined whether detection could inform situations in which a drug is detected in oral fluid but not reportedly used. METHODS:In 2025, we assessed self-reported drug use and analyzed oral fluid and swabs of mobile phones from 127 adults attending nightclubs in New York City. We compared the prevalence of detection of cocaine, ketamine, 3,4-methylenedioxymethamphetamine (MDMA), and 4-methylmethcathinone (4-MMC) across the three modes of collection. RESULTS:Cocaine was detected on 26.8% of phones, followed by ketamine (22.0%), 4-MMC (3.1%), and MDMA (2.4%). When classifying phone detection, reported past-48-hour use and oral fluid detection of cocaine and ketamine demonstrated high specificity (0.85-0.91), but lower sensitivity (0.37-0.73). Among participants with oral fluid positivity after not reporting use, 33.3% and 17.1% of these discordant cases had ketamine and cocaine detected on their phones, respectively. CONCLUSIONS:Phone swab results often align with self-reported use and, less consistently with biologically confirmed exposure. However, drugs detected on phones may reflect less recent use or unintentional environmental sources contributing to oral fluid detection, supporting the role of phone swabbing as a complementary tool for detecting possible drug exposure.

BACKGROUND AND AIMS/OBJECTIVE:Nitazenes are a novel subclass of synthetic opioids that have been increasingly implicated in the United States (US) overdose crisis. Despite their growing presence in the illicit drug supply, national trends have not been systematically evaluated. This study aimed to describe temporal and geographic patterns in nitazene detections and assess substances co-involved in nitazene-positive biospecimens. DESIGN/METHODS:Cross-sectional study using forensic data from two national sources: the US Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS) and the Center for Forensic Science Research & Education's (CFSRE) NPS Discovery Program. SETTING AND CASES/METHODS:Nitazene detections in all 50 US states and the District of Columbia between 2019 and 2024. MEASUREMENTS/METHODS:We quantified annual nitazene detections overall and by individual nitazene analog, US Census region and state. Temporal trends were modeled using piecewise linear regression with a Poisson distribution and log link, nationally and by region. NPS Discovery data were used to characterize substances co-involved with nitazene-positive biospecimens. FINDINGS/RESULTS:Between 2019 and 2024, 7117 nitazene analog reports were submitted to NFLIS, increasing from 43 in 2019 to 1905 in 2024. Counts rose sharply from 2019 to 2021 [count ratio = 7.32; 95% confidence interval (CI) = 2.22-24.20] but did not increase statistically significantly from 2021 to 2024 (count ratio = 1.08; 95% CI = 1.00-1.17). Early detections were predominated by isotonitazene (97.7% of NFLIS nitazene reports in 2019) but later shifted toward metonitazene and protonitazene (29.5% and 30.1%, respectively, in 2024). NPS Discovery identified 361 nitazene-positive biospecimens, increasing from 11 in 2019 to 113 in 2024, with counts increasing by approximately 45% per year (count ratio = 1.45; 95% CI = 1.23-1.71). Nearly all nitazene-positive biospecimens (98.3%) had at least one co-detected substance, most commonly fentanyl (54.6%). CONCLUSIONS:Nitazene detections increased sharply across the United States between 2019 and 2024, with shifting patterns in the prevalence of individual nitazenes and extensive polysubstance involvement. These findings highlight the need to strengthen drug testing capacity, expand epidemiological surveillance and implement targeted public health interventions to mitigate harms associated with this emerging class of synthetic opioids.