Faculty Bibliography

OBJECTIVES/OBJECTIVE:To estimate past-year prevalence and correlates of major depressive episode (MDE), characterize mental health treatment utilization, and identify barriers to care among community-dwelling US adults aged ≥50. DESIGN/METHODS:Cross-sectional analysis of a nationally representative survey. SETTING/METHODS:Noninstitutionalized US population. PARTICIPANTS/METHODS:20,580 respondents aged ≥50 from 2022 to 2023 National Survey on Drug Use and Health. MEASUREMENTS/METHODS:We estimated past-year MDE prevalence and delineated demographic and past-year substance use correlates; examined mental health treatment utilization among individuals with MDE; and identified barriers to care among untreated individuals. RESULTS:An estimated 4.6% (95% confidence interval: 4.2-5.2) of adults aged ≥50 experienced past-year MDE. In multivariable analyses, higher odds were estimated among females, divorced/separated or widowed individuals, college-educated individuals, and those with alcohol use disorder, cannabis use (with or without use disorder), and prescription opioid or tranquilizer/sedative misuse. Lower odds were estimated among adults aged ≥65, Non-Hispanic Black individuals, and those with income ≥$50,000. Among those with MDE, 66.2% received any mental health treatment. In bivariable comparisons, adults aged ≥65 were less likely than those aged 50-64 to receive outpatient mental health services (38.7% versus 50.1%, p = 0.032) and to report perceived unmet need for treatment (8.8% versus 23.3%, p = 0.019). Among untreated individuals with perceived unmet need, barriers to treatment were attitudinal (86.2%; e.g., thought could handle without treatment), access-related (73.1%), and financial (48.6%). CONCLUSIONS:MDE is prevalent among older adults with heterogeneity across demographic and substance use factors. Treatment disparities and high barrier rates highlight the need for targeted interventions in this population.

BACKGROUND:Cannabis consumption modalities such as smoking, vaping, and consumption of edibles differ in pharmacokinetics and potency, and vary by demographic characteristics. Data linking real-world consumption modality patterns to use frequency and cannabis use disorder (CUD) remain limited. METHODS:Latent class analysis (LCA) was applied to identify modality-based classes using data from 17,732 adults reporting past 30-day cannabis use on the 2022-2023 National Survey on Drug Use and Health. Multinomial logistic regression delineated associations of class membership with demographic characteristics, cannabis use frequency, and the presence/severity of CUD. RESULTS:LCA yielded four classes based on each modality likelihood: primary smoking (48.2 %), smoking and vaping (20.5 %), mainly edibles (16.9 %), and polymodal use (14.4 %). Compared to adults aged ≥ 50, those aged 18-25 years were more likely to belong to the smoking and vaping (aRRR = 2.52, 95 % CI: 1.77-3.61) or polymodal classes (aRRR = 3.58, 95 % CI: 2.48-5.18). Females were more likely to be in the mainly edibles class (aRRR = 1.78, 95 % CI: 1.48-2.13). Daily cannabis use was more likely among polymodal (aRRR = 2.67, 95 % CI: 2.25-3.17) and less likely among mainly edibles (aRRR = 0.49, 95 % CI: 0.35-0.68) classes, relative to the primary smoking class. Compared to the primary smoking class, risk of having CUD was higher among people in the smoking and vaping class, and in the polymodal class, but lower in the mainly edibles class. CONCLUSIONS:Cannabis use modalities were associated with differences regarding demographic characteristics and severity of use. Future interventions could account for route-specific use to improve prevention and harm reduction efforts.

Synthetic cathinones are a chemically diverse class of novel stimulants that continue to emerge in the U.S. and globally. Trends in overall and specific synthetic cathinone availability in the U.S. (as indicated by seizures) remain poorly characterized. We analyzed annual counts of reports submitted from 2010-2024 to the U.S. Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS). We grouped reports into chemical subclasses of beta-keto methylenedioxyamphetamines ("-ylones"), pyrrolidinophenones ("pyrros"), and beta-keto amphetamines ("-drones"). Temporal trends in total reports and subclasses were modeled using negative binomial regression spline models. To further contextualize subclass trends, we descriptively examined the contribution of individual synthetic cathinones over time. Between 2010 and 2024, 178,892 synthetic cathinone reports were submitted to NFLIS, of which 73.3% were classified as -ylones, 19.9% as pyrros, 5.2% as -drones, and 1.6% as other. 68.7% of total reports were from the South, with 33.5% from Florida. Nationally, total reports increased sharply in 2010-2013, declined mid-period, rose again from 2019-2020, and then stabilized. Additional regional and temporal heterogeneity was noted across subclasses. We identified patterns of rapid emergence and replacement of individual compounds within subclasses, particularly within the -ylone subclass. Overall, we found substantial temporal, regional, and subclass-specific variation in synthetic cathinone reports to NFLIS from 2010-2024, largely driven by reports from the South and from successive cycles of replacement of -ylones. These findings emphasize the need to strengthen forensic and epidemiological surveillance of the evolving synthetic cathinone landscape in the U.S.

Research is needed to establish optimal cutoffs to determine cocaine use via oral fluid testing while considering the possibility of unintentional exposure. We compared detection of cocaine and its metabolites to self-reported use while considering other drug use to determine optimal cutoffs to determine intentional use. In this study, 1819 adults entering randomly selected nightclubs were surveyed about cocaine and other drug use and had their oral fluid analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry. We compared self-reported use to detected exposure. 13.6% of participants reported past 24-hour cocaine use, 43.7% tested positive for cocaine exposure (≥1 ng/mL), and 11.8% tested positive for at least one metabolite. 28.6% either tested positive for or reported past 24-hour use of other drugs, primarily ketamine. Among those testing positive for cocaine exposure (n = 794), only 29.1% reported past 24-hour use. Among positive cases, the optimal cocaine concentration cut-point for predicting self-report was ≥ 26 ng/mL. When focusing on the full sample and a subsample with data on past 48-hour reported use, optimal cut-points were ≥ 6 ng/mL and ≥ 5 ng/mL, respectively. However, detection of metabolites was the strongest predictor of self-reported use. Using self-report as the gold standard, metabolite detection most accurately classified reported use, over and above detection of cocaine or other drugs; however, relying solely on detection of metabolites or higher cocaine concentration thresholds often led to under-detection. In conclusion, relying on detection of metabolites or higher concentrations most accurately detects intentional use, but these lack sensitivity to detect a portion of use.

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.