Faculty Bibliography

PURPOSE OF REVIEW/UNASSIGNED:As the overdose crisis evolves, it is important to monitor fentanyl consumption patterns. This review provides an overview of recent findings regarding illegally manufactured fentanyl (IMF) availability, use, and associated harms in the US. RECENT FINDINGS/UNASSIGNED:Availability of IMF has increased, especially in pill form, and the increasing adulteration of IMF with veterinary tranquilizers such as xylazine complicates overdose response. Prevalence in the general population based on self-reported IMF use is rare, and likely underestimated. Transitions from injection to smoking have been documented in recent years, particularly in the western US. Fentanyl-stimulant polysubstance use has also been observed increasingly among IMF-related overdose deaths. SUMMARY/UNASSIGNED:Shifts in routes of administration, availability of counterfeit pills containing fentanyl, and common adulterants add complexity to the landscape of IMF use and related harms. Additional data is needed for monitoring changes in consumption patterns to inform prevention and harm reduction efforts.

BACKGROUND/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:National Institute on Drug Abuse at the National Institutes of Health.

The U.S. Drug Enforcement Administration (DEA) proposed a rule in which they intend to place the psychedelic phenethylamines 2,5-dimethoxy-4-chloroamphetamine (DOC) and 2,5-dimethoxy-4-iodoamphetamine (DOI) into Schedule I of the Controlled Substances Act. We examined the epidemiology of use and availability of these substances. We examined national trends in seizures of these compounds (which indicate availability) using DEA National Forensic Laboratory Information System (NFLIS) and High Intensity Drug Trafficking Areas (HIDTA) data. We also examined the prevalence of self-reported use on the National Survey of Drug Use and Health (NSDUH), a nationally representative sample of noninstitutionalized individuals aged ≥12 in the United States. The scientific literature was also systematically searched for reports of poisonings linked to use. Between 2005 and 2024, NFLIS received 795 submissions of drugs testing positive for DOC, with a peak of 152 in 2012. There was then a decrease through 2024, with only two submissions containing DOC in 2023-2024. Forty submissions contained DOI, with no submissions testing positive in 2019-2024. Three DOC seizures were recorded by HIDTA in 2017-2021, with none in 2022-2024. HIDTA had no recorded seizures of DOI. Between 2005 and 2023, there were 37 and 10 type-in mentions of lifetime DOC and DOI use, respectively, in NSDUH responses, suggesting a lifetime prevalence of < 0.01% among the noninstitutionalized U.S. population. We located three reports of poisonings linked to DOC use (in 2008-2024) and none linked to DOI use. Availability, recreational use, and poisoning related to the use of DOC and especially DOI appear to be rare.

As the opioid crisis continues, now driven by use of fentanyl, naloxone is an increasingly important intervention to reverse overdoses. More research is needed on the willingness of populations at risk for unintentional fentanyl exposure (through adulterated drugs) to accept naloxone to reverse potential overdoses. Adults (n = 991) entering randomly selected nightclubs in New York City (NYC) were surveyed at the point-of-recruitment in 2024 and were asked about their willingness to accept a free naloxone kit. We examined the prevalence of reported willingness to accept naloxone and reasons for refusal, and we examined prevalence and correlates of participants accepting naloxone. During the survey, 65.2% of participants reported being familiar with naloxone, 62.1% agreed to accept naloxone, and 49.6% were recorded as accepting a kit. Those residing in NYC, compared to visitors, had a higher prevalence of recorded acceptance (aPR = 1.41, 95% CI: 1.11-1.79), as did those reporting familiarity with naloxone (aPR = 1.27, 95% CI: 1.02-1.58), and those with an average higher readiness to intervene in an opioid overdose (aPR = 1.18, 95% CI: 1.04-1.33). The majority who refused (56.1%) reported not being interested; 10.1% reported that they were not worried about overdoses, and 8.2% reported that they already had naloxone. Although 83.4% agreed that naloxone is used to reverse opioid overdoses, 35.4% reportedly thought that naloxone is used to reverse the effects of cocaine or any drug. While at least half of attendees were willing to accept a naloxone kit, lack of interest and lack of knowledge about naloxone were potential barriers to carrying naloxone.

BACKGROUND AND AIMS/OBJECTIVE:'Tusi', also known as 'tusibí' or 'pink cocaine', is a drug concoction which previously emerged in Latin America and Europe and has recently acquired popularity in the United States (US). Consumers are often unaware that Tusi contains a mixture of ketamine and other drugs, and the concoction can be confused with 2C/2C-B (ring-substituted phenethylamines/4-bromo-2,5-dimethoxyphenethylamine) or cocaine. This study aimed to estimate the prevalence and correlates of past-year Tusi use in the electronic dance music (EDM) nightclub-attending population in New York City (NYC), US. DESIGN AND SETTING/METHODS:This cross-sectional study included surveys and optional saliva testing of adults entering randomly selected EDM events in NYC in 2024. PARTICIPANTS/METHODS:Adults aged ≥18 years entering EDM events at nightclubs (n = 1465). MEASUREMENTS/METHODS:Exposures were demographic characteristics and past-year use of other drugs. The primary outcome was self-reported past-year use of Tusi, and in a subsample, biologically confirmed exposure to various drugs determined by saliva testing. FINDINGS/RESULTS:Based on self-report, an estimated 2.7% [95% confidence interval (CI) = 1.9-3.9] of adults in the NYC EDM nightclub-attending population have used Tusi in the past year. Compared with white individuals, Hispanic individuals were at higher odds for use [adjusted odds ratio (aOR) = 5.10, 95% CI = 1.96-13.25]. Compared with those who did not use, those who used ecstasy/3,4-Methylenedioxymethamphetamine (MDMA) (aOR = 6.59, 95% CI = 1.60-27.16), ketamine (aOR = 3.44, 95% CI = 1.18-10.08) and/or 2C series (aOR = 14.82, 95% CI = 4.77-46.04) in the past year were at higher odds for use. Compared with those not reporting Tusi use, those reporting past-year use were more likely to have saliva test positive for cocaine, ketamine, MDMA, methamphetamine and/or synthetic cathinones (Ps < 0.001). They were also more likely to test positive for cocaine, ketamine or methamphetamine after not reporting past-year use (Ps < 0.01). CONCLUSIONS:An estimated 2.7% of electronic dance music-nightclub attending adults in New York City appear to have used Tusi in the past year, with higher use among Hispanic individuals and people exposed (sometimes unintentionally) to other drugs.

BACKGROUND:Use of party drugs is common among nightclub attendees, but more information is needed regarding both intentional use and unknown exposure to synthetic cathinones, fentanyl, and xylazine in this high-risk population. METHODS:Throughout 2024, participants attending nightclubs in New York City were surveyed and had their saliva analyzed for drug exposure using targeted and untargeted analysis (n = 1024). We calculated the prevalence of synthetic cathinone, fentanyl, and xylazine exposure overall and in relation to demographic and drug use characteristics. RESULTS:11 (1.1 %) tested positive for one or more synthetic cathinones, 1.5 % (n = 15) tested positive for fentanyl or its precursor (4-ANPP), and 4 (0.4 %) tested positive for xylazine. All but one exposure to fentanyl was linked to unreported past-month use (93.3 %) and 54.5 % of synthetic cathinone exposures were linked to unreported past-month use (ps<.05). Three of four participants (75.0 %) testing positive for xylazine also tested positive for fentanyl exposure. Most (n = 8) synthetic cathinone exposures involved methylmethcathinone (MMC), and there were also detections of chloromethcathinone (CMC, n = 4), N-N-dimethylpentylone (n = 2), N-ethylpentylone (n = 2), and eutylone (n = 2). Compared to those testing positive for synthetic cathinones, those testing positive for fentanyl were more likely to identify as heterosexual and/or test positive for prescription opioid use, and less likely to have a college degree or to test positive for MDMA use (ps<.05). CONCLUSIONS:Unintentional exposure to these drugs is occurring, often because they have been added as adulterants in more common drugs. Results can inform prevention and harm reduction education in this population and in the general population.