Join us for the 5th annual NDEWS Summit (hybrid), register now! June 13, 2:00–6:00 pm PT

Aims: There are no approved medications to treat methamphetamine use disorder. We conducted a phase 1b inpatient randomized double-blinded placebo-controlled within-subject crossover study to evaluate the safety of mirtazapine, a potential treatment for methamphetamine use disorder with positive phase 2 trial findings, in people receiving intravenous methamphetamine.

Methods: Participants (N=15; 12 with no opioid use and three on methadone maintenance treatment) received mirtazapine 30mg or placebo daily for 5 days, underwent an intravenous methamphetamine 30mg challenge on Day 5 followed by 2 days of washout, and then switched to the other study arm and received a second methamphetamine infusion at Day 12. We monitored participants for adverse events, cardiovascular effects, and pharmacokinetics. The means of the
methamphetamine, amphetamine, and mirtazapine pharmacokinetic outcomes between phases and days were compared using two-sided T-tests. Linear models were fitted to assess the effects of mirtazapine versus placebo on methamphetamine pharmacokinetic outcomes, adjusted for participant age and weight.

Results: Participants (N=15; 12 with no opioid use and three on methadone maintenance treatment) reached steady state mirtazapine levels prior to methamphetamine infusions. During the mirtazapine phase, participants reached methamphetamine peak plasma concentration 0.26 hours earlier than the placebo phase (p=0.02); no other impacts on methamphetamine pharmacokinetics were observed. Methamphetamine 30mg was associated with increases in all cardiovascular measures (p<0.001) while mirtazapine was associated with a slight elevation in heart rate (4.9 bpm, p=0.04). Mirtazapine neither attenuated nor amplified the cardiovascular response to methamphetamine, including in patients on methadone. Adverse events were similar between mirtazapine 30mg and placebo.

Conclusions: Mirtazapine 30mg was safe and well tolerated in people receiving a clinically relevant intravenous methamphetamine challenge, supporting further development of this medication for the treatment of methamphetamine use disorder.

Aims: This study examined age-related variations in routes of opioid administration (ROA) among emergency department (ED) patients with confirmed opioid overdose.

Methods: This is a subgroup analysis of the Toxicology Investigators Consortium (ToxIC) Fentalog Study, an observational study at 11 participating medical centers between 9/21/20 – 4/14/25. Adults (≥ 18 years) presenting to the ED with suspected opioid overdose were included in this subgroup analysis if confirmatory testing was positive for opioids. Chart reviews were conducted, and toxicological analyses were performed centrally using quadrupole time of flight mass spectrometry. Multinomial logistic regression modeling assessed whether age predicted ROA (intranasal [IN] only, inhalation only, oral only, parenteral only, multiple), adjusting for sex, race and ethnicity, and US region. Central IRB approval was granted with waiver of consent.

Results: Among 1212 patients, mean age was 42.3 years old (SD: 14.8). Most used inhalation (n=352, 29.0%), oral (n=346, 28.5%), or intranasal (n=328, 27.1%) routes only. Patients using IN only were younger than those with other ROAs (41.7 years vs. 44.1 years, p=0.01), as were those with inhalation only (40.0 years vs. 43.3 years, p<0.01) and parenteral only (39.2 years vs. 42.8 years, p=0.03). Patients using multiple ROAs were significantly older than those using a single ROA (47.3 years vs. 42.2 years, p=0.03). Increased age was associated with lower odds of inhalation only use (AOR: 0.05, 95% CI: 0.31, 0.65) and higher odds of IN-only (AOR: 2.41, 95% CI: 1.10, 5.26) and multiple ROA use (AOR: 4.76, 95% CI: 3.27, 6.92), when compared to oral only use.

Conclusions: Age strongly stratified opioid use behavior; younger adults favored rapid-onset single routes such as inhalation or intranasal administration, whereas older adults were far more likely to employ multiple routes. These data underscore the need for age-specific approaches to overdose prediction, harm reduction, and ED management.

Aims: We describe how novel historic encounter data from Emergency Medical Services (EMS) can be used to enhance contextual findings related to fatal drug overdose events, building on traditionally leveraged sources (i.e., death certificate, postmortem toxicology, and coroner/medical examiner data) used in Kentucky’s abstractor-driven Drug Overdose Fatality Surveillance System (DOFSS).

Methods: We refined and deployed a probabilistic linkage, combining all prior decedent’s EMS encounters to fatal drug overdoses that occurred in the state of Kentucky. Successful joins are stored in a repeated instrument research database with encounters collated by date of death, the prior year, and greater than one year – In a sensitivity analysis to examine quality improvement on DOFSS, 75 randomly selected cases were copied to a blank dataset for abstraction, where abstractors used only the linked EMS records to complete DOFSS abstracted fields. In this sensitivity analysis, EMS-only DOFSS records were compared to original DOFSS records completed prior to linkage.

Results: In our implemented pipeline, the linkage has identified EMS matches for 83% (5,990 cases) of Kentucky fatal overdoses from 2022-2025. Of these, 72%, 44%, and 58% had matched encounter records for date of death, within the last year, and greater than one year, respectively. Sensitivity analysis of 75 EMS-linked cases revealed that linkage specifically contributed new information on: circumstances of death and preceding history (16%), medical history (19%), naloxone administration during the fatal event (13%), and prior overdoses and substance use (9%).

Conclusions: EMS data is often viewed as a novel data source for non-fatal surveillance efforts, but the potential impacts for fatal surveillance context enrichment are critical. Fatal overdose
surveillance efforts are enhanced when leveraging historic EMS encounter data.

Aims: Previous data from the Rapid Street Reporting (RSR) study of the National Drug Early Warning System (NDEWS) show that psilocybin is the third most frequently reported substance overall in the general population from late 2021 through fall 2025. Given changes in legislation and popular opinion surrounding psilocybin, we analyzed changes in reported rates of use over time in cities visited by the team on more than occasion.

Methods: Beginning in November 2021, RSR has deployed interviewing teams using a venue-intercept method to survey the general public about past 12-month use of substances in Sentinel Sites and hotspots across the US. We reviewed self-reported rates of use of psilocybin in cities visited more than once to determine statistically significant changes over time.

Results: Six cities of the nine with repeat visits showed significant changes to reported rates of use of psilocybin. Rates of use in Chicago doubled, from 7.4% to 15.5% between 2023 and 2025, and in Denver rates nearly doubled, from 17.2% to 32.8%, from 2022 to 2025. Similarly, use in San Francisco from 2021 to 2023 showed a strong increase from 23.9% to 37.6%. In New York City rates increased significantly from 13.4% to 21.9% from 2022 to 2023, then showed a non-significant decrease to 15.5% in 2025. Another Eastern city, Washington, DC, saw a sizeable decrease from 12.5% to 5.1% between 2022 and 2025, as did Southeastern city Charleston, from 14.1% to 6.8% from 2022 to 2025.

Conclusions: Trends in reported rates of psilocybin use varied across these cities geographically, with significant increases reported primarily in Midwestern and Western locations and decreases seen in Eastern and Southeastern areas. Variation in the timing of the visits prevents direct comparison, but it is likely that decriminalization of psilocybin in Colorado in November 2022 and in San Francisco in May 2019 have impacted the high rates of use (around one-third of those surveyed) reported in those locales. More research is needed to determine the specifics of these changes, for instance whether reported use includes microdosing, and what harms might emerge from the changing patterns of use.

Aims: Interventions to prevent fentanyl overdose focus on treating opioid use disorder (OUD), yet how much of the crisis is due to unintentional or otherwise non-regular fentanyl use is unclear. In seeking a means to determine intentionality of pre-mortem fentanyl use, we developed a simple method to estimate absence of regular fentanyl use, which is highly lipophilic and slowly releases from tissue, using norfentanyl.

Methods: We conducted a sequence of 3 studies in San Francisco, CA: (1) analysis of psychological autopsy (PA) data–including medical examiner, medical record, and informant interviews–from fentanyl deaths to categorize pre-mortem use as likely unintentional or intentional; (2) analysis of serum nor/fentanyl levels among people reporting regular fentanyl use, to confirm validity of norfentanyl as a proxy for regular use; and (3) analysis of all recent fentanyl overdose deaths by nor/fentanyl levels.

Results: An algorithm of 4 variables from medical review, death scene evidence, witness report, and toxicology were used to categorize PA cases as likely un/intentional, with 16 of 31 likely unintentional; presence of measurable norfentanyl aligned in all but 1 case. Serum analysis from 104 people regularly using fentanyl confirmed a 0.99 ratio (95% CI; 0.84-1.13) of serum fentanyl:norfentanyl, suggesting the metabolite as a valid proxy for regular use. Among 597 fentanyl overdose deaths, mean fentanyl concentration was 17.6 ng/mL; 264 (44%) lacked quantifiable norfentanyl (26% none, 18% below quantification limit), of which 252 (42% of total) also had no methadone or buprenorphine metabolites.

Conclusions: We developed a simple method to identify unintentional or otherwise non-regular fentanyl use among fentanyl overdose decedents, finding 42% of local deaths to lack evidence of regular fentanyl use or medications to treat OUD. A large proportion of fentanyl overdose deaths may be among people not candidates for OUD treatment, shifting the paradigm for how to address the overdose crisis. Strategies to address overdose risk among people who do not intentionally or regularly use fentanyl are urgently needed.

Aims: In late 2024, the US unregulated drug supply experienced a sharp decline in fentanyl potency and availability nationally, with local supplies stabilizing by mid-2025. This work summarizes significant shifts in the drug landscape, either coinciding with changing fentanyl concentrations or emerging afterwards, and associated harms, drawing on information gathered over 14 meetings, an annual Summit, 8 Sentinel Site reports, and 4 informal Network reports (2 from the Medicolegal Death Investigator-Network and 2 from the Community Overdose Response-Network) as part of a multifaceted early warning reporting system between 2024-2025.

Methods: The NIDA funded National Drug Early Warning System (NDEWS) utilizes an Early Warning Network (EWN), which integrates members of a Scientific Advisory Group, Sentinel Site Directors, and Community-Based Health Experts, with a newly added informal component. This addition engages informal expert networks who offer unique insights and multidisciplinary perspectives, enhancing the existing EWN and providing a more comprehensive overview of national and region-specific drug trends.

Results: Through EWN reports and discussions, NDEWS tracked xylazine’s westward spread and medetomidine’s emergence in the Eastern US, where xylazine declined, while also capturing the nationwide rise of BTMPS. EWN data showed overdoses initially declining post-fentanyl supply shifts but reported rebounds in early 2025. Drug checking and post-mortem reports indicate rising polysubstance use, particularly stimulant and fentanyl co-use or detections, heightening the risk of xylazine or medetomidine exposure. Emerging adulterants complicate overdose response, requiring more naloxone; and causing severe withdrawal or intensified effects like hallucinations. Contacts noted abnormal nonfatal overdoses presentations and complex withdrawal, attributed to medetomidine, often requiring ICU care. Reports of carfentanil reemerging increased in recent months.

Conclusions: The expanded EWN is a vital part of NDEWS’ broader drug monitoring system. It provides complementary data that enriches the understanding of substance use patterns and harm reduction strategies while underscoring the growing unpredictability of the unregulated drug supply.

The drug landscape and resulting drug-related harms have rapidly shifted in recent years, largely driven by increasing adulteration of illicit drug products. In addition to changes in the contents of common party drugs such as ecstasy and cocaine, the illicit opioid supply continues to evolve with the continued emergence of novel adulterants, including veterinary tranquilizers and a variety of new psychoactive substances. These adulteration trends can place people who use drugs at higher risk of overdose and other health complications, particularly those who are unknowingly exposed to adulterants. This session will provide an overview and discussion of recent trends in drug adulteration using the most up-to-date forensic data (e.g., from biospecimens, drug seizures) from the National Drug Early Warning System (NDEWS) and the Center for Forensic Science Research and Education (CFSRE). Dr. Joseph Palamar will provide an overview of surveillance methods and will present data on unintentional exposure to adulterants in common party drugs and psychostimulants. Dr. Joshua DeBord will present data on forensic detections of xylazine, medetomidine, and other novel adulterants in the context of the evolving illicit opioid supply. Dr. Nicole Fitzgerald will present data on the emergence of novel benzodiazepines (e.g., bromazolam) based on drug seizure data and forensic detections. Finally, David T. Zhu will present data on trends in nitazene analog detections. Together, this session provides an overview of the rapidly shifting drug adulteration landscape and the challenges this presents for researchers, providers, health educators, and people who use drugs in addressing the harms associated with adulterated drug products and in anticipating new and evolving trends.

Harm reduction services (HRS) are practices that aim to minimize the negative health, social and legal impacts associated with drug use and drug policies. HRS can provide alternatives for people who use drugs (PWUD), which could be especially impactful in Latin America (LA), given the lack of support, social exclusion and violence that these communities experience. In recent years, community-based movements have led to the implementation of novel HRS in LA cities. However, evidence on their impact is still limited, and research is needed to improve services and provide actionable recommendations that can improve the lives of PWUD. As the need and demand for HRS grows in the Pan-American region, this symposium will explore the landscape of HRS in LA, and the impact of specific programs implemented Colombia, Brasil and Mexico. First, Ignacio Bórquez will present examples and reflect on opportunities for HRS in the region, synthesizing results from a scoping review of literature published between 2013-2024 on HRS in LA and the Caribbean. Second, Jaime Arredondo will share findings from a study using an implementation science approach to evaluate overdose prevention and education services in Mexico and Colombia, and share lessons for replicating equitable responses for substance use across the Global South. Third, Andrea Gallassi will present results from a mixed-methods study assessing HIV and substance use/mental health among people experiencing homelessness in Brasilia, Brazil describing differences in uptake of treatment in community-based, government-funded settings vs. rehabilitation at religious/12-step-based therapeutic communities. Lastly, Julian Santaella will share results from a study evaluating the opening of a harm reduction center, including a supervised injection site, in Cali, Colombia. Chair Noa Krawczyk and Co-Chair Annick Borquez will lead a discussion on implications for advancing research and health services in the region.

Numerous studies have supported the premise that polysubstance use, or the use of more than one substance, is ubiquitous within certain populations of drug users. For example, 90% of people who use cocaine co-use alcohol and over 50% of treatment-seeking opioid users report stimulant use (Kidorf et al., J Dual Diagn 14(4):193-200, 2018; Fitzgerald et al., Drug Alcohol Dep 258: 111272, 2024). It is likely that treatment interventions will be different for individuals using more than one substance when compared to treatment-seeking patients using only one drug in isolation. Despite this, most preclinical research does not model the clinical reality of polysubstance use which may prevent the translation of research findings from bench to bedside. Also, most clinical research is not designed to assess polysubstance use. Thus, the overarching theme of this symposium will be a discussion of polysubstance use, and speakers will present research stressing the importance of incorporating polydrug use into current research models. First we will describe the complexities associated with modeling polysubstance use. Next, we will describe preclinical studies showing how the use of more than one substance affects the reinforcing strength of cocaine and opioids, respectively, and how different interventions may be required for polysubstance use vs. single-substance misuse. Finally, we will describe strategies for prioritizing translational polysubstance use research.