Illicitly Manufactured Fentanyl Research Articles

Managing Opioid Withdrawal Symptoms During the Fentanyl Crisis: A Review.

Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate opioid withdrawal syndromes (OWS) and the subsequent management of opioid use disorder (OUD). This scoping review aimed to collate the current OWS management of study populations seeking treatment for OWS and/or OUD directly from an unregulated opioid supply, such as IMF. Therefore, the focus was on therapeutic interventions published between January 2010 and November 2023, overlapping with the period of increasing IMF exposure. A health science librarian conducted a systematic search on November 13, 2023. A total of 426 studies were screened, and 173 studies were reviewed at the full-text level. Forty-nine studies met the inclusion criteria. Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation. Trials often have low retention rates, particularly when opioid agonist washout is required. Neurostimulation strategies were promising; however, they were developed and studied early. Precipitated withdrawal is a concern; however, the rates were low and adequately mitigated or managed with low- or high-dose buprenorphine induction. Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances.

Illicitly Manufactured Fentanyl Use Among Individuals in the U.S., 2022

IntroductionWhile morbidity and mortality related to synthetic opioids such as illicitly manufactured fentanyl (IMF) are monitored in the U.S., there has been a lack of national survey data focusing on use. Survey data are important as self-report can help estimate prevalence of use among living persons. MethodsData were examined from the 2022 National Survey on Drug Use and Health, a nationally representative probability sample of noninstitutionalized individuals age ≥12 in the U.S. (N=59,069). Prevalence and correlates of past-year use of IMF were estimated. Data were analyzed in 2024. ResultsThe estimated prevalence of past-year IMF use was 0.23% (95% confidence interval [CI]: 0.17-0.31). Compared to no past-year use, individuals were at increased odds for IMF use if proxy-diagnosed with use disorder involving use of cannabis (aOR=3.72, 95% CI: 1.34-10.32), cocaine (aOR=11.96, 95% CI: 4.78-29.93), methamphetamine (aOR=5.60, 95% CI: 1.65-19.02), heroin (aOR=20.56, 95% CI: 8.90-47.52), and/or prescription opioids (aOR=10.65, 95% CI: 3.54-32.03). (Mis)use without use disorder was only significant for prescription opioids (aOR=5.77, 95% CI: 2.55-13.06). Those receiving treatment for substance use in the past year were also at increased odds for use (aOR=5.79, 95% CI: 2.58-13.00). ConclusionsPrevalence of IMF use is rare in the general U.S. population. While past-year (mis)use of other drugs (without use disorder) was not consistently associated with IMF use, cannabis, cocaine, methamphetamine, heroin, and prescription opioid use disorder was associated with higher odds of IMF use, suggesting that more “severe” use of various drugs is more of a risk factor than use.

Characteristics of Overdose Deaths Related to Illicitly Manufactured Fentanyl – Arizona, July 2019 – June 2020

ABSTRACT Using the Arizona State Unintentional Drug Overdose Reporting System (AZ-SUDORS), the study aims to identify the social and drug characteristics of illicitly manufactured fentanyl (IMF)-related overdose deaths. The data include drug overdose deaths from July 1, 2019 to June 30, 2020. Decedents were categorized into four groups by types of opioids detected: (1) IMF-positive; (2) heroin-positive (negative for IMF); (3) pharmaceutical opioid-positive (negative for heroin or IMF); (4) nonopioid. Bivariate statistics were used to compare differences between IMF and other groups. Among 2,029 decedents, 77.8% tested positive for opioids. The IMF group included 57.9%, the heroin group included 9.5%, the pharmaceutical opioid group 10.5%, and the nonopioid group 22.2%. The IMF group was younger (mean age 35.0), more likely to be from a large urban area (78.2%), and with a greater proportion of ethnic/racial minorities (48.6%), compared to the other three groups. The IMF group was less likely to test positive for methamphetamine (24.9%), compared to heroin (63.7%) or pharmaceutical opioid groups (34.0%), but more likely to test positive for cannabis (31.3%), compared to the other three groups. Our data show disproportionate IMF impacts on younger persons and ethnic minorities. Interventions need to be tailored to account for distinct psychosocial profiles associated with IMF use.

B-327 Evidence of Missed Novel Psychoactive Substances (NPS) in Unexpected Fentanyl Positives

Abstract Background Recent data published by the CDC indicated that overdose deaths in the United States began to increase significantly in 2020 and continued throughout 2021. Synthetic opioids, such as illicitly-manufactured fentanyl (IMF), have been a primary driver in overdose deaths. There has been a concomitant increase in both the prevalence and diversification of novel psychoactive substances (NPS) and IMF. We performed a blinded secondary analysis of remnant samples to further characterize the incidence in which individuals are encountering NPS when using non-prescribed fentanyl. Various classes of NPS compounds (e.g., designer opioids, designer benzodiazepines, xylazine) were evaluated in samples that were originally positive for fentanyl but did not include a request from the provider for NPS testing to be performed. Methods This study was IRB approved. A sampling of 200 urine or oral fluid specimens collected from individuals as part of their routine medical treatment, wherein definitive testing for fentanyl and norfentanyl was performed and the drug and metabolite were both identified above the upper limit of quantitation of the assay, underwent additional analysis for NPS. Samples were excluded from blinded secondary analysis if any NPS testing, regardless of drug class, was originally ordered and performed. Additional testing that was performed included the following classes of drugs: designer opioids, designer benzodiazepines, synthetic cannabinoids, synthetic stimulants, hallucinogens/dissociatives, xylazine, tianeptine, and phenibut. Results Specimens within the sample set (N: 200) that were originally positive for fentanyl without a previous request for NPS testing originated from 30 different states within the US. These samples were originally collected between 9/19/2022–1/12/2023. Of those that underwent additional analysis after initial reporting of positive fentanyl results, 117 (58.5%) had at least one analyte within an NPS class identified. Designer opioids (N: 93, 47%), and xylazine (N: 76, 38%), followed by designer benzodiazepines (N: 16, 8%), synthetic stimulants (N: 4, 2%), and hallucinogens/dissociatives (N:3, 2%) were the most frequent compounds detected on a per sample basis. No synthetic cannabinoids were detected within this sample set. Conclusion Although much of the national focus around fatal and non-fatal overdoses centers on intentional and unintentional exposures to IMF, healthcare providers and the general public must be made aware of the prevalence of NPS. These compounds, which are often intentionally added to drugs sold as fentanyl to enhance the drug potency, can increase risk for an adverse event. Of paramount importance is that the effects of substances such as xylazine and designer benzodiazepines, which contribute to central nervous system depression, are not effectively reversed by administration of naloxone, a mainstay of harm reduction protocols. Knowledge of the prevalence of these compounds should impact clinical decision-making and individual risk mitigation plans. From a broader perspective, improving understanding of the incidence in which these drugs are found within communities could improve overall surveillance efforts on current drug use trends.

Fentanyl Absorption, Distribution, Metabolism, and Excretion: Narrative Review and Clinical Significance Related to Illicitly Manufactured Fentanyl.

This narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly manufactured fentanyl (IMF). Fentanyl is highly lipophilic, lending itself to rapid absorption by highly perfused tissues (including the brain) before redistributing from these tissues to muscle and fat. Fentanyl is eliminated primarily by metabolism and urinary excretion of metabolites (norfentanyl and other minor metabolites). Fentanyl has a long terminal elimination, with a documented secondary peaking phenomenon that can manifest as "fentanyl rebound." Clinical implications in overdose (respiratory depression, muscle rigidity, and "wooden chest syndrome") and opioid use disorder treatment (subjective effects, withdrawal, and buprenorphine-precipitated withdrawal) are discussed. The authors highlight research gaps derived from differences in medicinal fentanyl studies and IMF use patterns, including that medicinal fentanyl studies are largely conducted with persons who were opioid-naive, anesthetized, or had severe chronic pain and that IMF use is characterized by supratherapeutic doses and frequent and sustained administration patterns, as well as adulteration with other substances and/or fentanyl analogs. This review reexamines information yielded from decades of medicinal fentanyl research and applies elements of the pharmacokinetic profile to persons with IMF exposure. In persons who use drugs, peripheral accumulation of fentanyl may be leading to prolonged exposure. More focused research on the pharmacology of fentanyl in persons using IMF is warranted.

Attitudes and experiences with fentanyl contamination of methamphetamine: exploring self-reports and urine toxicology among persons who use methamphetamine and other drugs

BackgroundThere are growing concerns about illicitly manufactured fentanyl (IMF) contamination of methamphetamine. This study aims to characterize the lay views and experiences with IMF-contaminated methamphetamine (IMF/meth) and identify participants with unknown IMF exposures through urine toxicology analysis.MethodsBetween December-2019 and November-2021, structured interviews were conducted with 91 individuals who reported past 30-day use of methamphetamine and resided in Dayton, Ohio, USA. Lab-based urine toxicology analyses were conducted to identify fentanyl/analogs, methamphetamine, and other drugs. Bivariate analyses were conducted to identify characteristics associated with attitudes and experiences with IMF/meth, and unknown IMF exposures.ResultsThe majority (95.6%) of the study participants were non-Hispanic white, and 52.7% were female. Past 30-day use of methamphetamine was reported on a mean of 18.7 (SD 9.1) days, and 62.6% also reported past 30-day use of heroin/IMF. Most (76.9%) had a history of an unintentional drug-related overdose, but 38.5% rated their current risk for an opioid overdose as none. Besides fentanyl (71.9%), toxicology analysis identified nine fentanyl analogs/metabolites (e.g., 42.7% acetyl fentanyl, 19.0% fluorofentanyl, 5.6% carfentanil), and 12.4% tested positive for Xylazine. The majority (71.4%) believed that IMF/meth was common, and 59.3% reported prior exposures to IMF/meth. 11.2% tested positive for IMF but reported no past 30-day heroin/IMF use (unknown exposure to IMF). Views that IMF/meth was common showed association with homelessness (p = 0.04), prior overdose (p = 0.028), and greater perceived risk of opioid overdose (p = 0.019). Self-reported exposure to IMF/meth was associated with homelessness (p = 0.007) and obtaining take-home naloxone (p = 0.025). Individuals with unknown IMF exposure (test positive for IMF, no reported past 30-day heroin/IMF use) were older (49.9 vs. 41.1 years, p < 0.01), and reported more frequent past 30-day use of methamphetamine (24.4 vs. 18.0 days, p < 0.05). They indicated lower perceived risk of opioid overdose (0.1 vs. 1.9, scale from 0 = “none” to 4 = “high,” p < 0.001).DiscussionThis study suggests a need for targeted interventions for people who use methamphetamine and expansion of drug checking and other harm reduction services.

Association between law enforcement seizures of illicit drugs and drug overdose deaths involving cocaine and methamphetamine, Ohio, 2014–2019

BackgroundThe United States continues to experience a crisis of mounting opioid overdose deaths involving cocaine and methamphetamine (hereafter illicit stimulants). Law enforcement drug seizure data present a unique opportunity to examine the association between illicit-stimulant-involved overdose deaths (ISODs) and the illicit drug supply. Our objective is to better understand correlations between illicit drug market trends and increases in ISODs in Ohio in 2014–2019. MethodsThis observational study analyzes the universe of ISODs and drug seizures in Ohio from 2014 to 2019. We use graphs and descriptive statistics to characterize trends over time and estimate a time series model of their association. ISODs were summed to yield monthly statewide counts of seizures containing methamphetamine, cocaine, illicitly manufactured fentanyl (IMF), and other non-IMF opioids (e.g., heroin). All rates were calculated per 100,000 persons. ResultsRoughly 80% of ISODs in Ohio from 2014 to 2019 involved an opioid, with IMF co-occurring in 90% of ISODs by 2019. Methamphetamine and cocaine seizures containing IMF were associated with 0.439 (p < .01) and 0.457 (p < .01) additional deaths per 100,000 persons per month, respectively. IMF seizures not containing cocaine nor methamphetamine were also associated with additional ISODs (0.119, p < .01) and seizures of illicit stimulants not containing IMF were not associated with ISODs. ConclusionsThe number of ISODs was extremely high when IMF was co-involved and relatively low without IMF involvement. By demonstrating how supply-side trends correspond with ISOD rates, the current study bolsters the analytical utility of law enforcement seizures and complements growing literature in the field.

Simulating the impact of Addiction Consult Services in the context of drug supply contamination, hospitalizations, and drug-related mortality.

Illicitly manufactured fentanyl (IMF) is increasing in international drug supply chains, and IMF-related opioid overdose deaths are rising in North America. Hospitalizations among patients with opioid use disorder (OUD) are also rising; and, hospitalized patients are at increased risk of overdose and death following hospital discharge. Hospitalization is a key opportunity to engage patients with OUD. Addiction consult services (ACS) can provide effective treatment for patients hospitalized with OUD. This study aims to estimate the effect of increasing IMF contamination on drug-related death among patients hospitalized with OUD, and simulate the role of ACS expansion to mitigate these effects. We used a Markov model to mirror care systems for adult patients hospitalized with OUD in Oregon, from the time of hospital admission through 12-months post-discharge, and simulated patients through modeled care systems to evaluate the expansion of Addiction Consult Services in the context of increasing IMF in the drug supply. In a simulated cohort of 10,000 patients, we estimate that 537 patients would die from drug-related causes within 12-months of hospital discharge. In the context of increased IMF in the drug supply, this estimate increased to 913. ACS referral at baseline was 4%; increasing ACS referral to accommodate 10%, 50%, or 100% of hospitalized OUD patients in the state reduces drug-related deaths to 904, 849, and 780, respectively. The number needed to treat for ACS to avoid one drug-related death in the context of increased IMF was 73. Hospitals should expand interventions to help reduce IMF-related opioid overdoses, including through implementation of ACS. In the context of rising IMF-related deaths, ACS expansion could help connect patients to treatment, offer harm reduction interventions, or both, which can help reduce the risk of opioid-related death.

Using death scene and toxicology evidence to define involvement of heroin, pharmaceutical morphine, illicitly manufactured fentanyl and pharmaceutical fentanyl in opioid overdose deaths, 38 states and the District of Columbia, January 2018-December 2019.

Tracking specific drugs contributing to drug overdose deaths is limited when relying on death certificate (DC) data alone. This study aimed to determine whether integrating DC data with medical examiner/coroner reports, including postmortem toxicology and death investigation findings, would enhance identification of (1) heroin and pharmaceutical morphine involvement in overdose deaths and (2) fentanyl source (illicitly manufactured versus pharmaceutical). Retrospective analysis of heroin, pharmaceutical morphine, illicitly manufactured fentanyl (IMF) and pharmaceutical fentanyl involvement in fatal overdoses. DC and toxicology data were compared with enhanced definitions integrating overdose scene, witness and toxicology evidence. United States: 38 states and the District of Columbia, participating in Centers for Disease Control and Prevention (CDC)-funded opioid overdose death surveillance. Opioid overdose decedents from funded jurisdictions; deaths during 1 January 2018-31 December 2019. Using medical examiner/coroner report data, deaths with 6-acetylmorphine and/or morphine detected by postmortem toxicology were defined as confirmed, probable or suspected heroin deaths, or probable pharmaceutical morphine deaths. Fentanyl was defined as probable or suspected IMF or probable pharmaceutical fentanyl. The enhanced definition defined 18 393 deaths as confirmed, probable, or suspected heroin deaths (including 2678 with morphine listed as cause of death on the DC) and 404 as probable pharmaceutical morphine deaths. Among deaths with fentanyl detected, 89.3% were defined as probable or suspected IMF and 1.0% as probable pharmaceutical fentanyl. Fentanyl source could not be determined for 9.7% of deaths. Integrating drug overdose scene, witness and toxicology findings can improve identification of specific drugs contributing to overdose deaths and enhance overdose intervention targeting.

What Your Death Certificate Says About You May Be Wrong: A Narrative Review on CDC's Efforts to Quantify Prescription Opioid Overdose Deaths.

Mortality data in most countries are reported using the International Classification of Diseases (ICD), managed by the WHO. In this paper, we show how the ICD is ill-suited for classifying drug-involved deaths, many of which involve polysubstance abuse and/or illicitly manufactured fentanyl (IMF).Opioids identified in death certificates are categorized according to six ICD T-codes: opium (T40.0), heroin (T40.1), methadone (T40.3), other synthetic narcotics (T40.4), and other and unspecified narcotics (T40.6). Except for opium, heroin, and methadone, all other opioids except those that are unspecified are aggregated in two T-codes (T40.2 and T40.4), depending upon whether they are natural/semisynthetic or synthetic opioids other than methadone. The result is a system that obscures the actual cause of most drug overdose deaths and, instead, just tallies the number of times each drug is mentioned in an overdose situation.We examined the CDC’s methodology for coding other controlled substances according to the ICD and found that, besides fentanyl, the ICD does not distinguish between other licit and illicitly manufactured controlled substances. Moreover, we discovered that the CDC codes all methadone-related deaths as resulting from the prescribed form of the drug. These and other anomalies in the CDC’s mortality reporting are discussed in this report.We conclude that the CDC was at fault for failing to correct the miscoding of IMF. Finally, we briefly discuss some of the public policy consequences of this error, the misguided focus by public health and safety officials on pharmaceutical opioids, their prescribers and users, and the pressing necessity for the CDC to reassess how it measures and reports drug-involved mortality.

Illicitly Manufactured Fentanyl Entering the United States.

The 'third wave' of the ongoing opioid overdose crisis in the United States (US) is driven in large measure by illicitly manufactured fentanyl (IMF), a highly potent synthetic opioid or an analog developed in clandestine laboratories primarily in China and Mexico. It is smuggled into this country either as IMF or as precursors. The southern border of the US is a frequent point of entry for smuggled IMF and the amounts are increasing year over year. IMF is also sometimes mixed in with other substances to produce counterfeit drugs and dealers as well as end-users may not be aware of IMF in their products. IMF is inexpensive to produce and when mixed with filler materials can be used to cut heroin, vastly expanding profitability. It is an attractive product for smuggling as very tiny amounts can be extremely potent and highly profitable. Drug trafficking over the border also involves the tandem epidemic of money laundering as drugs enter the country and cash payments exit. While drug smuggling in and out of the US (and other nations) has been going on for decades, the patterns are changing. Highly potent and potentially lethal IMF is a dangerous new addition to the illicit drug landscape and one with disastrous consequences.

Consumer discernment of fentanyl in illicit opioids confirmed by fentanyl test strips: Lessons from a syringe services program in North Carolina.

The United States (U.S.) continues to witness an unprecedented increase in opioid overdose deaths driven by precipitous growth in the supply and use of illicitly-manufactured fentanyls (IMF). Fentanyl's growing market share of the illicit opioid supply in the U.S. has led to seismic shifts in the composition of the country's heroin supply. The growth in fentanyl supply has transformed illicit opioid markets once offering heroin with fairly consistent purity and potency to a supply overpopulated with fentanyl(s) of inconsistent and unpredictable potency. In response, people who inject drugs (PWID) have developed a number of sensory strategies to detect fentanyl in illicit opioids. The current study examined the accuracy of sensory discernment strategies by measuring study participants' descriptions of the last opioid injected and checked with a fentanyl test strip (FTS) by that test's positive/negative result. The primary objective was to determine associations between FTS results and descriptions of the illicit opioid's physical appearance and physiological effects. Between September-October 2017, a total of 129 PWID were recruited from a syringe services program in Greensboro, North Carolina and completed an online survey about their most recent use of FTS. Participants were instructed to describe the appearance and effects associated with the most recent opioid they injected and tested with FTS. We conducted bivariate and multivariate analyses to determine differences in positive vs negative FTS results and the physical characteristics and physiological experiences reported. An exploratory analysis was also conducted to describe the types and bodily locations of unusual sensations experienced by PWID reporting positive FTS results. For physical characteristics, 32% reported that the drug was white before adding water and 38% reported the solution was clear after adding water. For physiological effects compared to heroin, 42% reported a stronger rush, 30% a shorter high, 30% a shorter time to the onset of withdrawal symptoms, and 42% experienced unusual sensations. In the multivariable model adjusting for demographics and polydrug correlates, white color of drug before adding water, stronger rush, shorter time to withdrawal, and unusual sensations were significantly associated with a positive FTS result. The most common unusual sensations were pins and needles (51%), warming of the head and face (35%), and lightheadedness (30%), and the most common locations where sensations occurred were face and neck (61%), arms/legs (54%), and chest (37%). We found positive FTS results were significantly associated with the physical characteristics and physiological effects described by PWID. Descriptions concerning physical appearance were consistent with law enforcement profiles of illicitly-manufactured fentanyl and physiological effects were concomitant with scientific and clinical medical literature on iatrogenic fentanyl use. Taken together, these findings suggest sensory strategies for detecting fentanyl in illicit opioids may be an effective risk reduction tool to help consumers navigate unpredictable markets more safely.

Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis

BackgroundThe ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT. MethodsData were drawn from two community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We used generalized linear mixed-effects modeling, adjusted by relevant confounders, to investigate the relationship between cannabis use and recent fentanyl exposure (both assessed by urine drug testing) among participants on OAT between 2016 and 2018. ResultsAmong the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 – 0.99). ConclusionsParticipants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.

Barriers and facilitators to a novel low-barrier hydromorphone distribution program in Vancouver, Canada: a qualitative study

BackgroundNorth America is experiencing an overdose crisis driven by illicitly-manufactured fentanyl, related analogues, and fentanyl-adulterated drugs. The concept of ‘safe supply’ has been suggested as a potential measure to address the overdose crisis by providing a regulated alternative to illicit opioids to people at high risk of fatal overdose. In January 2019, a novel hydromorphone tablet distribution program was implemented within an overdose prevention site in Vancouver, Canada’s Downtown Eastside neighbourhood. This study explored barriers and facilitators to engagement with this program. MethodsIn-depth interviews were conducted with 42 participants enrolled in the hydromorphone tablet distribution program, and over 100 h of ethnographic observation were conducted in and around the study site. Thematic analysis of the interviews and ethnographic observation focused on program operation, including barriers and facilitators to program uptake, access, and engagement. ResultsBarriers to program engagement identified include: limited operating hours and dose schedule, co-location within the overdose prevention site (e.g., wait times), and receiving the generic formulation of hydromorphone. Facilitators identified include: having access to a reliable source of opioids, co-location within the overdose prevention site (e.g., low-barrier design), experiences of agency, and program flexibility. ConclusionOur findings demonstrate key implementation and operational considerations of safe supply programs. In particular, lower-barrier design and operational features should be considered to improve uptake and engagement. Safe opioid supply programs are a promising intervention to address North America’s ongoing overdose crisis by providing people at high risk of fatal overdose an alternative to the toxic drug supply.

Non-prescription Fentanyl Positive Toxicology: Prevalence, Positive Predictive Value of Fentanyl Immunoassay Screening, and Description of Co-substance Use.

Opioid overdose deaths in Massachusetts linked to illicitly-manufactured fentanyl have increased dramatically. In response, an urban safety-net hospital added urine fentanyl testing with reflex confirmation testing to its standard urine toxicology panel. The goals of this study were to describe fentanyl toxicology test results, identify the positive predictive value of presumptive fentanyl immunoassay, and describe co-substance use among those with unexpected fentanyl positive results. We included urine toxicology tests from January through June 2016 analyzed at an urban safety-net hospital. We excluded tests from individuals prescribed or administered fentanyl within the preceding 72 hours. Positive fentanyl immunoassay tests underwent reflex chromatography confirmation testing. Samples that confirmed positive for acetyl fentanyl and/or fentanyl and/or norfentanyl were considered true positives. Of 11,873 urine samples, 10.4% of samples screened fentanyl positive and 8.8% were confirmed fentanyl positive. The positive predictive value of a positive urine fentanyl screen was 85.7%. Of 4398 unique patients, 13.2% had at least 1 test confirmed positive for nonprescription fentanyl. Patients with a confirmed fentanyl positive drug test were more likely to have positive urine drug test for barbiturates, benzodiazepines, cocaine, methadone, and opiates, and less likely to have oxycodone or buprenorphine. At an urban safety-net hospital, nonprescription fentanyl use was common and was associated with greater use of other substances favoring routine fentanyl testing. Although the positive predictive value of the screening test was high, confirmation testing detected substantial numbers of false positives, especially in older patients. Therefore, fentanyl confirmation testing should be used when results will change treatment approach and patient education.

Changes in drug use behaviors coinciding with the emergence of illicit fentanyl among people who use drugs in Vancouver, Canada

ABSTRACT Background: With the emergence of illicitly-manufactured fentanyl, drug overdose deaths have risen in unprecedented numbers. In this context, there is an urgent need to characterize potential changes in drug use behaviors among people who use drugs (PWUD). Objective: To examine changes in drug use behaviors following the emergence of illicit fentanyl among people who use drugs (PWUD). Methods: Data for this cross-sectional analysis was derived from three prospective cohorts of PWUD between December 2016 and May 2017 in Vancouver, Canada. Multivariable logistic regression was used to determine factors associated with self-reported behavior changes (binary variable “yes” or “no”) following the emergence of illicit fentanyl. Results: Among 999 participants [363 (36.3%) females], 388 (38.8%) reported some behavior change. The remaining 611 (61.2%) reported no change in behavior; 240 (39.3%) of these individuals had recently been exposed to fentanyl. In multivariable analyses, factors independently associated with behavior change included recent non-fatal overdose (Adjusted Odds Ratio [AOR] = 2.28), active injection drug use (AOR = 1.96), being on opioid agonist therapy (AOR = 1.80), and urine drug screen positive for fentanyl (AOR = 1.45), (all p < .05). Conclusion: The majority of PWUD in our sample did not change their drug use behavior despite a high prevalence of fentanyl exposure, indicating a need for targeted behavior change messaging and overdose prevention efforts such as naloxone and addiction treatment for this sub-population of PWUD. Further, the high fentanyl exposure observed in our sample suggests a need to address upstream structural factors shaping the overdose risk in addition to individual behavioral change.

Drug and Opioid-Involved Overdose Deaths - United States, 2017-2018.

Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3). Efforts related to all opioids, particularly deaths involving synthetic opioids, should be strengthened to sustain and accelerate declines in opioid-involved deaths. Comprehensive surveillance and prevention measures are critical to reducing opioid-involved deaths, including continued surveillance of evolving drug use and overdose, polysubstance use, and the changing illicit drug market; naloxone distribution and outreach to groups at risk for IMF exposure; linkage to evidence-based treatment for persons with substance use disorders; and continued partnerships with public safety.

Racial/Ethnic and Age Group Differences in Opioid and Synthetic Opioid-Involved Overdose Deaths Among Adults Aged ≥18 Years in Metropolitan Areas - United States, 2015-2017.

Among the 47,600 opioid-involved overdose deaths in the United States in 2017, 59.8% (28,466) involved synthetic opioids (1). Since 2013, synthetic opioids, particularly illicitly manufactured fentanyl (IMF), including fentanyl analogs, have been fueling the U.S. overdose epidemic (1,2). Although initially mixed with heroin, IMF is increasingly being found in supplies of cocaine, methamphetamine, and counterfeit prescription pills, which increases the number of populations at risk for an opioid-involved overdose (3,4). With the proliferation of IMF, opioid-involved overdose deaths have increased among minority populations including non-Hispanic blacks (blacks) and Hispanics, groups that have historically had low opioid-involved overdose death rates (5). In addition, metropolitan areas have experienced sharp increases in drug and opioid-involved overdose deaths since 2013 (6,7). This study analyzed changes in overdose death rates involving any opioid and synthetic opioids among persons aged ≥18 years during 2015-2017, by age and race/ethnicity across metropolitan areas. Nearly all racial/ethnic groups and age groups experienced increases in opioid-involved and synthetic opioid-involved overdose death rates, particularly blacks aged 45-54 years (from 19.3 to 41.9 per 100,000) and 55-64 years (from 21.8 to 42.7) in large central metro areas and non-Hispanic whites (whites) aged 25-34 years (from 36.9 to 58.3) in large fringe metro areas. Comprehensive and culturally tailored interventions are needed to address the rise in drug overdose deaths in all populations, including prevention strategies that address the risk factors for substance use across each racial/ethnic group, public health messaging to increase awareness about synthetic opioids in the drug supply, expansion of naloxone distribution for overdose reversal, and increased access to medication-assisted treatment.

Designing traceable opioid material§ kits to improve laboratory testing during the U.S. opioid overdose crisis

In 2017, the U.S. Department of Health and Human Services and the White House declared a public health emergency to address the opioid crisis (Hargan, 2017). On average, 192 Americans died from drug overdoses each day in 2017; 130 (67%) of those died specifically because of opioids (Scholl et al., 2019). Since 2013, there have been significant increases in overdose deaths involving synthetic opioids – particularly those involving illicitly-manufactured fentanyl. The U.S. Drug Enforcement Administration (DEA) estimates that 75% of all opioid identifications are illicit fentanyls (DEA, 2018b). Laboratories are routinely asked to confirm which fentanyl or other opioids are involved in an overdose or encountered by first responders. It is critical to identify and classify the types of drugs involved in an overdose, how often they are involved, and how that involvement may change over time. Health care providers, public health professionals, and law enforcement officers need to know which opioids are in use to treat, monitor, and investigate fatal and non-fatal overdoses. By knowing which drugs are present, appropriate prevention and response activities can be implemented.Laboratory testing is available for clinically used and widely recognized opioids. However, there has been a rapid expansion in new illicit opioids, particularly fentanyl analogs that may not be addressed by current laboratory capabilities. In order to test for these new opioids, laboratories require reference standards for the large number of possible fentanyls. To address this need, the Centers for Disease Control and Prevention (CDC) developed the Traceable Opioid Material§ Kits product line, which provides over 150 opioid reference standards, including over 100 fentanyl analogs. These kits were designed to dramatically increase laboratory capability to confirm which opioids are on the streets and causing deaths. The kits are free to U.S based laboratories in the public, private, clinical, law enforcement, research, and public health domains.

Naloxone Dosing After Opioid Overdose in the Era of Illicitly Manufactured Fentanyl.

Illicitly manufactured fentanyl (IMF) is responsible for a growing number of deaths. Some case series have suggested that IMF overdoses require significantly higher naloxone doses than heroin overdoses. Our objective was to determine if the naloxone dose required to treat an opioid overdose is associated with the finding of fentanyl, opiates, or both on urine drug screen (UDS). A retrospective chart review was conducted at a single emergency department and its affiliated emergency medical services (EMS) agency. The charts of all patients who received naloxone through this EMS from 1/1/2017 to 6/15/2018 were reviewed. The study included patients diagnosed with a non-suicidal opioid overdose whose UDS was positive for opiates, fentanyl, or both. Data collected included demographics, vital signs, initial GCS, EMS and ED naloxone administrations, response to treatment, laboratory findings, and ED disposition. The fentanyl-only and fentanyl + opiate groups were compared to the opiate-only group using the stratified (by ED provider) variant of the Mann-Whitney U test. Eight hundred and thirty-seven charts were reviewed, and 121 subjects were included in the final analysis. The median age of included subjects was 38years and 75% were male. In the naloxone dose analysis, neither the fentanyl-only (median 0.8mg, IQR 0.4-1.6; p = 0.68) nor the fentanyl + opiate (median 0.8mg, IQR 0.4-1.2; p = 0.56) groups differed from the opiate-only group (median 0.58mg, IQR 0.4-1.6). Our findings refute thenotion that high potency synthetic opioids like illicitly manufactured fentanylrequire increased doses of naloxone to successfully treat an overdose. There wereno significant differences in the dose ofnaloxonerequired to treat opioid overdose patients with UDSevidence of exposure to fentanyl, opiates, or both. Furtherevaluation of naloxone stocking and dosing protocols is needed.