Illicit Fentanyl Research Articles

Three noteworthy idiosyncrasies related to Canada's opioid-death crisis, and implications for public health-oriented interventions.

Canada has been experiencing a prolonged public health-crisis of high rates of overdose deaths caused by exceptionally potent/toxic, illicit opioid use. While many key features of this drug death epidemic are well-documented, several idiosyncratic aspects with relevance for public health-oriented interventions are not adequately recognised. These include: (i) the discrepant opioid patterns pan-Canada, with large majorities of opioid deaths caused by illicit fentanyl drugs in Western, but not Eastern regions where prescription-type opioid prevail; (ii) the environments of overdose deaths, where vast majorities occur in 'residential' or other shelter-type settings, presenting barriers for emergency interventions rather than health protection; and (iii) shifting drug use modes, where now majorities of overdose deaths are associated with drug 'inhalation' (instead of 'injection') in contexts of potent/toxic drug supply. We briefly describe these factors and related implications for intervention programming towards an improved response to the drug death-crisis.

Health risks associated with smoking versus injecting fentanyl among people who use drugs in California

BackgroundGiven the attention, funding, and services that seek to reduce overdose mortality from fentanyl, it is important to understand whether a potential solution is for more people to switch from injecting to smoking fentanyl. As such, we set out to conduct a study to compare health and healthcare utilization outcomes associated with different modes of illicit fentanyl administration. MethodsFrom January to February 2023, we recruited people who use drugs from 34 syringe services programs across California, USA (N=999) and surveyed their substance use, health outcomes, and healthcare utilization. We compared health risks among people who injected fentanyl (78% of whom also smoked) to people who solely smoked fentanyl (n=563). ResultsOf the 563 participants, forty-one percent injected fentanyl and 59% only smoked fentanyl. People who injected fentanyl were 40% more likely to have experienced a non-fatal overdose in the past 3 months (27% vs. 19%; aRR=1.40; 95% CI=1.03, 1.93) and 253% more likely to have had a skin and soft tissue infection in the past 3 months (39% vs. 15%; aRR=2.53; 95% CI=1.74, 3.67), compared to people who only smoked fentanyl. The average number of nights spent in the hospital was higher among people who injected fentanyl (average 1.2 nights vs. 0.7 nights; aIRR=1.78; 95% CI=1.02, 3.09; p=0.04).There were non-significant associations between mode of fentanyl administration and number of emergency department visits and probability of hospitalization. ConclusionsFindings suggested that people who injected fentanyl were at higher risk for overdose and skin and soft tissue infections than people who only smoked fentanyl. Distribution of safe smoking supplies may facilitate transitions from injecting to smoking fentanyl, thereby reducing health risks associated with fentanyl use.

Infiltration of xylazine in illicit fentanyl

Learn how to identify the signs of this new drug.

Novel Therapeutic and Program-Based Approaches to Opioid Use Disorders.

Opioid use disorder continues to drive overdose deaths in many countries, including the United States. Illicit fentanyl and its analogues have emerged as key contributors to the complications and mortality associated with opioid use disorder. Medications for opioid use disorder treatment, such as methadone and buprenorphine, are safe and substantially reduce opioid use, infectious complications, and mortality risk, but remain underutilized. Polysubstance use and emerging substances such as xylazine and designer benzodiazepines create additional treatment challenges. Recent clinical and policy innovations in treatment delivery, including telemedicine, bridge clinics, and expanded models for accessing methadone have the potential to increase access to life-saving care for people living with opioid use disorder.

Millennium Health sounds the alarm on xylazine: It's moving west

Formerly restricted mainly to the East Coast, xylazine, a dangerous (if misused) animal tranquilizer, is moving into the West, according to a new epidemiological report from Millenium Health. Based on an analysis of 160,000 urine drug tests this year from treatment programs, xylazine — which is now present on the street combined with illicit fentanyl — is emerging as a threat in California, Oregon, New Mexico and Alaska, as well as the Rocky Mountain states. Currently, Pennsylvania, North Carolina and Ohio have the highest rates of xylazine positivity in the nation.

B-298 Retrospective Analysis of Fentanyl Positivity at a Large Academic Center Reveals Trends in Illicit Fentanyl Use

Abstract Background National drug-involved overdose deaths continue to rise with deaths involving synthetic opioids (primarily fentanyl) showing the most significant upward trend. Fentanyl is a synthetic opioid with short-acting analgesic activity and a 50–100 times higher potency compared to morphine. Pharmaceutical fentanyl is typically used to treat patients with severe or chronic pain. In contrast, “illegal” fentanyl has frequently been added to other drugs including heroin, cocaine, methamphetamine, and MDMA to increase their potency and contributing to overdose deaths. In this study, we have investigated trends in fentanyl and fentanyl analogs positivity at a large academic medical center. Methods Retrospective analysis of results reported over seven years (2015–2021) for untargeted urine drug screens included testing performed for acute exposure and compliance. Presence of fentanyl, fentanyl analogs, and other prescribed or illicit used drugs was determined by gas chromatography—mass spectrometry (GCMS). Overall positivity was calculated as a percentage of total reported results. Results Fentanyl, and fentanyl analog positivity was determined for 40 782 urine drug screen results. Overall positivity for fentanyl and fentanyl analogs increased 3.8-fold over the past seven year from 1.53% (2015) to 5.78% (2021). Co-positivity with other illicit drugs such as cocaine and heroin also increased from 7% and 8% respectively, in 2015, to 42% and 13%, in 2021. Presence of fentanyl analogs such as fluorofentanyl, despropionylfentanyl, and acetylfentayl increased in the recent years as well. Conclusion Our data reveals increased positivity of fentanyl and fentanyl analogs present with cocaine, heroin, or their metabolites suggesting increased use of illicit fentanyl. The high prevalence supports the inclusion of fentanyl on routine urine drug screen immunoassays, or at a minimum as a reflex with a positive opiate screen.

B-311 Increasing Xylazine Findings in Clinical Samples

Abstract Background Xylazine is a veterinary tranquilizer first appearing in illicit fentanyl preparations in 2019. It is believed to extend a fentanyl high and is now more commonly used as its own drug of abuse. Clinically, xylazine is of concern as it does not respond to naloxone or other antidote during overdoses. There are many forensic findings of increasing xylazine use since its original appearance, but little in the literature concerning clinical xylazine findings, possibly because xylazine is rarely screened in routine drug screening. We sought to find clinical cases with positive xylazine results from 2019–2022. Determined data included demographics (where possible to discern), sex distribution, age ranges, and frequency. Methods We queried our laboratory information management system (LIMS) for reported xylazine findings under expanded clinical drug screen utilizing liquid chromatography time of flight mass spectrometry (LC-TOF) for screening and liquid chromatography tandem mass spectrometry (LC-MS/MS) for confirmation, and specific xylazine testing utilizing LC-MS/MS. Results In 1928 clinical cases reported between January 2019 and January 2023, the xylazine positivity rate increased from 1.28% (2021; n = 13 positive xylazine results) to 5.05% positivity (2022; n = 29 positive xylazine results) despite a significant decrease in panels and tests with xylazine ordered (n = 1008 in 2021, n = 574 in 2022). The ages of the patients ranged 0–57 years; eleven cases concerned pediatric patients. Of cases that indicated the sex of the patient, 69% were male (n = 29). These cases were found in ten different states (AZ, CT, DE, IN, MA, NJ, OH, PA, UT, VA), with 18 incidental findings. While other drugs were present in incidental finding cases, all cases with an incidental positive xylazine result were also positive for fentanyl and norfentanyl, and several cases were also positive for fentanyl analogues, most commonly 4-ANPP, which occurred in 50% of these cases. Conclusion Xylazine use continues to be on the rise and should be of concern for emergency medicine doctors, poison control centers, and clinical laboratories.

Pakistan’s Opioid Squeeze: Impacts of Taliban Edicts, Indian Synthetics and Chinese Regulations

This study examines how the Taliban’s opium poppy eradication edict and the westward shift in illicit fentanyl production from China to India potentiates an opioid squeeze on Pakistan from its east-west flanks, influencing Pakistan’s opioid production, distribution and use. As opioid output sputters in Afghanistan, while Indian chemists increasingly normalise illicit fentanyl production in South Asia, opportunistic Pakistani chemists will be incentivised to supply synthetic opioids to high-demand international markets, just as Pakistani farmers supply opium and heroin to international clients. This convergence has ramifications for Pakistani law, drug enforcement and public health, as domestic production increases domestic access to synthetic opioids. The article conducts an empirical examination of current trends in South Asian opioid production, distribution and use, along with an exegesis of the legal and regulatory systems in Pakistan, Afghanistan and China. This study also details how the Pakistani government should respond to this challenge legislatively, foremost through blanket ban of fentanyl and its precursors. Pakistan can reduce domestic use through evidence-based treatment programmes, including discrete and confidential treatment administered by females to female users, opioid substitution therapy, safe needle exchange programmes, culturally sensitive drug awareness campaigns, and increased data collection to detect geographic hotspot locations of opioid use and overdoses.

The rise and rise of fentanyl in postmortem casework.

Forensic toxicology laboratories are navigating a period of time with increasing drug overdose deaths, an opioid epidemic, the impact of the COVID-19 pandemic, and the illicit drug market flooded with novel psychoactive substances. In New York City, the Department of Forensic Toxicology has experienced a 56% increase in postmortem casework in the past decade with fentanyl detected in 80% of all overdose deaths. Over a period of 2.5 years, 15,638 postmortem cases were tested for the presence of fentanyl and fentanyl analogs using liquid-chromatography tandem mass spectrometry (LCMSMS). Fentanyl was detected in approximately one third of cases and of these 4447 cases with femoral blood. A twofold increase in cases with high concentrations of fentanyl (>100 ng/mL) was observed between 2021 and 2022. The minor metabolite and precursor chemical, 4-ANPP (4-anilino-N-phenethylpiperidine) may help differentiate between illicit and licit fentanyl. 4-ANPP blood concentrations were <10 ng/mL in 98% of the cases and the 4-ANPP:fentanyl ratio was <0.67 for 99.1% of blood specimens. Only six cases had 4-ANPP concentrations higher than the corresponding fentanyl blood concentration. This study also highlights, the changing fentanyl analogs found in postmortem cases since 2016 in NYC with the emergence of fluorofentanyl initially identified in 2020 and continuing to dominate in comparison with the prevalence of other analogs, many of which are no longer detected in casework. The detection of one of the latest drugs to be mixed with fentanyl, namely xylazine, has also increased in prevalence by 36.7% in 2022 compared with 2021.

HALT Bill Targets Illicit Fentanyl Only, Not Medical Use

HALT Bill Targets Illicit Fentanyl Only, Not Medical Use

Decoding hidden darknet networks: What we learned about the illicit fentanyl trade on AlphaBay.

The opioid epidemic, impacted from the proliferation of fentanyl, has added impetus to the need to detect fentanyl, sources of fentanyl, and places where fentanyl and drugs adulterated with fentanyl are available. Many darknet marketplaces (DNMs) have rules that ban fentanyl. However, it is unclear how these affect the fentanyl market. Using the AlphaBay DNM as a case study, we conducted mixed methods qualitative research. We scraped and analyzed data from the AlphaBay I2P website using, among other methods,content and social network analysis, to uncover hidden fentanyl networks. Our research highlights the next evolution of darknet marketplaces - the migration of DNMs from Tor to I2P and the methods that can be used identify fentanyl networks, irrespective of where sites are: I2P, Tor, or multihomed on I2P and Tor. Despite its ban in the Global AlphaBay Rules, our research revealed the sale of fentanyl on the AlphaBay DNM. Unlike previous studies, our findings predominantly revealed the covert sale of fentanyl on AlphaBay and predatory vendors selling illicit drugs, which unbeknownst to buyers, contained fentanyl. To a lesser extent, our findings identified the overt sale of fentanyl patches on AlphaBay. Although we examined only one DNM, the prevalence of the covert sale of fentanyl and the presence of predatory vendors underscores the importance of research that decodes the language of vendors who surreptitiously sell fentanyl or drugs adulterated with fentanyl or other illicit substances. The results of our research can inform strategies aimed at disrupting and dismantling DNM fentanyl networks.

VP Harris meets with 8 AGs to discuss illicit fentanyl chain

Last week, Vice President Kamala Harris convened attorneys general from seven states and the District of Columbia for a conversation about federal and state efforts to disrupt the illicit fentanyl supply chain, and at the same time expand access to care for individuals at risk of an overdose. Exactly why the AGs, but not state health officials, were included to discuss how to expand treatment was not clear, and when asked for an explanation, ADAW received merely a readout of the entire meeting. However, the vice president announced that almost $50 million would be awarded in grants by the Substance Abuse and Mental Health Services Administration (SAMHSA) last week, as well.

CDC reports stimulant‐involved OD deaths up; Researchers look at why

Last month in the Morbidity and Mortality Weekly Report, the federal Centers for Disease Control and Prevention (CDC) reported a dramatic increase in the presence of cocaine and methamphetamine in opioid overdose (OD) deaths. The increase is largely driven by illicitly manufactured fentanyl, according to the CDC. Users are getting tired of illicit fentanyl, they try to boost it with methamphetamine (mainly, because methamphetamine is less expensive than cocaine), or find themselves exposed to stimulants when they weren't expecting to be due to sloppy lab techniques, according to a study, “The motives and methods of methamphetamine and ‘heroin’ co‐use in West Virginia,” published July 12 in Harm Reduction Journal (see https://harmreductionjournal.biomedcentral.com/articles/10.1186/s12954‐023‐00816‐8 for the full study).

Evaluating the sensitivity, stability, and cross-reactivity of commercial fentanyl immunoassay test strips.

Illicit fentanyl has flooded the United States' drug market, increasing the risk of overdose and poisonings throughout the general population and accidental exposure among law enforcement officers confiscating the increasing number of seizures. Fentanyl test strips (FTS) are used to obtain presumptive information about the presence of fentanyl in a suspected sample. However, their adoption by law enforcement personnel and seized-drug analysts has been limited because most products are advertised for urine testing, not for assays using water solutions. This study presents an evaluation of four commercial FTS: Rapid Response from BTNX, Inc.; T-Dip Fentanyl (FTY) Urine Dip Cards obtained from Amazon.com; Premier BioDip FYL10 from Premier Biotech Inc.; and MobileDetect Fentanyl strips from DetectaChem, Inc. Performance characteristics curves were used to compare the products' sensitivity, showing that all can reliably detect fentanyl in aqueous solutions at concentrations below 1 μg/mL, with some of the tests able to reliably detect the drug at 200 ng/mL. A stability study demonstrates the performance of all four FTS brands was only slightly affected after 30 days of storage at two extreme environmental conditions. Fentanyl-related substances are also evaluated using the Rapid Response FTS, which showed high cross-reactivity with para-fluorofentanyl and acetylfentanyl, but lower with ortho-chlorofentanyl, carfentanil, and 4-ANPP. Users should be aware that FTS may give false-negative results even when potentially dangerous levels of carfentanil are present. When testing other common drugs, adulterants, and diluents frequently encountered in seized tablets, concentration-dependent results were obtained and multiple instances of false positives were recorded.

Effects of xylazine in illicit fentanyl supply: Report from OASAS

At the COMPA (Coalition of Medication‐Assisted Treatment Providers and Advocates) Symposium last month in Albany, New York, officials from the New York Office of Addiction Services and Supports (OASAS) presented information on the effects of xylazine, increasingly present in the street supply of opioids, especially fentanyl. Pamela Mund, M.D., OASAS associate medical officer, and Sarah Gorry, M.S., an Empire State Fellow with OASAS, shared the following information. Xylazine is

Synthesis of nanoflower-like NiMnO3 combined with MWCNTs for the electrochemical determination of fentanyl

With the rapid increase in illicit usage of fentanyl, the number of deaths due to fentanyl abuse has also increased year by year, the demand for rapid screening methods for illicit fentanyl abuse is urgent. Herein, we propose to use nanoflower-like binary metal oxide NiMnO3 as electrocatalysts and combined with multi-walled carbon nanotubes (NiMnO3/MWCNTs) for the electrochemical detection of fentanyl. The as-synthesized nanoflower-like NiMnO3/MWCNTs composites show low electrochemical impedance and large electrochemical surface area, resulting in ultra-high sensitivity for the electrochemical detection of fentanyl. The limit of detection (LOD) of NiMnO3/MWCNTs/GCE for fentanyl is 0.013 μM and the linear range is 0.05–10 μM with satisfactory reproducibility, selectivity and stability. In addition, the developed electrodes performed well on real samples with recoveries from 61.45% to 84.25% and 84.80% to 96.25% in urine and blood respectively, at 0.2–1 μM concentrations. The high performance of composite materials for fentanyl detection is mainly due to the catalytic effect of NiMnO3 and the high electrical conductivity of MWCNTs. Therefore, the proposed NiMnO3/MWCNTs composite can be a new promising electrochemical rapid screening electrode material for the electrochemical detection of fentanyl and has great potential for rapid detection of fentanyl in police combating drugs or medical emergencies.

Best Practice Alerts: A Poke in the Eye or an Efficient Method for Safer Prescribing?

Best Practice Alerts: A Poke in the Eye or an Efficient Method for Safer Prescribing?

The effects of the (fentanyl-fueled) drug overdose epidemic on medicolegal death investigation in the United States.

The evolving opioid epidemic in the United States, fueled by illicit fentanyl, has greatly increased deaths from illicit drug use. These nonnatural deaths require formal death investigation. The National Association of Medical Examiners states in its Forensic Autopsy Performance Standards that autopsy remains a necessary component for proper investigation of suspected acute overdose deaths. If a death investigation office lacks adequate resources to investigate all deaths under its jurisdiction while meeting expected standards, then that office may be forced to consider altering its protocols for investigation by changing the types of deaths investigated or the extent of its investigations. Drug death investigations take longer to complete because novel illicit drugs and mixtures of drugs complicate toxicological analyses, prolonging a family's wait for completion of a death certificate and autopsy report. Public health agencies must also wait for results, but some agencies have developed mechanisms for rapid notification of preliminary results to allow timely deployment of public health resources. The increased deaths have strained the resources of medicolegal death investigation systems throughout the United States. Given the significant workforce shortage of forensic pathologists, newly trained forensic pathologists are too few to meet the demand. Nevertheless, forensic pathologists (and all pathologists) must make time to present their work and themselves to medical students and pathology trainees to encourage an understanding of the importance of quality medicolegal death investigation and autopsy pathology and to provide a model that can encourage interest in a career in forensic pathology.

Accelerated Fentanyl Metabolism During Pregnancy and Impact on Prenatal Drug Testing.

To evaluate the metabolic pattern of illicit fentanyl in a sample of pregnant patients with opioid use disorder. Fentanyl pharmacokinetics during pregnancy are currently understudied yet the interpretation of a fentanyl immunoassay during pregnancy has significant implications on maternal legal custody and child welfare. Through this medical-legal lens, we demonstrate the utility of an emerging metric, the metabolic ratio, for accurate analysis of fentanyl pharmacokinetics during pregnancy. We conducted a retrospective cohort analysis using the electronic medical records of 420 patients receiving integrated prenatal and opioid use disorder care at a large urban safety net hospital. Data related to maternal health and substance use were collected for each subject. The metabolic ratio was calculated for each subject to measure their rate of metabolism. The sample's (n = 112) metabolic ratios were compared with a large non-pregnant sample (n = 4366). The metabolic ratios of our pregnant sample were significantly (p = .0001) higher than the metabolic ratios of our non-pregnant sample, indicating that the rate of conversion to the major metabolite was faster in pregnant people. The effect size for this difference between the pregnant and non-pregnant sample was large (d = 0.86). Our findings characterize the unique metabolic pattern of fentanyl in pregnant people who use opioids, providing guidance for institutional policies around fentanyl drug testing. Additionally, our study warns of misinterpretation of toxicology results and stresses the importance of physician advocacy on behalf of pregnant women who use illicit opioids.

Examining Increasing Racial Inequities in Opioid Overdose Deaths: a Spatiotemporal Analysis of Black and White Decedents in St. Louis, Missouri, 2011-2021.

The third wave of the opioid overdose crisis-defined by the proliferation of illicit fentanyl and its analogs-has not only led to record numbers of overdose deaths but also to unprecedented racial inequities in overdose deaths impacting Black Americans. Despite this racialized shift in opioid availability, little research has examined how the spatial epidemiology of opioid overdose death has also shifted. The current study examines the differential geography of OOD by race and time (i.e., pre-fentanyl versus fentanyl era) in St. Louis, Missouri. Data included decedent records from the local medical examiners suspected to involve opioid overdose (N = 4420). Analyses included calculating spatial descriptive analyses and conducting hotspot analyses (i.e., Gettis-Ord Gi*) stratified by race (Black versus White) and time (2011-2015 versus 2016-2021). Results indicated that fentanyl era overdose deaths were more densely clustered than pre-fentanyl era deaths, particularly those among Black decedents. Although hotspots of overdose death were racially distinct pre-fentanyl, they substantially overlapped in the fentanyl era, with both Black and White deaths clustering in predominantly Black neighborhoods. Racial differences were observed in substances involved in cause of death and other overdose characteristics. The third wave of the opioid crisis appears to involve a geographic shift from areas where White individuals live to those where Black individuals live. Findings demonstrate racial differences in the epidemiology of overdose deaths that point to built environment determinants for future examination. Policy interventions targeting high-deprivation communities are needed to reduce the burden of opioid overdose on Black communities.