By Tse Yang Lim, Huiru Dong, Erin Stringfellow, Zeynep Hasgul, Ju Park, Lukas Glos, Reza Kazemi, and Mohammad S Jalali

Fentanyl and its analogs contribute substantially to drug overdose deaths in the United States. There is concern that people using drugs are being unknowingly exposed to fentanyl, increasing their risk of overdose death. This study examines temporal trends and spatial variations in the co-occurrence of fentanyl with other seized drugs.

Methods

We identified fentanyl co-occurrence (the proportion of samples of non-fentanyl substances that also contain fentanyl) among 9 substances or substance classes of interest: methamphetamine, cannabis, cocaine, heroin, club drugs, hallucinogens, and prescription opioids, stimulants, and benzodiazepines. We used serial cross-sectional data on drug reports across 50 states and the District of Columbia from the National Forensic Laboratory Information System, the largest available database on the U.S. illicit drug supply, from January 2013 to December 2023.

Findings

We analyzed data from 11,940,207 samples. Fentanyl co-occurrence with all examined substances increased monotonically over time (Mann-Kendall p < 0.0001). Nationally, fentanyl co-occurrence was highest among heroin samples (approx. 50%), but relatively low among methamphetamine (≤1%), cocaine (≤4%), and other drug samples. However, co-occurrence rates have grown to over 10% for cocaine and methamphetamine in several Northeast states in 2017–2023.

Interpretation:

Fentanyl co-occurs most commonly with heroin, but its presence in stimulant supplies is increasing in some areas, where it may pose a disproportionately high risk of overdose.

Lancet Reg Health Amicas, . 2024 Sep 27;39:100898. doi: 10.1016/j.lana.2024.100898

By Lauren J. Tanz, R. Matt Gladden, Amanda T. Dinwiddie, Kimberly D. Miller, Dita Broz, Eliot Spector, Julie O’Donnell

Summary

What is already known about this topic?

More than 109,000 drug overdose deaths occurred in the United States in 2022; nearly 70% involved illegally manufactured fentanyls (IMFs). Data from the western United States suggested a transition from injecting heroin to smoking IMFs.

What is added by this report?

From January–June 2020 to July–December 2022, the percentage of overdose deaths with evidence of smoking increased 73.7%, and the percentage with evidence of injection decreased 29.1%; similar changes were observed in all U.S. regions. Changes were most pronounced in deaths with IMFs detected, with or without stimulant detection.

What are the implications for public health practice?

Strengthening and expanding public health and harm reduction services to address overdose risk with smoking and other noninjection routes might reduce deaths.

Preliminary reports indicate that more than 109,000 drug overdose deaths occurred in the United States in 2022; nearly 70% of these involved synthetic opioids other than methadone, primarily illegally manufactured fentanyl and fentanyl analogs (IMFs). Data from the western United States suggested a transition from injecting heroin to smoking IMFs. CDC analyzed data from the State Unintentional Drug Overdose Reporting System to describe trends in routes of drug use in 27 states and the District of Columbia among overdose deaths that occurred during January 2020–December 2022, overall and by region and drugs detected. From January–June 2020 to July–December 2022, the percentage of overdose deaths with evidence of injection decreased 29.1%, from 22.7% to 16.1%, whereas the percentage with evidence of smoking increased 73.7%, from 13.3% to 23.1%. The number of deaths with evidence of smoking increased 109.1%, from 2,794 to 5,843, and by 2022, smoking was the most commonly documented route of use in overdose deaths. Trends were similar in all U.S. regions. Among deaths with only IMFs detected, the percentage with evidence of injection decreased 41.6%, from 20.9% during January–June 2020 to 12.2% during July–December 2022, whereas the percentage with evidence of smoking increased 78.9%, from 10.9% to 19.5%. Similar trends were observed among deaths with both IMFs and stimulants detected. Strengthening public health and harm reduction services to address overdose risk related to diverse routes of drug use, including smoking and other non-injection routes, might reduce drug overdose deaths.

Morbidity and Mortality Weekly Report; February 15, 2024

By Joseph Pergolizzi , Peter Magnusson , Jo Ann K. LeQuang , Frank Breve

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. 

Cureus  Open Access Review Article 2021. 11p

By Bryce Pardo, Jirka Taylor, Jonathan P. Caulkins, Beau Kilmer, Peter Reuter, Bradley D. Stein 

  The U.S. opioid crisis worsened dramatically with the arrival of synthetic opioids, such as fentanyl, which are now responsible for tens of thousands of deaths annually. This crisis is far-reaching and even with prompt, targeted responses, many of the problems will persist for decades to come. RAND Corporation researchers have completed numerous opioid-related projects and have more underway for such clients and grantors as the Agency for Healthcare Research and Quality, the Assistant Secretary of Health and Human Services for Planning and Evaluation, the National Institute on Drug Abuse, the White House Office of National Drug Control Policy, and Pew Charitable Trusts. Researchers have advanced an understanding of the dimensions of the problem, some of the causes and consequences, and the effectiveness of different responses. However, no one has yet addressed the full scope of the problems associated with opioid use disorder and overdose deaths. Beginning in late 2018, the RAND Corporation initiated a comprehensive effort to understand the problem and responses to help reverse the tide of the opioid crisis. The project involves dozens of RAND experts in a variety of areas, including drug policy, substance use treatment, health care, public health, criminal justice, child welfare and other social services, education, and employment. In this work, we intend to describe the entire opioid ecosystem, identifying the components of the system and how they interact; establish concepts of success and metrics to gauge progress; and construct a simulation model of large parts of the ecosystem to permit an evaluation of the full effects  of policy responses. We dedicated project resources and communications expertise to ensure that our products and dissemination activities are optimized for reaching our primary intended audiences: policymakers and other critical decision-makers and influencers, including those in the public, private, and nonprofit sectors. The project is ambitious in scope and will not be the last word on the subject, but by tackling the crisis in a comprehensive fashion, it promises to offer a unique and broad perspective in terms of the way the nation understands and responds to this urgent national problem. Ten years ago, few would have predicted that illicitly manufactured synthetic opioids from overseas would sweep through parts of Appalachia, New England, and the Midwest. As drug markets are flooded by fentanyl and other synthetic opioids, policymakers, researchers, and the public are trying to understand what to make of it and how to respond. The synthesis of heroin in the late 19th century displaced morphine and forever changed the opiate landscape, and we might again be standing at the precipice of a new era. Cheap, accessible, and mass-produced synthetic opioids could very well displace heroin, generating important and hard-to-predict consequences. As part of RAND’s project to stem the tide of the opioid crisis, this mixed-methods report offers a systematic assessment of the past, present, and possible futures of fentanyl and other synthetic opioids found in illicit drug markets in the United States. This research is rooted in secondary data analysis, literature and document reviews, international case studies, and key informant interviews. Our goal is to provide local, state, and national decision-makers who are concerned about rising overdose trends with insights that might improve their understanding of and responses to this problem. We also hope to provide new information to other researchers, media sources, and the public, who are contributing to these critical policy discussions  

Santa Monica, CA: RAND, 2019. 265p.

By Kristin M. Tennyson, Charles S. Ray,  Kevin T. Maass  

This report examines the relatively new and emerging problem of fentanyl and fentanyl analogue trafficking. It summarizes the Commission’s related policy work and discusses the continuing policy-making efforts of Congress and the Department of Justice in this area. Finally, the publication presents data about fentanyl and fentanyl analogue offenses since 2005 and provides an in-depth analysis of fiscal year 2019 fentanyl and fentanyl analogue offenses and offenders.

Washington, DC; United States Sentencing Commission, 2021. 60p.

By Jonathan P. Caulkins and Keith Humphreys

If, in 2015, someone had told you that the number of overdose deaths caused solely by the two most historically lethal drugs—heroin and cocaine—would drop by more than half by 2021, you would likely have assumed that the overdose crisis in the U.S. was finally coming to an end. Instead, drug overdose deaths soared to more than 100,000 per year due to the rise of synthetic drugs, a truly disruptive innovation with which U.S. drug policy is only beginning to grapple.

To clarify the key term: synthetic drugs are substances that can be produced in a lab and are not from plant-derived components. In Canadian and U.S. illegal opioid markets, synthetic fentanyl and its analogues are outcompeting heroin, which is made from the poppy plant. These synthetics claimed the lives of more than 70,000 Americans in 2021 (out of 106,699 total drug-involved overdose deaths, or 66%), either by themselves or in combination with other drugs.[1] Methamphetamine, another synthetic, has attained a larger share of the stimulant market than cocaine, which is made from coca leaves.[2] The rapid expansion of synthetic tranquilizers—such as xylazine and benzodiazepines—has spread addiction and death, particularly when these drugs are used in combination with opioids. The U.S. is also facing a bevy of so-called new psychoactive substances (NPS), such as MDMA and mephedrone, that collectively attract more users than do older, “minor” drugs such as LSD, GHB, and PCP.

Drug policy analysts, including the authors of this brief, are swamped with requests from desperate policymakers, clinicians, parents, and activists to find solutions to the problem of synthetic drugs. This brief comprises our answer. Unfortunately, it is not particularly upbeat. All four traditional pillars of drug policy—enforcement, treatment, harm reduction, and prevention—have limits, and there is no simple solution for the synthetic drug market. Nonetheless, the nation can do some things better and should stop doing other things that are harmful. Policymakers must:

• Maintain prohibition of the production and sale of synthetic drugs

• Expect law enforcement to shrink market-related harms, such as violence, but not necessarily to shrink the supply of the drugs themselves

• Keep expanding medication-assisted treatment and access to naloxone

• Embrace the shunning of illegal drugs as a cultural norm

• Be generous toward those who are struggling, including those suffering from drug addiction

Unfortunately, the widespread availability of potentially lethal temptations in the U.S. may be the new normal, and overdose deaths will continue to remain higher than historical norms. Such realism is depressing but honest, and honesty is the best foundation for policy.

New York: Manhattan Institute, 2023. 13p.

By Raminta Daniulaityte, Kaylin Sweeney , Seol Ki, Bradley N. Doebbeling and Natasha Mendoza

Background: Worsening of the overdose crisis in the USA has been linked to the continuing proliferation of non-pharmaceutical fentanyl (NPF). The recent wave of NPF spread in the USA has been fueled by an increased presence of counterfeit pills that contain NPF. This qualitative study aims to characterize the motivation and practices of counterfeit NPF pill initiation and use among individuals using illicit opioids in Arizona. Methods: Between October 2020 and May 2021, semi-structured interviews were conducted with 22 individuals meeting the following eligibility criteria: (1) 18 years or older; (2) residence in Arizona; and (3) use of illicit opioids in the past 30 days and/or opioid use disorder treatment in the past 12 months. Participants were recruited through referrals by a harm reduction organization, craigslist ads, and referrals by other participants. Interviews were conducted virtually via Zoom. Qualitative interviews were transcribed and analyzed thematically using NVivo. Results: Out of 22 participants, 64% were male, and 45% were ethnic minorities. Age ranged between 25 and 51 years old. Participants noted significant recent increases in the availability of counterfeit NPF pills (“blues,” “dirty oxys”) that were most commonly used by smoking. The majority indicated frst trying NPF pills in the past year, and the frst use often occurred in situations of reduced access to heroin or pharmaceutical opioids. Participant decisions to switch over to more frequent NPF pill use or to maintain some levels of heroin use were shaped by local drug availability trends and personal experiences with NPF efects. They were also infuenced by conficting views of social acceptability of pharmaceutical-like drugs, perceived harms of NPF in terms of overdose risks and increased difculty of quitting, and perceived benefts of switching to the non-injection route of opioid administration (e.g., from injecting heroin to smoking NPF pills). Conclusion: Our fndings highlight the need for the implementation of novel policy, treatment, and harm reduction approaches to address the growing unpredictability of drug supply and NPF pill-specifc risks, attitudes, and behaviors.

Harm Reduction Journal (2022) 19:52

United States. Executive Office Of The President; United States. Office Of National Drug Control Policy

From the document: "On April 12, 2023, Dr. Rahul Gupta, Director of the Office of National Drug Control Policy (ONDCP), formally designated fentanyl adulterated or associated with xylazine as an emerging drug threat, pursuant to 21 U.S.C. [United States Code] § 1708. [...] The emerging threat designation, made under the authority provided by 'The Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018' (P.L. [Public Law] 115-271), requires the Executive Branch to take several steps: First, ONDCP, in collaboration with relevant federal agencies, must draft and publicly issue a fentanyl adulterated or associated with xylazine Response Plan (within 90 days of designation). Second, ONDCP must issue Implementation Guidance to agencies (120 days after designation). Third, agencies must provide a specific Agency Implementation Report to ONDCP (180 days after designation). Fourth, ONDCP must publish a National Implementation Report on the Response Plan (in February 2024, with other ONDCP annual reports). The response plan presented here fulfills the first of these requirements and addresses urgent public health and safety needs. The SUPPORT Act also requires that the ONDCP Director decide whether a stand-alone national media campaign would be effective in addressing the emerging threat. In the case of xylazine-adulterated fentanyl, Director Gupta has determined that it will be productive to include such public messaging on fentanyl adulterants in existing campaigns and other federal messaging on fentanyl, in lieu of establishing a new stand-alone campaign focused solely on xylazine. The SUPPORT Act requires that an emerging threat response plan include evidence-based prevention, treatment, and supply reduction action steps, in addition to establishing goals and performance measures informed by comprehensive data. In the plan outlined below, we apply those requirements to the case of fentanyl adulterated or associated with xylazine and describe critically important and urgent next action steps."

United States. Executive Office of the President. United States. Office of National Drug Control Policy 2023. 15p.

By Jeffrey A. Singer and Trevor Burrus

Fifty‐one years after President Richard M. Nixon declared a “war on drugs,” overdose deaths from illicit drug use have climbed to record levels. Last November, the Centers for Disease Control and Prevention reported 100,000 overdose deaths for the 12‐month period ending in April 2021, a 28.5 percent increase over the year before. Nearly 76,000 of those deaths were opioid related, and 83 percent of opioid‐related deaths involved illicit fentanyl.

Fentanyl is a highly potent opioid—about 50 times stronger than heroin—that can easily cause overdoses, particularly if users don’t know if it is in their drug supply or how much. Over the past decade, drug traffickers have increasingly preferred fentanyl because of its compact size. The smuggler’s preference for higher potency drugs is a manifestation of the “iron law of prohibition,” and it is almost the entire reason fentanyl has poisoned the American drug supply. The iron law of prohibition states that, all things being equal, as enforcement ramps up, smugglers prefer higher potency forms of a drug for the same reason those who sneak alcohol into a football game prefer hard alcohol in flasks to 12‐packs of beer. The lethal logic of the iron law of prohibition means that we cannot enforce our way out of the opioid crisis. And if fentanyl smugglers bexcome somehow easy to catch, there’s always carfentanil, which is about 100 times more potent than fentanyl and has already been showing up in America’s drug supply.

Washington, DC: Cato Institute, 2022. 10p.

By Lauren Greenwood and Kevin Fashola

The issue brief examines the evolution of China’s role in global illicit fentanyl trade. China placed all forms of fentanyl and its analogues on a regulatory schedule in 2019, but the U.S. Drug Enforcement Administration (DEA) assesses China remains the primary country of origin for illicit fentanyl and fentanyl-related substances trafficked in the United States. While Mexican drug cartels have always been a critical node for smuggling illicit fentanyl into the United States, this brief finds that the links between Chinese and Mexican actors in the fentanyl trade has grown in complexity, including the development of sophisticated money laundering operations. Finally, the brief concludes that while cooperation between the United States and China remains limited, there are opportunities for the United States to work with other countries on counter-narcotic enforcement.
 Washington, EC:  U.S.-China Economic and Security Review Commission,   

By Bryce Pardo and Peter Reuter

  The synthetic opioid crisis in North America has increased fatal overdose rates to unprecedented levels within a matter of a few years. It involves new technologies, a new source of supply (the chemical industry in China), and new forms of distribution (the internet and mail). These elements are perhaps even more difficult to suppress than other supply sources from foreign countries. This has led to an assumption that nothing can be learned from prior experience in trying to control drug markets. In this paper, we first explore what might be learned from some notable past successes. We begin by examining a set of episodes in which enforcement against a specific illegal drug market had more than a brief impact on supply, though the enforcement may have caused other harms. Examples include the near-elimination of the quaaludes market in the 1980s and the “heroin drought” in Australia in the early 2000s. Exploring common features of these past successes reveals insights that may reduce the risk of fatal overdose. We then examine the characteristics of fentanyl distribution in detail, noting that taken individually, the

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  differences (such as the low costs of fentanyl production and its distribution by mail) are in fact not so distinctive: it is the combination of many differences that creates the unique threat. In response, authorities need to change priorities in supply control domestically. Prior to the arrival of fentanyl and other synthetic opioids, it was reasonable for police and prosecutors to focus on (1) raising prices and restricting availability to reduce consumption and (2) minimizing the violence and disorder around street markets. Yet today, a more important goal may be to reduce the toxicity of the supply and thus the number of drug overdoses. This paper applies the insights of the “focused deterrence” approach developed by David Kennedy and Mark Kleiman, which involves using multiple levers to attain a specific policy goal. We conclude with some specific suggestions for local and national supply-control agencies— including the need to focus more on regulating rather than reducing markets to minimize harm, and to distinguish between markets not yet swamped by fentanyl or in transition and those where the drug is entrenched. Strategies appropriate in one context may not serve well in another.

Washington, DC: Brookings Institution, 2020. 21p.

By United Nations Office on Drugs and Crime (UNODC)

The report provides a regional analysis of the key trends and emerging developments of the synthetic drugs and NPS market as well as options for response in Latin America and the Caribbean. Over the past years, the synthetics drug market has experienced a massive expansion and diversification in the region and seen a rapid emergence of a wide range of NPS.

The latest developments include an expanding methamphetamine market, growing concerns around the non-medical use of ketamine, the emergence of fentanyl and MDMA manufacture, as well as new “ecstasy” trends such as higher dosed MDMA tablets and new forms of presentation such as crystalline MDMA. Moreover, the report sheds light on the comparatively high prevalence of use of hallucinogens in the region and the high prevalence of use of tranquilizers among women.

Vienna: UNODC, 2021. 56p.