How much illegally manufactured fentanyl could the U.S. be consuming?

The spread of illegally manufactured opioids, including fentanyl, has brought unprecedented levels of drug overdose deaths in North America. In some markets, illegally manufactured fentanyl (IMF) is essentially displacing heroin, not just being used to adulterate it. It is not possible at this time to provide an accurate point estimate of the amount of IMF consumed in the United States. Yet for various purposes (e.g. assessing changes in production levels and the appropriate role for various supply reduction efforts), it is important to have a sense of scale. This article provides guidance through two thought experiments that provide a hypothetical upper bound on U.S. consumption. The first considers a scenario in which IMF replaces heroin in all illegal opioid markets. The second starts with the number of individuals with an opioid use disorder and considers what total consumption would be if IMF was the only opioid they consumed. Both calculations suggest it is unlikely that the annual consumption of IMF in 2021 could have been more than single digit pure metric tons. For comparison, the most recent best estimates of the amount of cocaine and heroin consumed in the U.S. are 145 and 47 pure metric tons, respectively. The article also raises questions about the limitations of using traditional equianalgesic morphine equivalent dose conversions to estimate the total market consumption of IMF.

Modelling the amount of inputs needed for methamphetamine manufacture in Afghanistan.

BACKGROUND AND AIMS: The use and manufacture of methamphetamine has increased in Afghanistan in recent years. Recent research and reports have pointed to the ephedra plant, which grows wildly, as a key source of ephedrine used in the manufacture of methamphetamine. This paper aimed to estimate the relative efficiencies and scale of inputs required to manufacture methamphetamine in Afghanistan. METHODS: Monte Carlo simulations model of the amount of ephedra or cold medications needed to render a pure kilogram of methamphetamine in Afghanistan, accounting for uncertainty in ranges of key parameters informed from the literature and elsewhere. Final estimates were extrapolated to recent seizure totals. RESULTS: For dried ephedra, the median estimate is 196.8 kg (25th-75th percentiles 119.3-346.6 kg) needed to produce 1 kg of methamphetamine compared with 27.9 kg (25th-75th percentiles 21.9-36.8 kg) for cold medications. Nearly 2.7 t of methamphetamine were seized in Afghanistan in 2021. Assuming a purity range of 50%-90%, some 266-478 t of dried ephedra or 38-68 t of cold medication would need to have been processed. CONCLUSION: Simulated estimates show that considerable amounts of either ephedra or cold medication are needed to produce 1 kg of methamphetamine in Afghanistan. This raises questions about the plausibility of ephedra as the dominant source of Afghanistan's methamphetamine.

America's Opioid Ecosystem: How Leveraging System Interactions Can Help Curb Addiction, Overdose, and Other Harms.

Opioids play an outsized role in America's drug problems, but they also play a critically important role in medicine. Thus, they deserve special attention. Illegally manufactured opioids (such as fentanyl) are involved in a majority of U.S. drug overdoses, but the problems are broader and deeper than drug fatalities. Depending on the drugs involved, there can be myriad physical and mental health consequences associated with having a substance use disorder. And it is not just those using drugs who suffer. Substance use and related behaviors can significantly affect individuals' families, friends, employers, and wider communities. Efforts to address problems related to opioids are insufficient and sometimes contradictory. Researchers provide a nuanced assessment of America's opioid ecosystem, highlighting how leveraging system interactions can reduce addiction, overdose, suffering, and other harms. At the core of the opioid ecosystem are the individuals who use opioids and their families. Researchers also include detail on ten major components of the opioid ecosystem: substance use disorder treatment, harm reduction, medical care, the criminal legal system, illegal supply and supply control, first responders, the child welfare system, income support and homeless services, employment, and education. The primary audience for this study is policymakers, but it should also be useful for foundations looking for opportunities to create change that have often been overlooked. This study can help researchers better consider the full consequences of policy changes and help members of the media identify the dynamics of interactions that deserve more attention.

Rapid changes in illegally manufactured fentanyl products and prices in the United States.

BACKGROUND AND AIMS: Synthetic opioids, mostly illegally manufactured fentanyl (IMF), were mentioned in 60% of United States (US) drug overdose deaths in 2020, with dramatic variation across states that mirrors variation in IMF supply. However, little is known about IMF markets in the United States and how they are changing. Researchers have previously used data from undercover cocaine, heroin, and methamphetamine purchases and seizures to examine how their use and related harms respond to changes in price and availability. This analysis used US Drug Enforcement Administration (DEA) data to address two questions: (i) "To what extent does IMF supply vary over time and geography?" and (ii) "What has happened to the purity-adjusted price of IMF?" METHODS: We developed descriptive statistics and visualizations using data from 66 713 observations mentioning IMF and/or heroin from the DEA's System to Retrieve Information from Drug Evidence (STRIDE; now STARLIMS) from 2013 to 2021. Price regressions were estimated with city-level fixed effects examining IMF-only powder observations with purity and price information at the low-to-medium wholesale level (>1 g to ≤100 g; n = 964). RESULTS: From 2013 to 2021, the share of heroin and/or IMF observations mentioning IMF grew from near zero to more than two-thirds. The share of heroin observations also containing IMF grew from <1% to ~40%. There is important geographic variation: in California, most IMF seizures involved counterfeit tablets, whereas New York and Massachusetts largely involved powder formulation. The median price per pure gram of IMF powder sold at the >10 to ≤100 g level fell by more than 50% from 2016 to 2021; regression analyses suggested an average annual decline of 17% (P < 0.001). However, this price decline appears to have been driven by observations from the Northeast. CONCLUSIONS: Since 2013, the illegally manufactured fentanyl problem in the United States has become more deadly and more diverse.

Supplying synthetic opioids during a pandemic: An early look at North America.

International commerce and travel have been restricted in order to limit the spread of COVID-19. The illegal trafficking in drugs, which is often concealed in other commercial activity, will be affected by these disruptions. This is particularly true for precursor chemicals, controlled substances of synthetic origin, and new psychoactive substances coming from Asia. China hosts large and under-regulated pharmaceutical and chemical sectors that provide many of the active ingredients used both in legitimate medicines and illicit fentanyl and methamphetamine. Unregulated producers and vendors in China have been supplying drug trafficking organizations in Mexico or using the internet and postal service to directly sell fentanyl to buyers in North America. The magnitude of supply shortages and interrupted trade of chemicals and synthetic drugs coming from China will depend on the breadth and depth of COVID-19's disruptions. In turn, this could impact vulnerable drug-using populations. Drawing on historical accounts of prior supply disruptions, this commentary offers some initial speculation as to the possible effects of COVID-19 on the supply of synthetic drugs like fentanyl and precursor chemicals supplied to North America from China, which may have important lessons for other parts of the globe. Prior supply disruptions coincided with elevated prices and reduced purities of street drugs as well as increases in the number of users entering treatment. However, it is challenging to predict how developments will unfold given the unprecedented nature of this pandemic. A short-term breakdown in supply chains, interrupted trade, or social distancing mandates may not have much of an effect on the availability of synthetic drugs. Yet, disruptions in trade for months or years could shape how drugs are supplied or used. Drug policy will need to evaluate market indicators as soon as they are available but responding now with expanded medication therapies, like methadone, may help save lives. The drug policy landscape could look different in a post-COVID world.

Systematic review of the emerging literature on the effectiveness of naloxone access laws in the United States.

BACKGROUND AND AIMS: Naloxone access laws (NALs) have been suggested to be an important strategy to reduce opioid-related harm. We describe the evolution of NALs across states and over time and review existing evidence of their overall association with naloxone distribution and opioid overdose as well as the potential effects of specific NAL components. METHODS: Descriptive analysis of temporal variation in US regional adoption of NAL components, accompanied by a systematic search of 13 databases for studies (published between 2005 and 20 December 2019) assessing the effects of NALs on naloxone distribution or opioid-related health outcomes. Eleven studies, all published since 2018, met inclusion criteria. Study time-frames spanned 1999-2017. Opioid-related overdose mortality, emergency department episodes and naloxone distribution were correlated with the presence of a NAL and, where data were available, NAL components. RESULTS: Existing evidence suggests mixed, but generally beneficial, effects for NALs. Nearly all studies show that NALs, particularly those that permit naloxone distribution without patient-specific prescriptions, are associated with increased naloxone access [incidence rate ratios (IRR) range from 1.40, 95% confidence interval (CI) = 1.15-1.66 to 7.75, 95% CI = 1.22-49.35] and increased opioid-related emergency department visits (IRR range from 1.14, 95% CI = 1.07-1.20 to 1.15, 95% CI = 1.02-1.29). Most studies show NALs are associated with reduced overdose mortality, although findings vary depending on the specific NAL components and time-period analyzed (IRR range from 0.66, 95% CI = 0.42-0.90 to 1.27, 95% CI = 1.27-1.27). Few studies account for the variation in opioid environments (i.e. illicit versus prescription) or other policy dimensions that may be correlated with outcomes. CONCLUSIONS: The existing literature on naloxone access laws in the United States supports beneficial effects for increased naloxone distribution, but provides inconclusive evidence for reduced fatal opioid overdose. Mixed findings may reflect variation in the laws' design and implementation, confounding effects of concurrent policy adoption, or differential effectiveness in light of changing opioid environments.

Imagining a fentanyl future: Some consequences of synthetic opioids replacing heroin.

For nearly a century heroin has dominated the illegal opioid trade. The global supply of heroin is estimated to generate tens of billions of dollars in revenues a year and its illegal use has long been the source of many societal harms. The arrival of inexpensive and mass-produced synthetic opioids, such as fentanyl, to parts of North America and Europe may signal the beginning of the end of heroin's dominance. Data from several places suggest that fentanyl and other synthetic opioids can quickly supplant heroin. Taking the extreme case, we calculate the estimated wholesale revenues of heroin currently and contrast that with fentanyl prospectively in the United States and in the rest of the world if fentanyl were to supplant heroin entirely. Heroin traffickers in the United States generate about $2.5 billion in revenues; the total import value of fentanyl, after replacing heroin, could be less than $100 million. For the rest of the world we project a reduction from $6.7 billion to less than $300 million. Retailer revenues on the other hand would probably rise because individuals may consume more frequently and with greater intensity due to fentanyl's shorter duration of action and so far there has been no indication of a notable reduction in retail prices. It is unlikely that heroin will entirely disappear, but very likely that globally heroin will account for a declining share of illegal opioids. Violence and corruption may decline but opioid related mortality and morbidity, as well as property crime, are likely to rise. Policy makers will face difficult challenges. Economics provides limited help in forecasting which opioid markets are likely to convert to synthetic opioids.

The dawn of a new synthetic opioid era: the need for innovative interventions.

BACKGROUND: Overdose deaths related to illegal drugs in North American markets are now dominated by potent synthetic opioids such as fentanyl, a circumstance foreshadowed by often-overlooked events in Estonia since the turn of the century. Market transitions generate important and far-reaching implications for drug policy. ARGUMENT AND ANALYSIS: The supplier-driven introduction of illegally manufactured synthetic opioids into street opioids is elevating the risk of fatal overdose. Using the most recent overdose mortality and drug seizure data in North America, we find that overdose deaths and seizures involving synthetic opioids are geographically concentrated, but this might be changing. Examination here suggests that in some places fentanyl and its analogues have virtually displaced traditional opioids, such as heroin. The concealing of synthetic opioids in powders sold as heroin or pressed into counterfeit medications substantially increases harms. The nature and scale of the challenge posed by synthetic opioids is unprecedented in recent drug policy history. CONCLUSIONS: There is urgent need for policy and technological innovation to meet the challenges posed by illegally produced synthetic opioids. Novel interventions worth examining include supervising drug use, proactively deterring on-line distribution and new technologies aimed at improving transparency, such as point-of-use drug content testing. Continuing to approach this problem only with existing policies and available methods, such as naloxone, is unlikely to be enough and will result in many premature deaths.

Illicit synthetic opioid consumption in Asia and the Pacific: Assessing the risks of a potential outbreak.

BACKGROUND: Illegally manufactured potent synthetic opioids (IMPSO) like fentanyl have contributed to rises in overdose deaths in parts of North America and Europe. While many of these substances are produced in Asia, there is little evidence they have entered markets there. We consider the susceptibility to IMPSO's encroachment in markets in the Asia-Pacific region. METHODS: Our analysis focuses on Australia, China, India, and Myanmar. Using a mixed-methods approach comprising interviews, literature review, and secondary data analyses, we examine factors facilitating or impeding incursion of IMPSO. Finally, we illustrate the potential for IMPSO fatalities in Australia. RESULTS: Australia reports some signs of three facilitating factors to IMPSO's emergence: 1) existing illicit opioid markets, 2) disruption of opioid supply, and 3) user preferences. The other three countries report only existing illicit opioid markets. While diverted pharmaceutical opioids are a noted problem in Australia and India, heroin is the dominant opioid in all four countries. There are divergent trends in heroin use, with use declining in China, increasing in India, and stable in Australia and Myanmar. If IMPSO diffused in Australia as in North America from 2014 to 2018, and our assumptions generally hold, deaths from IMPSO could range from 1500-5700 over a five-year period. CONCLUSIONS: This analysis and illustrative calculations serve as an early indication for policymakers. With the exception of Australia, many countries in the region fail to properly record overdose deaths or monitor changes in local drug markets. Early assessment and monitoring can give officials a better understanding of these changing threats.

Intensity of cannabis use: Findings from three online surveys.

BACKGROUND: Drug use is often measured in terms of prevalence, meaning the number of people who used any amount in the last month or year, but measuring the quantity consumed is critical for making informed regulatory decisions and estimating the effects of policy changes. Quantity is the product of frequency (e.g., number of use days in the last month) and intensity (amount consumed per use day). Presently, there is imperfect understanding of the extent to which more frequent users also consume more intensively. METHODS AND DATA: We examine cannabis flower consumption reported in three similar online surveys fielded in times and places where cannabis was and was not legal. These convenience samples returned enough valid responses (n = 2,618) to examine consumption across different frequencies of use via analyses of measures of central tendency, data visualizations, and multivariate regressions. Additional calculations incorporate data from the National Survey on Drug Use and Health. FINDINGS: Respondents who reported using daily (i.e., 30 days in the past month) consumed almost twice as much per day of use on average as did those reporting less than daily. We find only modest increases in intensity among those using less than daily, but then a substantial increase (p< 0.001) for those who use daily. Most respondents report that on heavy or light use days their consumption differs from a typical day of use by a factor of 2 or more, but only about 25% of days were described as heavy or light. We estimate those using cannabis 21+ days a month account for 80% of consumption vs. 71% of the days of use. DISCUSSION: Daily cannabis users consume more intensively than others, including near-daily users. When possible, survey questions should move beyond the presence or absence of use and number of days used.

The state of the science in opioid policy research.

OBJECTIVE: Characterize the state of the science in opioid policy research based on a literature review of opioid policy studies. METHODS: We conducted a scoping review of studies evaluating the impact of U.S. state-level and federal-level policies on opioid-related outcomes published in 2005-2018. We characterized: 1) state and federal policies evaluated, 2) opioid-related outcomes examined, and 3) study design and analytic methods (summarized overall and by policy category). RESULTS: In total, 145 studies were reviewed (79 % state-level policies, 21 % federal-level policies) and classified with respect to 8 distinct policy categories and 7 outcome categories. The majority of studies evaluated policies related to prescription opioids (prescription drug monitoring programs (PDMPs), opioid prescribing policies, federal regulation of prescription opioids, pain clinic laws) and considered policy impacts with respect to proximal outcomes (e.g., opioid prescribing behaviors). In total, only 29 (20 % of studies) met each of three key criteria for rigorous design: analysis of longitudinal data with a comparison group design, adjustment for difference between policy-enacting and comparison states, and adjustment for potentially confounding co-occurring policies. These more rigorous studies were predominately published in 2017-2018 and primarily evaluated PDMPs, marijuana laws, treatment-related policies, and overdose prevention policies. CONCLUSIONS: Our results indicated that study design rigor varied notably across policy categories, highlighting the need for broader adoption of rigorous methods in the opioid policy field. More evaluation studies are needed regarding overdose prevention policies and policies related to treatment access. Greater examination of distal outcomes and potential unintended consequences are also warranted.

Supervised consumption sites: a nuanced assessment of the causal evidence.

BACKGROUND AND AIMS: Supervised consumption sites (SCS) operate in more than 10 countries. SCS have mostly emerged as a bottom-up response to crises, first to HIV/AIDS and now overdose deaths, in ways that make rigorous evaluation difficult. Opinions vary about how much favorable evidence must accumulate before implementation. Our aim was to assess the nature and quality of evidence on the consequences of implementing SCS. METHODS: We reviewed the higher-quality SCS literature, focusing on articles evaluating natural experiments and mathematical modeling studies that estimate costs and benefits. We discuss the evidence through the lens of three types of decision-makers and from three intellectual perspectives. RESULTS: Millions of drug use episodes have been supervised at SCS with no reported overdose deaths; however, uncertainties remain concerning the magnitude of the population-level effects. The published literature on SCS is large and almost unanimous in its support, but limited in nature and the number of sites evaluated. It can also overlook four key distinctions: (1) between outcomes that occur within the facility and possible spillover effects on behavior outside the SCS; (2) between effects of supervising consumption and the effects of other services offered, such as syringe or naloxone distribution; (3) between association and causation; and (4) between effectiveness and the cost-effectiveness of SCS compared to other interventions. CONCLUSIONS: The causal evidence for favorable outcomes of supervised consumption sites is minimal, but there appears to be little basis for concern about adverse effects. This raises the question of how context and priors can affect how high the bar is set when deciding whether to endorse supervised consumption sites. The literature also understates distinctions and nuances that need to be appreciated to gain a rich understanding of how a range of stakeholders should interpret and apply that evidence to a variety of decisions.

Do more robust prescription drug monitoring programs reduce prescription opioid overdose?

BACKGROUND AND AIMS: In the United States, overdose deaths attributed to opioid pain relievers (OPR) have quadrupled since 1999, prompting many states to adopt Prescription Drug Monitoring Programs (PMP). This study aimed to: (1) estimate the relationship of PMP strength with OPR overdose deaths across states and over time; (2) measure what threshold in PMP strength is associated with the greatest reduction in OPR overdose; and (3) assess the relationship of medical marijuana dispensaries with OPR overdose deaths. DESIGN: Panel data from the Centers for Disease Control and Prevention's (CDC's) Wide-ranging Online Data for Epidemiologic Research database (WONDER) were analyzed using fixed effects to regress state-year death rates on an index variable compiled from the Prescription Drug Abuse Policy System (PDAPS) while controlling for PMP administration, demographic factors and laws that might affect OPR overdose. SETTING AND PARTICIPANTS: Age-adjusted opioid overdose death rates for all 50 states and the District of Columbia between 1999 and 2014 for a total of 816 observations. MEASUREMENTS: PMP strength was calculated using legal data compiled by the Prescription Drug Abuse Policy System (PDAPS). In addition to demographic controls, other covariates included laws that regulate pain clinics, access to naloxone, use of emergency services (Good Samaritan Laws) and medical marijuana. FINDINGS: PMP strength was associated negatively with OPR overdose deaths. Every 1-point increase in PMP strength was associated with a 1% [95% confidence interval (CI) = 0.2-2%] reduction in overdose deaths. When collapsed into quartiles, PMPs in the third quartile were associated with an approximately 18% (95% CI = 1.6-29%) reduction in OPR overdose death rates compared with states without a PMP. States with medical marijuana dispensaries reported a 16% (95% CI = 1-30%) reduction in OPR overdoses. CONCLUSIONS: US states that have more robust prescription drug monitoring programs have fewer prescription opioid overdose deaths than states with weaker PMPs. States with medical marijuana dispensaries also report fewer opioid overdose deaths than states without these.

New psychoactive substances: Are there any good options for regulating new psychoactive substances?

Advances in chemistry, technology, and globalization have contributed to the rapid development and diffusion of NPS (new psychoactive substances), creating perhaps the most serious challenge to the century-old international drug control system and to national systems. Very little is known about the effects of these substances which fall outside of national and international controls. The predominant response to the flood of NPS has been the development of more expeditious methods of prohibiting a new chemical entity. This article explores alternative mechanisms that have been considered: foodstuffs, alcohol and tobacco and medicines. None seems promising in terms of avoiding the problems of prohibition without permitting unsafe substances on the market. The article then considers whether there is a bias in the existing system toward excessive prohibition. In public discussion, no attention is given to the pleasures that users obtain from any NPS, to the possibility of substitution for a more dangerous legal or illegal drug or to the consequences of illegal markets for prohibited NPS. On the other hand, it may well be impossible to obtain meaningful assessments on any of these matters at the time when decisions are made. These complexities have led a number of countries, most recently Australia and the UK, to impose total bans, the effects of which are impossible to predict.

Can new psychoactive substances be regulated effectively? An assessment of the British Psychoactive Substances Bill.

The regulation of new psychoactive substances (NPS) has confounded governments throughout the western world. In 2014 the UK government convened an NPS Review Expert Panel to consider a range of approaches. Ultimately the Panel recommended that the government ban all new psychoactive drugs and allow only psychoactive substances specifically exempted, such as alcohol, tobacco and those allowed as medicines. The government introduced the Psychoactive Substances Bill (PSB) in response to that recommendation. Passed in 2016, the Bill has attracted a torrent of criticism from scientists and experts. The Bill could be improved with revision, but the problems of the total ban, as envisioned by the PSB, with respect to the NPS, may be inherent: (1) defining psychoactivity is conceptually fraught, with great consequence for the scope of the prohibition; (2) operationalizing psychoactivity as a usable concept for legal control purposes is extremely difficult, perhaps impossible; and (3) the detachment of penalties for violating a total ban from establishing the harmfulness of a substance is normatively troubling. Given the uncertainties about the effects of a total ban, it is appropriate at this time for other governments to assess more fully the nature of the NPS problem, and the potential control approaches.

The Dangerous Drugs Act Amendment in Jamaica: Reviewing goals, implementation, and challenges.

BACKGROUND: After decades of internal discussion, the Government of Jamaica recently amended its laws to create a regulated and licensed cannabis industry for medical and scientific purposes. The new law also decriminalizes personal possession and use of cannabis; allows cannabis to be used by individuals for religious, medical, scientific and therapeutic purposes; and permits home cultivation of up to five plants. METHODS: We first describe the statutory changes under the Dangerous Drugs (Amendment) Act of 2015 and compare it with other jurisdictions. We provide an analytical framework for understanding how the DDA Amendment affects key populations and achieves its stated goals, drawing on publicly available information and unstructured interviews with non-governmental stakeholders in Jamaica. RESULTS: The Amendment's primary goals are to deliver economic impact and reduce criminal justice costs. A relaxed policy of enforcement toward possession and use seems to have occurred even before the law's passage; after the law's passage, enforcement remains limited. To access medical cannabis under the DDA residents must receive authorization from a certified health professional in Jamaica; tourists may self-declare their medical need; and Rastafarians may grow and exchange non-commercially for religious purposes. CONCLUSION: Internally, many see "ganja" as an industry sorely needed to drive economic growth in Jamaica. Indeed, the potential impacts could be large, especially if Jamaica draws additional tourism or creates a viable export industry. A growing cannabis-related tourism industry seems more realistic. We maintain that policymakers and observers should proceed in an orderly fashion, continuing to identify and resolve remaining uncertainties, initiate new types of data collection, and make decisions based on realistic assessments of potentials for economic impact.