Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement.

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug-testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug-testing postal service with the date, location, purchase intent and co-detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. RESULTS: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug-testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. CONCLUSIONS: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies.

Shifts in drug seizures in the United States during the COVID-19 pandemic.

BACKGROUND: Little is known regarding how the COVID-19 pandemic has affected patterns of drug use in the United States. Because drug seizures can serve as a proxy for drug availability, we examined shifts in drug seizures in the US during the pandemic. METHODS: We examined trends in seizures of marijuana, cocaine, methamphetamine, heroin, and fentanyl within five High Intensity Drug Trafficking Areas-Washington/Baltimore, Chicago, Ohio, New Mexico, and North Florida. Trends were examined for number and total weight of seizures from March 2019 through September 2020 using Joinpoint regression. RESULTS: Significant decreases in seizures involving marijuana (ß = -0.03, P = 0.005) and methamphetamine (ß = -0.02, P = 0.026) were detected through April 2020, and then seizures of marijuana (ß = 0.10, P = 0.028) and methamphetamine (ß = 0.11, P = 0.010) significantly increased through September 2020. The number of seizures involving marijuana and methamphetamine peaked in August 2020, exceeding the highest pre-COVID-19 number of seizures. Fentanyl seizures increased overall (ß = 0.05, P < .001), but did not significantly drop during the start of COVID-19, and significant changes were not detected for cocaine or heroin. We also detected a significant increase in weight of marijuana seized from April through September 2020 (ß = 0.40, P = .001). The weight of marijuana seized in August 2020 exceeded the highest pre-COVID-19 weight. CONCLUSION: The COVID-19 pandemic was associated with an immediate decrease in marijuana and methamphetamine seizures, and then increases throughout 2020 with some months exceeding the number (and weights) of seizures from the previous year. More research is warranted to determine the extent to which these seizures reflect changes in drug use.

The temporal influence of a heroin shortage on pregnant drug users and their newborn infants in Sydney, Australia.

BACKGROUND: Heroin availability and purity decreased precipitously in Australian markets between 2000 and 2001. This led to increased use of non-opiate drugs in the general community but whether pregnant drug users and their newborn infants were affected remains unknown. AIM: To determine if perinatal drug exposure and outcomes are affected by changes in street drug availability. METHODS: Retrospective review was carried out of known drug-exposed mothers delivering live-born infants at the Royal Hospital for Women, Randwick, Australia (n = 316). Study periods were divided into preshortage (A = 1998-2000, n = 79), shortage (B = 2001-2002, n = 92) and post-shortage (C = 2003-2006, n = 122) periods. Cannabis-only users were excluded (n = 23). RESULTS: The percentage of confined women who admitted to using heroin decreased significantly (65%(A) vs 34%(B), P < 0.01) as did women on methadone programmes (90%(A), 80%(B), 75%(C), P = 0.024). The use of cocaine (7% (A) vs 33% (B), P = 0.031) and amphetamines (4% (A) vs 22% (C), P = 0.01), tripled. Most infants were born full-term and healthy but the duration of infant hospitalisation increased significantly from (median [interquartile range]) 8 [10, 38](A) to 13 [7, 23](C) days (P < 0.01). Approximately 50% of infants required withdrawal treatment but more needed phenobarbitone as an adjunct to morphine during the shortage (4/80 (0.5%) vs 15/93 (16%), P = 0.026), probably because of increased exposure to non-opiate drugs. CONCLUSIONS: The types of drugs used by pregnant drug users follow street trends and may affect infant hospitalisation and withdrawal treatment. Of concern is the rise in amphetamine-use and there needs to be increased vigilance for similar trends, especially in previously unidentified drug users.

When does the cutting of cocaine and heroin occur? The first large-scale study based on the chemical analysis of cocaine and heroin seizures in Switzerland.

BACKGROUND: Illicit drug profiling can provide knowledge about illicit drug markets, informing on the level of distribution and its evolution in space and time. Illicit drug profiling is usually limited to impurities originally present in the illicit drug (e.g. alkaloids, co-extracted compounds or by-products). However, the benefit of a comprehensive analysis of cutting agents in drug seizures for law enforcement agencies, intelligence and health policy has not been thoroughly investigated in the literature and is the focus of this research. AIM: This research aims at assessing when and how cutting (i.e. adulteration and dilution) occurs in the supply chain by analysing cocaine and heroin seizures made between 2006 and 2015 in Switzerland. METHODS: Cocaine and heroin seizures made along the supply chain by law enforcement agencies in the Western region of Switzerland were investigated for adulteration and dilution. A total number of 7841 cocaine and 3476 heroin specimens coming from 1341 and 721 seizures, respectively, were analysed. RESULTS: The results show that, for both illicit drugs, adulteration and/or dilution occur before arrival into Switzerland as well as in Switzerland. While cocaine is adulterated and diluted, heroin is only adulterated. Interestingly, the same mixture of adulterants (i.e. caffeine-paracetamol) is used to cut heroin at each step in the supply chain. CONCLUSION: Gaining knowledge about adulteration and dilution at different stages in the supply chain enhances our understanding of drug markets. It also highlights differences along the supply chain and in the distribution of both drugs in Switzerland.

Illicit fentanyls in the opioid street market: desired or imposed?

BACKGROUND: Illicitly manufactured fentanyl and its analogues are appearing in countries throughout the world, often disguised as heroin or counterfeit prescription pills, with resulting high overdose mortality. Possible explanations for this phenomenon include reduced costs and risks to heroin suppliers, heroin shortages, user preferences for a strong, fast-acting opioid and the emergence of Dark Web cryptomarkets. This paper addresses these potential causes and asks three questions: (1) can users identify fentanyl; (2) do users desire fentanyl; and (3) if users want fentanyl, can they express this demand in a way that influences the supply? ARGUMENT/ANALYSIS: Existing evidence, while limited, suggests that some users can identify fentanyl, although not reliably, and some desire it, but because fentanyl is frequently marketed deceptively as other drugs, users lack information and choice to express demand effectively. Even when aware of fentanyl's presence, drug users may lack fentanyl-free alternatives. Cryptomarkets, while difficult to quantify, appear to offer buyers greater information and competition than offline markets. However, access barriers and patterns of fentanyl-related health consequences make cryptomarkets unlikely sources of user influence on the fentanyl supply. Market condition data indicate heroin supply shocks and shortages prior to the introduction of fentanyl in the United States and parts of Europe, but the much lower production cost of fentanyl compared with heroin may be a more significant factor CONCLUSION: Current evidence points to a supply-led addition of fentanyl to the drug market in response to heroin supply shocks and shortages, changing prescription opioid availability and/or reduced costs and risks to suppliers. Current drug users in affected regions of the United States, Canada and Europe appear largely to lack both concrete knowledge of fentanyl's presence in the drugs they buy and access to fentanyl-free alternatives.

Sold as Heroin: Perceptions and Use of an Evolving Drug in Baltimore, MD.

Since 2001, heroin-related overdose deaths in the United States have risen six-fold, a rise unaccounted for by the expanding user population. Has heroin become a more dangerous drug? Reports of fentanyl and its analogs, often concealed in or sold as heroin, have also increased sharply. This article investigates heroin injectors' perceptions and experiences of changes in the heroin supply in the East Coast city of Baltimore, Maryland, currently facing an epidemic in heroin- and fentanyl-related overdose deaths. Unusually, Baltimore's heroin market is divided between two types: "Raw," believed to be Colombian in origin and relatively pure, and the more adulterated "Scramble" (raw heroin traditionally blended with quinine and lactose). Users reported that Scramble heroin, while gaining market share, has become a highly unstable product, varying dramatically in appearance, intensity of onset, duration of action, and effect. Some considered that Scramble was no longer "heroin," but was heavily adulterated or even replaced, mentioning fentanyl, benzodiazepines, and crushed opioid pills as additives. There was intense awareness of overdose as a present danger in users' lives, which they linked to the recent adulteration of the heroin supply. Responses to this perceived adulteration varied, including information gathering, attraction, avoidance, taking precautions, and acceptance.

Impact of a reduction in heroin availability on patterns of drug use, risk behaviour and incidence of hepatitis C virus infection in injecting drug users in New South Wales, Australia.

In early 2001, Australia experienced a sudden and dramatic reduction in the availability of heroin. Research examining the impact of the reduction on drug-related harms has yielded a conflicting picture. The current study uses data from a prospective cohort study of anti-HCV negative injecting drug users (IDU) (n=368) to examine patterns of injecting drug use, risk behaviours and HCV incidence before and after the reduction. The proportion of participants mainly injecting heroin declined sharply from 74% to 47% after the onset of the reduction and continued throughout 2001. There was marked shift to other drugs, mainly cocaine and amphetamine. Cocaine injectors had the highest risk profile and the highest incidence of HCV (82.6 per 100 person years, 95% CI 52.0-131.0). While HCV seroconversions increased by year, this increase was not statistically significant. We observed a reduction in heroin injection and a concomitant increase in cocaine injection and a significant association between cocaine injection and incident HCV infection during a period of reduced heroin availability. Results suggest that attempts to suppress drug markets by manipulating availability may result in collateral damage in the form of drug-related harms, indicating a need for more sophisticated understandings of the potential trade-offs involved in attempting to suppress the supply of illicit drugs.

The hidden web and the fentanyl problem: Detection of ocfentanil as an adulterant in heroin.

BACKGROUND: The popularization of anonymous markets such as Silk Road is challenging current drug policy and may provide a new context for old issues, such as adulteration of heroin with fentanyl derivatives. The aims of this paper are to report the presence of ocfentanil, a novel, potent, non-controlled fentanyl analog, in samples sold as heroin in the hidden web, and to summarize the effects reported by users. METHODS: In 2015, four samples allegedly bought as heroin in cryptomarkets of the hidden web were sent to Energy Control for analysis. Energy Control is a Spanish harm reduction NGO that offers anonymous drug checking with the purpose of adapting counselling to the specific substances present in the drug and monitor the drug market. Identification was performed by GC/MS and LC/MS/MS. We contacted the submitters of the samples and performed an Internet search to retrieve additional information. RESULTS: One sample contained ocfentanil, caffeine and heroin. Three samples contained the aforementioned substances plus paracetamol. Two out of the four contacted users reported distinct short acting, opioid-like effects. No fora discussion could be found about the effects of ocfentanil, neither web pages nor individuals advertising the substance. CONCLUSION: We report the presence of a new substance detected in the hidden web as an adulterant of heroin, ocfentanil. It has short acting opioid-like effects, roughly the same potency as fentanyl, and can be injected, snorted or smoked. Severe side effects have been associated with its use, including one death. No discussion about this substance could be found in the Internet, which suggests this substance has not been sold as such. Available data about purities of drugs purchased in cryptomarkets suggest that adulteration is not a severe problem and this agrees with users' perceptions. However, this study suggests that adulteration is a real threat not only at the street level, but also for users that buy substances in cryptomarkets, and suggest the need for harm reduction initiatives in this setting.

Silicon to syringe: Cryptomarkets and disruptive innovation in opioid supply chains.

Cryptomarkets offer insight into the evolving interplay between online black markets and cartel-based distribution. The types and forms of heroin, fentanyl, and prescription drugs show wide diversification. In this commentary we describe changes in the conceptualizations, technologies and structures of drug supply chains in the 21st Century, with special attention to the role of cryptomarkets as tools, contexts, and drivers of innovation in public health research.

Today's fentanyl crisis: Prohibition's Iron Law, revisited.

More than a decade in the making, America's opioid crisis has morphed from being driven by prescription drugs to one fuelled by heroin and, increasingly, fentanyl. Drawing on historical lessons of the era of National Alcohol Prohibition highlights the unintended, but predictable impact of supply-side interventions on the dynamics of illicit drug markets. Under the Iron Law of Prohibition, efforts to interrupt and suppress the illicit drug supply produce economic and logistical pressures favouring ever-more compact substitutes. This iatrogenic progression towards increasingly potent illicit drugs can be curtailed only through evidence-based harm reduction and demand reduction policies that acknowledge the structural determinants of health.

Association between availability of heroin and methadone and fatal poisoning in England and Wales 1993-2004.

BACKGROUND: The UK heroin market is the biggest in Europe and approximately 70% of heroin deaths are due to fatal poisoning. Methadone treatment for heroin addiction in the UK, the 'British system', is unique as it is largely provided by General Practitioners. METHODS: The Office for National Statistics provided data on deaths, the Home Office provided law enforcement data on drug seizures and the Department of Health data on prescriptions. For methadone treatment we calculated the death rate per 1000 patient years. We used Spearman's rank correlation to assess the association between illicit drug seizures for heroin and methadone and deaths. RESULTS: Between 1993 and 2004 there were 7072 deaths involving heroin/morphine (86% males) and 3298 deaths involving methadone (83% male). From 1993-1997, directly age-standardized mortality rates for males were similar for both drugs, increasing from approximately 5 to 15 per million. Mortality rates for heroin continued to increase until 2000, subsequently decreasing from 30 to 20 per million by 2003, and rising again to 24 per million in 2004. In contrast, mortality rates for methadone decreased between 1997 and 2004 to just above 1993 levels. Among females the mortality rate for both drugs was lower than for males throughout the study period, remaining relatively stable. Methadone deaths per 1000 patient years remained similar between 1993 and 1997, after which they fell by three quarters. For both heroin/morphine and methadone, deaths were strongly associated with seizures (Spearmans' coefficient for males: heroin, P = 0.95, P < 0.001 and methadone, P = 0.83, P = 0.0013). CONCLUSIONS: Our study suggests the 'British System' can deliver substantial expansion of treatment without increased mortality risk. The fall in heroin/morphine deaths since 2000 may also be an indication of success of increasing methadone treatment. Data on mortality risk is needed to determine whether increased methadone treatment has reduced drug-related deaths.

Changes in Canadian heroin supply coinciding with the Australian heroin shortage.

AIMS: Previous studies have largely attributed the Australian heroin shortage to increases in local law enforcement efforts. Because western Canada receives heroin from similar source nations, but has not measurably increased enforcement practices or funding levels, we sought to examine trends in Canadian heroin-related indices before and after the Australian heroin shortage, which began in approximately January 2001. METHODS: During periods before and after January 2001, we examined the number of fatal overdoses and ambulance responses to heroin-related overdoses that required the use of naloxone in British Columbia, Canada. As an overall marker of Canadian supply reduction, we also examined the quantity of heroin seized during this period. Lastly, we examined trends in daily heroin use among injection drug users enrolled in the Vancouver Injection Drug Users Study (VIDUS). RESULTS: There was a 35% reduction in overdose deaths, from an annual average of 297 deaths during the years 1998-2000 in comparison to an average of 192 deaths during 2001-03. Similarly, use of naloxone declined 45% in the period coinciding with the Australian heroin shortage. Interestingly, the weight of Canadian heroin seized declined 64% coinciding with the Australian heroin shortage, from an average of 184 kg during 1998-2000 to 67 kg on average during 2001-03. Among 1587 VIDUS participants, the period coinciding with the Australian heroin shortage was associated independently with reduced daily injection of heroin [adjusted odds ratio: 0.55 (95% CI: 0.50-0.61); P < 0.001]. CONCLUSIONS: Massive decreases in three independent markers of heroin use have been observed in western Canada coinciding with the Australian heroin shortage, despite no increases in funding to Canadian enforcement efforts. Markedly reduced Canadian seizure activity also coincided with the Australian heroin shortage. These findings suggest that external global heroin supply forces deserve greater investigation and credence as a potential explanation for the Australian heroin shortage.

Using intervention time series analyses to assess the effects of imperfectly identifiable natural events: a general method and example.

BACKGROUND: Intervention time series analysis (ITSA) is an important method for analysing the effect of sudden events on time series data. ITSA methods are quasi-experimental in nature and the validity of modelling with these methods depends upon assumptions about the timing of the intervention and the response of the process to it. METHOD: This paper describes how to apply ITSA to analyse the impact of unplanned events on time series when the timing of the event is not accurately known, and so the problems of ITSA methods are magnified by uncertainty in the point of onset of the unplanned intervention. RESULTS: The methods are illustrated using the example of the Australian Heroin Shortage of 2001, which provided an opportunity to study the health and social consequences of an abrupt change in heroin availability in an environment of widespread harm reduction measures. CONCLUSION: Application of these methods enables valuable insights about the consequences of unplanned and poorly identified interventions while minimising the risk of spurious results.

Identification and quantification of change in Australian illicit drug markets.

BACKGROUND: In early 2001 Australia experienced a sudden reduction in the availability of heroin which had widespread effects on illicit drug markets across the country. The consequences of this event, commonly referred to as the Australian 'heroin shortage', have been extensively studied and there has been considerable debate as to the causes of the shortage and its implications for drug policy. This paper aims to investigate the presence of these epidemic patterns, to quantify the scale over which they occur and to estimate the relative importance of the 'heroin shortage' and any epidemic patterns in the drug markets. METHOD: Key indicator data series from the New South Wales illicit drug market were analysed using the statistical methods Principal Component Analysis and SiZer. RESULTS: The 'heroin shortage' represents the single most important source of variation in this illicit drug market. Furthermore the size of the effect of the heroin shortage is more than three times that evidenced by long-term 'epidemic' patterns. CONCLUSION: The 'heroin shortage' was unlikely to have been a simple correction at the end of a long period of reduced heroin availability, and represents a separate non-random shock which strongly affected the markets.

Examining links between cocaine use and street-based sex work in New South Wales, Australia.

We examined potential links between cocaine use and street-based sex work in New South Wales (NSW), Australia, following reports of increased cocaine use among injection drug users (IDU). Police data on prostitution and possession/use of cocaine was analysed using time series analysis. Interviews with key informants and IDU were also conducted, and data on cocaine use from ongoing monitoring systems targeted at IDU were analysed. There was a clear increase in cocaine use among IDU which occurred in 2001. This occurred at the same time as an increase in prostitution offenses. Qualitative data suggested that a greater number of primary heroin users were engaging in street-based sex work, which was driven in part by the increases in cocaine use among this group. Subsequent reductions in cocaine availability led to decreased cocaine use and possession offenses, along with reductions in prostitution offenses.

Documenting the heroin shortage in New South Wales.

Australian heroin markets have recently undergone dramatic change, sparking debate about the nature of such markets. This study aimed to determine the onset, peak and decline of the heroin shortage in New South Wales (NSW), using the most appropriate available methods to detect market level changes. The parameters of the heroin shortage were determined by reviewing: reports of heroin users about availability and price (derived from the existing literature and the Illicit Drug Reporting System); qualitative interviews with injecting drug users, and health and law enforcement professionals working in the illicit drug field; and examining data on heroin seizures over the past decade. There was a marked reduction in heroin supply in NSW in early 2001. An increase in the price of heroin occurred in 2001, whereas it had decreased steadily since 1996. A reduction in purity also occurred, as reported by drug users and heroin seizures. The peak period of the shortage appears to have been January to April 2001. The market appears to have stabilised since that time, although it has not returned to pre-2001 levels: heroin prices have decreased in NSW for street grams, but not to former levels, and the price of 'caps' (street deals) remain elevated. Heroin purity in NSW has remained low, with perhaps a 10% increase above the lowest recorded levels. These data support the notion that the heroin market in NSW underwent significant changes, which appear to have involved a lasting shift in the nature of the market.

Changes in the initiation of heroin use after a reduction in heroin supply.

Increasing heroin use in Australia over the past 30 years has been associated with a decline in the age of initiation to heroin use. The 2001 Australian heroin shortage was used to assess the effects of a reduction in heroin supply on age of initiation into heroin injecting. Data collected from regular injecting drug users (IDU) over the period 1996 - 2004 as part of the Australian Illicit Drug Reporting System were examined for changes in self-reported age of first heroin use after the onset of the heroin shortage. Estimates were also made of the number of young people who may not have commenced injecting heroin during the heroin shortage. The proportion of IDU interviewed in the IDRS who were aged