Harm Reduction and Risk Management

"Harm reduction is a set of practical strategies and ideas aimed at reducing negative consequences associated with drug use.

"Harm Reduction is also a movement for social justice built on a belief in, and respect for, the rights of people who use drugs.

"FOUNDATIONAL PRINCIPLES CENTRAL TO HARM REDUCTION

"Harm reduction incorporates a spectrum of strategies that includes safer use, managed use, abstinence, meeting people who use drugs 'where they’re at,' and addressing conditions of use along with the use itself. Because harm reduction demands that interventions and policies designed to serve people who use drugs reflect specific individual and community needs, there is no universal definition of or formula for implementing harm reduction.

"However, National Harm Reduction Coalition considers the following principles central to harm reduction practice:

"Accepts, for better or worse, that licit and illicit drug use is part of our world and chooses to work to minimize its harmful effects rather than simply ignore or condemn them

"Understands drug use as a complex, multi-faceted phenomenon that encompasses a continuum of behaviors from severe use to total abstinence, and acknowledges that some ways of using drugs are clearly safer than others

"Establishes quality of individual and community life and well-being — not necessarily cessation of all drug use — as the criteria for successful interventions and policies

"Calls for the non-judgmental, non-coercive provision of services and resources to people who use drugs and the communities in which they live in order to assist them in reducing attendant harm

"Ensures that people who use drugs and those with a history of drug use routinely have a real voice in the creation of programs and policies designed to serve them

"Affirms people who use drugs (PWUD) themselves as the primary agents of reducing the harms of their drug use and seeks to empower PWUD to share information and support each other in strategies which meet their actual conditions of use

"Recognizes that the realities of poverty, class, racism, social isolation, past trauma, sex-based discrimination, and other social inequalities affect both people’s vulnerability to and capacity for effectively dealing with drug-related harm

"Does not attempt to minimize or ignore the real and tragic harm and danger that can be associated with illicit drug use"

"A 2014 meta-analysis of 75 studies concluded that OPCs have largely fulfilled their initial objectives;³⁹ the implementation of new OPCs in places with high rates of IDU and its associated harms appears to be supported by the existing evidence.³⁹ Methodological caveats notwithstanding, drug use supervision and overdose management have the potential to provide health benefits to at-risk PWID as well as economic advantages to the larger community. The preponderance of the evidence suggests these sites are able to provide sterile equipment, overdose reversal, and linkage to medical care for addiction, in the virtual absence of significant direct risks like increases in drug use, drug sales, or crime. OPCs may represent a novel way of addressing some of the many challenges presented by the overdose crisis, and they could contribute to reduced morbidity and mortality, and improved public health.

"Based on the above considerations, there is a clear need for more rigorous research and evaluation of OPCs. Given the amount and quality of the existing data, it may be prudent to consider the American Medical Association’s recommendation of developing and implementing OPC pilot programs in the United States designed, monitored, and evaluated to generate locality-relevant data to inform policymakers on the feasibility and effectiveness of OPCs in reducing harms and health care costs related to IDU.⁹⁴

"Our review found at the individual-level that SCFs were efficacious in reducing drug use related infection and disease transmission, enhancing access to addiction and other health services, and reducing the risk of non-fatal overdoses, and were not associated with a significant increase in drug use. These findings challenge the notion that SCFs may perpetuate substance use and lead to increased use among PWID. With regard to non-fatal overdose, the evidence over the past ten years have been largely been qualitative and would benefit from the use of quantitative methods that help to approximate causality. For example, the use of a propensity score modeling may help to determine the effectiveness of SCFs for individual-level outcomes based on observational or cross-sectional data (Hullsiek and Louis, 2002). Future studies may also want to consider the use of comparison groups or cities to examine the different factors influencing the effectiveness of SCFs. Additionally, we found emerging evidence that SCFs provide PWID with a sense of community that may support their overall wellbeing, thereby increasing their chances of accessing addiction treatment services. However, this evidence came qualitative studies (Rance and Fraser, 2011; Jozaghi and Andresen, 2013; Davidson et al., 2018; Kerman et al., 2020), and provides a future direction for research examining the impact of SCFs."

"Future quantitative studies may want to include a validated measure of wellbeing and sense of belonging. In particular, longitudinal studies should examine the degree to which a sense of belonging and having a supportive community may play a role in injection cessation and help-seeking behaviors for SCF attenders. At the community level, the evidence shows that SCFs were not associated with an increased rate of drug-related crime, and were linked to a decrease use of other costly public services (e.g. ambulance transport to hospital following an overdose). However, this evidence is still growing and requires additional research that accounts for other cofounding relationships using a longitudinal, inferential research design. Furthermore, we found that SCFs were associated with a reduction in public disorder, including less public disposal of syringes and use in public spaces. Future research should consider the gathering information from multiple sources (e.g. community members, service providers, police services) to examine the impact of SCFs on the public. Finally, there appear to be significant cost-benefits associated with SCFs, yet all of these studies have focused on the benefits related to the reduction of infectious disease transmission and injection-related death. Future studies should consider additional benefits related to the families of SCF attenders and reduction in community costs associated with decrease in public disorder."

"Harm reduction refers to interventions aimed at reducing the negative effects of health behaviors without necessarily extinguishing the problematic health behaviors completely or permanently. Though the harm reduction model as we know it rose in prominence in the 1970s and 1980s in response to infectious diseases such as hepatitis B and HIV [1], its roots extend at least as far back as the early 1900s with narcotic maintenance clinics [2, 3]. In the context of substance use, harm reduction disentangles the notion that drug use equals harm and instead identifies the negative consequences of drug use as the target for intervention rather than drug use itself [4]. Harm reduction strategies include syringe exchange programs, safer injection facilities, overdose prevention programs and policies, and opioid substitution treatment. Harm reduction as an approach stands in opposition to the traditional medical model of addiction which labels any illicit substance use as abuse, as well as to the moral model, which labels drug use as wrong and therefore illegal [5]. While most often applied in treatment for illicit substance use, harm reduction is increasingly used in many different settings, with a variety of populations, and in instances where there is a desire to reduce the negative effects of legal/licit substances, such as in tobacco smoking reduction and e-cigarette substitution programs [6, 7], in programs to reduce the harms associated with alcohol [6, 8, 9], in interventions addressing eating disorders or domestic violence [10], or with people who exchange sex for drugs, money, or material goods [11,12,13]. Nevertheless, harm reduction has not been formally incorporated into the daily repertoires of healthcare providers who aim to improve health behaviors (e.g., physical activity, nutrition) among their patients."

"A public health intervention operating for more than 50 years, drug checking services (DCS) allow the public to submit drug samples from unregulated drug markets (i.e. illegal and legal drugs sold through criminal channels) for chemical analysis. DCS emerged across the United States in the late 1960s and early 1970s during the rise of a psychedelic counterculture that championed the use of psychoactive substances to expand consciousness [1, 2]. DCS were later expanded in European settings throughout the 1990s, beginning in the Netherlands, primarily in response to the popularity of dance events and associated use of 3,4-methylenedioxymethamphetamine (MDMA) and other drugs [3, 4]. More recently, DCS have been implemented in Australasia, the Americas and the United Kingdom, often with an emphasis on preventing harms from new psychoactive substances (NPS), including synthetic opioids. A global review of DCS conducted in 2017 identified 31 services operating across 20 countries [5]. Notably, the contamination of unregulated drug markets with fentanyl and the resulting opioid overdose crisis has motivated the recent expansion of DCS in Canada [6] and the United States [7].

"DCS provide people who use drugs (PWUD) with information on the chemical composition of their drug samples to facilitate more informed decision-making [8]. While some analysis methods can be operated by PWUD, DCS typically offer tailored harm reduction advice with the provision of analysis results to PWUD [9]. By aggregating data on the composition of drug samples, DCS provide insight into trends in the unregulated drug supply and inform policymaking and harm reduction activities at the population level [10]. DCS can inform public health alerts [11] when drugs of concern are detected, thus offering potential benefits to the broader community of PWUD and service providers [12]. DCS differ globally in terms of their legality and degree of government support, as well as where and how samples are collected and analysed. Models include mobile services at events, fixed services where samples can be dropped off or mailed and the distribution of analysis methods for personal use, all of which employ a variety of technologies with differing benefits and drawbacks [8, 13, 14]."

"Studies found that DCS [Drug Consumption Services] influenced intended behaviour and, although less researched, enacted behaviour. Among studies of PWUD [People Who Use Drugs] in party settings (referred to as ‘partygoers’ in studies), greater intention to not use the analysed substance was consistently reported if analysis results were unexpected [33, 35, 40, 42, 43, 45, 48, 52] or ‘questionable’/‘suspicious’ [49–51]. For example, a cross-sectional study from Australia (n = 83) in 2018 found partygoers were more likely to change their intention to use when analysis results were unexpected [odds ratio (OR) = 2.63, 95% confidence interval (CI) = 0.85–8.16] [35], as did two cross-sectional studies from Portugal (n = 310, n = 100) in 2016 and 2014 [40, 43]. Similarly, other intended behaviour changes—such as using less of a substance or seeking more information about it—were more common among partygoers when analysis results from DCS suggested that substances were ‘questionable’/‘suspicious’ [49, 51].

"The proportion of participants reporting analysis results from DCS influenced their drug use varied by population and setting. Among partygoers, 16% of participants in the Netherlands in 1996 [29], 50% in Austria in 1997–99 [37] and 87% in New Zealand (n = 47) in 2018–19 [33] reported that analysis results impacted their drug use. A cross-sectional study in 2017 from the United States among people who inject drugs (n = 125) found 43% changed their behaviour, and this was more likely when fentanyl was detected [adjusted OR (aOR) = 5.08, 95% CI = 2.12–12.17] [22]. Qualitative and longitudinal studies of young PWUD (n = 81) in the United States in 2017 supported this finding, and found that fentanyl detection was associated with positive changes in overdose risk behaviours (i.e. using less, using with others, doing a test shot) [31, 34]. Overall, and in alignment with findings on intended drug use behaviour in response to ‘questionable’/‘suspicious’ analysis results, self-reported behaviour was more likely to change when analysis results detected fentanyl. Beyond individual analysis results, a repeated cross-sectional study from Colombia (n = 1533) in 2013 and 2016 examined the influence of alerts from DCS and found that a majority of partygoers reported an impact on their behaviour [36].

"Only one study linked intended behaviours to observed health outcomes for PWUD accessing DCS. A Canadian cross-sectional study of DCS at a supervised injection site (n = 1411) in 2016–17 found that people who inject drugs were more likely to report the intention to use a smaller quantity than usual when fentanyl was detected by DCS (OR = 9.36, 95% CI = 4.25–20.65) [41]. In turn, those intending to use a smaller quantity were found to be less likely to overdose (OR = 0.41, 95% CI = 0.18–0.89) and be administered naloxone (OR = 0.38, 95% CI = 0.15–0.96).

"Disposal of the analysed substance was observed [24, 26, 27, 32, 35] or self-reported [22, 31, 34] as an outcome of DCS in eight studies. Like other behaviours, disposal was more frequent when analysis results from DCS were unexpected [24, 27, 32, 52]."

"We observed that the increase in crack pipe distribution services coincided with a corresponding increase in the uptake of crack pipes obtained through health service points only. Further, rates of reporting health problems associated with crack smoking declined significantly after the crack pipe distribution program was implemented. In the multivariable analysis, compared to obtaining crack pipes through other non-health service sources only, obtaining pipes through health service points only was significantly and negatively associated with reporting health problems from smoking crack. These findings suggest that the recent expansion of crack pipe distributions in this setting has likely served to reduce health problems experienced by crack smokers, achieving the desired outcome of the program.

"While crack users are obtaining their safe crack smoking equipment from health service points, they may also be exposed to education around safer smoking techniques and practices, by being in direct contact with service providers in the community. This may also have the benefit of exposing drug users with no connections to health care to available providers in their area [27]. A previous study of an outreach-based crack smoking kit distribution service indicated that unsafe smoking practices such as using Brillo pads and sharing crack paraphernalia remained prevalent, even after the implementation of the service [10], suggesting the importance of placing such service in a continuum of broader health service system and ensuring the availability of smoking kits to reduce risky smoking behaviours."

"Our findings of a reduction of health problems, are consistent with harm reduction programs for people who inject drugs [19], including needle exchange programs and supervised injection sites, where they are effective in reducing overall negative health consequences. By providing users with high-quality smoking equipment and reducing the dependence on unsafe equipment, the unintended negative consequences, including exploding pipes, burns, and inhaling brillo fragments, are further reduced."

"Between November 30, 2021, and January 31, 2022, 613 individuals used OPC services 5975 times across 2 sites. Most individuals identified as male (78.0%), and 55.3% identified as Hispanic, Latino, or Latina. The mean (range) age was 42.5 (18-71) years. A plurality of individuals (36.9%) reported being street homeless. Fewer than one-fifth of individuals (17.8%) were living in their own rooms or apartments (Table).

"In self-reported data, the drug most commonly used across 2 sites was heroin or fentanyl (73.7%) and the most frequent route of drug administration at the OPC was injection (65.0%). Among all participants, 75.9% reported that they would have used their drugs in a public or semipublic location if OPC services had not been available (Figure).

"During the first 2 months of OPC operation, trained staff responded 125 times to mitigate overdose risk. In response to opioid-involved symptoms of overdose, naloxone was administered 19 times and oxygen 35 times, while respiration or blood oxygen levels were monitored 26 times. In response to stimulant-involved symptoms of overdose (also known as overamping), staff intervened 45 times to provide hydration, cooling, and de-escalation as needed. Emergency medical services responded 5 times, and participants were transported to emergency departments 3 times. No fatal overdoses occurred in OPCs or among individuals transported to hospitals.

"More than half of individuals using OPC services (52.5%) received additional support during their visit. This included, but was not limited to naloxone distribution, counseling, hepatitis C testing, medical care, and holistic services (eg, auricular acupuncture)."

"Increasingly, SCS are incorporating services to address the risks associated with consuming adulterated drugs from the toxic drug supply. These services include incorporating drug checking services [60, 61] and the provision of pharmaceutical grade alternatives to street drugs (e.g., safe supply) [62, 63]; although these services are largely targeted to people who use opioids and often do not address the needs of people who use stimulants [64]. As these services are relatively recent developments, they were not discussed in the included articles and therefore the extent to which they are incorporated within SCS that allow non-injection routes of consumption remains unclear. However, the current emphasis on innovative solutions to the overdose crisis [65] highlights the need for SCS to be responsive to the needs of their participants. Furthermore, the current COVID-19 pandemic has also demonstrated the importance of flexibility in response to the evolving needs of SCS participants [66]. People who smoke illegal drugs may be particularly at risk for complications associated with respiratory illness [67]. Many people who use drugs have been impacted by sudden closures of their SCS due to their inability to meet public health directives [68, 69], while other SCS had to reduce their capacity to meet physical distancing requirements [70]. The operational characteristics of both injection and non-injection SCS should be flexible and continuously adapted to address local needs and context."

"Supervised inhalation rooms (SIR) have the potential to minimise the aforementioned barriers to care and harms associated with crack cocaine smoking [12,21]. Modelled after supervised injection facilities, SIRs are regulated environments in which people can smoke pre-obtained drugs with sterile equipment under the supervision of nurses or other trained staff [22]. These facilities aim to reduce high-risk drug use practices and blood-borne infections, increase contact between PWUD and health and social services, and improve public order through reductions in public drug use [23]. To date, SIRs have been implemented in seven countries: Canada, Germany, Luxembourg, Netherlands, Switzerland, Spain and France [24–26]. In contrast with the significant evidence of the health and community benefits of supervised injection sites, rigorous evaluation of the specific outcomes of SIRs is lacking [24,27]. However, it is plausible that many of the demonstrated health benefits associated with supervised injection sites could extend to SIRs, with available evidence suggesting that SIRs have potential to improve public order, connect PWUD with health and social services, and reduce drug-related harms [11,25]."

"The period from 2020 to 2022 has seen increased uptake of harm reduction interventions. For the first time since 2014, the Global State of Harm Reduction has found an increase in the number of countries implementing key harm reduction services.

"This growth has been driven by new needle and syringe programmes (NSPs) opening in five African countries as well as four new countries having officially sanctioned drug consumption rooms (DCRs).a This includes a site in Mexico that had been operating without formal approval since 2018 but now has approval from local authorities. Three countries have introduced opioid agonist therapy (OAT) for the first time.

"No country has stopped the implementation of NSP, OAT [Opiate Assisted Treatment] or DCRs since 2020."

On November 30, 2021, the Office of the Mayor of the City of New York announced that "the first publicly recognized Overdose Prevention Center (OPC) services in the nation have commenced in New York City. OPCs are an extension of existing harm reduction services and will be co-located with previously established syringe service providers."

According to the release:
"OPCs, also referred to as supervised consumption sites or facilities, are safe places where people who use drugs can receive medical care and be connected to treatment and social services. OPC services are proven to prevent overdose deaths, and are in use in jurisdictions around the world. There has never been an overdose death in any OPC. A Health Department feasibility study found that OPCs in New York City would save up to 130 lives a year.

"Additionally, OPCs are a benefit to their surrounding communities, reducing public drug use and syringe litter. Other places with OPCs have not seen an increase in crime, even over many years.

"OPCs will be in communities based on health need and depth of program experience. A host of City agencies will run joint operations focused on addressing street conditions across the City, and we will include an increased focus on the areas surrounding the OPCs as they open."

"We estimated nearly 3.7 million people, or 1.5% of the US adult population, injected drugs in 2018. This estimate is more than 5 times the most recent US estimate of ∼774,000 from 2011 [25]. Much of this increase is likely attributable to increases in IDU, but it is important to consider methodological differences in the creation of this 2018 estimate vs the 2011 estimate. The 2011 estimate was based on self-reported IDU among respondents to household surveys [26], but the present estimate combines available data on substance-specific overdose deaths and treatment admissions with cohort and cross-sectional data collected from known PWID. Applying the same data sources and analytic methods used for the 2018 estimate to 2011 yields an estimated 1.3 million PWID in 2011, which suggest the 2018 estimate is closer to 3 times higher than in 2011. By any measure, these estimates suggest the number of PWID has increased substantially in the U.S. during the past decade.

"One of the primary contributions of this estimate is the transparent, replicable nature of the methods described. Overdose data specifically among PWID in the United States continue to be relatively sparse, both in research and surveillance data. We used the best data currently available for each input, which are subject to limitations in some cases given data sparsity. For example, we used the meta-analyzed ratio of fatal to nonfatal overdose among PWID in OECD countries rather than a ratio specific to the United States, which was unattainable given currently available data. The uncertainty associated with this meta-analyzed ratio is reflected in confidence intervals around estimates presented here. Our intention is that, as surveillance systems implemented in the United States in recent years mature [39], resulting data can be used to refine and update this PWID population size estimate.

"Notwithstanding data input limitations, this updated estimate provides a data point for monitoring the US PWID population size over time and can inform strategies to reduce transmission of infectious diseases. In recent years, political will has been building to eliminate HCV and HIV infections in the United States [27, 28]. Both bloodborne infections disproportionately affect PWID but are highly preventable using evidence-based interventions, such as provision of sterile syringes through syringe services programs and substance use treatment [40–43], as well as treatment of prevalent infections with antiretroviral therapy [44] and direct-acting antivirals [45]. Increases in IDU prevalence will threaten the success of elimination strategies for HCV and HIV infections in the absence of concomitant increases in availability of harm reduction services and treatment for both infectious diseases and substance use. These services will need to be substantially scaled up nationally to meet the needs of nearly 4 million people [46].

"In addition to the high burden of infectious diseases, PWID experience preventable mortality and morbidity due to drug overdose. Overall, the rate of overdose deaths increased from approximately 6 per 100,000 persons to 22 per 100,000 persons during 1999–2019 [21], and provisional data indicate the number of overdose deaths increased by another 31% during just 1 year of the pandemic era from March 2020 to March 2021 [24]. During the pandemic era in particular, many questions remain about the extent to which increased overdose mortality rates are attributable to injection initiation vs changes in injection behaviors or the drug supply as well as to disruptions in access to treatment and recovery support services and harm reduction services. These estimates provide a prepandemic baseline and can improve our understanding of potential increases vs changes in pandemic-era injection behavior."

"Gov. Dan McKee has signed legislation introduced by Majority Floor Manager John G. Edwards (D-Dist. 70, Tiverton, Portsmouth) and Sen. Joshua Miller (D-Dist. 28, Cranston, Providence) that authorizes a two-year pilot program to prevent drug overdoses through the establishment of harm reduction centers, which are a community-based resource for health screening, disease prevention and recovery assistance where persons may safely consume pre-obtained substances.

"The law (2021-H 5245A, 2021-S 0016B) authorizes facilities where people may safely consume those substances under the supervision of health care professionals. It requires the approval of the city or town council of any municipality where the center would operate."

"Harm reduction is a collection of concepts and strategies that can be used to reduce adverse health consequences associated with drug use [1]. Harm reduction strategies can be conceptualized as a continuum of approaches from safer drug use practices to abstinence, with an underlying core ethos of a desire to meet people where they are at. As an alternative to the “zero tolerance” abstinence-only models of addiction treatment, the harm reduction model recognizes that abstinence may not be a desirable or achievable outcome for all people who use drugs [2]. Thus, practical strategies are necessary to reduce health-related harms associated with drug use (e.g., viral transmission of Human immunodeficiency virus (HIV) and Hepatitis C (HCV) through shared drug use equipment, fatal and nonfatal overdose), rather than exclusively targeting drug consumption itself [3,4,5,6,7]."

"Fentanyl test strips (FTS) emerged in this context as a drug checking tool to address the burgeoning fentanyl crisis. FTS was originally developed as a field immunoassay to screen for the presence of fentanyl in urine, but harm reduction organizations discovered that FTS can also detect fentanyl in illicit drug solutions. This realization has led many harm reduction organizations to distribute FTS to people who consume street opioids as an off-label approach to test street drugs for fentanyl (Peiper et al., 2019). Research published during this early period exposed a growing concern of unwitting fentanyl exposure among heroin consumers and a general willingness to use FTS. Studies showed a high percentage of PWID were interested in using FTS to test heroin (Allen et al., 2020; Krieger, Goedel, et al., 2018; Park et al., 2021; Sherman et al., 2019) and syringe services programs were making them increasingly available alongside naloxone in OD prevention kits (Beharie et al., 2023).

"Of particular significance were a handful of studies showing PWID modifying their drug use behavior upon receiving positive FTS results (Goodman-Meza et al., 2022; Krieger, Goedel, et al., 2018; Peiper et al., 2019). Notably, a community-based study in North Carolina found that PWID with positive FTS results had 5 times higher odds of practicing safer drug use compared to PWID with negative results (Peiper et al., 2019). Similar studies arrived at comparable effects and together confirmed that PWID were willing to use FTS and initiate risk reduction behaviors when consuming fentanyl (Park et al., 2020, 2021)."

"In conclusion, we found that areas where SCS were implemented in Toronto subsequently had significant reductions in overdose mortality incidence, although other areas in the city did not. Furthermore, we found an inverse spatial association between SCS and overdose mortality incident locations, and this association increased in magnitude over time. This finding suggests that the implementation of SCS could contribute to reductions in overdose mortality in proximal areas. Criticisms of SCS have focused on the lack of evidence of their capacity to meaningfully affect population-level overdose mortality.8 Our finding of potential positive community spillover effects of SCS suggests that, beyond their immediate capacity to reverse onsite overdoses among onsite clients, they might also contribute to population-level overdose prevention efforts. As such, the inclusion of population-level metrics to evaluate the effectiveness of SCS is not only warranted but can also inform policy planning regarding SCS service design, implementation, and operation."

"In the Global State of Harm Reduction 2020 we reported on the wave of reflection on racism and colonialism that followed the murder of George Floyd by a police officer in Minneapolis, United States. These shifts have continued to influence thinking about drug policy and harm reduction globally.^{13,14,15,16,17}

"In November 2021, a group of advocates and academics published a paper detailing the ways in which drug policy has been used to uphold colonial and racist power structures around the world.15 Over recent years, this has been a theme of advocacy and research carried out by many organisations in different countries, including Bolivia, Brazil, Indonesia, South Africa and the United States.^{13,14,18,19,20,21,22}

"The implementation of harm reduction continues to be affected by racism and colonial structures. Black, Brown and Indigenous people who use drugs have less access to harm reduction services.¹⁵ Direct and structural racism makes it harder for Black, Brown and Indigenous people to access services, it results in Black, Brown and Indigenous communities being targeted by drug law enforcement agencies and disproportionately detained or imprisoned, and means the needs of these communities are often deprioritised or ignored.²³ People who are migrants or refugees face particular challenges, to the extent that experiencing migration can be a major detriment to a person’s health.²⁴"

"Drug safety testing (drug checking) is a public health service whereby service users receive test results for a substance of concern submitted for forensic analysis as part of a harm reduction consultation.^12-14 Testing of submitted samples may be conducted onsite in rapid realtime as part of an integrated testing service, or elsewhere by a partner laboratory. Whilst these services vary widely in terms of types of consultations, forensic analyses, staffing, funding, waiting times, whether community or event-based, static or mobile, permanent or temporary, and whether the testing service is integrated or split into individual components, their shared core aim is harm reduction and their shared core service characteristic is direct user engagement. The rationale for these services is that drug-related harm can arise from the consumption of illicit psychoactive substances of unknown content and strength. Therefore, if testing services share results and other relevant information directly with service users, and potentially also other interested parties such as wider drug using communities and support services, they can communicate the risks associated with consuming that substance and enhance users' ability to make educated and informed decisions to reduce or avert future harm, protect their health and reduce the burden on health services. For stakeholders and support services, testing provides an opportunity to monitor trends in illegal drug markets and associated harms, and for alerts to be issued that are timely and accurately targeted to the appropriate drug using communities by utilising information that links composition of individual samples with what they were sold as, a distinct added value of drug safety testing.^14,15 A global audit¹⁶ identified 31 such drug safety testing programmes operated by 29 organisations in 20 countries at that time, with the largest and longest standing being the Dutch Drugs Information Monitoring System,^17-19 and more services have started operating since that audit."

"As of 2020, 86 countries globally have at least one NSP [Needle and Syringe Program], though on the ground this has meant NSP closures and openings in several countries since 2018. Algeria opened NSPs in the Middle East and North Africa region, but in Palestine and Jordan, NSPs stopped completely; in Asia, NSPs closed in Mongolia; in sub-Saharan Africa, NSPs opened in Benin, Nigeria and Sierra Leone, while in Uganda NSPs ceased to operate. Eurasia, North America, Oceania and Western Europe remained the regions where almost all countries with reported injecting drug use implemented NSPs.^[1]

"The availability of NSPs, however, does not ensure adequate coverage and accessibility. There is a large disparity in NSP implementation globally. While NSPs in Australia distribute almost 700 syringes per person who injects drugs per year, in Benin in sub-Saharan Africa, only ten syringes are given in a month to a client visiting the programme.² In Macau, Asia, the number of NSPs has decreased since 2018, and only one NSP is still open. While NSPs are available in the majority of countries in Eurasia, there are several countries where coverage is very limited as services are implemented solely on a volunteer basis.^[3,4] New estimates from India suggest that just 35 syringes (down from 250) are distributed per person who injects drugs, despite an increase in the number of NSP sites in the country. Coverage could also vary within a country. In Western Europe, for example, the coverage of NSPs in urban areas is sufficient and there are no major barriers in access, but rural areas have less coverage in many countries (e.g. Austria, Belgium, the Netherlands, Germany and Portugal).^[5–9] Rural populations are also underserved in both the United States and Canada, and an uneven geographical distribution of NSPs is a problem in Australia and New Zealand.^[10,11]"

"Common SSTIs include cellulitis (Figure 1) and skin abscesses (Figure 2),⁵ and SSTI is common in PWIDs. In one needle exchange program (N = 152), 17.8% (n = 27) had an active abscess and 19.7% (n = 30) had a chronic wound.⁶ The upper extremities were the most common place for an abscess, and the lower extremities were most common for chronic wounds. In a study of active (injected in the past 30 days) PWIDs (N = 201) recruited in San Francisco between 2011 and 2013, Dahlman and colleagues⁷ noted the self-reported prevalence of lifetime SSTIs was about 70%. These infections can lead to serious morbidity and costly emergency room visits and hospitalizations. By assessing billing records through chart abstraction for 349 PWIDs in Florida, SSTIs were reported in 64% (n = 223); the total cost to the hospital for services rendered to treat injection drug use-related infections for a year was approximately $11.4 million.⁸ According to the Hospital Episode Statistics for England 1997–2016, about 6% (n = 63,671) of SSTIs and vascular infections are injection related.9 The most common causes were cutaneous abscess, phlebitis, and cellulitis. The number of injection-related admissions increased 33% per year from 1997 and 1998 through 2003 and 2004.⁹

"Two terms are important to aid in the understanding of SSTIs in PWIDs: skin popping and speedballing. Skin popping is extravasal (intramuscular or subcutaneous) injection into confined tissue compartments. When injected into a vascular space, drugs are quickly diluted. This dilution effect does not occur when drugs are injected into skin or muscle.¹⁰ Subcutaneous and intramuscular injections also bypass exposure to the bloodborne immunologic response, which may increase the risk of infection.¹¹

"Speedballing is injecting heroin in combination with a vasoconstrictor such as cocaine or methamphetamine. This decreases local blood flow to the injection site and exacerbates ischemia.11 The addition of crack cocaine to heroin is rationalized as providing a 'better high.'¹² The use of crack cocaine in speedballing has been associated with the deterioration of injection sites.¹² In general, speedballing is associated with an increased risk of infection.¹³"

"Stigma and discrimination against people who inject drugs continue to exist and hinder service access in all contexts,^{[12–15] [16]} affecting organisations implementing NSPs. In South Africa, for example, one NSP was closed in 2018 due to concerns of insufficient stakeholder consultation and the systems available for waste management.^[17] Though the service was reinstated in late June 2020, programme staff have yet to reach the previous cohort of clients that had accessed the service before its closure.^[18]

"In addition to geographical gaps and stigmatisation of people who inject drugs, there are groups of people who inject drugs that experience barriers to access. The lack of appropriate, gender-specific programmes for women who use drugs is a recurring issue throughout most regions. Furthermore, the needs of Indigenous people are not appropriately met in Oceania,^[10,11] and there are reports of migrants who inject drugs facing barriers to accessing harm reduction services in Western Europe.^[6,9,19] NSP provision for people who use stimulants is suboptimal in many regions despite the risks involved. In Western Europe, for example, stimulant injecting has been associated with local HIV outbreaks in five countries in the past five years.^[20–22]"

"Few stimulant-specific harm reduction responses are implemented globally. Though NSPs and drug consumption rooms (DCRs) can be accessed by people who use stimulants, existing harm reduction services might not always be adequate for their needs.^[34] For example, stimulant use is associated with more frequent injection than opioids, but limits in NSPs on the number of syringes that can be acquired at any one time represent a particular barrier for those injecting stimulants. Stimulants are also more likely to be smoked or inhaled than opioids, but not all DCRs permit inhalation on premises, and smoking equipment is rarely distributed. However, safer smoking kits for crack cocaine, cocaine paste and ATS are distributed in several territories, including Portugal^[5][35] and harm reduction programmes for people who use non-injectable cocaine derivatives are in place in several countries in Latin America. There have been promising pilot programmes in Asia focusing on people who use methamphetamine, including outreach programmes distributing safer smoking kits, plastic straws, harm reduction education, and access to testing and treatment for HIV, hepatitis C, TB and other sexually transmitted diseases (see page 75 in Asia Chapter 2.1).

"Drug checking (services that enable people to voluntarily get the contents of their drugs analysed) is an important harm reduction intervention for people who use stimulants. These services are implemented in at least nine countries in Western Europe³, are available in the United States, Australia and New Zealand, and are increasingly available in Latin America⁴. Eight countries in Eurasia⁵ have some form of drug checking services through distribution of reagent test kits at music festivals and nightlife settings. Other methods of drug checking include the use of mobile testing equipment to determine the contents of what is sold using tiny samples of the product, allowing for identification of both drugs and contaminants. Though availability of drug checking is growing globally from a low baseline, implementation faces serious legal barriers in many countries as it involves handling controlled substances, and drug checking services often require formal exemption from drug laws in order to operate legally.

"No approved substitution therapy for ATS exists, although pharmacologically-assisted treatment with methylphenidate for ATS users was authorised by the government in Czechia during the COVID-19 pandemic, and in Canada, the British Columbia Centre on Substance Use released interim clinical guidance recommending the prescription of dexamphetamine and methylphenidate to people who use stimulants.^[36]"

"Effective treatment has increased life expectancy after HIV infection, and deaths from non-AIDS-related causes now exceed deaths from AIDS for those with HIV in the US [35]. Medical costs of treating HIV-infected individuals as they age now include costs of both HIV-related and HIV-unrelated medical care. We estimated the medical cost saved by averting one HIV infection in the United States, taking into account the costs that would have been incurred by similar at-risk individuals in the absence of HIV infection. We project discounted medical cost savings of $229,800 by permanently averting one HIV infection based on current care patterns in the US and $49,500 if one HIV infection is delayed by 5 years. Our analysis shows that as HIV care becomes more effective, the cost avoided by averting one HIV infection also increases. Improved care is cost-effective by accepted standards in the US, it is not cost-saving [36]. The added years of life, however, result in additional costs for treatment that would not have occurred in the absence of an infection.

"Our projections of lifetime medical costs for HIV-infected individuals of $326,500 in the base case and $435,200 in the optimal care case are comparable to recent model-based estimates of lifetime costs for individuals in the US entering care with CD4 201–350/μl ($332,300 in 2012 US dollars) and >500/μl ($443,000) respectively [37], and costs from entry into care (not shown) are consistent with previous estimates of these costs in France using the CEPAC model [38]. Our projection of medical cost savings of $229,800 is substantially lower than the previous estimate of $303,100 in 2004 US dollars ($361,400 in 2012 US dollars) [7] for several reasons. First, we now account for medical costs that would have been incurred in the absence of an HIV infection. Second, our previous analysis did not adjust mortality for risk group characteristics that lower average life expectancy [23], thereby reducing costs, nor did they adjust costs for health service utilization by different risk groups. Our life expectancy estimates are lower than two other recent model-based analyses in the United States and the United Kingdom [37, 39], likely reflecting the race/ethnicity and risk-category mortality effects in our model. Our results are consistent with these models, however, in projecting substantial life expectancy losses associated both with becoming HIV infected and with delayed initiation of treatment after infection.

"Consistent with other analyses [7, 37], we found that ART medications represent the largest component of cost for HIV-infected individuals. We found that non-HIV chronic care medications represent a substantial component of cost as well, emphasizing the significant cost of managing non-HIV comorbidities in an aging HIV-infected population [13, 40]. These comorbidities are frequently managed by HIV primary care providers [41]. Our results are somewhat sensitive to assumptions about future use of generic HIV drugs in the US. This points to the potential importance of future availability of generic drugs in lowering the cost of HIV care, depending on regimens selected and adherence [32].

"Our analysis also indicates that the value of HIV primary prevention may be greater when the effects of preventing secondary transmission to HIV-uninfected partners are taken into account, which would increase the value of interventions targeting individuals at high risk of transmitting to multiple partners. The magnitude of this impact is greater the longer individuals remain uninfected after avoiding a secondary transmission. The current relatively stable HIV incidence trends in the US [15] suggest these uninfected partners are at high risk for eventual HIV infection. If the probabilities of secondary transmission we used already take into account this additional risk, the value of primary prevention would be even higher."

"As shown above, the data supports that these stronger, longer-acting agents may be unnecessary, with other research suggesting their existence may also cause undue harm. Using a stronger or longer-acting antagonist as a one-size-fits-all approach may put patients at greater risk for experiencing more severe and/or prolonged withdrawal symptoms.(Bennett et al., 2020; Hill et al., 2022; Neale & Strang, 2015) Providers may find it difficult to manage withdrawal symptoms and comorbidities like chronic pain, forcing the patient to suffer until the reversal agent wears off. It is also notable to consider how patients who are naïve to nalmefene may react upon discharge following administration. These patients may attempt to self-manage withdrawal symptoms or cravings only to find higher opioid doses are required to overcome the nalmefene blockade, increasing their propensity to overdose as was observed when patients began adjusting to naloxone.(Neale & Strang, 2015) Alternatively, patients accustomed to opioid withdrawal symptoms subsiding within 1 to 2 h after naloxone administration may not be able to tolerate several hours of withdrawal, increasing both the likelihood of attempts to overcome the blockade and resistance to using reversal agents in the future.(Neale & Strang, 2015) Considering the average layperson likely does not fully grasp the potential harm of nalmefene, and that any opioid overdose education they may have received from an opioid overdose education & naloxone distribution (OEND) program would have been naloxone and harm reduction focused, adding these agents into the market creates opportunities for greater clinical complication. This lack of familiarity combined with the lack of clinical discretionary knowledge by the layperson who may be administering these medications in the field sets the stage for nalmefene exposure to elicit prolonged agitation and negative consequences.(Brenner et al., 2021) Furthermore, it is possible that nalmefene administration may complicate the initiation of medications for opioid use disorder such as buprenorphine/naloxone, which can be done in as little as three hours following the last opioid use when co-administered with naloxone.(Randall et al., 2023) Additionally, the FDA approved intranasal naloxone for over-the-counter use in March 2023. It is yet to be seen how this will affect its insurance coverage and medication access.(Harris, 2023b) This may especially affect vulnerable patient populations such as those with limited disposable income. Coverage for prescription nalmefene may serve some relief when naloxone is not covered or attainable by other means."

"Drug consumption rooms have been defined as professionally supervised healthcare facilities where people who use drugs can do so in safer and more hygienic conditions (Hedrich et al., 2010). Importantly, they aim to offer hygienic conditions, often supervision by medically trained staff, and a safe environment where people can use drugs without fear of arrest or legal repercussions. DCRs are intended to complement existing prevention, harm reduction and treatment interventions, and are known by various names (see Box 1). DCRs may differ significantly across, and even within, jurisdictions as they are adapted to local needs and regulatory frameworks. This is also an intervention area that is rapidly changing both in terms of approach and models of service delivery. It is important to note that both the diversity in programme design and the dynamic nature of service development in this area means that generalisations need to be made with caution.

"To date there are more than 140 legally-sanctioned DCRs operating in a number of cities in 11 European countries, as well as in Australia, Canada, Mexico and the USA."

Editor's Note: This article has the following correction:

"In the December 1, 2019 Supplement 2 of JAIDS Journal of Acquired Immune Deficiency Syndromes, in the article titled 'Using Interrupted Time Series Analysis to Measure the Impact of Legalized Syringe Exchange on HIV Diagnoses in Baltimore and Philadelphia', the authors mistakenly reported the estimated cost savings for Baltimore to be $62.4 million annually and $624 million over 10 years, and the 1-year return on investment (ROI) factoring in the cost of syringe exchange programs to be $46.8 million. The correct cost savings estimates are $43.4 million annually and $434.3 million over 10 years, and the correct 1-year ROI estimate is $32 million."

Following is the original, uncorrected quote:

"Our findings also demonstrate that averted HIV diagnoses translated to cost savings for cities where most PLWH are recipients of publicly funded healthcare. The forecasts estimated an average of 1059 HIV diagnoses in Philadelphia and 189 HIV diagnoses in Baltimore averted annually. Multiplying the lifetime costs of HIV treatment per person ($229,800)²⁵ by the average number of diagnoses averted annually in both cities yields an estimated annual saving of $243.4 million for Philadelphia and $62.4 million for Baltimore. Considering diagnoses averted over the 10-year modeled period, the lifetime cost savings associated with averted HIV diagnoses stemming from policy change to support SEPs may be more than $2.4 billion and $624 million dollars for Philadelphia and Baltimore, respectively. Because SEPs are relatively inexpensive to operate,²⁶ overall cost savings are substantial even when deducting program operational costs from the total amount. Considering annual program expense ($390,000 in 2011 for Philadelphia²⁷ and $800,000 estimated in FY 2017 for Baltimore²⁸) (Kathleen Goodwin, Baltimore City Health Department, personal communication, January 3, 2017) and cost savings in each city, and a conservative estimate that 75% of these savings would be experienced in the public sector, the 1-year return on investment in SEPs remains in the hundreds of millions of dollars ($182.5 M for Philadelphia, $46.8 M for Baltimore). Small investments in SEPs may yield large savings in HIV treatment costs, so implementing SEPs may liberate resources for other important interventions, such as expanded access to medication-assisted treatment, overdose prevention, and housing.

"Another implication pertains to how variations in SEP implementation may have influenced intervention effectiveness. Policies governing SEPs affect not only the overall number of syringes distributed annually but also the ability of PWID to obtain sufficient coverage for all injection events. For example, PPP's clients may exchange syringes for themselves and others; recent data show that the mean number of syringes exchanged per exchange event increased from 1.53 in 1999 to 1.82 in 2014.¹³ In addition, PPP's annual syringe distribution has consistently increased from approximately 811,000 in 1999 to 1.2 million in 2014,¹³ allowing for greater coverage of injection events and more opportunities for disease prevention.

"By contrast, Baltimore's SEP had a one-for-one (1:1) exchange policy from 1994 to 1999 but, in 2000, switched to a more restrictive policy, where clients were allowed 1:1 exchange for program-distributed syringes but could receive 1 sterile syringe in exchange for 2 nonprogram syringes. From 2005 to 2014, the SEP returned to the less restrictive 1:1 policy, after which they shifted to a need-based distribution model whereby PWID could access as many syringes as needed. Baltimore City's health commissioner estimated that moving from the 1:1 to the needs-based distribution policy could increase coverage of injection events from 42% to 61%.²⁹ More flexible approaches to syringe access in Baltimore could have resulted in greater injection coverage and more dramatic declines in IDU-associated HIV diagnoses earlier. Regulations limiting clean needle and syringe distribution are important operational issues to consider if policy changes supporting harm reduction for PWID are to have optimal impact."

"DCRs are generally established with the aim of addressing a mix of individual health, public health and public order objectives. These services typically aim to reach out to and maintain contact with the most marginalised populations of people who use drugs — those experiencing high barriers to accessing medical and social support — and to provide a gateway through which these groups can connect with a broader range of health and social support services. DCRs further seek to reduce overdose-related morbidity and mortality, and prevent the spread of infectious diseases by offering access to sterile equipment, safer use advice and emergency interventions. By giving people who use drugs the opportunity to consume in a calm, hygienic and supervised environment DCRs also aim to reduce harms resulting from the broader ‘risk environment’ that socially marginalised or excluded groups may be exposed to as a consequence of multiple interacting physical, social, economic and policy factors (Rhodes, 2002).

"In addition, DCRs aim to play a role in combating stigma by treating people who use drugs with dignity and supporting them in multiple aspects of social integration, such as finding employment and housing.

"DCRs are usually set up in areas near urban drug markets that are characterised by high rates of public drug use. By providing a space for safe consumption that is sheltered from public view they may also have the objective of reducing drug use in public and to improve public amenities (e.g., through fewer improperly discarded syringes and less drug-userelated waste in general). In this respect DCRs can be characterised as a response to public order and safety concerns regarding drug scenes while creating an improved environment for local residents (see, e.g., Hedrich et al., 2010; Potier et al., 2014; Schäffer et al., 2014; EMCDDA, 2018).

"The specific goals and objectives of DCRs can vary between cities and may change over time. The first DCRs, established in the 1980s and early 1990s in Swiss, Dutch and German cities, emerged as a local component of HIV prevention and focused on bringing populations of street-based heroin injectors closer to care. Three decades later, the most prominent argument for supporting the scaling up of DCRs in North America relates to their role as part of a comprehensive response to the opioid/fentanyl overdose crisis and the need to curb extremely high levels of opioid-related morbidity and mortality in this region."

"In total, there were 10,514 injections and 33 opioid-involved overdoses over 5 years, all of which were reversed by naloxone administered by trained staff (Table 1). No person who overdosed was transferred to an outside medical institution, and there were no deaths. The number of overdoses increased over the years of operation, due partially to the number of injections increasing over the same period of time (Fig. S1 in the Supplementary Appendix). The types of drugs used at the site changed over the 5 years of operation, with a steady increase in the proportion of injections involving the combination of opioids and stimulants, from 5% in 2014 to 60% in 2019 (Fig. S2).

"Although this evaluation was limited to one city and one site that is unsanctioned, and therefore the findings cannot be generalized, our results suggest that implementing sanctioned safe consumption sites in the United States could reduce mortality from opioid-involved overdose. Sanctioning sites could allow persons to link to other medical and social services, including treatment for substance use, and facilitate rigorous evaluation of their implementation and effect on reducing problems such as public injection of drugs and improperly discarded syringes."

"Methods

"The research literature on the effectiveness of syringe services programs in controlling HIV transmission among persons who inject drugs and guidelines for syringe services program that are 'functioning very well' were used to estimate the cost-saving threshold at which a syringe services program becomes cost-saving through preventing HIV infections versus lifetime treatment of HIV. Three steps are involved: (1) determining if HIV transmission in the local persons who inject drugs (PWID) population is being controlled, (2) determining if the local syringe services program is functioning very well, and then (3) dividing the annual budget of the syringe services program by the lifetime cost of treating a single HIV infection.

"Results

"A syringe services program in an area with controlled HIV transmission (with HIV incidence of 1/100 person-years or less), functioning very well (with high syringe coverage, linkages to other services, and monitoring the local drug use situation), and an annual budget of $500,000 would need to prevent only 3 new HIV infections per year to be cost-saving.

"Conclusions

"Given the high costs of treating HIV infections, syringe services programs that are operating according to very good practices ('functioning very well') and in communities in which HIV transmission is being controlled among persons who inject drugs, will almost certainly be cost-saving to society."

"Relevant literature on overdose response included 3 clinical guidelines,1,21,32 3 grey literature reports (a rapid review,36 an evidence brief37 and a report of a technical working group on resuscitation training38), and a pilot and feasibility study.39 The conclusions in these resources differ on overdose response, notably on the role of rescue breathing and the order in which resuscitation steps occur. An in-depth discussion of the literature is available in Appendix 1, and Appendix 3 contains more detail on findings and included studies.

"As the mandate of THN [Take Home Naloxone] programs includes overdose response training, our recommendation focuses on trained overdose response. Evidence from the Naloxone Guidance Development Group indicates that community overdose responders are effectively trained through different methods. For the purposes of this document, we recognize that people using THN programs may be trained on overdose response through their peers, using online resources, THN programs or cardiopulmonary resuscitation (CPR) training courses.

"In the literature, multiple sources identified naloxone administration and calling 911 or other emergency response numbers as critical steps in overdose response.1,21,32,36,38,39 Three guidance documents included verbal and physical stimulation to assess whether someone is experiencing overdose and to stimulate breathing.21,32,38

"For a responder trained in overdose response, guidance may differ according to whether the responder suspects respiratory depression or cardiac arrest. Overdose response must take the pathophysiology of opioid overdose into account. When someone experiences opioid overdose, regulation of breathing is impaired, respiration is depressed and insufficient oxygen reaches the brain and other organs.1 Because the person experiencing overdose is not breathing effectively, oxygen also cannot reach the heart and the individual may experience cardiac arrest (i.e., their heart stops beating or beats too ineffectively to support their vital organs).1"

"Globally, there are nearly 15.6 million people (aged 15–64) who inject drugs (PWID), with an estimated 2.6 million PWID in North America (Degenhardt et al., 2017). Canada and the United States (US) have both seen significant increases in the rate of injection drug use, as well as a rise in the rate of infections and fatal overdose related to injection drug use (Jacka et al., 2020; Levitt et al., 2020). The risk of fatal overdose significantly increases when people inject drugs alone, and may be prevented with timely intervention (i.e. administration of naloxone, an overdose prevention medication) (Colledge et al., 2019). There is also an increased risk of disease transmission (e.g. HIV, hepatitis) and serious infections associated with injecting drugs, which are often related to using unsterile equipment, injecting in unhygienic settings, or rushed injections (Colledge et al., 2019). The increase in injection drug use and the risks associated with using alone, in unhygienic or unsupervised settings necessitate the need for services that support safe injection practices among PWID."

"In this study, there was no indication that needle-exchange use was associated with increasing drug use. Indeed, IDUs who were former users of the exchange were more likely than never-users to report substantial reductions in drug use or stopping injection altogether. Our analysis also suggested that among heroin injectors, needle-exchange participation was wholly compatible with the goals of drug treatment. Compared to those who had never used an exchange, new exchange users were five times more likely to enter methadone treatment and ex-exchangers were 60% more likely to remain in methadone treatment over the 1-year study period.

"Many factors may influence drug injection frequency in a population, including cost and availability of different drugs and access to drug treatment (Frykholm & Gunne 1980, Nurco et al. 1981, Robins 1980). The natural history of drug injection is also characterized by a progression toward daily use (Robins 1980). The ability of an exchange program to override these underlying factors is not well-understood, however, there is a well-recognized motivation to reduce or cease drug use exhibited by some users (Koester et al. 1999). It is conceivable that exposure to needle exchange could accelerate or facilitate this process by offering encouragement and support for risk reduction and improved self-care, and as a conduit to drug treatment services.

"In this study, baseline rate of injection was an important determinant of subsequent change in injection frequency. In all subject categories, most subjects who initially reported fewer than one injection per day progressed to daily injection by the end of the follow-up period. In contrast, reduction in drug use was more common among those who were daily injectors at the baseline visit. Since it was a potential confounder, we examined the association between needle exchange and reduction in injection, adjusted for baseline injection frequency and within separate strata of daily and nondaily injectors. This method of analysis would tend to reduce the influence of regression to the mean on our results. Further, we found that the group with the highest proportion of subjects reporting reduction in injection frequency (ex-exchangers) reported a relatively lower mean number of injections at study enrollment. Thus, it was unlikely that regression to the mean was responsible for the observed association."

"Rescue breathing for persons suspected of having an opioid overdose has considerable support among harm reduction programs and in the medical literature.¹⁸ This preference is based on the physiology of an opioid overdose. Opioids suppress the autonomic respiratory response to declining oxygen saturation and rising carbon dioxide levels. If this response remains suppressed, the consequences are hypoxia, acidosis, organ failure and death. The majority, if not all, of the community-based naloxone programs in the United States train responders in a rescue breathing technique. In this technique, the nostrils of the unconscious individual are pinched closed, a seal is formed between the mouths of the victim and the responder, and breaths are introduced every five seconds by the responder. Further support for rescue breathing comes from the Substance Abuse and Mental Health Services Administration (SAMHSA) in its Opioid Overdose Toolkit.¹⁹ In late 2014, WHO issued guidelines on community management of opioid overdose recommending, 'In suspected opioid overdose, first responders should focus on airway management, assisting ventilation and administering naloxone.'²⁰ This was rated as a strong recommendation based on a weak quality of evidence."

"As physicians, pharmacists, scientists, and specialists in poison information, we are experts in pharmacology, toxicology, and the management of opioid overdose and addiction. We applaud the effort to seek out new therapeutic strategies for the management of these patients.

"We are concerned that the use of a longer-acting reversal agent would not improve on current practice and could potentially cause harm. When withdrawal is precipitated by an opioid antagonist, there are few good management options. In most cases, the best strategy is to address and support the patient’s signs and symptoms until the effects of the antagonist wane. In the case of naloxone, which has a relatively short duration of action, severe withdrawal usually lasts less than an hour with symptoms typically persisting no more than 90 min [Citation25–27]. A longer-acting antagonist is anticipated to cause longer-lasting precipitated withdrawal and may lead to worse patient outcomes. Clinical experience with both naltrexone and nalmefene suggests prolonged withdrawal is a complication of longer-acting opioid antagonists [Citation28]. Although a longer-acting antagonist may be theoretically beneficial for the resuscitation of opioid-naive individuals in an opioid-induced mass casualty incident, this type of event has never been reported in North America and this application is unstudied.

"We are also concerned that patients who receive nalmefene may require longer periods of observation, by up to several hours, to observe for recrudescent effects as the antagonist effects wane. Patients who receive nalmefene will still need medical observation to ensure that respiratory depression does not recur after the effects of the medication subside. This will prolong emergency department visit length and challenge patient and clinician expectations, further burdening a taxed system. Further clinical study is needed to understand whether a reduction in repeat antagonist use justifies a longer length of stay or longer period of withdrawal.

"Finally, we are concerned that intranasal nalmefene has not been adequately studied for effectiveness in the actual setting and patient population: for patients with severe opioid intoxication in the out-of-hospital environment. Lack of proof of safety and efficacy in real-world use could result in significant harm if widely utilized.

"The potential benefits of nalmefene over naloxone (greater opioid receptor affinity, longer duration action) carry the risk of causing harm. These benefits, if present, should be demonstrated in the clinical environment, balanced with the risks, and compared to naloxone prior to the broad adoption of nalmefene."

"Results  No significant changes were detected in violent crimes or property crimes recorded by police, 911 calls for crime or medical incidents, or 311 calls regarding drug use or unsanitary conditions observed in the vicinity of the OPCs. There was a significant decline in low-level drug enforcement, as reflected by a reduction in arrests for drug possession near the OPCs of 82.7% (95% CI, −89.9% to −70.4%) and a reduction in their broader neighborhoods of 74.5% (95% CI, −87.0% to −50.0%). Significant declines in criminal court summonses issued in the immediate vicinity by 87.9% (95% CI, −91.9% to −81.9%) and in the neighborhoods around the OPCs by 59.7% (95% CI, −73.8% to −38.0%) were observed. Reductions in enforcement were consistent with the city government’s support for the 2 OPCs, which may have resulted in a desire not to deter clients from using the sites by fear of arrest for drug possession.

"Conclusions and Relevance  In this difference-in-differences cohort study, the first 2 government-sanctioned OPCs in the US were not associated with significant changes in measures of crime or disorder. These observations suggest the expansion of OPCs can be managed without negative crime or disorder outcomes."

"Syringe services programs are harm reduction programs that provide a wide range of services including, but not typically limited to, the provision of new, unused hypodermic needles and syringes and other injection drug use supplies, such as cookers, tourniquets, alcohol wipes, and sharps waste disposal containers, to PWID. Comprehensive SSPs also either directly provide, or offer linkage or referrals to entities that provide: substance use disorder treatment, including medication for addiction treatment; vaccination for viral hepatitis; screening for viral hepatitis, HIV, sexually transmitted infections, tuberculosis, and other infectious diseases; provision of pre- and post-exposure prophylaxis for HIV; naloxone and other overdose prevention tools; peer support services; educational materials and training in areas related to injection drug use; and referral and linkage to other services, including medical care, mental health services, and other support services.¹⁶ Contrary to popular perception, SSPs do not increase crime in areas where programs are based and do not increase illegal drug use.¹⁷ Further, “Nearly 30 years of research has shown that comprehensive SSPs are safe, effective, and cost-saving … and play an important role in reducing the transmission of viral hepatitis, HIV, and other infections.”¹⁸ Additionally, PWID who participate in an SSP are “five times more likely to enter drug treatment and about three times more likely to stop using drugs than those who don’t use the programs.”¹⁹ Individuals who regularly use an SSP are also “nearly three times as likely to report a reduction in injection frequency as those who have never used an SSP.” SSPs are also an important tool in the fight against unintentional drug overdose by teaching PWID how to recognize and respond to a drug overdose, as well as by providing participants with naloxone and training on administration.²¹

"Although only 38 states, the District of Columbia, and Puerto Rico either explicitly or implicitly authorize SSPs through statute, regulation, or executive order, as of September 2021, there are 392 operational SSPs in 44 states, the District of Columbia, and Puerto Rico.^22,23

"This study indicates that the SSP+MOUD [Syringe Service Program + Medications for Opioid Use Disorder] combination program is an effective harm-reduction strategy to prevent HCV cases among opioid IDUs and is cost-effective if payers are willing to pay $4,699 or more per avoided case of HCV. There is evidence to support the effectiveness of these harm-reduction strategies in reducing injection-risk behaviors as well as reducing HCV and HIV transmission.^17,18 The base-case analysis suggested that (a) the combination strategy, compared with SSP alone, would cost $4,699 to avoid an additional HCV case; (b) the combination and the SSP-alone groups dominated both the MOUD-alone and no intervention groups; and (c) the MOUD-alone group dominated the no intervention group.

"Most of the recent studies on the cost-effectiveness of SSP and MOUD alone and in combination were conducted outside the United States, were conducted from a societal or health care system perspective, did not directly compare the interventions used in the base case, had moderate evidence of the cost-effectiveness in some sites, estimated the outcome in terms of quality-adjusted life years, and did not examine the number of cases avoided in a 1-year time horizon.^{19,31,32,37-39} To date, studies have not examined the cost-effectiveness of these harm-reduction strategies in terms of incremental cost savings per HCV case avoided, and none has undertaken a public payer perspective in the United States.

"Based on the analysis, the combination of MOUD and SSP appears to be the most effective policy, from a public health perspective. By including both the direct medical and nonmedical costs due to injection drug use-related crime in the calculation, the combination program will save public payers $347,573 per HCV case avoided compared with costs for no intervention. SSP-alone and MOUD-alone interventions will also save public payers $363,821 and $317,428, respectively. Given that the total direct economic burden of HCV-related liver disease in the United States is estimated to be $6.5 billion ($4.3 to $8.2 billion) annually and 2.4 million people in the United States live with an HCV infection, these interventions could dramatically reduce HCV-related annual costs.^7,40,41 The savings associated with these interventions would allow public institutions to redirect funds toward other health care services or public service investments. In addition, the results indicated that all the harm-reduction strategies were less costly and more effective than no intervention even though they required some up-front investments. It is also important to point out that the largest benefits could occur in the future. This is because HCV-related liver disease such as cirrhosis and hepatocellular carcinoma may take several years to occur, and SSPs are associated with reducing the risk of other diseases transmitted via needle sharing, such as HIV.^23,26

"The 1-way sensitivity analysis shows that the base-case cost effectiveness analysis was sensitive to the probabilities of injection-risk behavior for the SSP and SSP+MOUD combination groups, probability of no HCV with no intervention, and costs of MOUD and HCV antivirals. Despite varying the model parameters by ± 50%, the base-case ICER was not sensitive to a majority of the key variables in the model. Considering that the cost for the combination intervention was assumed to be the sum of the costs of the SSP and MOUD individual interventions, our results can be considered as conservative estimates, given that in reality, savings and economies of scale can be achieved by a combination of efforts."

"While the addition of stronger, longer-acting opioid overdose reversal agents expands the options available to combat the fatal opioid overdose crisis, their inception is perhaps without clinical grounds. Data supports continued practice without these stronger, longer acting nalmefene agents, and it is unclear whether any benefits nalmefene offers outweigh the apparent risks of its use. Nalmefene may yet find a clinical niche, but at this time, appears to be a solution designed to resolve hypothetical complications without fully understanding the unintended consequences of use. As such, without further evidence healthcare professionals should not support the use of stronger, longer-acting opioid overdose reversal agents. Further study is necessary, before nalmefene, or other naloxone alternatives should be incorporated into general practice."

"In conclusion, we found that areas where SCS were implemented in Toronto subsequently had significant reductions in overdose mortality incidence, although other areas in the city did not. Furthermore, we found an inverse spatial association between SCS and overdose mortality incident locations, and this association increased in magnitude over time. This finding suggests that the implementation of SCS could contribute to reductions in overdose mortality in proximal areas. Criticisms of SCS have focused on the lack of evidence of their capacity to meaningfully affect population-level overdose mortality.8 Our finding of potential positive community spillover effects of SCS suggests that, beyond their immediate capacity to reverse onsite overdoses among onsite clients, they might also contribute to population-level overdose prevention efforts. As such, the inclusion of population-level metrics to evaluate the effectiveness of SCS is not only warranted but can also inform policy planning regarding SCS service design, implementation, and operation."

"This analysis presents the first study, to our knowledge, to quantitively examine the impact of SSP closure on HIV incidence using a modeling approach. In a rural American setting that had previously experienced an HIV outbreak among PWID, our modeling results suggest that closing an existing SSP would likely lead to a rebound HIV outbreak, with a 1.6-fold increase in incident infections among PWID in 5 years relative to SSP sustainment. The potential impact of SSP closure was found to be substantially greater for other settings with lower baseline HIV prevalence (in which a larger share of the population is susceptible to HIV infection). Although delaying SSP closure with another renewal was found to reduce the size of the rebound, sustaining SSP operation and associated health services will be imperative to maintain long-term epidemic control."

"People who use heroin (PWUH) have increased morbidity and mortality compared to the general population [1]. A syndemic of opioid overdose, human immunodeficiency virus (HIV), hepatitis C virus (HCV), skin and soft tissue infections (SSTI), and infective endocarditis accounts for many of the poor health outcomes among PWUH [2,3,4,5]. Heroin can be consumed in several ways, including injection and smoking [6]. High-risk injection behaviors, including syringe sharing and reuse of non-sterile injection equipment, are established routes of HIV and HCV transmission and increase risk of SSTI and infective endocarditis [7,8,9]. Opioid overdose is a common cause of mortality among PWUH, with higher overdose risk among those who inject [10,11,12].

"Because smoking heroin does not injure the skin or introduce non-sterile equipment into blood or tissue, this method of consumption does not entail the same risk of blood-borne infections or SSTI compared to injection. While similar pharmacological effects can be achieved by smoking or injecting heroin, peak plasma concentrations are 2–4 times lower when heroin is smoked, which may reduce risk of lethal opioid overdose [13, 14]. Programs that encourage PWUH to transition from injecting to smoking heroin may decrease injection frequency and thereby reduce harms associated with heroin use, including risks of infection and overdose [15]. Distribution of smoking equipment may also help PWUH avoid using pipes fashioned from cans or other poor-quality materials that easily crack or overheat, thereby reducing risk of developing burns or cuts on the lips that can serve as sites of infection [16,17,18]. Pipe distribution programs may also reduce pipe sharing, a risk behavior potentially associated with respiratory virus or HCV transmission [17,18,19,20]."

"Crack users often use and share pipes made of various makeshift materials, including broken glass pipes, metal tubing, aluminum cans, car antennas, or glass ginseng bottles, all of which can cause cuts, sores, burns, and blisters in and around the user’s mouth (Faruque et al., 1996; Porter & Bonilla, 1993; Porter, Bonilla, & Drucker, 1997; Shannon, Kerr et al., 2008). A number of recent studies point to nonIDU equipment sharing as possible routes of infectious disease transmission (Fischer, Powis, Firestone-Cruz, Rudzinski, & Rehm, 2008; Macias et al., 2008; McMahon & Tortu, 2003; Roy et al., 2001; Shannon, Rusch et al. 2008: Tortu, Neaigus, McMahon, & Hagen, 2001). In a study of drug users with no history of drug injection, Tortu et al. (2004) found noninjection drug use equipment sharing to be a risk factor for HCV infection, suggesting that HCV transmission may occur through noninjection routes such as oral and intranasal drug use methods. This is particularly concerning given that HCV is almost 30 times more infective that HIV through blood contact (Sulkowski & Thomas, 2003)."

"Drug checking, or the use of technology to provide insight into the contents of illicit drug products, is an evidence-based strategy for overdose prevention [10,11,12,13,14]. Drug checking services of various kinds have been operating across Europe and North America for several decades, with an estimated 31 services operational in 20 countries by 2017 [15]. In the United States, the use and distribution of fentanyl test strips is a relatively new but increasingly common drug checking strategy employed by SSPs and other programs, typically provided alongside harm reduction materials like sterile syringes and naloxone [16]. More complex technologies, like portable spectrometry devices, have been used for drug checking in several European countries since at least the 1990s [15] yet are only now emerging as an approach to drug checking in the United States [17,18,19]."

"SCS are a core part of a public health response to an unprecedented poisoning epidemic that has resulted in 36,442 opioid toxicity deaths between January 2016 and December 2022, driven largely by the production and trafficking of novel illegally manufactured opioids (Public Health Agency of Canada, 2021). SCS provide monitored spaces where people can consume drugs without risk of criminal sanction, receive emergency health care if needed, and access sterile harm reduction supplies and health and social supports (Health Canada, 2020). The number of federally sanctioned SCS in Canada increased from two in 2016 to a peak of 42 in 2020 (Health Canada, 2020). Additionally, more than 40 overdose prevention sites—a low-threshold form of SCS meeting an immediate community need and requiring less pre-implementation consultation—have opened in Canada since 2016. Collectively, these services have prevented and managed thousands of drug poisoning events and saved thousands of lives (Irvine et al., 2019).

"SCS are designed to reduce health and social risks, including risks associated with using drugs alone amid a toxic drug supply crisis. They also provide social support for structurally vulnerable populations who experience barriers to accessing health care (Kennedy et al., 2017). A substantial body of peer-reviewed research demonstrates the positive impacts of SCS. A systematic review by Kennedy et al. (with findings later corroborated by Levengood et al.) synthesized 47 studies from Vancouver, Australia, Germany, Denmark, Spain, and the Netherlands (Kennedy et al., 2017; Levengood et al., 2021). Studies adopted a mix of prospective cohort, time series or pre/post ecological, cross-sectional, mathematical simulation, or series cross-sectional designs and the majority were assessed to have good methodological quality. The review found that SCS mitigate drug poisoning–related harm and unsafe drug use practices, facilitate uptake of substance use treatment and other health services, are associated with improvements in public order (e.g., reductions in publicly discarded syringes), do not increase drug-related crime, and are cost-effective. A subsequent modelling study estimated that British Columbia’s overdose prevention sites averted 230 deaths in a 20-month period (Irvine et al., 2019). A study from Calgary, Alberta, found significant health system cost-savings arising from decreases in opioid-related ambulance responses and emergency department visits following the implementation of an SCS (Khair et al., 2022)."

"In this pilot pretest–posttest quasi-experimental study, we saw a lower proportion of SSP clients exclusively inject heroin and a higher proportion of SSP clients consume heroin through both injection and smoking after the implementation of a heroin pipe distribution program. The proportion of SSP clients who reported syringe reuse was also lower following the heroin pipe distribution intervention. We did not observe any difference in self-reported health outcomes associated with drug use between the pre- and post-intervention periods; however, the short follow-up period and small sample size of this pilot study may have contributed to this null finding. Our results suggest heroin pipe distribution may be a novel RTI that can be added to existing SSPs to further reduce harms associated with heroin use. This study also highlights the potential for public health service innovations to be developed by marginalized communities and the importance of placing PWUD in leadership positions in efforts to optimize harm reduction programming.

"Despite the non-randomized design of this pilot study, several findings suggest heroin pipe distribution may have prompted changes in heroin consumption behaviors among PWUH. The proportion of SSP clients who exclusively injected heroin was lower by a quarter, while the proportion who both injected and smoked heroin was higher by over a quarter after heroin pipe distribution began. Twenty-four percent of respondents who used heroin reported heroin pipe distribution had reduced their heroin injection. Higher proportions of SSP clients who received heroin pipes exclusively smoked heroin or both smoked and injected heroin compared to SSP clients who did not receive a heroin pipe. We are unaware of any prior published research investigating heroin pipes as an RTI; however, pre–post-analyses examining foil distribution at SSPs in Europe found similar changes in drug consumption behaviors, with up to 85% of SSP clients having used foil to inhale rather than inject heroin on at least one occasion [23, 28]. Our non-randomized study design cannot control for confounding and prevents firm conclusions as to whether this observed shift from injection to smoking can be attributed to the intervention. Additionally, only 14% of respondents who used heroin completed surveys during both the pre- and post-intervention periods, and thus, outcomes may have been impacted by changes in the SSP client population across time periods. Further experimental research is needed to clarify the causal relationship between heroin pipe distribution and reductions in heroin injection. Study designs that are randomized by individual may be complicated by heroin pipe sharing across intervention and control groups. Cluster randomization may better control for contamination given extensive social networks and resource exchange among PWUD [29]."

"In 2021, due to the widespread availability of high-potency synthetic opioids like fentanyl, the US FDA approved two high-dose naloxone products, an 8 mg IN spray (Kloxxado) and a 5 mg IM injectable (Zimhi). The only studies reported in the FDA package inserts for both products are pharmacokinetic studies in healthy volunteers, which demonstrated substantially higher naloxone plasma levels than standard doses of naloxone (0.4 mg IM vs. 8 mg IN and 2 mg IM vs. 5 mg IM, respectively). In April 2024, based on a pharmacokinetic study of 30 healthy adult subjects, the FDA approved a 10 mg IN naloxone, Rezenopy. None of these approval trials was conducted among opioid overdose patients at risk for naloxone-precipitated withdrawal. In 2023, the FDA approved a 2.7 mg IN formulation of nalmefene (Opvee), a more potent and longer acting opioid antagonist than naloxone. The approval of nalmefene was also based on pharmacokinetic studies performed in healthy volunteers that showed higher plasma levels than standard naloxone doses and one pharmacodynamic study among opioid-experienced, but “non-depen­dent” participants which showed successful reversal of respiratory depression induced by laboratory administered remifentanil."

"Studies in two states in the US have found that there is no association between the introduction of fentanyl into the drug supply and naloxone dosing required to reverse opioid overdoses. This conclusion emerged from data collected over four years at a SSP in Pittsburgh, PA, that distributed primarily 0.4 mg IM naloxone to people who use drugs (Bell et al., 2019; Bell & Dasgupta, 2024). Although the proportion of opioid overdose deaths attributed to fentanyl grew from 3.5% in 2013 to 68.7% in 2016, the average number of doses of naloxone administered by SSP participants to reverse overdoses did not change significantly, 1.62 doses in 2013 and 1.52 doses in 2016. An additional study of the naloxone doses used in opioid reversals reported to this Pittsburgh SSP, from August 2005 to January 2023, found that from 2010 to 2023, the average dose per reversal was below two administered doses (Bell & Dasgupta, 2024). In Kentucky, Rock et al. evaluated emergency services personnel-administered intranasal-equivalent naloxone doses and observed a clinically insignificant increase from 4.5 mg to 4.7 mg over four years to reverse overdoses during which fentanyl became ubiqui­ tous in the drug supply (Rock et al., 2024). In both studies, the rate of successful overdose reversal was 99%.

"Administration of additional doses of naloxone or increasing the dose or half-life of a single product do not reverse an opioid overdose more quickly (Hill et al., 2022; Klebacher et al., 2017). In a 2018 literature review of naloxone dosing, administration, and timing, Lynn and Gal­ ankin conclude, “the interactions between the opioid agonist and the mu-opioid receptor may be the greatest determinant of the speed of recovery from the respiratory effects of many opioids, which may not markedly accelerate with increasing doses of naloxone, but rather respond to a minimum effective dose” (Rzasa Lynn & Galinkin, 2018)."

"Around the world, there is no evidence of the need or benefit of higher dose products, particularly from people to whom they would be administered (Saari et al., 2024). People who used opioids, in one qualitative study, preferred lower dose IN products (Neale et al., 2022). In 2024, the Michigan Drug User Health Alliance surveyed 108 people who use drugs about their reversal product preferences. Respondents overwhelmingly preferred standard-dose products to high dose or long-acting products (Michigan Drug User Health Alliance, 2024). Medical personnel also prefer to titrate naloxone dose based on the medical presentation of their patient (Tylleskar et al., 2020)."

"Findings show that smoking drugs is a popular route of administration among people who use drugs and evidence from this review suggests that expanding access to safer smoking within harm reduction services is crucial to risk mitigation. Within the studies included in this review, most study participants, including people who smoke drugs, peers, and service providers, believed safer smoking services to be a necessary harm reduction intervention, especially when considered in relation to existing safer injection services [39, 40, 42,43,44, 51, 54, 56, 63, 64, 67, 68]. Further, across studies, people who use drugs reported a high willingness to utilize these services, and in places where services were offered, many studies reported high utilization of safer smoking services. Additionally, although efficacy data were limited, across studies, people who use drugs reported decreasing their injection drug use in favor of smoking, reducing the sharing of smoking equipment, and in some cases improved health outcomes (e.g., decreased burns and cuts). Despite the clear benefits of safer smoking practices, some people who use drugs and service providers reported ongoing barriers to accessing and delivering these services, respectively. Findings underscore the need for ongoing research and structural interventions to increase access to safer smoking programs and reduce drug use related morbidity and mortality.

"This is a burgeoning area of research, which we expect to grow and evolve as policies shift, more funding becomes available for the inclusion of safer smoking kits into harm reduction service offerings, and the benefits of these practices become more well known. In fact, since the time that this search was conducted, a new study was published in May 2023 that showed high interest in using safer smoking materials, with participants believing it would reduce their injection use of drugs. As additional studies are published, including those that are based on higher quality evidence, we anticipate a need to update this review in future years [70].

"Despite evidence that smoking has benefits over injecting [39, 40, 42,43,44, 51, 54, 56, 63, 64, 67, 68], across studies, people who use drugs report programs providing safer smoking materials are a minority among harm reduction organizations globally. Ongoing work is needed to incorporate safer smoking materials into the services provided by existing harm reduction organizations. The studies reviewed here provide evidence of the presence of peer workers who are part of these communities as people with lived experience and found peers to be integral in engaging people who use drugs and assisting them with changing their practices. Further outreach to educate people who use drugs about smoking as a harm reduction practice is necessary, including the nuanced benefits and risks associated with it."

"Some participants noted that in their country there was a move towards greater recognition of the need for public health-oriented approaches to tackle drug problems accompanied by a shift in the goals of drug policies towards reducing drug-related harms. However, the relatively limited set of indicators that has historically been used to evaluate drug policy may have limited utility for informing on outcomes relevant to this perspective. Some drug policy experts have argued, for example, that a preoccupation with drug use prevalence as a primary outcome measure for drug policy is problematic, as it does not sufficiently consider the complexity of patterns of use or harms, nor distinguish sufficiently between different forms of drug use and the harm attributed to them. Taken together, trends suggest that moving towards drug policies that accentuate targeted approaches to reducing drug harms necessitates concomitant shifts in the focus and priorities of drug monitoring and evaluation systems. This would imply giving greater attention to indicators that monitor harm. In addition, approaches which can more holistically consider different patterns of use and how these may interact are likely to be necessary for informing future drug policy evaluations (Rhodes, 2019).

"A drug policy shift towards a focus on harms to target responses may also be accompanied by arguments for drug law reform. It is argued for example that there is evidence that suggests the criminalisation of drugs can increase some health, social and economic harms. Accordingly, there is a momentum towards seeking alternatives to criminalisation for simple possession and greater consideration in policy discourse on the possible unintended negative consequences of different policy options (Rhodes, 2019)."

"The adulteration of illicit drugs is not a new phenomenon, with evidence of it occurring as early as the 1930s (Morgan, 1982). Ecstasy, in particular, has a long history of adulteration (Hayner, 2002; Morelato et al., 2014; Verweij, 1992) which has been exacerbated in recent years by the emergence of new psychoactive substances (NPS; ~900 identified to date, United Nations Office on Drugs and Crime, 2019). The composition of drugs sold as MDMA/Ecstasy/Molly in particular varies substantially over time and across countries (Brunt et al., 2017) – currently, adulterated ecstasy remains a concern in North America and Australia (primarily among nightclub and dance festival attendees; Australian Criminal Intelligence Commission, 2019; Mohr, Friscia, Yeakel & Logan, 2018; Palamar et al., 2017), while high dose/purity ecstasy is dominating the European market (European Monitoring Centre for Drugs and Drug Addiction, 2019). Drugs adulterated with fentanyl and its analogs are now of particular concern in the US as tens of thousands of people are now dying in the US per year from fentanyl exposure (Scholl, Seth, Kariisa, Wilson & Baldwin, 2018) and it is likely that many of these deaths result from unknown exposure (Ciccarone, Ondocsin & Mars, 2017). To mitigate the risks associated with consuming unregulated substances, drug-checking services have been operating for decades, whereby individuals submit drug samples to have the contents identified and analyzed for purity (Barratt, Kowalski, Maier & Ritter, 2018; Brunt, 2017; Renfroe, 1986). A global review of drug checking services operating in 2017 identified 31 services, three of which were operating in North America: DanceSafe, EcstasyData, and ANKORS (Barratt, Kowalski et al., 2018). These services reported using reagent tests kits, often in combination with other methodologies, including thin layer chromatography and gas chromatography mass spectrometry (Harper, Powell & Pijl, 2017).

"In addition to formal drug-checking services, the use of personal reagent test kits appears to be relatively common (i.e., ‘informal’ drug checking). A recent study estimated that over one-fifth (23%) of past-year ecstasy consumers in New York City had tested (or had someone test) their ecstasy using a drug testing kit in the past year (Palamar & Barratt, 2019). Similarly, a study of ecstasy consumers in Australia found that 22% reported personal use of testing kits (Johnston et al., 2006). However, while numerous studies have explored the prevalence, acceptability, and behavioral outcomes associated with both formal and informal drug checking (e.g., Barratt, Bruno, Ezard & Ritter, 2018; Day et al., 2018; Goldman et al., 2019; Measham, 2019), little attention has been devoted to understanding the role and broader experiences of ‘drug-checkers’ (i.e., people who test their own and/or other people’s substances). As such it remains unknown who is testing drugs, the motivations for doing so, and what barriers they may experience. This omission is particularly concerning given that many of these individuals are volunteers, operating in environments which are fraught with political and legal challenges (Barratt, Kowalski et al., 2018), and may be taking a considerable personal risk in providing such services."

"This research sought the perspectives of people involved in the unregulated drug market on how drug checking could be implemented as a market intervention within the current context of a highly unpredictable drug supply and unprecedented rates of overdose. Currently, drug checking is positioned as a public health intervention promoted to people who use drugs within supervised consumption sites while being averse to aiding people who sell or produce drugs. Drug checking does not need to be limited to an individual-level behavioral intervention targeted at the end user of a substance, but holds the potential to also function as a supply-side intervention within the drug market linked to overdose. However, careful consideration is needed to design and deliver appropriate drug checking services within the context of the criminalization of substances and the drug market. The demand for quality and product assurance within the illicit supply may operate as a potential driving force to facilitate drug checking and we identified several novel strategies to this end; however, there are also significant implementation challenges.

"We heard that criminalization was the most critical barrier to accessing drug checking services for those within the supply chain. While unsurprising, there are particular considerations and intervention design factors to be addressed to engage sellers and potentially function at a market level. Overall, the benefits of drug checking services need to ensure high-quality services that enable quality products, provided by knowledgeable peers and scientists, and establish trust and safety to outweigh the risks of arrest for accessing services. Promoting drug checking for marketing quality products may be more successful than relying on traditional health promotion messages. Safer settings within the context of criminalization are critical and yet not clearly defined and vary depending on the person and context. Trust was identified as central to successful implementation and may be enhanced through engaging peers and word of mouth."

"Historically, harm reduction principles are actualized when individuals and groups take sometimes illegal measures to protect their communities. Once systemic structures recognize the value in these practices, they might become decriminalized and widely supported by public health institutions. As an example, supervised consumption sites have been created; these are spaces where individuals can use drugs in a sterile and monitored space with access to supplies and care. Legalized in certain European nations, Canada, and Australia, supervised consumption sites in the U.S. operated quietly and against the law [8]. With increased evaluations published globally, and within the country on unsanctioned supervised consumption sites [9], we see increased receptiveness in academic circles. In the U.S., this illicit practice of providing safe spaces to consume drugs recently gained popular ground with Rhode Island becoming the first state to legalize supervised consumption sites [10], and OnPoint in New York City opening the first SCS in the U.S. [11]. Other recent innovations in public health lifted up by the advocacy of people who use drugs include drug checking and safer smoking initiatives."

"Illicit drug use at music festivals has been the subject of Australian public and media attention following the drug-related deaths of six young Australians across two festival seasons in 2019 and 2020 (Lee, 2019), and a further young Australian at a festival in February 2023 (Australian Associated Press, 2023). Internationally, studies show higher rates of drug use among music festival attendees compared to the general population (Day et al., 2018; Fox et al., 2018; Hughes et al., 2019; Hughes et al., 2017; Measham and Simmons, 2022). A substantial proportion of the health risks associated with illicit drug use relate to the lack of regulated drug supply caused by prohibition; for example, there is risk of variable purity, whereby the substance is stronger than anticipated (Day et al., 2018; Hughes et al., 2017), or risk of unexpected substances (e.g., fentanyl) being ingested at unknown doses or causing harm via interaction effects due to adulteration (Atherton et al., 2019; Karamouzian et al., 2018; Maghsoudi et al., 2022).

"Methods used to characterise drug use at music festivals include drug checking, in situ surveys and wastewater analysis. Drug checking services conduct chemical analyses of substances of concern submitted directly by the public and return the results to the service user through a tailored intervention that aims to reduce drug-related harms (Barratt and Measham, 2022). A secondary benefit of these services is their ability to generate unique and timely information about drug markets that can be disseminated rapidly via text message or social media alerts (Barratt and Ezard, 2016; Brien et al., 2023; Sample, 2015; Measham, 2019). Next, a handful of studies have used in situ patron surveys to investigate patterns of drug use at music festivals (e.g., (Day et al., 2018; Barratt et al., 2018; Southey et al., 2020)); while valuable, surveys are limited in their ability to accurately capture the full range of substances used due to sampling constraints and reliance on self-report (Lancaster et al., 2019; Zuccato et al., 2005; Tscharke et al., 2015; Gjerde et al., 2019). In contrast, other studies have analysed wastewater samples collected from festival-based sewage sources, essentially conducting an anonymised urine test on the whole festival (Bijlsma et al., 2020; Lai et al., 2013; Bade et al., 2020; Mackulak et al., 2019). While wastewater analysis cannot provide insight into individuals' experiences of substance use (e.g., amount used per person, motivations for use), it provides an objective, non-intrusive method of measuring substance use without raising major ethical issues (Gjerde et al., 2019; Lai et al., 2013; Mackulak et al., 2019; Mackulak et al., 2015), thus overcoming many of the limitations of survey data in these settings. A novel approach combines survey and wastewater data to compare substances that participants believe that they are using (via surveys) versus the drugs they are actually using (via wastewater analysis). We are aware of only one study internationally using this method among festival attendees; Brett and colleagues (2022) reported the detection of cathinones in wastewater at music festivals in New South Wales, Australia, yet no survey respondents reported intentional cathinone use, showing the value of this complementary approach (Brett et al., 2022). Using similar methodology to Brett et al. (Brett et al., 2022), and within the context of the imminent implementation of drug checking services in Queensland, this study aims to characterise the differences between drugs that participants self-report using or intending to use in surveys versus the drugs detected in wastewater at a Queensland-based music festival across two consecutive years (2021 and 2022)."

"One of the consequences of drug prohibition is the lack of knowledge regarding the composition and purity of illicit substances (Miron, 2003; Taylor et al., 2016). This information gap poses significant risks to individuals who consume drugs, as they lack knowledge of the contents which can lead to physical harm (Darke & Farrell, 2014; Unick et al., 2014). In the context of harm reduction, drug checking has emerged as a strategy to address this issue. Drug checking programs aim to provide consumers with accurate and timely information about the content and potential harms associated with the substances they intend to consume (Maghsoudi et al., 2022). Drug checking was traditionally designed to provide harm reduction services and information about illicit substances in party scenes, however, the remit of drug checking has expanded significantly (see Barratt & Measham, 2022). Drug checking programs can be traced back to the late 1960s in the United States (Barratt et al., 2018). According to a recent systematic review, these programs have expanded globally and are now implemented in many countries including the United States, United Kingdom, Netherlands, Switzerland, Spain, Portugal, Belgium, France, Australia, and Canada (Colledge-Frisby et al., 2023).

"Drug checking initiatives seek to empower individuals to make informed decisions about their drug use (Weicker et al., 2020). These programs typically involve analysing drug samples using various methods, such as spectrometry or reagent testing, to identify the presence of specific substances and potential adulterants as well as dosage or strength (Barratt & Measham, 2022). The provision of drug testing results to consumers provides some information about the potential risks associated with their drug use (Barratt & Measham, 2022), although it is important to note that these results may not encompass all possible risks due to limitations in testing methodologies and the multifaceted nature of drug-related harms (Masterton et al., 2022). Risks associated with drug use can be influenced by various factors, including the environment and co-substance consumption, which may significantly impact the overall risk profile beyond the specific drug content or purity (Masterton et al., 2022). However, the implementation of drug checking programs has shown positive outcomes and increased safety among drug consumers in jurisdictions where it has been applied (Bardwell & Kerr, 2018; Measham, 2019). Feasibility studies indicate acceptance and willingness among consumer populations to engage with these services (Kennedy et al., 2018; Krieger et al., 2018; Palamar et al., 2019; Sherman et al., 2019). The positive reception among consumer populations to engage with these services align with the call for widely accessible harm reduction measures."

"PWUD demonstrated a predominantly protective approach to xylazine emergence by modifying their drug consumption routes and reducing injection drug use, aiming to mitigate potential harms associated with xylazine adulteration. While often discussed in the context of xylazine here, this echoes a broader literature that reveals an elevated prevalence of smoking among people who previously injected opioids on the West Coast of North America [30–32].

"Xylazine use has been associated with severely necrotizing skin infections that produce wounds even distal to the injection site or when individuals are smoking [10, 12, 33]. While more research is needed on the health implications of transitioning away from injection drug use towards other routes of administration (e.g., smoking) and its consequences, it is possible that transitioning away from injecting could reduce the likelihood of tissue necrosis or subsequent SSTIs [34]. However, it is still unclear if transitioning from injecting to smoking opioids (especially those adulterated with xylazine) decreases one’s risk for overdose and what the impacts are on cardiovascular health [35].

"While clients’ reliance on alternative consumption routes and peer networks for safety highlights the importance of peer-based harm reduction approaches, increased stimulant use and ‘human testing’ practices, intended to counteract xylazine’s sedative effects and verify drug safety, raises concerns about heightened susceptibility to overdose and other adverse outcomes [3, 36]. Increased polysubstance use with stimulants may increase clients’ overall drug consumption, thereby increasing their risk for additional adverse events (e.g., cardiac arrest, overdose, and SSTIs) [37–39]. Also, reports of using drugs alone underscore the need for additional interventions to address social isolation and enhance safety while people consume unregulated substances. One such intervention that may overcome these challenges could be implementing a phone-based overdose response service, as seen in Canada [40].

"The phenomenon of clients seeking out xylazine for its unique effects challenges existing literature on individuals’ preferences for xylazine and has implications for addiction treatment in the context of an evolving drug supply [41–43]. For example, more research is needed to develop guidelines for managing buprenorphine initiation while individuals are using xylazine-adulterated opioids to help mitigate anxiety and xylazine-related withdrawal symptoms [44]. On the other hand, despite efforts to reduce exposure to xylazine, some clients reported increasing their consumption of opioids, driven by the need to counteract diminished opioid availability and withdrawal symptoms associated with xylazine’s short half-life [45]. This finding contradicts previous hypotheses suggesting xylazine’s role in extending the duration of opioids’ effects [12, 46], indicating a nuanced interplay between substance availability, dependence, and desired effects."

"RAD involves a four-step process. First, wearing gloves, SSP staff members wipe or swab used drug paraphernalia received from registered SSP participants. Each individual wipe or swab is then placed into a small paper envelope that is collected in a larger mailing envelope (2). Program staff members administered a deidentified questionnaire simultaneously with paraphernalia sample collection and linked the questionnaire and sample with a unique barcode number.§§ Second, samples are mailed to NIST in accordance with U.S. Postal Service regulations. Third, samples are extracted and analyzed using direct analysis in real time mass spectrometry (DART-MS), a rapid ambient ionization mass spectrometry screening technique capable of analyzing a sample in seconds and detecting more than 1,100 drugs, cutting agents, and related substances¶¶ (3). Fourth, within 48 hours, NIST reports substances identified in each sample to CHRS and SSPs.*** SSPs are then responsible for sharing individual results back to the participant who submitted the sample. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.†††

"During November 19, 2021–August 31, 2022, staff members from eight SSPs asked program participants for permission to collect a sample from their used paraphernalia for drug testing and to complete a questionnaire about the drugs they had intended to purchase. A total of 496 paraphernalia samples were collected. For 248 (50.0%) of these samples, the program participant completed the questionnaire. No overdoses occurred on-site during sampling. The five most common types of paraphernalia tested, accounting for 95.7% of samples, were plastic bags (54.8%), cookers (16.3%), capsules (11.7%), vials (6.9%), and pipes or straws (6.0%). Among the 496 samples, one or more opioids were detected in 367 (74.0%) and cocaine in 77 (15.5%); none of the screened drugs were detected in 26 (5.2%) samples. Among the 367 opioid-positive samples, 363 (98.9%) contained fentanyl, 23 (6.3%) fluorofentanyl, and six (1.6%) fentanyl carbamate. One sample contained fluorofentanyl only; all other fentanyl analogs (e.g., fluorofentanyl and fentanyl carbamate) were also detected with fentanyl. Nonfentanyl opioids were detected infrequently: heroin (1.9%), tramadol (1.6%), methadone (0.5%), and protonitazene (0.3%). Among samples positive for fentanyl or a fentanyl analog (364), 84.4% had at least one other stimulant, sedative, or benzodiazepine detected: 293 (80.5%) had xylazine, 23 (6.3%) cocaine, 10 (2.7%) synthetic cathinones, six (1.6%) benzodiazepines, and three (0.8%) amphetamines (Figure)."

"The misrepresentation of illicit drugs is a persistent problem in unregulated markets (Barratt et al., 2024, Marshman and Gibbins, 1969). Misrepresentation can take several forms, including dilution of alleged drugs with inactive fillers, adulteration with other active drugs or contaminants, and substitution with other substances. When users consume illicit drugs of unknown content, quality, and dosage, their risk of overdose and other adverse health events increases significantly (Singh et al., 2020, van Amsterdam et al., 2020). Even innocuous fillers can be harmful if administered in novel or unintended ways (Cook et al., 2021, Sehdev et al., 2022). Due to such concerns, many jurisdictions have implemented drug checking programs where users may voluntarily and anonymously submit drug samples for chemical analysis (Davis et al., 2022, Green et al., 2022, Park et al., 2023). Results about drug content, including potentially dangerous substances, are then reported back to users and the community-at-large (Barratt and Measham, 2022). Recent systematic reviews conclude that drug checking programs can effectively monitor drug trends, identify the emergence of novel and dangerous substances, and promote harm reduction and safer use practices (Giulini et al., 2023, Maghsoudi et al., 2022)."

"Most of the concern with MDMA adulteration focuses on the plethora of other substances that have been detected in the MDMA supply. This includes novel designer drugs with potentially serious health risks such as synthetic piperazine and cathinone compounds, which were detected in about 5 % of samples overall. Piperazines first appeared in 2000 but saturated the market from 2008–2013, when these compounds were detected in about one-quarter (24 %) of drug items. Cathinones first appeared in our sample in 2010 but predominated from 2012–2016, when they were detected in more than one-sixth (17 %) of samples.

"Other stimulants excluding synthetic piperazines and cathinones were found in one-quarter (25 %) of drug items overall but peaked from 2006–2009 when they were detected in the majority (52–78 %) of samples. Across all years, caffeine (18 %) and methamphetamine (9 %) were the most prevalent stimulant-class adulterants. Pseudo/ephedrine detections peaked in 2004 (17 %) but practically disappeared after 2006, when the federal ban on over-the-counter pseudoephedrine sales took effect (Rigdon, 2012). Two related designer drugs, the substituted amphetamines paramethoxyamphetamine (PMA) and paramethoxymethamphetamine (PMMA), have been singled out in the literature as particularly toxic (e.g., Refstad, 2003) but were rarely detected in our sample (n=3), the last time in 2012.

"Psychedelic and dissociative drugs showed sizable fluctuations as adulterants over time. Dextromethorphan (DXM) peaked as an adulterant in 1999 (23 %), ketamine reached maximum prevalence in 2007 (21 %), and the novel psychedelic 5-MeO-DiPT spiked in 2011 (9 %). Since 2015, neither psychedelics nor dissociatives have been detected in more than 2.5 % of samples. Notably, cannabinoids and opioids were rarely detected in alleged MDMA. Overall, just six items (0.1 %) contained cannabinoids, and opioids were detected in only 23 items (0.5 %). Very few opioid detections involved fentanyl or fentanyl analogs (n=6), all of which were reported in 2005 and 2015. Pharmaceuticals (5 %) and supplements (4 %) appeared consistently as adulterants, but their prevalence has generally declined over time. The most commonly detected pharmaceuticals were procaine (18 %), acetaminophen (16 %), lidocaine (11 %), and diphenhydramine (10 %), whereas 78 % of supplement detections involved methylsulfonylmethane (MSM), a substance often prescribed for joint health but also commonly used as an MDMA diluent. Chemical precursors and byproducts were detected in about 3 % of samples overall but reached as high as 12–13 % in certain years. The most common substances identified in this category were MDA 2-aldoxime analog (24 %), a synthesis byproduct of MDA, and dibenzylpiperazine (22 %), a synthesis byproduct of benzylpiperazine (BZP). Lastly, unidentified drugs (2 %) and samples with no active drug (3 %) recorded relatively low prevalence overall.

"Not only did patterns of adulteration vary temporally, but they also differed across representations of MDMA. In Table 3, we report the distribution of detected drugs by the type of MDMA misrepresentation. Adulterated MDMA was significantly more likely to contain other stimulants (62.3 % vs. 41.9 %, p<0.001) and supplements (13.2 % vs. 4.9 %, p<0.001). Conversely, substituted MDMA was significantly more likely to contain MDMA analogs (28.6 % vs. 23.5 %, p<0.05), piperazines (13.2 % vs. 3.1 %, p<0.001), cathinones (14.4 % vs. 2.8 %, p<0.001), psychedelics (4.3 % vs. 0.9 %, p<0.001), opioids (1.5 % vs. 0.1 %, p ≤ 0.01), and unidentified drugs (5.1 % vs. 2.4 %, p<0.05). No significant differences were observed for dissociatives, cannabinoids, pharmaceuticals, and precursors/byproducts."

"Results from samples expected to be stimulants were divergent between testing groups. Crystal methamphetamine samples tested using take-home drug checking were reported as fentanyl positive more often than on-site samples (27.6% vs. 5.2%). The same pattern was seen for cocaine samples tested using take-home drug checking (17.2% vs. 1.1%). However, the study was underpowered to evaluate equivalence between these testing groups. A small portion of the test strips (3.8%) yielded an unclear or illegible response. It is unclear what the participants did in these cases, but the inclusion of multiple test strips would have allowed for repeat testing.

"Notably, when the results of take-home drug checking were stratified based on previous experience with fentanyl test strips, there was a trend towards a smaller difference between the results of take-home drug checking and on-site drug checking. For opioids, when only results from those who were using fentanyl test strips for the first time were included, there was a difference of 1.6% between take-home drug checking and on-site drug checking. This difference was reduced to 0.6% when only including samples from those who had self-reported prior experience with using fentanyl test strips. Similar results were seen for crystal methamphetamine (28.9% to 15.2%) and cocaine (28.3% to 7.8%)."

"In a harm reduction setting, a FTS might be used to test the drug residue in a cooker or baggie for fentanyl before use of the drug. Our results show that the concentrations of diphenhydramine, methamphetamine, and MDMA commonly found in street drugs are at levels that could generate false positives on the FTS. Many cookers and small baggies hold about 0.75–1 mL of water. If we assume there is 5 mg of methamphetamine in the container that is diluted with 1 mL of water, the concentration of methamphetamine will be 5 mg/mL and would trigger a false positive on the FTS. If the residue were dissolved with 10 mL of water, the methamphetamine concentration would be 0.5 mg/mL and would render a true negative on the FTS. If the drug residue instead consisted of 95% methamphetamine and 5% fentanyl, the 10 mL dilution would ensure that the methamphetamine concentration would not interfere with the FTS while the true positive result would come from the fentanyl present in the sample. As practical guidance for harm reduction groups, a dilution with at least 50 mL of water will provide a good margin of error for accurate detection of fentanyl in cooker or powder residues while avoiding false positives from other drugs. Over dilution is not a likely problem; the FTS is sensitive enough that if there was just 0.5 mg of fentanyl residue in a cooker and it is dissolved in a 10-L bucket of water (50 µg/L or 50 ng/mL), the FTS will still detect the fentanyl present."

"The Massachusetts Drug Supply Data Stream (MADDS) is the country's first statewide community drug checking program. Founded on public health-public safety partnerships, MADDS collects remnant drug packaging and paraphernalia with residue from people who use drugs and noncriminal samples from partnering police departments. MADDS tests samples using simultaneous immunoassay fentanyl test strips, Fourier-transform infrared spectrometry (FTIR), and off-site laboratory testing by gas chromatography-mass spectrometry (GC/MS). Results are accessible to community programs and municipalities, while trend analyses inform public health for cross-site alerts and informational bulletins.

"Implementation:

"MADDS was launched statewide in 2020 and rapidly expanded to a multisite program. Program staff approached communities and met with municipal police and community partners to secure written agreements to host drug checking. Community partners designed sample collection consistent with their pandemic era workflows. Consultations with stakeholders gathered feedback on design and deliverables.

"Evaluation:

"The program tests sample donations on-site from community agencies and police departments, incorporates review by a medical toxicologist for health and safety concerns, crafts stakeholder-specific communications, and disseminates English, Spanish, and Portuguese language materials. For 2020, a total of 427 samples were tested, of which 47.1% were positive for fentanyl. By early 2021, MADDS detected shifts in cocaine purity, alerted communities of a new toxic fentanyl analogue and a synthetic cannabinoid contaminant, and confirmed the increase of xylazine (a veterinary sedative) in Massachusetts.

"Discussion:

"Community drug checking programs can be collaboratively designed with public health and public safety to generate critical health and safety information for people who use drugs and the communities where they live."

"In order to help prevent overdoses, lateral flow immunoassay test strips originally designed for monitoring traces of fentanyl and its analogs in urine are being explored as a drug checking technology in harm reduction contexts [17,18,19,20]. One commonly used fentanyl test strip or “FTS” (BTNX Inc., Markham, ON, Canada) is a lateral flow chromatographic immunoassay for the qualitative detection of fentanyl in urine at the cutoff concentration of 20 ng/mL. A positive result on this test strip gives one line, a negative result gives two lines, and an invalid test gives either no line or no control line [21]. The “off label” use of the FTS in a harm reduction context involves preparation of a solution of the drug to be checked. For example, the residue in a cooker or baggie may be dissolved in a little water and then tested with the FTS. BTNX Inc. provides information about specificity of their test strip response, but for fentanyl 20 ng/mL FTS, the only drugs tested were fentanyl (detected at 20 ng/mL in urine) and norfentanyl (detected at 375 ng/mL in urine). In addition, a suite of pharmaceuticals were found to be non-interfering at levels of 100 ug/mL in a urine matrix [21, 22]. We have found that common stimulants and cutting agents that are often present in illicit drugs can create false positives. The problem arises from the cross-reactivity of the antibody for these other substances [23]. Although the affinity of the antibody for these substances is much lower than for fentanyl, if they are present at sufficiently high concentrations, they can cause a false positive result [24, 25]. As we consider the 4th wave of the pandemic, it can be expected that drug users will need to test stimulants to see if they contain fentanyl."

"Based on our findings, distributed fentanyl test strips would be reliable for the testing of samples identified as opioids and should be more widely distributed. There is growing evidence that fentanyl test strips may help prevent overdose when included with other evidence-based strategies (Peiper, 2019). Other informal techniques such as visual inspection of a substance have been applied by PWUD, but may not be effective in substances that contain traces of fentanyl (Peiper et al., 2019). Our study situated fentanyl test strips within sites that provide naloxone kits, drug use supplies such as syringes, supervised consumption of substances, and drug checking using both test strips and more sophisticated technologies. In contrast to the potential for behaviour change from drug checking results, analysis of several cohort studies within Vancouver during the period of increasing fentanyl contamination in late 2016 showed that a majority of PWUD did not change their drug use behaviours nor translate the knowledge of a changing drug supply to an increased risk of overdose (Brar et al., 2020; Moallef et al., 2019). These findings indicate the need for targeted education and harm reduction interventions for those at risk. Distribution of testing supplies provides an opportunity for further engagement. In BC, an expansion of this pilot program, including continuation at sites included in this evaluation, has occurred to distribute fentanyl test strips labelled with instructions for use. Notably, the described positive behaviour changes rely on an individual possessing knowledge around safer ways to use substances, including knowledge around using a small amount (“test dosing”) and using with others or not alone to avoid overdose and allow for naloxone administration. Furthermore, participants identified using at an OPS/SCS as a potential behaviour, which necessitates that these services exist. Our findings around behaviour change in response to a positive fentanyl result underscore the need for comprehensive harm reduction services and education."

"Perhaps our most significant finding is that all of this SSP’s success in implementing drug checking was achieved in spite of, rather than thanks to, the legal and policy environment in which it operates. The COVID-19 pandemic made drug checking practically impossible, but only after systematic police violence against participants and threats against staff had already curtailed provision of this harm reduction service. Indeed, it is likely that drug checking could have persisted during the pandemic absent the very real risk of police interference. This finding mirrors that of qualitative pre-implementation studies of drug checking services in Canada and the United States, which found the criminalization and stigmatization of substance use to be the most likely barriers to implementation [31, 32].

"There is clear, scholarly consensus that law enforcement and criminal justice responses to substance use exacerbate—and sometimes even generate—the individual-level harms of substance use [37,38,39,40,41,42]. This study demonstrates in striking terms how essential harm reduction organizations are equally vulnerable to the misguided, punitive responses so often directed at the people they serve. Policymakers have not sufficiently protected harm reduction efforts from state violence. Stricter, more reliable, more enforceable protections against the impacts of drug criminalization are desperately needed. De-criminalization of substance use remains an effective strategy for resolving these and other related concerns [43, 44].

"Another barrier was the ambiguous legal status of drug checking activities. Some states have enacted laws that unambiguously legalize the distribution of fentanyl test strips but fail to clarify the legal status of using advanced technologies like portable spectroscopy devices for the same purpose (examples include Illinois Public Act 101–0356 and North Carolina § 90–113.22). As of May, 2021, at least 10 U.S. states had legislation pending that would create a legal framework for some drug checking activities [45]. In light of the fact that the U.S. Department of Health and Human Services (HHS) explicitly endorsed community drug checking by permitting grantees to spend federal funds on fentanyl test strips [46], any absence of a legal framework for making use of those technologies, including in Massachusetts where this study took place, is particularly glaring. This study demonstrates the importance of providing a clear legal framework for community drug checking with any technology."

"Globally, community drug checking programs (CDCPs) allow people to submit drug samples for chemical analysis. The results are shared with the donating individual or organization for their health and safety.³,⁴ Data about the samples help drug supply monitoring and constitute a valid, nonduplicative source of information.⁴,⁵ While this strategy is an established harm-reduction tool in Europe,⁴ it is a new endeavor in the United States. Permissions to use federal funds to distribute immunoassay fentanyl test strips (FTS) came in 2021, indicating support for expansion of drug checking to detect fentanyl and raise community awareness of this approach.⁶,⁷

"Determining whether drug samples contain IMF or analogues can help mitigate consumers' risk of overdose and promote safety interventions.⁸–¹³ One study found substantial changes in overdose safety and drug use behaviors following FTS utilization.¹⁴ Our 3-city FORECAST Study found that many people who use drugs (PWUD) do not prefer drugs containing IMF¹³ and 39% employ practices to reduce risk, given unknown drug purity and content,¹⁵ suggesting advantages to disseminating drug checking results and harm-reducing messages.¹⁶ Drug checking with FTS and a handful of comprehensive CDCPs have been implemented in the United States alongside activities such as syringe service programs (SSPs),¹⁷ but no CDCPs operate as both a harm-reduction service and a drug supply monitoring program in the United States, and none globally integrate public safety partnerships or test noncriminal drug samples from police. We describe the approach and initial uptake of a harm-reduction service and public health monitoring tool, the Massachusetts Drug Supply Data Stream (MADDS), a statewide CDCP built upon public health, harm reduction, and public safety partnerships."

"This study also demonstrates that available technologies fail to fully meet the needs of drug checking programs. As legal avenues for drug checking services expand, additional resources at the local, state, and federal levels should be directed towards the improvement of portable spectrometry devices and other technologies that might be useful for drug checking. The organization included in this study, and the broader drug checking peer-network in which they participate, has already made enormous advancements in the use of these devices for community drug checking [47]. Dedicated and well-resourced efforts to leverage that expertise and advance existing technologies could quickly bring drug checking out of its proverbial “Bronze Age.”

"The cost of acquiring and using this technology is one that many harm reduction organizations cannot manage. The 26-billion-dollar global settlement from opioid litigation will soon be distributed to cities and counties across the United States, creating unprecedented opportunity to invest in high-demand, high-impact interventions like community drug checking. As states are developing their global settlement spending plans [48], numerous experts have urged state leaders to dedicate that funding toward the support of essential harm reduction services, including drug checking [49]. Further, as portable spectroscopy devices perform the same function as fentanyl test strips, but do so more expansively, there is a strong rationale to expand the use of federal funds to include both fentanyl test strips and other drug checking equipment. These instruments are often purchased for forensic reasons and maintained by law enforcement and forensic laboratories. Support for their purchase, use, and extension to public health and harm reduction realms would be a way for HHS to explicitly support community drug checking."

"Community pharmacies are essential healthcare destinations that serve as an optimal resource for addressing non-urgent inquiries, such as safe injecting practices, management of adverse drug reactions, and medication provision, thus reducing the burden on general practitioners (GPs) [1, 2]. Pharmacists also have a role in addressing social determinants of health and promoting health equity, including the support of primary prevention strategies such as harm reduction interventions [3], for example through needle and syringe programs (NSPs) [4, 5]. In addition to offering advice and facilitating HIV/Hepatitis testing, pharmacists serve as a vital referral mechanism to various social, medical, and treatment services [6]. The experiences of pharmacists in this context have demonstrated predominantly positive outcomes associated with NSP provision [7, 8]. However, consumer attitudes to harm reduction service provision have been mixed [9], largely as a result of perceived systemic barriers for consumers which are often evident at sites of delivery [10, 11]. McVeigh et al. underscored the necessity for enhancing pharmacists' harm reduction training and implementing appropriate strategies to raise awareness of the needs of substance consumers, cater to the diverse needs of individuals who inject drugs, foster trusting relationships, and facilitate engagement within a confidential service setting [12]."

"Although model projections can only provide estimates of health benefits and costs, such analyses can provide intuition around critical mechanisms and assumptions to inform decision making. Our main finding is that, over 20 y, high coverage (enrollment of 50% of the eligible population) of OAT [Opioid Agonist Therapy], NSPs [Needle and Syringe Programs], and Test & Treat in combination could avert nearly 43,400 (95% CI: 23,000, 74,000) HIV infections among PWID [People Who Inject Drugs] and reduce HIV prevalence among PWID by 27% (95% CI: 12%, 45%). The construction of such a portfolio has the potential to be cost-effective at each incremental expansion, with projected ICERs below US$50,000 per QALY [Quality-Adjusted Life Year] gained. Moreover, our analysis suggests that the estimated benefit obtainable by PrEP alone (measured in QALYs) could potentially be achieved and even surpassed at substantially lower cost by combining other prevention interventions into high-value portfolios.

"Advocates for efficient investment in PWID-specific interventions have asked, “What good is preventing HIV if we do not first save that life at HIV risk?” [77]. Our analysis suggests that the high competing mortality risks of PWID can explain why interventions that immediately improve quality of life can have substantially higher estimated benefits than those that focus on HIV prevention alone. Our analysis estimates that OAT, in particular, which we assume has a direct impact on the length and quality of life of treated individuals [27,28,30–32,60,61], can provide substantially more benefit, measured in QALYs, than other interventions, even when it prevents fewer infections (Table 2).

"Although our analysis did not identify a scenario in which OAT was not a cost-effective addition to a high-value portfolio, deterministic and probabilistic sensitivity analyses can provide intuition regarding scenarios in which NSPs could replace OAT as the priority investment. Because the assumed delivery cost of NSPs is so much lower than that of other programs, our findings suggest that it is reasonable to invest in NSPs concurrent with OAT scale-up. While Test & Treat is often estimated in our analysis to be a cost-effective addition to the portfolio, our model does not project it to be a priority investment. Our estimates for ART’s reduction of transmission risk via injection-based contact [13,44] are lower than those for sexual contact [14,41,44], which may explain our projection of smaller benefits in the PWID population. It should also be noted that HIV prevalence in US PWID is less than 10% [18], and the direct QALY increases from Test & Treat programs were therefore low relative to programs that served the entire PWID population."

"In June 2020, the presence of xylazine, a veterinary sedative, was first detected as an active cut in heroin/fentanyl MADDS samples but in very low or trace quantities from 2 sites. By fall 2020, the ratio of xylazine to other active drugs had increased, and by the end of the year, xylazine was identified in 6.3% of MADDS samples (13.4% of fentanyl, 22.2% of heroin) and detected at all sites. At the close of 2020, some samples were found to contain more xylazine than fentanyl (eg, https://DrugsData.org/9661).

"The stimulant supply also exhibited dynamic changes during 2020. In prior work,²¹ FTIR scans of cocaine street samples found few active cuts, the modal cut being levamisole, a deworming agent. However, the 2020 samples exhibited high ratios of phenacetin, an obsolete pain-relieving medication unavailable in the United States. The high ratio of phenacetin found in powder cocaine (eg, https://drugsdata.org/9491) and crack (rock) cocaine samples (eg, https://drugsdata.org/9314) across MADDS sites was of concern because it was unexpected and, if ingested, may have negative health effects for people regularly using cocaine. Phenacetin is a carcinogen and can be harmful to the kidneys,²⁸,²⁹ which is of concern for PWUD. In many drug markets, phenacetin is a common active cut of cocaine. Its presence in 17.1% of cocaine samples and in high ratio (eg, https://drugsdata.org/9588) suggests that cocaine supply chains in Massachusetts were disrupted by SARS-CoV-2. The prevalence of phenacetin might have been to “stretch” the available cocaine supply. Our review of the literature on xylazine and phenacetin prompted an informational bulletin on both substances in early 2021."

"With the growing availability of AAS [Anabolic-Androgenic Steroids] through online platforms [71, 72] the traditional reliance on social networks and healthcare providers for access to injecting equipment and safer use information has diminished [73–76]. This unregulated supply of AAS and other PIEDs from online sources is accompanied by misleading information regarding the benefits and risks associated with their use [13, 23], posing significant concerns. Given the potential harms of AAS use among the general population [14, 77], current evidence indicates the potential of their growing impact on the health of this substance cohort globally [78, 79]. Therefore, enhanced harm reduction measures are imperative to effectively engage with the increasing diversity of individuals currently engaged in AAS use [41, 80], particularly considering the potential for emerging dangers associated with the uptake of harsher AAS varieties [81]. Our data indicate that community pharmacies represent sites which can establish an enabling environment conducive to harm reduction for this group, and so we provide an immediate practical application of doing so drawn from our data.

"To enhance privacy and confidentiality, community pharmacies can utilise dedicated spaces more effectively, such as private counselling rooms, where AAS consumers can have confidential discussions with pharmacists [55, 82]. Increasing awareness among both pharmacists and consumers about these private spaces has been met with receptivity in relation to mental health [82] and licit substance use [59]. As trust is a crucial component in the pharmacist-consumer relationship, pharmacists have a professional responsibility to establish community pharmacies as ‘safe spaces’ where individuals feel comfortable discussing their health concerns, including AAS use. By adhering to the Code of Ethics, which prioritises the health and wellbeing of consumers [83], pharmacists should set aside judgments and create a non-judgmental environment that fosters open communication. However, our findings revealed a knowledge gap among pharmacists regarding these substances, highlighting the need for further training and education initiatives. Despite this gap, pharmacists demonstrated receptivity to learning and enhancing their understanding of AAS and other PIEDs, indicating a potential for improved engagement in harm reduction efforts within community pharmacy settings. Further research is needed to understand knowledge gaps, training needs, and the effectiveness of educational interventions for pharmacists in addressing AAS use. These efforts can contribute to fostering a conducive environment for harm reduction for AAS consumers, a necessity that demands immediate attention."

"These pilots suggest that community-based drug safety testing can provide, first, engagement with more diverse drug–using communities than event-based testing—in terms of demographics, drugs of choice and risk taking behaviours—and therefore potentially can be more inclusive and impactful across drug–using communities including with marginalised groups. Second, there is the potential benefit of issuing proactive alerts for substances of concern in local drug markets ahead of specific leisure events, as happened with a mis-sold ketamine analogue identified in this study. Third, community testing can benefit from accessing fixed site laboratory facilities (in this case, a university chemistry department) to complement the speed and convenience of mobile laboratories with potentially greater analytical capabilities and trialling of new technological developments.

"These benefits cannot be presumed, however. The community pilots highlighted that service design characteristics and operational variations such as venue, day of week, prior publicity and outreach activities all can influence outcomes. Moving to a neutral central building attracted larger numbers and a greater diversity of service users as well as building trust with new service user groups, with drugs outreach staff further enhancing engagement with more marginalised drug using communities."

"DCRs have been legally possible in Portugal for almost two decades but have not before been implemented. The overhaul of Portugal’s drug policy is summarized in the 1999 National Drug Strategy, which lays out a shift toward a less repressive drug policy and one centered on humanism, pragmatism, and public health. In 2001, both the decriminalization of low-level possession and use of illicit drugs and the Decree-law 183, regulating harm reduction responses, came into effect. DCRs are among the harm reduction measures detailed. However, the relevant law restricts DCR locations to areas that are not densely populated. The opening of a MDCR, which is part of a larger initiative by the city government and harm reduction NGOs to open 3 DCRs, two fixed and one mobile, allows service of the densely populated urban center. Only injection consumption is possible in the van due to limited space and lack of smoke extraction capacities."

"GAO found that 48 jurisdictions (47 states and D.C.) have enacted both Good Samaritan and Naloxone Access laws. Kansas, Texas and Wyoming do not have a Good Samaritan law for drug overdoses but have a Naloxone Access law. The five U.S. territories do not have either type of law. GAO also found that the laws vary. For example, Good Samaritan laws vary in the types of drug offenses that are exempt from prosecution and whether this immunity takes effect before an individual is arrested or charged, or after these events but before trial.

"GAO reviewed 17 studies that provide potential insights into the effectiveness of Good Samaritan laws in reducing overdose deaths or the factors that may contribute to a law’s effectiveness. GAO found that, despite some limitations, the findings collectively suggest a pattern of lower rates of opioid-related overdose deaths among states that have enacted Good Samaritan laws, both compared to death rates prior to a law’s enactment and death rates in states without such laws. In addition, studies found an increased likelihood of individuals calling 911 if they are aware of the laws. However, findings also suggest that awareness of Good Samaritan laws may vary substantially across jurisdictions among both law enforcement officers and the public, which could affect their willingness to call 911."

"Each year, OMACs [One-Month Alcohol Abstinence Campaigns] attract an increasing number of participants. For example, even if it still represents less than one percent of the Australian adult population in 2019, 44,000 people officially registered for Dry July [28], while they were 16,787 in 2016 and 9,532 in 2010 [34]. Regarding Dry January, 4,000 people participated in the 2014 campaign while they were 3.9 millions in 2020, that is, approximately 7.5% of the UK adult population [35, 36]. However, for ensuring the continued success of such campaigns, it is important to inform participants whether these programs meet harm reduction objectives. This review thus aimed to determine the profile of participants in the different national one-month abstinence campaigns, to estimate the rates and factors of success, and to explore the associated subjective benefits in participating in or completing the challenge.

"Based on the studies pertaining to Dry January, it seems that those taking part in the challenge were more likely to be heavier drinkers, more concerned about their health, and had higher levels of incomes and education. The latter aspects are consistent with those reported elsewhere: the concern for healthy behaviors is more developed among individuals with higher education and incomes [37, 38]. However, this relationship is probably mediated, at least partially, by the overall level of education received, including during school years, suggesting that sustained and universal health education programs could help to bridge this gap [39]. The finding that females were more attracted in participating in abstinence campaigns is possibly in line with the fact that females are in general more concerned about health-related behaviors [40]. However, being a male led to better chance of successfully complete the abstinence campaign, specifically for campaigns promoting restriction of alcohol use. These results may reflect cultural differences across gender, with respect to alcohol use and alcohol-related representations [41].

"Completing the one-month abstinence challenge was found to be associated with lower drinking patterns and better psychosocial functioning at baseline. Thus, it is interesting to note that those participating in the abstinence campaigns had more elevated drinking patterns compared to the non-participating alcohol users, whereas those achieving the challenge had lower drinking patterns compared to those who did not. Another important factor of success was the registration and active participation in social media communities. This is in line with the overall finding that interactive social media on the Internet can be a very effective tool to change health behaviors in the general population [42]. There may be some biases in this finding as participants who registered on social communities might be the most motivated ones, which could explain a better success in achieving the challenge. However, sharing the experience and the difficulties encountered during of a long time period of alcohol abstinence on a virtual community was designated as the most efficient strategy to successfully reach the abstinence goal during the online HSM program [7]. In this program, other strategies which were reported to be efficient to abstain from alcohol include the engagement in alcohol-free activities, the use of non-alcoholic beverages instead of alcohol, support from family and friends, and anticipation of social events [7]. On the contrary, anxiety, stress, negative emotions, social pressure to drink, loneliness, boredom, and no social support were reported as barriers to maintain alcohol abstinence [7]. Considering those dimensions as potential factors for success or failure in national one-month abstinence campaigns would be relevant in further studies.

"Many participants in OMACs reported subjective improvements in health, including improved sleep, weight loss, an increased “energy”. An important finding is that Dry January participants also reported to have tried to increase their physical activity and to improve their diet, which was also reported by Dry July participants during the mid-year health check. This may suggest that these campaigns are actually not merely alcohol-focused for many participants, and might consist for them to a health-focused month, in particular when it is the first month of the year immediately after the end of year celebrations. This finding might have important implications for the evolution of the communication around these prevention campaigns. Moreover, improvement in health after one-month alcohol abstinence was objectively demonstrated for several parameters in a study with drinkers drinking above national guidelines where one-month alcohol abstinence led to a decrease in blood pressure, decrease in circulating concentrations of cancer-related growth factors, decrease in insulin resistance and weight reduction compared to the non-abstinent group [43]."

"Regardless of what led these individuals to become drug checkers, most appeared to be motivated by altruism and the desire to increase safety and minimize risks associated with others’ drug consumption. We describe their efforts in terms of altruism not only because they act in a selfless manner and donate their time and services, but also because unlike many other volunteers, drug checkers also risk arrest by handling illegal drugs, in order to promote the safety of others. Thus, they essentially place themselves under legal risk to help protect others.

"Many checkers mentioned the desire to educate the public about the importance of drug checking as there is a high prevalence of adulterated drugs in North American drug markets. Desire to educate was often two-fold—to directly educate those about to consume a specific drug (typically through the participants testing drugs in front of the individuals providing them), and to educate PWUD more broadly. Even participants who only tested for themselves often disseminated results, publicly, on social media, in order to inform harm reduction efforts for others. The work of drug checkers is driven primarily by the idea that drug checking allows PWUD to be more aware of the actual contents of the substance they intend to consume, so they believe checking reduces the risk of consuming an unknown substance which could produce untoward or unpleasant side effects."

"Our systematic review identified 55 NSP unit cost estimates from 14 middle and high-income countries. Higher unit costs were associated with countries with higher HSRI and fewer syringes distributed, and with newer programs, which confirmed our hypothesis. The number of intervention components included was not seen to affect the unit cost, possibly because the majority of programs did not include any additional WHO-recommended intervention components. Using our best performing model, the cost per syringe distributed of a comprehensive NSP was extrapolated to 137 countries. We find that current spend on NSP among 68 countries examined needs to increase by 2.1-times the current spend to achieve the WHO/UNODC/UNAIDS 2020 target goals of 200 syringes distributed per PWID. Reaching the high-coverage targets for NSPs can reduce the burden of HIV and HCV infection among PWID ^[22] and has been found cost-effective in several settings ^[15,23,24]."

"Xylazine is currently not a scheduled substance under the United States Controlled Substances Act, though some efforts are underway to change this (Drug Enforcement Administration, 2021; Murphy, n.d.). However, supply side efforts to control xylazine adulteration of fentanyl/heroin are unlikely to work and – similar to trends seen when trying to decrease the availability of alcohol, cannabis, and cocaine – will likely exacerbate adulteration (Cowan, 1986). Xylazine test strips, by contrast, are a demand-driven response to unwanted adulterants and may be able influence the composition of the drug supply if xylazine is linked to specific stamps (i.e., how fentanyl/heroin products are branded in Philadelphia) (Friedman et al., 2022). This new form of drug checking represents a potential tool to further empower PWUD to make informed choices about what and how they consume drugs.

"All participants who spontaneously discussed wanting xylazine test strips, or were asked if they would want them, indicated they would use them to test their fentanyl/heroin before drug consumption, if available. Xylazine test strips are not currently available and, to our knowledge, are not in development. Research is needed from broader monitoring and analysis of the drug supply to determine whether xylazine in fentanyl/heroin is pharmaceutical grade. Additionally, it is important to understand if a xylazine test strip would be capable of detecting any xylazine analogs.

"A xylazine test strip may have the potential to positively impact drug use in a similar manner to fentanyl test strips. Fentanyl test strips have been found to significantly alter drug use behavior and foster safer drug use practices with continued testing. Individuals using fentanyl test strips prior to drug use did so in order to prevent fentanyl overdose and the potential need for emergency interventions (Peiper et al., 2019). Additionally, there have been studies reporting fentanyl test strip use following drug use. Among these individuals, positive results for fentanyl were associated with use of reduced doses on subsequent drug consumption occasions (Karamouzian et al., 2018)."

"Although many checkers mentioned that they had not heard of anyone being prosecuted for possession of test kits, many were more directly affected by party promoter and venue owner reluctance to allow their services due to fear of fines or even prison sentences. Checkers affiliated with formal drug checking organizations in particular expressed concern over potential legal barriers associated with drug checking at festivals or other events. The main concern cited by many formal checkers is the “RAVE Act” (the “Reducing Americans’ Vulnerability to Ecstasy Act”). Although this bill in 2002 was never passed, it was reintroduced in US Congress the following year as the Illicit Drug Anti-Proliferation Act which made it illegal to knowingly lease, rent, or use a space for the purpose of distributing or using controlled substances. In response to this Act, party promoters and venue owners fear they would be prosecuted if their venue could be deemed a place where drug consumption was “allowed”. According to this Act, property owners or promoters could be fined up to $250,000 and face up to 20 years in prison if their parties were deemed places where illegal drug use was taking place.

"Checkers commonly cited this law (which they still refer to as the “RAVE Act”) as a major barrier to their harm reduction services as such organizations are often not given permission by party promoters or venue owners, because permitting them to operate on-site could be seen as encouraging or allowing drug use. There were also instances mentioned in which drug checking organizations acquire initial approval to set up a booth at a festival, and then the organization is denied access the day of the festival due to fear of legal liability."

"We did not find evidence that THN [Take-Home Naloxone] training was associated with risk compensation behavior in this cohort of people who inject drugs. Rather, there was no significant change in frequency of injecting any drugs, injecting opioids, or using benzodiazepines after accessing THN. There was also no change in the proportion of time that participants reported using drugs alone, a key indicator of overdose mortality risk.^30,38,39

"There was no evidence of THN-associated compensatory risk behavior in this cohort. While not all overdose risk behaviors were examined in this study (eg, injecting in public, concomitant use of alcohol or benzodiazepines, and use of fentanyl),^40,41 frequency of opioid injecting and frequency of benzodiazepine use are 2 of the most important risk factors for overdose. The association between knowledge of and engagement in overdose risk behaviors is complex,³⁸ and THN is designed to be used on other people who may be at risk of overdose; therefore, it may be pertinent to examine the implications of naloxone availability for drug use in peer networks. In a qualitative study, participants with opioid use disorder residing in residential drug treatment programs in the US described both no change to their drug use and some engagement in riskier behavior by themselves or peers (eg, injecting heroin laced with fentanyl).⁴² However, this finding has not been borne out in empirical evidence and does not appear to correspond with increases in overdose at the population level.^3,4

"Findings from this work are consistent with an emerging evidence base suggesting that concerns about risk compensation with naloxone availability are unfounded.⁴ Yet, these concerns continue to be raised as objections for expanding THN supply.^7,11 For example, a number of pharmacists in a recent Australian study expressed concerns about distributing naloxone, as they believed that recipients would feel comfortable increasing their opioid use.⁴³ However, because naloxone administration can be associated with opioid withdrawal and reverses the effects of any opioids that have been recently taken, the outcomes of naloxone are considered unpleasant by people who inject drugs, meaning that they are typically reluctant to administer the drug.^42,44 Furthermore, it is questionable whether this concern is reason enough to withhold a lifesaving medication from people. Only 40.4% of participants in the SuperMIX study reported THN training, despite most of the sample reporting the use of opioids. There is a clear need for widespread education among health care practitioners and other key stakeholders to enable them to address this common assumption about THN, which can act as a barrier to THN supply so that coverage is increased."

"According to the latest report from the United Nations Office on Drugs and Crime (UNODC), an estimated 11.3 million people inject drugs globally, while HIV prevalence is estimated to be 12.6% and hepatitis C prevalence 48.5% among this population. However, while 179 of 206 countries report some injecting drug use, 110 countries and territories worldwide have no data on its prevalence. This data gap highlights the need for more and higher quality data to inform our efforts to implement appropriate harm reduction services that can address public health issues, including HIV and hepatitis C, soft tissue infections, and overdose."

"Drug consumption rooms (DCR) are in place for more than three decades in Europe and have been proven to be effective as a public health response. However, their implementation remains slow and controversial in many countries. In Portugal, despite being legal since 2001, the first DCR only came into reality in 2019 by the initiative of the City Council of Lisbon."

"This term, which we hope can over time be employed as a keyword in the literature, is intended to foreground children under the age of majority and for whom child rights laws apply in harm reduction theory, policy and practice. Child-centred harm reduction draws attention to the specificities of childhood in harm reduction work. Existing theories of harm reduction may need adaptation to the sociology and psychology of childhood, including the interconnected relationship between parent and child, family-centred care, and attention to children’s rights (see Maynard et al., 2019). Some interventions may not be practical, effective or ethical for children (Watson et al., 2015). Research on existing harm reduction services that work with minors – including those that may not strictly be permitted to do so - may place those children or the service at risk. Issues of consent, identity, agency and maturity, as well as the child’s ‘best interests’ may challenge the assumptions and premises upon which ‘low threshold’ harm reduction services are delivered (Barrett, Petersson, & Turner, 2022). Different legal and human rights standards are engaged, from drug laws to family law to child rights. Child protection laws may require duties of reporting that affect harm reduction service provision and research (ibid). In some cases both parent and child can be legal minors, leading to further challenges and complications regarding assessments of best interests. National, regional and international policy frameworks may need renewed scrutiny through a child-centred harm reduction lens (see for example Barrett, 2015).

"The term is not perfect. For example, ‘child’ may conjure the image of only very young children, when the majority of drug use would involve older adolescents. Few seventeen year-olds would refer to themselves as children. However, those under the age of 18 are legal minors in most contexts, and are ‘children’ for the purposes of child rights. Other terms, such as ‘youth harm reduction’ reproduce the problem of age ranges noted above, while ‘adolescent harm reduction’ omits younger children. ‘Adolescence’ can also extend beyond the age of majority. ‘Paediatric harm reduction’ was considered, but implied an overly medical approach.

"The word ‘centred’ is critical. Our view of child-centred harm reduction extends from neonates to adolescents, with all of the challenges and differing capacities and relationships that arise at these stages of development. Centring the child is key and draws our attention also, for example, to dependent children in adult harm reduction work. We believe that ‘child-centred’ focuses on the specificities of childhood in harm reduction and captures a holistic, rights-based, and person-centred approach."

"Harm reduction is an influential approach to drug policy and practice that ‘encompasses interventions, programmes and policies that seek to reduce the health, social and economic harms of drug use’ (Rhodes & Hedrich, 2010 p. 19). While a universal definition is lacking, harm reduction is distinguished by its focus on incremental positive change regarding targeted harms, which neither presupposes nor precludes abstinence as a goal. NGOs further emphasise a commitment to human rights and social justice, necessitating the separation of drug use harms from drug policy harms, and highlighting the role of policy and legal frameworks as a driver of vulnerability (e.g. HRI, n.d; HRC, n.d). Harm reduction is a cornerstone of HIV and overdose prevention, endorsed by every relevant UN agency in this regard (United Nations, 2019). It is also increasingly influential for other forms of drug use and drug related harms. However, harm reduction has primarily developed around adult drug use, obscuring theoretical, practical, ethical and legal issues pertaining to children and adolescents under the age of majority – both relating to their own use and the effects of drug use among parents or within the family."

"Creating a bridge between public health and drug policy in the context of AAS would be a significant step towards providing adequate healthcare to this, often overlooked, group of substance consumers (Dunn et al., 2023; Piatkowski et al., 2022, 2023a). The risk environments framework provides a theoretical foundation for doing so (Rhodes, 2002), emphasising the importance of enabling contexts and resources in advancing harm reduction (Duff, 2009, 2011). Substance use, including AAS, is influenced by various interacting factors within a social context. Hanley Santos and Coomber (2017) indicate that patterns of AAS use among consumers varied based on their motivations, prior knowledge, and experiences. Many users had limited knowledge about AAS before starting their use, relying on information from peers or suppliers, which was sometimes inaccurate or incomplete (Hanley Santos & Coomber, 2017). As Hanley Santos and Coomber (2017) suggest, when developing interventions targeting AAS use, it is crucial to consider the broader context (e.g., motivations and experiences). Therefore, we extend this study by investigating how individuals' social contexts and cultural interpretations of risk practices shape their engagement with and perceptions of drug checking services, aiming to enhance our understanding of the complexities surrounding risk behaviours and informing drug policy and practice in the context of drug checking. While there is some integration of AAS consumers in harm reduction, predominantly through needle service provision (Kimergard & McVeigh, 2014; Piatkowski, Hides et al., 2022), ensuring the delivery of sterile injecting equipment should be regarded as a minimal requirement (Bates et al., 2021), Scholars have suggested harm reduction frameworks should expand to encompass a comprehensive range of harm reduction interventions that address the needs of individuals using AAS throughout their entire usage cycle, including those who opt for temporary or permanent cessation of use (Bates et al., 2021; Bates & Vinther, 2021). Therefore, further establishing the position of AAS within harm reduction frameworks can facilitate an alliance between public health policy and AAS consumers."

"In 2021, NY State and the USA elected executive branch leaders who publicly supported harm reduction as a public health approach to reducing overdose deaths. In April 2021, the Biden administration explicitly listed “enhancing evidence-based harm reduction efforts” as a drug policy priority for its first year in office, which NYC interpreted as potentially aligned with the concept of OPCs. Similarly, members of President Biden’s senior leadership team, including Secretary of Health and Human Services Xavier Becerra, voiced harm reduction as a priority, although they did not go so far as to endorse OPCs as a strategy. At the state level, NYS ushered in a new administration in 2021, including newly appointed health leadership who had previously contributed to efforts to explore OPCs in prior roles and was on record as supporting OPCs. Although NYS was not on an immediate path to formally authorize OPCs through executive or legislative action, it appeared that NYS would not interfere if an OPC were to open in NYC."

"Our research demonstrates that a number of harm reduction-related needs among PWUD [People Who Use Drugs] can be met entirely through web outreach work, while some can only be partially met online. These findings are in line with the existing literature on online platforms bringing new opportunities to harm reduction services provision [18–20]. They also contribute to the growing amount of literature regarding the processes of web outreach work [22, 23] and bring new evidence on how various needs of PWUD are addressed by web outreach services.

"We identified a three-stage process of web outreach work. The process illustrates the benefits that PWUD gain from online harm reduction services provision without face-to-face contact with web outreach workers. An absence of requirement for physical presence of PWUD at a harm reduction organization facilitates greater level of anonymity in comparison with offline harm reduction services provision. In addition, the use of text messages brings greater convenience to PWUD, who do not feel comfortable with discussing drug use-related issues in person. These factors indicate that web outreach work helps to encourage harm reduction behaviors among PWUD who, otherwise, might not seek or have access to brick-and-mortar harm reduction services."

"• Naloxone access laws that ease restrictions on naloxone possession and distribution are associated with a 20% reduction overdose deaths among African-Americans.

"• Good Samaritan laws, providing immunity from prosecution for those calling emergency services, are associated with broad reductions in overdose deaths, reducing overdose deaths by 13% overall.

"• None of these harm reduction measures result in increase in opioid or heroin use.

"• These laws are effective at reducing overdose mortality without creating additional opioid use. Correspondingly, these measures should be considered an important part of the strategy used to address the opioid epidemic."

"Findings from our study illustrate that many substance use programs do not fit directly into a binary of “harm reduction” or “treatment.” Most of the participating programs in this study reported offering a spectrum of harm reduction and treatment services. Still, SSPs [Syringe Service Programs] were most likely to offer harm reduction services, MOUD [Medications for Opioid Use Disorder] programs were most likely to offer treatment services, and those characterized as offering both MOUD & SSPs were most likely to offer the broadest services. Program clients also did not fit into the supposed binary of “active drug use” vs. “abstinence.” In fact, of the clients who attended MOUD only programs, nearly three quarters reported using non-prescribed drugs in the past week, and more than half reported injecting drugs in the past week; these rates were similar to those reported by clients who attended combined MOUD & SSP programs. Meanwhile, more than 40% of those who attended SSP only programs reported attending some type of drug treatment service in the past month.

"Our results reveal some important incongruencies between services being offered by substance use programs and characteristics and behaviors reported by clients who attend such programs. For example, while three-quarters of MOUD program clients reported using non-prescribed drugs (one-quarter reported using opioids), only two-thirds of these programs offered overdose education or naloxone distribution and one-third offered fentanyl testing or test strips. This is highly concerning given the high prevalence of fentanyl in both the opioid and non-opioid illicit drug supplies [21] and may partly reflect the presence of policies that criminalize possession of fentanyl test strips in some of the sampled states [22]. Moreover, half of clients who attended MOUD programs without SSP or wound care actively injected drugs. While it is possible that these clients seek safe injection supplies elsewhere, a minority (14%) reported visiting an SSP in the past month.

"There were also discrepancies in services offered by SSPs relative to client-reported service utilization. Of clients recruited from SSPs without MOUD, 22% indicated receiving methadone and 8% reported receiving buprenorphine in the past month. This implies clients are either seeking these medications via other service providers or acquiring them on the street, which has been reported to often be easier than enrolling in formal treatment [9, 23, 24]. Roughly half of MOUD programs offered same-day treatment initiation. Additionally, SSP programs were reaching the highest risk population that with the greatest rates of active drug use. Yet, on average, these programs reported having the smallest number of staff and the least available treatment or social services relative to the other programs types. The limited workforce and services offered may reflect the limited budgets often used to operate these programs. Many harm reduction services operate independently from the medical system and are not eligible for insurance reimbursement. Additionally, programs have been historically banned from accessing federal and local funds for SSPs; programs have had to depend on scarce funds acquired a combination of small grants, individual donations, and charitable foundations [4, 25]. The Biden Administration’s 2021 American Rescue Act was the first federal action to allocate targeted funding toward harm reduction services and SSPs [25, 26]. While this was an important step to potentially help scale up these services, local and national resistance and stigma to these programs remains persistent (highlighted by the recent resistance to federal funding sterile pipes [27]). Continued efforts to combat ongoing stigma and political resistance to these programs are needed [25]."

"While cultural and structural differences continue to divide many substance use treatment and harm reduction services, the needs and goals of people who seek these two services may have always been much less distinctive. For example, many who attend substance use treatment continue to use drugs [5]. Similarly, many who attend harm reduction programs seek to engage in treatment at some points [6]. Indeed, clients of SSPs are approximately five times more likely to engage in treatment and three times more likely to stop using drugs than persons who do not access SSPs [7]. In recent decades, harm reduction and treatment goals have become increasingly blurred with the growing uptake of medications for opioid use disorder (MOUD). In particular, methadone and buprenorphine are used by some with a goal of abstaining from opioid use; for others, MOUD are used to help mitigate withdrawal and overdose risk without abstaining from drug use [8, 9].

"Despite this reality, programs that successfully combine treatment and harm reduction services and principles are often the exception rather than the rule [8, 10, 11]. Yet, the increasing severity of the opioid overdose crisis in North America and the rise in viral and bacterial infections among PWUD [12–14] have led to a recognition of the urgent need to utilize multiple approaches toward the joint goal of reducing drug-related harms [15]. In particular, concerns about the increasingly lethal opioid supply [16] have emphasized the need to use any available evidence-based strategies known to reduce opioid-related overdose mortality. These concerns have encouraged more treatment providers to incorporate harm reduction approaches (e.g., naloxone distribution and overdose education) [17], and harm reduction providers to integrate MOUD as a direct service [18]."

"In 2021, the SFDPH [San Francisco Department of Public Health]/DOPE [Drug Overdose Prevention & Education] Project collaboration initiated a pilot program designed to reduce fatal overdoses in permanent supportive SROs by mobilizing and supporting tenant overdose response within these buildings. Known as the DOPE SRO Project, this program recruited, trained, and compensated tenants to serve as overdose prevention specialists (hereafter referred to as 'specialists') who help prevent overdose deaths in the building through naloxone distribution and peer-to-peer training in overdose identification and response. The program was piloted in two supportive housing sites that have experienced escalating overdose death. The first site is a large SRO (160 units) located in the Tenderloin neighborhood that has been operating for over four decades and is home to a mix of long-term and recently housed tenants. The second site is a smaller SRO (50 units) located in the South of Market Street (SoMa) that has been operational since 2018. Both buildings offer case management services and other supports (e.g. food programs, community programming) to tenants, who are referred through the city's Coordinated Entry Systems for homelessness services (Department of Homelessness and Supportive Housing 2022)."

"Findings from this study demonstrate that in many ways, existing programs are not adequately meeting the service needs of or catering to the realities of PWUD. Creating a substance use service system that is truly person-centered and successful at improving health and dignity will necessitate moving away from the binary mentality of harm reduction vs. treatment to one which is better tailored to individual clients. This includes offering a continuum of co-located treatment, harm reduction, and social services that can meet individuals where they are. This would help facilitate access to life-saving services and greater socioeconomic stability [28, 29]. This may be particularly important for individuals with multiple vulnerabilities, as well as during emergencies—such as the COVID-19 pandemic—when minimizing travel and co-locating access to multiple health and social services is key [30]. In our study, programs that included both MOUD & SSP offered the greatest range of treatment and harm reduction services, including naloxone distribution, overdose prevention education, same-day treatment initiation, drop-in spaces, peer services/street outreach, and counseling services. However, these programs were the rarest in our sample of providers and remain largely under-resourced and at the periphery of the substance use service system. Moreover, such integrated models have been made possible by the ability to prescribe buprenorphine in non-traditional treatment settings [31]. Methadone, which may be the most effective and desirable MOUD option for some individuals, and used by many participants in our study, is still largely restricted to the opioid treatment program system bound by regulations on staffing, zoning, and hefty requirements for patients such as frequent urine drug screening [32, 33]. While there are some successful models of lower threshold methadone in other countries[34], scaling up methadone to meet needs of PWUD in the USA will require rethinking some of the core federal and state regulations, including expanding methadone availability beyond the opioid treatment program system [35]. It is important to note that most participating clients reported using drugs other than opioids; thus, integrating interventions for stimulant and other drug use should be central to efforts to better align programs with client behaviors."

"Our analysis of the needs of PWUD [People Who Use Drugs] and services provided to them demonstrates two major functions performed by web outreach workers: 1. They can provide certain services completely online, and 2. They navigate clients within the organization in order to match the needs of the PWUD with a person who can address them. Our research on web outreach work indicates an increasing level of efficiency that comes from online provision of harm reduction services. Instead of traveling to a harm reduction facility, PWUD can contact the organization via an online platform. Furthermore, harm reduction services provided entirely online gain particular relevance amidst the COVID-19 pandemic when offline harm reduction organizations experienced new challenges to providing in-person outreach services.

"Our findings suggest that online harm reduction services provision can be improved in terms of accessibility and efficiency. A challenge for web outreach work, as described by informants, was the inability of workers to communicate with PWUD after hours. One possible solution is to automatize some processes with Telegram bots, as it was done with the cases of OD [Overdoses]. Currently, web outreach workers manually send information to PWUD. If automatized, then PWUD themselves could use a bot to get necessary information at any time of the day. However, not all services can be automatized with a bot; therefore, it may be necessary to employ some workers, who could reply to clients’ requests after hours. This is especially important in emergency situations, such as OD. Another way to develop provision of online harm reduction services is to increase their presence on darknet forums. Greater presence could potentially make online services accessible to more groups of PWUD, who request urgent help after hours and/or who do not use Telegram. Another obstacle in increasing accessibility of online harm reduction services was that some clients refused to continue communication with web outreach workers via the phone. More research is needed to explore the needs that PWUD have in such cases, identify the reasons why certain PWUD refuse to communicate via the phone, and explore how web outreach work can be provided in such instances."

"Canada is in the midst of a devastating overdose crisis that has been further exacerbated by the COVID-19 pandemic and, in particular, the subsequent increased toxicity of the drug supply [1]. Between January 2016 and June 2022, close to 33,000 people died from an overdose in Canada, with the provinces of British Columbia, Ontario, and Alberta accounting for 88% of those deaths [2]. Fentanyl, and to a lesser extent fentanyl analogues, have contributed to a sharp rise in the toxicity of the unregulated drug supply and fatal overdoses [2]. Between January and June 2022, fentanyl was detected in 76% of overdose deaths in Canada [2]. In Ontario, fentanyl is involved in 88% of fatal overdoses [3]. In Toronto, this number rises to 93% [3]."

"Our findings contribute further evidence supporting tenant-led naloxone distribution and overdose education as a critical intervention to address overdose vulnerability in SRO [Single Room Occupancy] settings (Bardwell et al., 2019; Nowell & Masuda, 2020). At the time of writing, the City of San Francisco funds naloxone distribution in seven of its approximately 75 supportive housing SROS, and has committed to making naloxone available in all its supportive housing facilities by 2026 (San Francisco Department of Public Health 2022; Thadani & Palomino, 2022). Rapidly increasing naloxone availability is crucial to reducing overdose deaths in SROs (Bardwell et al., 2017; Rowe et al., 2019). This evaluation foregrounds the benefits of pairing targeted naloxone distribution with programs that train and compensate tenants to lead overdose education and response in their buildings. The city has so far earmarked $1 million dollars to expand the SRO program model into eight supportive housing facilities (San Francisco Department of Public Health 2022). This investment is promising and will allow the specialist program to run in eight additional SROs until June 2023. However, this evaluation highlights the need for enhanced training and psychosocial supports for the housing staff and tenants who are routinely responding to overdoses. Given the broader forms of support and mutual aid that specialists described in this evaluation, they could benefit from expanded training in other social competencies such as collaborative leadership, crisis response, violence prevention, and conflict de-escalation. Involving tenants early on in program planning and training curriculum development may help better tailor training to needs of different SRO environments. Psychosocial supports including grief counseling and post-overdose de-briefing were also requested by specialists and supportive housing team members to address the emotional burden of overdose response work. Regular check-ins with specialists about their workloads will continue to be important to identify and mitigate scope creep."

"Scaling-up interventions such as naloxone distribution programs, supervised consumption services, and opioid agonist treatment have averted thousands of overdose-related deaths in Canada, but the persistent predominance of fentanyl in the unregulated drug supply continues to fuel overdose-related deaths [4]. To complement existing interventions, many have pointed out that providing an alternative to the unregulated toxic drug supply in the form of safer supply is critical to preventing overdose-related deaths and addressing the needs of people for whom current treatment models do not work or are not a good fit [5,6,7,8,9,10,11]. This approach builds on the premise that harms caused by the unregulated drug supply can be averted by providing access to a regulated drug supply [12].

"Over the past few years, there has been a rapid scale up of safer supply programs in Canada [13]. Ontario is home to a dozen safer supply programs where primary care physicians and/or nurse practitioners work with other health care and service providers to embed safer supply prescribing within a broader model of care and supports for clients with complex health and social needs [14]. At the time of the study, safer supply medications in this province consisted of take-home hydromorphone tablets and directly observed slow-release morphine tablets, dosed and titrated to meet clients’ needs. Some programs required both medications to be directly observed for high-risk clients, such as those who report high-volume alcohol consumption or benzodiazepine use. Early evidence suggests that clients enrolled in safer supply programs have significantly reduced emergency room visits and hospitalizations, improved health care engagement, fewer overdoses and overdose-related deaths, reduced drug-related harms, and improved health and social outcomes [14,15,16,17,18,19,20,21,22]."

"The Global Commission on Drug Policy recently advised governments to make harm reduction measures, including drug checking services, widely accessible (Bewley-Taylor & Tinasti, 2020; Buxton et al., 2020). Although there have been calls for drug checking in Australia for some time (Ritter, 2020), initially there were only two Australian trials of drug checking, both performed in a festival context (Byrne et al., 2018; Olsen et al., 2019). This comprised a fixed site trial service launched in Canberra in 2022, which has been extended and is expected to become a permanent service (Olsen et al., 2022). In February 2023, the government of Queensland (the second largest and third most populous state in Australia) announced support for the introduction of drug checking services (Australian Broadcasting Corporation, 2023). The recent recommendation to make drug checking services widely accessible aligns with the harm reduction approach, which recognises the social context and influences surrounding substance use (Bewley-Taylor & Tinasti, 2020; Buxton et al., 2020). The support for introducing drug checking services by the government of Queensland reflects a step towards implementing population-level interventions aimed at reducing drug-related harms and addressing health inequalities. While previous studies surrounding these services have focused on populations such as the nightlife/festival attendees, particularly ecstasy consumers, there is still a gap in research regarding the perspectives and experiences of those involved in the consumption of performance and image enhancing drugs (PIEDs) such as anabolic-androgenic steroids (AAS). Therefore, in the context of the Queensland government's commitment to supporting such services, this study specifically aimed to explore AAS consumers attitudes, perceptions, and needs regarding drug checking. Doing so aligns service provision with broader goal of enhancing health outcomes for this population given the high representation of AAS consumption in Queensland, accounted for by the overrepresentation of AAS-related arrests compared to other states and territories (Australian Criminal Intelligence Commission, 2021)."

"Safer supply programs are not designed or implemented with the explicit goal of changing injection practices. However, the experiences of clients and providers help us understand how a structural intervention, such as safer supply, can impact other aspects of IDU (e.g., frequency of injection) and its associated health risks (e.g., HIV, HCV, etc.). As Perlman and Jordan [37] point out, structural interventions are important because “structural factors contribute potently to creating the context that renders individuals and areas vulnerable to the syndemic of [overdose, HCV, and HIV]” (p.109). These interventions work upstream, to change the “risk environment” [38, 39], rather than solely focusing on mitigating the downstream consequences at the level of the individual. Our study findings suggest that changing the “risk environment,” by providing an alternative to the toxic drug supply, creates more opportunities for risk reduction. Changes in injection practices identified in this analysis offer a compelling example.

"Our findings suggest that clients enrolled in safer supply programs changed their injection practices in three intersecting ways: (1) they changed how often they injected, (2) they changed what they injected, and (3) they changed their mode of consumption (from injecting to swallowing or snorting). These findings add to existing research [16,17,18] by providing a more dynamic understanding of injection practices in the context of safer supply programs and further supporting the idea that safer supply can contribute to reducing injection-related health risks in addition to overdose risks [40]. We posit that safer supply programs have the potential to address disease prevention and health promotion gaps that other stand-alone downstream harm reduction interventions (e.g., needle and syringe programs) cannot address, by working upstream and providing a safer alternative to fentanyl. As Rhodes [38] reminds us, harm reduction interventions such as needle and syringe exchange programs are crucial, but their effectiveness at preventing injection-related health risks can be undermined by a particular “risk environment.” For example, if a particular shift in the drug supply results in people injecting more frequently, such is the case with fentanyl, an HIV outbreakFootnote1 could occur even in jurisdictions where needle and syringe exchange programs are available [38].

"It is important to note, however, that not all changes in injection practices could be attributed directly to safer supply programs. We identified several indirect factors, such as poor venous access and having to inject hydromorphone tablets not intended for intravenous administration (for more on this, see study by Ivsins and colleages [17] and guidance by the British Columbia Centre on Substance Use [42]), which shaped the decision to stop injecting. Having the option of taking safer supply medications orally made this decision possible, but it is unclear if all clients who stopped injecting would have done so if they had access to a range of injectable safer supply medications and/or had better venous access. Moreover, it is unclear to what extent clients continued to inject because the safer supply medications dosage/potency was not meeting their needs, as suggested by clients who spoke of the need to supplement with fentanyl, and/or because they wanted to continue injecting. Future research should aim at exploring these nuances because safer supply programs are not intended as interventions to stop clients from injecting. If clients want to inject, they should be able to do so and access injectable safer supply medications (including injectable hydromorphone) as well as sterile supplies and supervised safer consumption services—a priority echoed in a recent report on substance use patterns and safer supply preferences of PWUD in British Colombia [43]."

"Our analysis of the characteristics of the 48 Good Samaritan laws found that they differ in the protections they offer to individuals who call for medical assistance for an overdose victim. First, there is variation in whether criminal immunity—an exemption from prosecution—is offered and, if so, for which type of drug offense, such as possessing or delivering drugs in violation of an otherwise applicable drug law. Second, there is variation in when criminal immunity takes effect—the timing can be before an individual would otherwise be arrested and charged as a criminal defendant or after these events but before an individual is prosecuted.

"Finally, because a jurisdiction retains the power to prosecute individuals who do not have criminal immunity, some Good Samaritan laws offer either an affirmative defense at trial or a mitigating factor at sentencing, or both."

"Of the 47 laws that provide criminal immunity to individuals who call for medical assistance, 44 cover drug possession offenses. The other three laws (Iowa’s, South Carolina’s, and Vermont’s) cover both drug possession offenses as well as more serious drug delivery offenses, such as selling, dispensing, or possessing drugs with an intent to sell or dispense.25 The 47 laws vary in the specific drug possession and drug delivery offenses covered by criminal immunity (immunized offenses). At the broadest level, Vermont’s law provides immunity for any drug offense.26 In comparison, the other 46 laws limit immunity to a subset of drug offenses. For example, in regards to immunized drug possession offenses, Alabama’s law limits immunity to misdemeanor drug offenses, such as possession of marijuana for personal use, whereas Illinois’s law includes some felonies, such as possession of less than 3 grams of heroin or morphine.27 In regards to immunized drug delivery offenses, Iowa’s law provides immunity if the drugs were delivered without profit, while South Carolina’s law provides immunity if the drugs were delivered to the overdose victim."

"A growing body of data supports the need to deliver HIV prevention in low-barrier settings where PWUD already access services [9]. With opioid use disorder (OUD) increasingly recognized as a chronic and relapsing disease, evidence-based treatment (including medications for OUD [MOUD], harm reduction services, and others) should be integrated into primary care, pharmacies, methadone clinics, social services organizations, fire stations, or other settings alongside other chronic conditions. For example, a clinic may designate a clinic room as their OPS, with injection supplies, peer support, and healthcare personnel available to respond in case of an overdose. To patients, this could signal a non-stigmatizing culture, acknowledge that clinicians should support a patient when their substance use disorder is most active, and may facilitate discussions on MOUD during ongoing use. Drawing on successes of syringe exchange and other peer-based approaches to harm reduction, PWUD should be meaningfully included throughout program development and implementation.

"A decentralized model may have additional benefits. A majority of clients may travel only 1 mile or less to use an OPS [10], meaning that any single location may be inaccessible to some. Decentralized services would assist regions without geographically concentrated drug use. Additionally, the current epidemics, driven by illicitly manufactured fentanyl and stimulants, require frequent injection events—suitable to a decentralized model allowing multiple access points throughout the day. Finally, as federal approval or funding for OPS operation is unlikely in the near future, a decentralized model using existing healthcare infrastructure may minimize costs and improve feasibility."