Psychedelic Drug Checking: Analytical and Strategic Challenges in Harm Reduction for Classic Psychedelics.

Recently, there have been calls for pill testing to be introduced at music festivals. Advocates say that this would inform consumers and reduce risks. However, there are a number of technical and laboratory limitations of such an intervention that need to be considered. This editorial will highlight these limitations. The recent deaths and hospitalisation of young people from illicit drug use has led to calls for the introduction of on-site testing of tablets and capsules containing illicit drugs (‘pills’) at music festivals and events.1, 2 Pill testing, both on- and off-site, is available in several European countries, with individuals submitting samples for drug identification and purity analysis. These services are aimed at both harm minimisation and providing information on the availability and emergence of new psychoactive substances.3 Death and morbidity data are unavailable to ascertain the effectiveness or harm of this intervention. Advocates for pill testing argue that by providing information on content, the person can reconsider taking the pill.4 To support that, an online survey by the Australian National Council on Drugs reported that most young people supported pill testing being available and wanted access to reliable and balanced information so that they would be more equipped to make informed decisions about the risks of using drugs.5 A field survey of Swiss attendees at dance music events reported that respondents were receptive to harm reduction measures, including pill testing. However, 27.4% responded that they would never use pill testing; 31.1% would use it systematically before taking a pill, and 41.6% would not use unless they did not know the substance, dealer or both.6 The introduction of pill testing is perceived as a way to monitor pill composition and encourage information exchange. However, it is possible that information received from this may also be seen as affirming the quality and purity of the pill.7 The testing of illicit drug formulations does not guarantee the safety of the product or protect the person consuming the drug from harm. In a research report on ecstasy pill testing, the authors concluded that pill testing at best gave an artificial ‘shine of safety’, and other simpler harm reduction mechanisms were more likely to be effective.7 Although some would consider some information better than nothing, false reassurance because of false negative results is a concern. Thus, this editorial focuses on the technical and laboratory limitations of such an intervention. On-site pill testing procedures include pill identification, reagent testing kits and chromatographic techniques. Pill identification relies on visually comparing pills supplied by the consumer with formerly analysed pills. This approach has limited utility if testing is to be performed at different geographically distinct locations. Even if the tablets are similar in appearance, it assumes that each batch contains the same excipients and the same dose and that each tablet in a batch contains a uniform dose or that the same tablet press has not been used to manufacture another batch of tablets containing a different drug. Reagent testing involves mixing a small sample of powder scraped or removed from the illicit drug formulation with chemical reagents to produce a colour change. The class of drug present is identified by the colour produced. Some kits are labelled semi-quantitative and use colour intensity to classify tablet content from very low to very high. Problems with reagent testing include lack of specificity between similar compounds, cross-reactivity with non-related compounds producing incorrect results and the inability to detect other potentially dangerous compounds that may be present. As the distribution of the illicit drug in the tablet may not be uniform, samples taken from multiple scrapings of the same tablet surface may give results varying from little or no drug to high concentration. In terms of actual dose that will be administered, the interpretation of what low or very high means is variable. It may be argued that, given the flaws of pill identification and chemical reagent testing, sophisticated techniques, such as liquid or gas chromatography with mass spectrometry, could be employed for on-site pill testing. These techniques involve expensive and technical equipment and highly trained personnel just to undertake the analytical work. For chromatography to be effectively used, there needs to be a previously determined reference library of drugs, likely contaminants and harmful excipients in a tablet or capsule to which test samples can be matched. Any drug testing method needs to know what drug or chemical it is looking for. Therefore, unknown substances in a preparation may not be detected if the testing method is not set up to detect this. The analysis may find the substance it is looking for but miss a dangerous adulterant or, if a new designer drug is present that is not in the assay library, it could be missed completely. This testing method also suffers from the fact that a scraping or sample of powder from one tablet or capsule will not accurately reflect either the dose in that particular tablet or capsule or indeed the dose in any of the tablets or capsules from the same batch. Commonly used chromatographic testing will also not determine the ratio of isomers present if the drug is a racemic compound. Different processes used to manufacture the illicit drug may influence the ratio of each isomer present. As different isomers can vary significantly in potency and psychoactive effect, quantifying the total amount of drug present will not be a useful guide to pharmacological effect.7 Time taken for analysis is also a factor. A reagent test takes minutes, but how many potential pill takers would be willing to delay consumption for the still incomplete but more comprehensive chromatography testing, which may take hours depending on sample numbers. In comparison, production of tablets and capsules in the pharmaceutical industry is highly regulated and subject to strict quality control and safety guidelines to ensure products are safe for the consumer. Any tablet or capsule may contain diluents, disintegrant, binding agents and glidants in addition to the drug. Diluents are added to increase the powder mass. Tablets may also contain a binding agent to help the tablet maintain its shape after compression and a disintegrant so that the tablet breaks into small fragments when swallowed, aiding absorption. A glidant may be added to help powder flow evenly from the machine hopper into the tablet die or capsule shell. This ensures that each tablet or capsule contains the same amount of powder and therefore the same dose. The active ingredient and the excipients must undergo satisfactory mixing to ensure that every tablet or capsule contains the correct dose of drug. Determining the correct manufacturing procedure is in itself a time-consuming process that is strictly controlled. In registered pharmaceutical products, the active ingredient (drug) undergoes identity and purity testing to ensure that no harmful levels of residual ingredients, by-products or other contaminants are present. Excipients are also tested to ensure no effect on drug stability or the performance of the tablet or capsule when administered. During and post-production, tablets and capsules undergo tests, such as uniformity of content and weight, to ensure that each tablet or capsule produced contains the appropriate dose and dissolution and disintegration testing to ensure that the tablet or capsule will disintegrate, and the drug will dissolve at an appropriate rate to produce the desired effect. The stability of the drug in the dosage form over time is also tested to ensure that the drug does not break down to inactive or toxic products. In distinction, the production of illicit drug formulations is not controlled. Illicit drug dosage forms are not subject to any quality control measures, meaning that whilst a drug may be sold as ‘drug X’, it may in fact contain pure drug, no drug, another drug or a toxic or non-toxic diluent. The stability of an illicit drug in the formulation is not known, and there is less, if any, data on potential toxicity of decomposition products. Even if the product contains the active ingredient, it may also contain dangerous by-products of the drug synthesis process. Mixing of ingredients prior to preparing the tablets and capsules is unlikely to be satisfactory, resulting in uneven distribution of drug through the powder bed. This will result in some tablets from the same batch having very little drug while others have a very high dose. As distribution of drug within a tablet or capsule is usually not uniform, a portion of powder taken from one part of a tablet by scraping the surface of the tablet or by opening the capsule for testing may not be representative of what the entire tablet or capsule contains. The pharmacological effects of illicit drugs or other excipients also appear to have been forgotten. Even if the likely drug and dose is determined, drugs exhibit inter-individual variability in their pharmacokinetics and pharmacodynamics. The same dose of drug administered to different people may produce markedly different responses. Observed differences may be because of any number of factors, including genetic polymorphism, interaction with other co-administered drugs and physiological factors affecting drug distribution and elimination. Formulations may also influence how much of the illicit drug is absorbed. If a tablet disintegrates rapidly, a rapid rise in plasma drug concentration may occur, whereas if the tablet does not disintegrate in the gastrointestinal tract, the drug may not be released from the formulation. A delayed release of the drug resulting in delayed onset of action may result in the consumer taking additional pills, thinking the pills they have are ‘weak’.7 For many illicit drugs, the full pharmacological spectrum of action is not known. The lack of pharmacokinetic data for many illicit drugs also poses a concern in an emergency situation with illicit drug intoxication. Often, the pharmacological and toxicological effects of other excipients, by-products and contaminants are not known, producing an unpredictable spectrum of effect. Even reflecting on the small percentage of potential analytical factors discussed here, it is evident that the consumer considering taking an illicit drug may have a false sense of security, particularly if their decision to take the drug is based only on information provided by quantitative and qualitative on-site pill testing. The failure to detect an agent that could be life-threatening is of great concern. Although the ‘harm reduction’ argument is noted, equally, the many unknown and potentially unidentifiable factors that could cause mortality are noted. On-site testing will thus not solve this problem and could lead to other problems of an unpredictable and tragic nature.

Interest of drug checking supply: Results of 3 years of activity in Geneva

Different psychoactive substances are widely used in today's society. So far limited data are available on the use of psychedelics in the general population. The main aim of this study is to estimate the numbers of users of substances with psychedelic properties (classical psychedelics, cannabis, ecstasy, and ketamine) in the Czech Republic. Data from two samples enrolled in representative cross-sectional questionnaire surveys in the Czech adult population in 2016 (n = 2,785) and 2018 (n = 1,665) were analysed. Prevalence rates were extrapolated to estimate numbers of current, i.e., last-year, users of psychedelics, and their socio-demographic profiles were compared with non-users and users of cannabis. An estimated 5-6% of the Czech adult population (350-430 thousand people) used classical psychedelics (LSD, psilocybin mushrooms, ayahuasca) in their lifetime, increasing up to 28-30% when cannabis is included (1.9-2.1 million users). Current use of classical psychedelics reached 0.7-1.9% (50-130 thousand people), and 9-11% (590-750 thousand users) when cannabis was included. Users of psychedelics were more often males, of younger age and single. No significant socio-demographic differences were found between users of classical psychedelics and recreational cannabis users, however, differences were significant when compared to non-users and users of other illicit drugs. Findings should further serve to inform drug policy and social and healthcare systems in respect to the use of psychedelics.

"All it's gonna tell you is if it has fentanyl or not:" Perceptions of fentanyl and drug checking among first responders and people who use drugs.

The emergence of fentanyl and its analogues have contributed to a drastic rise in overdose-related mortality in recent years. The objective of this study was to determine the number of drug checking samples containing fentanyl and fentanyl analogues using both point of care and confirmatory drug checking technologies. Point-of-care drug checking data, using a combination of fentanyl immunoassay strips and Fourier-transform infrared spectroscopy (FTIR), were collected at harm reduction sites in Vancouver and Surrey, British Columbia. Based on current recommendations from the British Columbia Centre on Substance Use Drug Checking Project, a subset of these samples was sent for confirmatory analysis using quantitative nuclear resonance spectroscopy, gas chromatography-mass spectrometry and/or liquid chromatography-mass spectrometry. A total of 22,916 samples were tested using FTIR and fentanyl immunoassay strips, of which 6125 (29%) were positive for fentanyl and/or fentanyl analogues. FTIR identified a fentanyl analogue in five samples (all carfentanil). Of the 1467 samples sent for confirmatory analysis, fentanyl was identified in 855 (58%) and fentanyl analogues in 85 (6%), including: carfentanil (n=56), acetyl fentanyl (n=15), furanyl fentanyl (n=9) and cyclopropyl fentanyl (n=5). Our research found that FTIR does not consistently distinguish between fentanyl and its analogues at point of care and that highly sensitive confirmatory drug checking technologies are needed to identify fentanyl analogues. These findings underscore the limitations of current drug checking technologies and the importance of using both point of care and confirmatory drug checking initiatives for monitoring changes in the drug supply.

Drug checking is an evidence-based harm reduction strategy that can contribute to safer use by providing people who use drugs (PWUD) with actionable information about the contents of the drugs they are using and ways to reduce harm. In response to persistently high overdose rates largely driven by adulteration and volatility of the unregulated drug supply, the New York City Department of Health & Mental Hygiene (NYC DOHMH) initiated a point-of-care drug-checking pilot study in partnership with syringe service programs. Drug-checking services were piloted at 6 sites over the study period. DOHMH staff were trained to use immunoassay test strips and Fourier-transform Infrared Spectrometers, analyze and interpret drug-checking results, and provide tailored harm reduction education to participants. Samples were sent for secondary testing to support technician training and quality assurance. Participant demographics, information about the drug sample, and how individuals planned to use the results were collected and entered into a REDCap database. From November 2021 through December 2023, more than 1600 samples were submitted for analysis. Over half of the samples were sold as opioids (55%; n = 903). The presence of fentanyl in samples sold as opioids was very high (95%; n = 859). Xylazine was detected in 35.0% (n = 201) of opioid samples for which secondary laboratory results were available. 51.5% of participants indicated that they planned to employ a harm reduction strategy or take some other action following receipt of their drug-checking results. Findings from the pilot study demonstrate that it is feasible and acceptable for local health departments to implement point-of-care drug-checking services in partnership with programs that serve PWUD. For some participants, drug-checking interactions may support behavioral intention changes about the drugs they use. Key implementation considerations include the importance of a robust technician training model, selection of appropriate and complementary drug-checking technologies, and availability of secondary lab testing.

A survey of regular ecstasy users’ knowledge and practices around determining pill content and purity: Implications for policy and practice

BackgroundPolysubstance use is common at electronic dance music (EDM) events and hazards associated with polysubstance use may be exacerbated when people who use drugs are unaware of the contents of their drug sample. Reagent test kits (RTK) and fentanyl test strips (FTS) are two efficacious drug checking tools that people who use drugs might use to protect themselves from risks associated with contamination, adulteration, and misrepresentation of unregulated substances. In the current study, we aimed to (1) characterize the use of RTK and FTS among attendees of a 4-day music festival in Colorado and (2) qualitatively capture perceived barriers to using RTK and FTS within festival settings.MethodsWe surveyed 227 music festival attendees on their use of drug checking tools (i.e., RTK and FTS) and behavior in response to drug checking. We also collected qualitative data on perceived barriers of using RTK and FTS within a festival setting using survey-based open-ended text response questions.ResultsThe percentage of participants having ever used RTK and FTS was 75.3% and 66.5% respectively. When asked how often participants ensure their drugs are tested prior to consumption, participants responding “always” or “most of the time” was 54.4% for use of RTK and 59.4% for use of FTS. Additionally, 60.8% of participants reported that they had never consumed a drug that reagent tested differently than expected and 87.9% of participants reported that they had never consumed a drug that tested positive for fentanyl. Perceived barriers to using RTK and FTS within a festival setting encompassed the following themes: (1) accessing testing materials (2) environmental or ecological barriers (3) legal concerns (4) social dynamics (5) lack of education/training and (6) limits of individual drug checking tools.ConclusionsRTK and FTS appear to empower festival attendees in the U.S. to make informed decisions related to their substance use. However, there is a critical need to reduce barriers associated with drug checking for this at-risk population.

The prevalence of fentanyl in New York City's unregulated drug supply as measured through drug checking offered at syringe service programs.

Drug checking is increasingly being explored outside of festivals and events to be an ongoing service within communities, frequently integrated within responses to illicit drug overdose. The choice of instrumentation is a common question, and the demands on these chemical analytical instruments can be challenging as illicit substances may be more complex and include highly potent ingredients at trace levels. The answer remains nuanced as the instruments themselves are not directly comparable nor are the local demands on the service, meaning implementation factors heavily influence the assessment and effectiveness of instruments. In this perspective, we provide a technical but accessible introduction to the background of a few common drug checking methods aimed at current and potential drug checking service providers. We discuss the following tools that have been used as part of the Vancouver Island Drug Checking Project in Victoria, Canada: immunoassay test strips, attenuated total reflection IR-absorption spectroscopy, Raman spectroscopy from powder samples, surface-enhanced Raman scattering in a solution of colloidal gold nanoparticles, and gas chromatography–mass spectrometry. Using four different drug mixtures received and tested at the service, we illustrate the strengths, limitations, and capabilities of such instruments, and expose the scientific theory to give further insight into their analytical results. Each case study provides a walk-through-style analysis for a practical comparison between data from several different instruments acquired on the same sample. Ideally, a single instrument would be able to achieve all of the objectives of drug checking. However, there is no clear instrument that ticks every box; low cost, portable, rapid, easy-to-use and provides highly sensitive identification and accurate quantification. Multi-instrument approaches to drug checking may be required to effectively respond to increasingly complex and highly potent substances demanding trace level detection and the potential for quantification.

Impact of having a regular drug dealer on obtaining drug checking results consistent with expectations during a drug toxicity crisis in a Canadian setting.

ABSTRACTDrug checking services provide individuals who use drugs with the ability to test samples of their drugs for the presence of highly potent substances. However, there has been recent concern about whether the existing repertoire of point-of-care drug checking technologies, such as immunoassay strips and Fourier-transform infrared spectroscopy (FTIR), are adequate in identifying substances in the unregulated drug supply. Carfentanil and nitazene opioids, substances that are even more potent than fentanyl in vitro, have been found in the unregulated supply in North America and pose a challenge to our existing drug checking strategy. For example, etizolam has recently permeated the unregulated drug supply in North America, and has demonstrated the ability to evade point-of-care drug checking technologies. In response to the incessantly changing nature of the unregulated supply, we argue that drug checking technologies and service delivery models must continuously adapt alongside constantly changing drug markets. We provide two examples of emerging technologies, paper spray-mass spectrometry and surface-enhanced Raman spectroscopy, which address many of the shortcomings of existing technologies. For both technologies, we discuss their feasibility, where they can be offered, their advantages, and how they address gaps in our existing technologies. We contend that these technologies, and other emerging technologies, can be integrated into a future approach to drug checking that flexibly uses different technologies and service delivery methods to adapt to changes in the drug supply.

The illicit drug landscape in the United States is dynamic, featuring a risky and erratic drug supply. Drug checking programs (DCP) have been successfully implemented and studied extensively in Canada and Europe but are scarce in the United States. Integrating DCP at harm reduction programs provides an opportunity to engage people at the point-of-care and deliver a combination of harm reduction services, access to healthcare services, and linkages to treatment. The New York State Department of Health (NYSDOH) developed and supports operation of 8 pilot community DCP sites throughout the state. The DCP were trained to utilize Fourier-transform infrared spectroscopy (FTIR) technology to deliver real-time results to participants. The NYSDOH community DCP pilot began development in 2022. Partnerships were formed across multiple domains including other DCP, universities, forensic laboratories, syringe service and harm reduction programs, and legal and regulatory offices within the NYSDOH. The first pilot sites began operating in mid-2023 and program expansion is on-going. Evaluation staff were extensively engaged in development and implementation phases. Qualitative evaluation focused on barriers, facilitators, and lessons learned from program staff and technicians. Quantitative evidence was gathered to assess the reach of the DCP and accuracy of results attained by drug checking technicians during their training periods. Drug checking results helped characterize the illicit drug supply. Development and implementation of DCP in NYS was facilitated by strong partnerships across sectors including public health and harm reduction. DCP may involve diverse partners who do not regularly collaborate, and health departments are positioned to build relationships and convene partners for program implementation. Evaluation findings highlight the importance of facilitating on-going training and technical assistance to DCP for quality assurance. The initial successes and lessons learned from the NYSDOH DCP demonstrate state public health departments' ability to successfully deploy this innovative harm reduction strategy.

Climate change increases the average temperature and reduces precipitation, leading to an increased risk of rural fires around the world, but mainly in regions with a Mediterranean climate, such as Portugal. Despite the high risk of rural fires, fire is still a traditional land management practice. Beyond fire misused risk, the accumulation of fuel loads, due to the high population dispersion and lower interaction of communities with the land, also drives rural fires risks. Thus, researchers have sought to understand the key features of communication practices to achieve the most desired natural risk management results in relation to rural fires. According to the Committee on Risk Perception and Communication, in 1989, risk communication is defined as “an interactive process of exchanging information and opinions between individuals, groups, and institutions”. However, there is a need for dialogue between the responsible for communication and relevant stakeholders. The Carnegie Mellon mental-models approach encompasses participatory processes to translate the nature and magnitude of the risk, allowing for a deeper understanding of what can be done to mitigate social and environmental impacts in the future. Considering rural fires risks and risk communication challenges, this study aims to design an effective risk communication plan oriented to the rural population, in the context of rural fires. For this objective to be achieved, the mental models approach was developed, exploring the underlying reasons for resistance to behavioral change and defining guidelines to support the design of new risk communication strategies, including the dissemination of new behaviors and practices that mitigate the ignition of rural fires. This systemic approach has been applied and tested in the rePLANT project, whose purpose is the development of research activities, innovation and transfer of knowledge and technology, to increase sustainable forest management, the competitiveness of the Portuguese forestry sector and reduce the impact of rural fires. Preliminary findings show what must be communicated about rural fires risk, how must be communicated, target audiences' profiles, the role of actors for effective risk communication on rural fires, attributes of good risk communication on rural fires, evaluation of the risk communication results. Finally, it is expected that this research provides guidelines to help decision-makers and stakeholders to design an effective risk communication plan oriented to prevent traditional burning practices, as well as to mitigate socioeconomic and environmental impacts in the future. This approach also highlights the importance of exploring the underlying reasons for resistance to behavioral change and defining guidelines to support the design of new risk communication strategies.

Adulterants and altruism: A qualitative investigation of “drug checkers” in North America