Drug checking: what sample analysis reveals

A young man arrives at a harm reduction tent at a festival with a white powder he bought as MDMA. He agrees to let the team scrape a small amount for testing. Within minutes, the technician explains that the result suggests another substance, with a longer effect. The young man asks what he should do now. The scene is fictional and was written for teaching.

This text is about drug checking, also called drug checking: services where a person hands over a sample of the substance they intend to use and receives back an analysis of what it contains, along with guidance. The goal here is to look at what studies show about the analysis methods, what the samples revealed and how people react to the result. If you play the case of the day on NEXO, you will recognize the logic: the label the patient brings is a hypothesis, and confirmation depends on the right test, read with its limits.

Key points

• Drug checking analyzes the sample before use and returns the result with guidance.
• Methods range from strips that detect a single substance to laboratory mass spectrometry.
• In several services, a relevant share of the samples contained something different from what was expected.
• Unexpected results were associated with the intention to reduce the dose or discard the drug.
• Fear of the police, stigma and long waits appear as important barriers.
• The service also works as an entry point to care.

What drug checking is

A systematic review with 90 studies described checking services as interventions that analyze substances provided by the users themselves and return the results to them, usually together with harm reduction counseling (Maghsoudi and colleagues, 2022). Most of the studies in this review came from Europe, and the most reported domain was monitoring the drug market (Maghsoudi and colleagues, 2022).

The models vary. The same review described mobile services at parties and festivals, fixed services at community sites and the distribution of tests for people to use themselves (Maghsoudi and colleagues, 2022). A realist review with 133 sources gathered seven program theories to explain how and for whom checking works (Masterton and colleagues, 2022). These theories cover legislation and police activity, the local market and the level of harm, integration with existing services, the participation of people with lived experience, accessibility, the testing process and users' previous experience with the service (Masterton and colleagues, 2022).

The same review notes that checking is often associated with parties and so-called recreational use, but that community services can reach more marginalized people and people with dependence (Masterton and colleagues, 2022). This point changes the audience the clinician should picture when thinking about the service: it includes both the festival young person and the person who uses opioids every day and lives on the street. Legislation also weighs in, and New Zealand was the first country to explicitly legalize drug checking, according to this review (Masterton and colleagues, 2022).

From a clinical point of view, the idea resembles that of any test: there is a question, a sample, a method with its own sensitivity and specificity and a conversation about what to do with the result. The reasoning is similar to interpreting tests by pre-test probability, because the same result weighs differently depending on the context of the local market.

Why the content of the drug matters

The illicit drug market changes fast. 2021 was the year with the most overdose deaths in the United States and Canada, in a scenario where fentanyl came to dominate local markets (Ondocsin and colleagues, 2023). Professionals interviewed in a study with 11 people described the market as a "moving target", in which new substances appear and mix with known ones (Ondocsin and colleagues, 2023).

Fentanyl is the most studied example. At Insite, the supervised consumption site in Vancouver, 1411 checks were done, and 1121 of them tested positive for fentanyl, the equivalent of 79.8 per 100 (Karamouzian et al., 2018). In a mass spectrometry analysis in Toronto, with 2263 samples, xylazine appeared in 46 of them, which corresponded to 7.2 per 100 samples that had fentanyl as the only opioid (Bowles et al., 2021).

The presence of adulterants has a direct consequence for care. Xylazine is a sedative for veterinary use, and naloxone acts on opioids, without reversing its effects (Bowles et al., 2021). In a pilot with mass spectrometry, etizolam, a benzodiazepine, appeared in 10 samples, and no client expected to find it; the authors note that naloxone may not fully reverse an intoxication of this kind (Borden et al., 2022).

For anyone treating an intoxication, this information changes the differential. The patient who reports having used heroin may have received a mixture with sedatives that respond only partially to naloxone. Knowing what circulates in the local market helps to interpret signs, symptoms and history with fewer assumptions.

Which analysis methods exist

A review of methods for on-site analysis pointed to portable infrared spectroscopy, Raman spectroscopy and ion mobility spectrometry as the most promising options for field services, and mass spectrometry as the forensic reference standard (Harper et al., 2017). Each technique answers a different question, and the choice depends on what the service wants to know.

The main method families appear in the studies as follows:

• Immunochromatographic strips: detect a specific substance, such as fentanyl, with a yes or no answer (Gozdzialski et al., 2023).
• Colorimetric reagents: change color in the presence of certain substances and exist for most commonly used drugs (Harper et al., 2017).
• Infrared spectroscopy: portable and suited to the point of care, with a higher detection limit (Grace Rose et al., 2023).
• Raman spectroscopy and ion mobility: portable options cited among the best for the point of care (Harper et al., 2017).
• Mass spectrometry: more precise, requires specialized training and space (Grace Rose et al., 2023).

Infrared spectroscopy has become one of the most used instrumental methods in checking, for ease of operation, speed and the little sample preparation it requires (Gozdzialski et al., 2023). Another point in favor of infrared is that the analysis preserves the sample and delivers the result in minutes (Grace Rose et al., 2023). Ion mobility spectrometry separates and identifies ions by the speed at which they cross a gas, and Raman spectroscopy relies on the scattering of light after it interacts with the sample (Harper et al., 2017). For identification techniques like these, the result depends on a library of known molecules to compare the spectrum, and building that library requires a trained chemist (Harper et al., 2017).

The combination of instruments appears often. A study on strips and other methods concluded that approaches with several instruments may be needed to cover what a single technique misses (Gozdzialski et al., 2023).

The table summarizes the differences described in the studies read.

Method	What it reports	Advantages	Limitations
Fentanyl strip	Presence or absence of fentanyl above a limit (Gozdzialski et al., 2023)	Simple, fast and easy to distribute (Krieger et al., 2018)	False positives with some substances (Lockwood et al., 2021) and a faint line near the limit (Gozdzialski et al., 2023)
Portable infrared	Profile of the main components (Harper et al., 2017)	Portable and suited to the point of care (Grace Rose et al., 2023)	Higher limit of detection (Grace Rose et al., 2023)
Raman and ion mobility	On-site identification (Harper et al., 2017)	Cited among the best field methods (Harper et al., 2017)	They depend on a reference spectra library (Harper et al., 2017)
Mass spectrometry	Detailed composition, including adulterants (Borden et al., 2022)	Reference standard and quantification (Harper et al., 2017)	Requires a specialist, space and time (Grace Rose et al., 2023)

From strips to spectrometry: what each test finds

Fentanyl test strips are the simplest and most widely distributed method. The result is binary, and the limit of detection was around 0.150 micrograms per milliliter in one evaluation (Gozdzialski et al., 2023). Near that limit, the result line may appear faint, which makes reading difficult (Gozdzialski et al., 2023).

False positives also exist. A laboratory study found falsely positive results with methamphetamine, MDMA and diphenhydramine at concentrations of 1 milligram per milliliter or more (Lockwood et al., 2021). This matters because the person may discard a drug that has no fentanyl or, conversely, start to distrust the test.

The strips used for fentanyl and for benzodiazepines were originally designed for urine samples (Gozdzialski et al., 2023). With benzodiazepine strips, etizolam reacts poorly to the test, and the result may be a false negative (Gozdzialski et al., 2023). This detail gains weight when one remembers that etizolam was precisely one of the unexpected adulterants in the spectrometry pilot (Borden et al., 2022).

Like any qualitative test, the strip says whether the substance passed a threshold, and leaves open how much of it is in the sample. This point connects with the theme of overdiagnosis: a very sensitive test, applied without context, can lead to decisions the person did not need to make.

Reading the strip also calls for attention. In the study with young adults in Rhode Island, the material given to participants explained that one red line indicates a positive test and two lines indicate a negative test, with the warning to stay cautious anyway (Goldman et al., 2019). The logic is counterintuitive for anyone used to other rapid tests, and a reading error reverses the meaning of the result. The strips also detect only fentanyl and some analogues, without producing a quantitative result (Grace Rose et al., 2023).

In service practice, the strips were accepted by those who used them. In a study with 93 participants, 37 out of 100 had already had an overdose, and 86 of them, or 92 out of 100, said they wanted to know whether the drug had fentanyl (Krieger et al., 2018). After training, all felt confident to use the strip, and most preferred testing the drug to testing urine (Krieger et al., 2018).

Laboratory methods show a more complete picture of the market. In a two-day pilot with paper spray mass spectrometry, 113 samples were analyzed, and 88 of them contained the expected substance, which gives 78 out of 100 (Borden et al., 2022). Fentanyl appeared in 50 samples, 44 out of 100, and 4-ANPP, a synthesis precursor, was present in 74 out of 100 of the samples with fentanyl (Borden et al., 2022).

Spectrometry also quantifies. Users interviewed in a study preferred quantitative results, which report how much of each substance is in the sample (Grace Rose et al., 2023). The same study described the barriers of the method: waiting time and the destruction of part of the sample in the test (Grace Rose et al., 2023).

Continuous monitoring reveals trends. In Toronto, analysis by gas chromatography and high-resolution mass spectrometry identified the arrival of xylazine in the local opioid market (Bowles et al., 2021). This kind of data helps health services warn the community and adjust care protocols.

How people react and what keeps them away

The central question is whether the result changes what the person does. In the review of 90 studies, the services influenced intentions to use, especially when the result was unexpected (Maghsoudi et al., 2022).

Demand, on the other hand, was still small compared with the flow of the service: at Insite, checking was done in about 1 in every 100 visits during the study period (Karamouzian et al., 2018). This suggests that offering the test is different from seeing it built into the routine of people who use drugs.

At Insite, among people with a positive test before use, 36.3 in 100 planned to reduce the dose and 11.4 in 100 planned to discard the drug (Karamouzian et al., 2018). A positive result before use was associated with a higher chance of reducing the dose, with an odds ratio of 9.36, and no association with discarding (Karamouzian et al., 2018).

In young adults in Rhode Island, 93 participants received strips, 81 returned for the second interview and 62 had used at least one strip (Goldman et al., 2019). The reported changes included discarding the drug, using with someone else present and keeping naloxone nearby, and some participants passed strips on to friends (Goldman et al., 2019).

In the second phase of this study, participants were trained to test the sample or the drug residue before consumption, rather than urine after use (Goldman et al., 2019). For the health service, this change matters, because testing before use is what allows a decision about the dose.

At an Australian festival, 642 people answered a questionnaire, and 73.4 in 100 reported drug use (Day et al., 2018). Among the participants, 54.4 in 100 said they were very likely and 32.7 in 100 said they were somewhat likely to use a checking service (Day et al., 2018). They would avoid drugs containing methamphetamine (65.1 in 100), ketamine (57.5 in 100) or PMA (58.4 in 100), according to the same study (Day et al., 2018).

These data recall the clinical conversation about decision making: a test has value when the result can change the course of action, and the course of action depends on the person understanding what the result means.

Interviews with 27 people pointed to criminalization, stigma and trauma as the main barriers, and showed that confidentiality and anonymity are essential (Wallace et al., 2020). Professionals also described trust and fear of the police as decisive points for uptake (Ondocsin et al., 2023). For these professionals, the trusting relationship between client and team, more than formal integration with other services, was the main path to bringing the person to treatment and other care (Ondocsin et al., 2023). The authors of a study on instruments sum up the issue another way: the benefits of using the service must outweigh the risks of seeking it out (Gozdzialski et al., 2023).

Strips given out for home use reduce contact with institutions, which can ease distrust of authorities, according to the professionals interviewed (Ondocsin et al., 2023). On the other hand, the person loses the conversation with the team, which is precisely the moment when guidance, naloxone and referral come up.

There is also a concern raised by users themselves. At the Australian festival, 68.6 out of every 100 participants feared that sellers would use the service as quality control (Day et al., 2018). In another study with 27 interviews, market quality control appeared as one of the needs shared by people who use drugs, alongside health, healthier environments and public policy (Wallace et al., 2021). In the authors' reading, the check meets a need shared by the community of people who use drugs, and the service is no longer seen only as an individual test (Wallace et al., 2021). For service design, this means listening to users before deciding where to set up the point, what hours to offer and how to return the result.

What the clinician can take into the consulting room

Drug checking usually happens outside the hospital. Even so, the data it produces and the logic it uses are valuable to those who provide care.

Some practical points appear in the studies:

• Ask what the person thinks they used and treat the answer as a hypothesis, since the market changes (Ondocsin et al., 2023).
• Remember that adulterants such as xylazine and benzodiazepines respond poorly or not at all to naloxone (Bowles et al., 2021).
• Know that a positive test for fentanyl can lead to reducing the dose, and that this opens space to talk about safety (Karamouzian et al., 2018).
• Recognize that strips have false positives and a detection limit (Lockwood et al., 2021).
• Use the contact as a gateway to care, as the professionals at these services describe (Ondocsin et al., 2023).

This stance fits what we discussed in harm reduction and clinical reasoning beyond all or nothing. It also helps to think about diagnostic uncertainty, because the history of use rarely describes with precision what the patient actually received.

For those working in a team, checking shows the value of work across areas: laboratory technicians, harm reduction workers and clinicians share the interpretation of the same result, as happens in interprofessional clinical reasoning. Reviewing intoxication cases in morbidity and mortality sessions with local market data can also reveal patterns that would go unnoticed.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by searching for the ICD-10 code.

The limits of using the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information in Curator and in Creators, and institutions can learn about the proposal on the partnerships page. Training with differential diagnosis and clues and knowing how to find the right ICD-10 code complete this practice.

Frequently asked questions

What is drug checking?

It is a service that analyzes samples of substances brought by users themselves and returns the result with harm reduction guidance (Maghsoudi et al., 2022).

Are fentanyl strips reliable?

They detect fentanyl above a limit of about 0.150 micrograms per milliliter, with reading more difficult near that value (Gozdzialski et al., 2023), and they can give a false positive with methamphetamine, MDMA and diphenhydramine at high concentrations (Lockwood et al., 2021).

Does the result change people's behavior?

The services influenced intentions to use, especially in the face of unexpected results (Maghsoudi et al., 2022), and at Insite a positive result before use was associated with a greater chance of reducing the dose (Karamouzian et al., 2018).

Which method is the most accurate?

Mass spectrometry is the forensic reference standard (Harper et al., 2017), and it requires a specialist, space and a longer waiting time (Grace Rose et al., 2023).

Does naloxone resolve any overdose from adulterated drugs?

Naloxone reverses the effect of opioids, and adulterants such as xylazine are beyond its reach (Bowles et al., 2021), just as intoxications with etizolam may respond only in part (Borden et al., 2022), so checking helps anticipate this risk.

What keeps people away from the service?

Criminalization, stigma and trauma were the main barriers reported, and confidentiality and anonymity appear as essential (Wallace et al., 2020).

Take-home messages

• Drug checking analyzes the sample before use and returns the result with guidance.
• Strips are simple and accepted, with a detection limit and known false positives.
• Mass spectrometry shows unexpected adulterants, such as xylazine and etizolam.
• Unexpected results are associated with the intention to reduce the dose or discard the drug.
• Fear of the police, stigma and waiting are central barriers.
• For the clinician, the history of use is a hypothesis, and the local market changes the differential.

Want to practice reasoning with progressive clues? Play the case of the day.

References

1. Borden SA, Saatchi A, Vandergrift GW, et al. A new quantitative drug checking technology for harm reduction: Pilot study in Vancouver, Canada using paper spray mass spectrometry. Drug Alcohol Rev. 2022. PMID 34347332.
2. Bowles JM, McDonald K, Maghsoudi N, et al. Xylazine detected in unregulated opioids and drug administration equipment in Toronto, Canada: clinical and social implications. Harm Reduct J. 2021. PMID 34645480.
3. Day N, Criss J, Griffiths B, et al. Music festival attendees' illicit drug use, knowledge and practices regarding drug content and purity: a cross-sectional survey. Harm Reduct J. 2018. PMID 29304871.
4. Goldman JE, Waye KM, Periera KA, et al. Perspectives on rapid fentanyl test strips as a harm reduction practice among young adults who use drugs: a qualitative study. Harm Reduct J. 2019. PMID 30621699.
5. Gozdzialski L, Wallace B, Hore D. Point-of-care community drug checking technologies: an insider look at the scientific principles and practical considerations. Harm Reduct J. 2023. PMID 36966319.
6. Grace Rose C, Kulbokas V, Carkovic E, et al. Contextual factors affecting the implementation of drug checking for harm reduction: a scoping literature review from a North American perspective. Harm Reduct J. 2023. PMID 37667312.
7. Harper L, Powell J, Pijl EM. An overview of forensic drug testing methods and their suitability for harm reduction point-of-care services. Harm Reduct J. 2017. PMID 28760153.
8. Karamouzian M, Dohoo C, Forsting S, et al. Evaluation of a fentanyl drug checking service for clients of a supervised injection facility, Vancouver, Canada. Harm Reduct J. 2018. PMID 30200991.
9. Krieger MS, Yedinak JL, Buxton JA, et al. High willingness to use rapid fentanyl test strips among young adults who use drugs. Harm Reduct J. 2018. PMID 29422052.
10. Lockwood TE, Vervoordt A, Lieberman M. High concentrations of illicit stimulants and cutting agents cause false positives on fentanyl test strips. Harm Reduct J. 2021. PMID 33750405.
11. Maghsoudi N, Tanguay J, Scarfone K, et al. Drug checking services for people who use drugs: a systematic review. Addiction. 2022. PMID 34729849.
12. Masterton W, Falzon D, Burton G, et al. A Realist Review of How Community-Based Drug Checking Services Could Be Designed and Implemented to Promote Engagement of People Who Use Drugs. Int J Environ Res Public Health. 2022. PMID 36231262.
13. Ondocsin J, Ciccarone D, Moran L, et al. Insights from Drug Checking Programs: Practicing Bootstrap Public Health Whilst Tailoring to Local Drug User Needs. Int J Environ Res Public Health. 2023. PMID 37297603.
14. Wallace B, van Roode T, Pagan F, et al. The potential impacts of community drug checking within the overdose crisis: qualitative study exploring the perspective of prospective service users. BMC Public Health. 2021. PMID 34134698.
15. Wallace B, van Roode T, Pagan F, et al. What is needed for implementing drug checking services in the context of the overdose crisis? A qualitative study to explore perspectives of potential service users. Harm Reduct J. 2020. PMID 32398090.