Drug Decriminalization, Fentanyl, and Fatal Overdoses in Oregon.

Importance: With the implementation of Measure 110 (M110) in 2021, Oregon became the first US state to decriminalize small amounts of any drug for personal use. To date, no analysis of the association of this law with overdose mortality has fully accounted for the introduction of fentanyl-a substance that is known to drive fatal overdose-to Oregon's unregulated drug market. Objective: To evaluate whether the decriminalization of drug possession in Oregon was associated with changes in fatal drug overdose rates after accounting for the rapid spread of fentanyl in Oregon's unregulated drug market. Design, Setting, and Participants: In this cohort study, the association between fatal overdose and enactment of M110 was analyzed using a matrix completion synthetic control method. The control group consisted of the 48 US states and Washington, DC, all of which did not decriminalize drugs. The rapid spread of fentanyl in unregulated drug markets was determined using the state-level percentage of all samples reported to the National Forensic Laboratory Information System that were identified as fentanyl or its analogues. Mortality data were obtained from the Centers for Disease Control and Prevention for January 1, 2008, to December 31, 2022. Data analysis was performed from fall 2023 through spring 2024. Exposures: Measure 110 took effect in Oregon on February 1, 2021. Main Outcomes and Measures: The primary outcome assessed was fatal drug overdose rates per half-year. A changepoint analysis also determined when each state experienced a rapid escalation of fentanyl in its unregulated drug market. Results: In this analysis, rapid spread of fentanyl in Oregon's unregulated drug supply occurred in the first half of 2021, contemporaneous with enactment of M110. A positive crude association was found between drug decriminalization and fatal overdose rate per 100 000 per half year (estimate [SE], 1.83 [0.47]; P < .001). After adjusting for the spread of fentanyl as a confounder, the effect size changed signs (estimate [SE], -0.51 [0.61]; P = .41) and there was no longer an association between decriminalization and overdose mortality in Oregon. Sensitivity analyses were consistent with this result. Conclusions and Relevance: In this cohort study of fatal drug overdose and the spread of fentanyl through Oregon's unregulated drug market, no association between M110 and fatal overdose rates was observed. Future evaluations of the health effects of drug policies should account for changes in the composition of unregulated drug markets.

New Psychoactive Substances Toxicity: A Systematic Review of Acute and Chronic Psychiatric Effects.

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae.

Differences in toxicology reports and hospital emergency care for patients suspected of experiencing drug-facilitated crimes: an analysis according to gender. / Atención de pacientes con sospecha de sumisión química en un servicio de urgencias hospitalario y resultados del análisis toxicológico: diferencias según el sexo.

OBJECTIVE: To analyze gender-related differences in patient and care characteristics and in toxicology findings in suspected cases of drug facilitated crime (DFC). METHODS: Observational cross-sectional study of all patients in suspected DFC cases attended in the emergency department of Hospital Clínico San Carlos and of their blood or urine samples analyzed by the National institute of Toxicology and Forensics in Madrid between March 1, 2015, and March 1, 2023. We analyzed variables from patient records and the toxicology reports according to gender. RESULTS: A total of 514 suspected DFC episodes were studied; 101 (19.6%) were proactive crimes, 61 (11.9%) opportunistic, and 352 (68.5%) mixed. The median (interquartile range) age was 25 years (21-34 years), and 370 (72%) were women. Eighty-three percent of the patients had amnesia, and 48% of the cases involved sexual assault or robbery. Toxicology identified substances in 78% of the patients (alcohol, 53%; street drugs, 37%; and/or psychopharmaceuticals or opioids, 23%). Independent variables associated with female gender in the multivariate analysis, according to adjusted odds ratio (aORs) were age less than 25 years (aOR, 2.73; 95% CI, 1.75 4.24; P < .001); physician-referred emergency (aOR, 1.77; 95% CI, 1.12-2.80; P = .03); robbery (aOR, 0.25; 95% CI, 0.15-0.41; P < .001); alcohol-positive test result (aOR, 1.91; 95% CI, 1.21-3.00; P = .01); and a drug-positive result (aOR, 0.43; 95% CI, 0.28-0.64; P < .001). Police and a forensic physician intervened in 13% of the cases, and in such cases the victim was more likely to be female (aOR, 3.97; 95% CI, 1.41-11.13; P < .001). Toxicology identified the presence of an unknown substance in 39%, and a woman was less likely to be involved in such cases (aOR, 0.43; 95% CI, 0.28-0.67; P < .001). CONCLUSIONS: The majority of victims of DFCs were female, and the crimes were mixed, involving involve alcohol, psychopharmaceuticals or street drugs. Female victims were more likely to be under the age of 25 years, be referred to the emergency service by a physician, be attended by a forensic physician for sexual assault, and have an alcoholpositive toxicology report. Women were also less likely to report a robbery or have a toxicology report identifying drugs or an unknown substance.

OBJETIVO: Analizar las diferencias en las características de los pacientes atendidos por sospecha de sumisión química (SQ) y en los resultados del análisis toxicológico (AT) en función del sexo. METODO: Estudio observacional transversal retrospectivo que incluyó a todos los casos con SQ atendidos en el servicio de urgencias del Hospital Clínico San Carlos y las muestras (sangre o orina) para el AT en el Instituto Nacional de Toxicología y Ciencias Forenses de Madrid entre el 1 de marzo de 2015 y el 1 de marzo de 2023. Se analizan variables de la historia clínica y del AT según el sexo. RESULTADOS: Se incluyeron 514 episodios con sospecha de SQ [101 (19,6%) proactiva, 61 (11,9%) oportunista y 352 (68,5%) mixta] en pacientes con una mediana de 25 años (RIC: 21-34), 370 (72%) de sexo femenino. El 83% presentó amnesia y el 48% asoció agresión sexual o robo. En el 78% se identificó alguna sustancia en el AT (53% alcohol etílico, 37% drogas y/o 23% psicofármaco u opiáceos). En el análisis multivariado las variables que se asociaron de manera independiente con el sexo femenino fueron la edad menor de 25 años con ORa de 2,73 (IC 95%: 1,75-4,24; p < 0,001), con médico deriva a urgencias con ORa de 1,77 (IC 95%: 1,12-2,80; p = 0,03), delito de robo con de ORa 0,25 (IC 95%: 0,15-0,41; p < 0,001), alcohol etílico en el AT con ORa 1,91 (IC 95%: 1,21-3,00; p = 0,01) y alguna droga en el AT con ORa 0,43 (IC 95%: 0,28-0,64; p < 0,001). En el 13% de casos hubo intervención policial y médico-forense y fue más probable que fuera a una mujer, con ORa 3,97 (IC 95%: 1,41-11,13; p < 0,001). En el 39% de AT se identificó alguna sustancia desconocida y fue menos probable que fuera mujer, con ORa de 0,43 (IC 95%: 0,28-0,67; p < 0,001). CONCLUSIONES: La mayoría de casos registrados fueron mujeres con sospecha de SQ mixta por alcohol, psicofármacos o drogas de abuso. Las mujeres presentaron mayor probabilidad de tener menos de 25 años, ser derivada a urgencias por un médico, de intervención médico-forense por agresión sexual y encontrar alcohol etílico en el AT.

Evaluating fentanyl test strips as a harm reduction strategy in rural and urban counties: study protocol for a randomized controlled trial.

BACKGROUND: Opioid-related fatalities are a leading cause of death in Ohio and nationally, with an increasing number of overdoses attributable to fentanyl. Rapid fentanyl test strips can identify fentanyl and some fentanyl analogs in urine samples and are increasingly being used to check illicit drugs for fentanyl before they are used. Fentanyl test strips are a promising harm reduction strategy; however, little is known about the real-world acceptability and impact of fentanyl test strip use. This study investigates fentanyl test strip distribution and education as a harm reduction strategy to prevent overdoses among people who use drugs. METHODS: The research team will recruit 2400 individuals ≥ 18 years with self-reported use of illicit drugs or drugs purchased on the street within the past 6 months. Recruitment will occur at opioid overdose education and naloxone distribution programs in 16 urban and 12 rural Ohio counties. Participating sites will be randomized at the county level to the intervention or non-intervention study arm. A brief fentanyl test strip educational intervention and fentanyl test strips will be provided to participants recruited from sites in the intervention arm. These participants will be eligible to receive additional fentanyl test strips for 2 years post-enrollment. Participants recruited from sites in the non-intervention arm will not receive fentanyl test strip education or fentanyl test strips. All participants will be followed for 2 years post-enrollment using biweekly, quarterly, and 6-month surveys. Primary outcomes include (1) identification of perceived barriers and facilitating factors associated with incorporating fentanyl test strip education and distribution into opioid overdose education and naloxone distribution programs; (2) differences in knowledge and self-efficacy regarding how to test drugs for fentanyl and strategies for reducing overdose risk between the intervention and non-intervention groups; and (3) differences in non-fatal and fatal overdose rates between the intervention and non-intervention groups. DISCUSSION: Findings from this cluster randomized controlled trial will contribute valuable information about the feasibility, acceptability, and impact of integrating fentanyl test strip drug checking in rural and urban communities in Ohio and help guide future overdose prevention interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05463341. Registered on July 19, 2022. https://clinicaltrials.gov/study/NCT05463341.

Potential developmental effects of licit and illicit substances in humans: An approach to risk-specific dose and incidence.

Teratogens encompass any agent capable of causing a birth defect or elevating the incidence of defects within the population. This category includes substances like drugs, both legal and illegal. These substances cause congenital anomalies depending on the stage of development at the time of exposure, the dose, and the exposure time associated with the embryo. The most sensitive period is the embryonic stage, when the three leaflets give rise to tissues and organs. Susceptibility to teratogenesis decreases during the fetal phase but morphological and functional disturbance of the fetus may still occur. Substance use during pregnancy and its adverse effects are a public health problem and the lay population does not have access to this information. Particularly concerning is the period within the first six weeks of pregnancy, often before a woman realizes she is pregnant. Developmental data for many substances are simply not available, which makes the problem more serious. The aim of this study is to reflect on the teratogenic effects of licit and illicit substances in humans, focusing particularly on the dose that can induce malformations and their incidence in humans.

Can mind-altering prescription medicines be safe? Lessons from ketamine and esketamine.

INTRODUCTION: Recent decades have witnessed an extraordinary global crisis of drug misuse. Although opioid analgesics receive the most attention, numerous other drugs have increased rates of misuse. KETAMINE AND ESKETAMINE: Ketamine and esketamine offer a unique natural experiment to explore two medications that are similar pharmacologically but differ in their availability to users and in their regulation by government agencies. MISUSE AND ABUSE OF KETAMINE AND ESKETAMINE: Multisystem "mosaic" surveillance of many drugs using real-world data has emerged in recent years. Ketamine and esketamine have been monitored concurrently. Ketamine is much more widely available than esketamine and shows clear signs of increasing misuse and abuse. In contrast, esketamine is difficult to detect in postmarket surveillance even though availability is increasing. DISCUSSION: Ketamine and esketamine offer insights regarding the safety of prescription medications with the potential for misuse. Since the pharmacology of ketamine and esketamine are similar, the regulatory apparatus may be the primary difference that limits misuse. Ketamine has few restrictions and can be prescribed or administered by many healthcare providers, and is available as an illicit drug. In contrast, the product labeling for esketamine has rigorous restrictions on its use. Many important issues remain to be addressed. We need a more rigorous evaluation of the natural experiment of ketamine and esketamine. How does this experience relate to the introduction of new psychedelics? CONCLUSIONS: Ketamine misuse use and misuse are increasing while esketamine use in increasing, but misuse is not increasing. It is reasonable to reevaluate the regulatory controls on ketamine to reduce its misuse and abuse.

A lot testing protocol for quality assurance of fentanyl test strips for harm reduction applications.

Fentanyl test strips (FTS) are lateral flow immunoassays that were originally designed and validated for detecting low concentrations of fentanyl in urine. Some FTS are now being marketed for the harm reduction purpose of testing street drugs for the presence of fentanyl. This manuscript provides a simple protocol to assess whether different brands and lots of fentanyl test strips perform adequately for use in drug checking. The results gathered from this protocol will document problems with particular lots or brands of FTS, help buyers choose from among the array of products, provide feedback to manufacturers to improve their products, and serve as an early warning system for ineffective products.

Contamination of a drug consumption room with drugs and potential risks for social health care workers.

BACKGROUND: Studies have shown that contamination of surfaces by illicit drugs frequently occurs in forensic laboratories when manipulating seized samples as well as in pharmacies and hospitals when preparing medicinal drugs. In this project, we extended these studies to a Drug Consumption Room to investigate drug levels and possible exposure of the staff members. METHODS: We investigated pre and post cleaning contamination by heroin and cocaine and their degradation products 6-monoacetylmorphine and benzoylecgonine on different surfaces (tables, counters, computers and door handles) and in the ambient air. We also collected urine and hair samples from staff members to check for potential short and long term contaminations. RESULTS: Medium to heavy contamination has been detected on most surfaces and door handles; as expected, air contamination was particularly high in the smoking room. Drug levels were < LOD to very low in the urine and the hair samples of staff members tested. CONCLUSION: The cleaning efficiency of the surfaces, carried out by staff and drug users after drug consumption, was often not satisfactory. The very low drug levels in hair indicate that acute health risks for staff members are low.

Cardiovascular and pulmonary complications of recreational drugs: A pictorial review.

Recreational drug abuse constitutes a serious health problem worldwide. Consumption of cocaine, amphetamine-type stimulants, opioids and cannabis can lead to multiple acute and chronic cardiopulmonary complications, resulting in high morbidity and mortality. These complications may be first detected at imaging, since clinical presentation is usually non-specific. Cardiovascular complications include myocardial infarction, endocarditis, aortic dissection, infectious pseudoaneurysm, retained needle fragments, cardiomyopathy and pulmonary arterial hypertension. Pulmonary complications encompass pulmonary oedema, crack lung, pneumonia, septic emboli, barotrauma, airway disease, emphysema and excipient lung disease. Knowledge of the cardiopulmonary imaging manifestations of illicit drug use in conjunction with clinical history and a high grade of suspicion enable an accurate diagnosis and appropriate management plan. In this article we aim to provide a pictorial review of the most frequent cardiopulmonary manifestations of recreational drugs, emphasizing the underlying pathophysiologic mechanisms and the various imaging appearances.

Development and evaluation of portable NIR technology for the identification and quantification of Australian illicit drugs.

The efficient and accurate analysis of illicit drugs remains a constant challenge in Australia given the high volume of drugs trafficked into and around the country. Portable drug testing technologies facilitate the decentralisation of the forensic laboratory and enable analytical data to be acted upon more efficiently. Near-infrared (NIR) spectroscopy combined with chemometric modelling (machine learning algorithms) has been highlighted as a portable drug testing technology that is rapid and accurate. However, its effectiveness depends upon a database of chemically relevant specimens that are representative of the market. There are chemical differences between drugs in different countries that need to be incorporated into the database to ensure accurate chemometric model prediction. This study aimed to optimise and assess the implementation of NIR spectroscopy combined with machine learning models to rapidly identify and quantify illicit drugs within an Australian context. The MicroNIR (Viavi Solutions Inc.) was used to scan 608 illicit drug specimens seized by the Australian Federal Police comprising of mainly crystalline methamphetamine hydrochloride (HCl), cocaine HCl, and heroin HCl. A number of other traditional drugs, new psychoactive substances and adulterants were also scanned to assess selectivity. The 3673 NIR scans were compared to the identity and quantification values obtained from a reference laboratory in order to assess the proficiency of the chemometric models. The identification of crystalline methamphetamine HCl, cocaine HCl, and heroin HCl specimens was highly accurate, with accuracy rates of 98.4 %, 97.5 %, and 99.2 %, respectively. The sensitivity of these three drugs was more varied with heroin HCl identification being the least sensitive (methamphetamine = 96.6 %, cocaine = 93.5 % and heroin = 91.3 %). For these three drugs, the NIR technology provided accurate quantification, with 99 % of values falling within the relative uncertainty of ±15 %. The MicroNIR with NIRLAB infrastructure has demonstrated to provide accurate results in real-time with clear operational applications. There is potential to improve informed decision-making, safety, efficiency and effectiveness of frontline and proactive policing within Australia.

Assessment of illicit drug use in Seoul, the capital of South Korea for 21 days by wastewater-based epidemiology.

22 illicit drugs were monitored in Seoul, the capital of South Korea for 21 days using wastewater-based epidemiology to assess the drug usage patterns for the first time by region and social status. Among the targeted compounds, 10 were detected, with consistent detection of methamphetamine in samples over the entire sampling period. In addition, ketamine had the highest estimated consumption rate at 47.5 mg/day/1000 people, followed by methamphetamine at 12.5 mg/day/1000 people. Methamphetamine and MDMA(3,4-methylenedioxymethamphetamine) exhibited relatively stable daily patterns, with coefficients of variation of 7.03 %, and 13.4 % respectively. Furthermore, no statistically significant differences were observed between weekends and weekdays for all compounds (Mann-Whitney Rank Sum test, p > 0.05). Statistically significant regional differences in drug consumption were observed for methamphetamine, MDMA, and ketamine (Mann-Whitney Rank Sum test, p < 0.05). These differences were found to be related to average annual income and educational levels.

Essential/precursor chemical control research: Giommoni's review, understanding multi-replication interrupted time series analysis, and next steps.

Controls on essential/precursor chemicals from commercial companies have been associated with many large downturns in illicit drug markets and attendant problems. My colleagues and I brought this to light in the studies that are the subject of Giommoni's review. McKetin et al. in an earlier review considered several of our studies on chemical controls for methamphetamine, all centered in North America. Giommoni discusses not only those studies but also our later work on chemical controls for cocaine and heroin. This later work evaluates US essential/precursor chemical policies targeting illicit drug producers outside of North America, and it examines impacts on illicit drug availability and use (the studies reviewed by McKetin et al. predominantly focused on outcomes such as drug-related hospitalizations, arrests, and treatment). Giommoni's review is a new resource that will help make the varied topics in essential/precursor chemical control research more accessible to many readers. After noting this, I discuss some common methodological misconceptions about our studies. For example, our studies generally used multi-replication interrupted time series analysis, a research design among the most powerful of all quasi-experimental designs. Authors, however, typically discuss the studies as if they used single-intervention interrupted time series analysis, a less powerful design. Multi-replication and single-intervention interrupted time series analyses also differ regarding likely confounders; awareness of this is critical to accurately assessing our findings and critiquing alternative explanations. Finally, I note that commercial chemical companies function as the silent, albeit usually unwitting, partners in the large-scale production of several illicit drugs, including fentanyl. And many governments are implementing essential/precursor chemical controls to help stymie this partnership. But they are doing so largely without evaluation and study-a poor policy practice. To remedy this, I suggest establishing multi-disciplinary applied research teams to help assess, guide and improve essential/precursor chemical control efforts.

Monitoring illicit pentobarbital availability in the United States: A National Drug Early Warning System briefing.

BACKGROUND: Pentobarbital is a Schedule II/III short-acting barbiturate with limited medical use in humans. Veterinary professionals use pentobarbital to euthanize dogs, cats, and other companion animals. Pentobarbital is also utilized in capital punishment and small amounts are illegally shipped or diverted to assist in suicides. However, five kilograms of pentobarbital smuggled in from Mexico was recently seized by an organized crime drug enforcement task force (along with fentanyl, heroin, and cocaine), which may suggest a shift in illicit supply. We investigated potential indicators of illicit pentobarbital use or availability in the US to help determine whether this drug is becoming an emerging public health concern. METHODS: The National Drug Early Warning System requested information on pentobarbital from its sentinel surveillance sites and collaborators and conducted a search of current literature. RESULTS: In early 2024, multiple batches of counterfeit pills (e.g., pressed as "M30s" to represent oxycodone) confiscated near the Southwest border tested positive for pentobarbital plus combinations of fentanyl, fentanyl analogs, and xylazine. Other indicators suggest pentobarbital is being smuggled in powder form and possibly sold as another drug such as heroin. One national drug analysis program detected pentobarbital in 217 drug submissions from 2020 to 2023, and there were at least 12 fatal exposures linked to use from 2020 to 2022. CONCLUSION: Continued monitoring of illicit use and availability is needed as pentobarbital may continue to appear on the illicit market. Unknown exposure can occur if the drug is mixed into counterfeit pills or sold in powder form represented to be another drug.

Detection of N-desethyl etonitazene in a drug checking sample: Chemical analysis and pharmacological characterization of a recent member of the 2-benzylbenzimidazole "nitazene" class.

The emergence of 2-benzylbenzimidazole "nitazene" opioids is stirring up the recreational synthetic opioid market. Many nitazene analogues act as potent agonists at the µ­opioid receptor (MOR), as demonstrated in various in vitro and in vivo studies. Severe intoxication and overdose deaths associated with nitazene analogues are increasingly being reported. Nitazene opioids are classified as a public health threat, stressing the need for close monitoring of new developments on the recreational drug market. This study reports on the detection of N-desethyl etonitazene in a sample handed in by a recreational drug user at a Swiss drug checking service in August 2023. The person bought the sample through an internet source where it was stated to contain isotonitazene. Chemical analyses were conducted to characterize the sample, i.e. nuclear magnetic resonance (NMR), capillary electrophoresis (CE), and high-resolution mass spectrometry (HRMS). The sample was additionally investigated using two different in vitro MOR activation assays. NMR and high-performance liquid chromatography (HPLC) coupled to HRMS confirmed the presence of N-desethyl etonitazene at a high purity and in the absence of isotonitazene and etonitazene. N-Desethyl nitazene analogues have been detected before as metabolites of isotonitazene and etonitazene. However, as first seen with N-desethyl isotonitazene, they are now emerging as standalone drugs. The applied bioassays demonstrated increased efficacy and approximately 6-9-fold higher potency of N-desethyl etonitazene at MOR compared to fentanyl. N-Desethyl etonitazene showed EC50 values of 3.35 nM and 0.500 nM in the ß-arrestin 2 recruitment and Aequoscreen® assays, respectively. The opioid activity present in the collected sample was additionally evaluated using the bioassays and showed good overlap with the reference standard, in line with the analytical purity assessment. This demonstrates the potential of these bioassays to provide a rapid opioid activity assessment of authentic samples. The emergence of other N-desethyl nitazene analogues must be considered during forensic and clinical toxicology casework, to avoid misclassification of intake of such analogues as metabolites. Finally, drug checking services enable the close monitoring of market developments and trends and are of great value for early warning and harm reduction purposes.

[The challenges for psychiatric care posed by synthetic drugs]. / Die Herausforderungen für die psychiatrische Versorgung durch synthetische Drogen.

BACKGROUND: In addition to the drugs that have been known for decades, several hundred mainly synthetic substances have been identified as drugs for the first time in the last 20 years. AIM OF THE WORK: Presentation of the various groups of substances and their psychotropic effects, the epidemiology of their use and the legal and social background of this development. MATERIAL: Narrative literature review. RESULTS: The most important new psychoactive substances (NPS) are synthetic cannabinoids, synthetic stimulants (cathinones), halluginogens and new synthetic opioids (NSO), in particular fentanyl and related substances. The new substances do not have any qualitatively new psychotropic effects. They were brought onto the market in particular as substitutes for substances subject to the Narcotics Act but are often associated with dangerous side effects and even mortality. The increasing availability of these substances has gone hand in hand with the establishment of the Internet as a source of knowledge (e.g. for synthesis routes) and as a marketplace. Substance group-related regulations have also been established in Germany (New Psychoactive Substances Act). In Germany the prevalence of NPS use is significantly lower than that of cannabis; however, there are indications that the production and distribution of synthetic drugs is more profitable for drug dealers than with conventional plant-based drugs, such as heroin. In the USA, for example, NSOs are the primarily drugs used for opioid addiction. DISCUSSION: It remains to be seen whether NPS and NSOs will replace conventional drugs. The availability of synthetic drugs is more difficult to reduce than that of plant-based drugs. Harm reduction measures should be expanded, e.g., early warning systems for new drugs, drug checking and naloxone programs.

A novel method for the simultaneous determination of drugs of abuse, ethyl glucuronide and synthetic opioids in human hair through a single digestion, purification and analysis in LC-MS/MS.

Polydrug use is a serious health and social problem worldwide. Over the past several years, there has been an increasing tendency to combine narcotics, alcohol, sedatives, and/or stimulants. To the traditional drugs of abuse and alcohol, an increase of new abuse drugs such as synthetic opioids has been added. In the current study, the development and validation of an innovative and fast analytical procedure has been presented to determine drugs of abuse, ethyl glucuronide and synthetics opioids in 30 mg of human hair through a single digestion, purification and analysis in LC-MS/MS. A combine simple preparation of hair sample followed to a single chromatographic run of 10 min has been proposed. A full validation for 54 target analytes for the parameters of selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, recovery, and dilution integrity was successful completed. The method was linear in different ranges with r values of at least 0.990; the value to the validated LLOQ values were in the range 0.1-100 pg/mg. The method offered satisfactory precisions (CV<15 % and accuracy ± 20 %). In conclusion, a significant reduction in the overall times of the analytical procedure and the reduction of consumables costs make this method extremely advantageous and undoubtedly useful in routine laboratory workflow analyses and open the way to the prospect of a further implementation which also includes other classes of xenobiotics.

Interpreting mono- and poly-SCRA intoxications from an activity-based point of view: JWH-018 equivalents in serum as a comparative measure.

Synthetic cannabinoid receptor agonists (SCRAs) are a class of synthetic drugs that mimic and greatly surpass the effect of recreational cannabis. Acute SCRA intoxications are in general difficult to assess due to the large number of compounds involved, differing widely in both chemical structure and pharmacological properties. The rapid pace of emergence of unknown SCRAs hampers on one hand the timely availability of methods for identification and quantification to confirm and estimate the extent of the SCRA intoxication. On the other hand, lack of knowledge about the harm potential of emerging SCRAs hampers adequate interpretation of serum concentrations in intoxication cases. In the present study, a novel comparative measure for SCRA intoxications was evaluated, focusing on the cannabinoid activity (versus serum concentrations), which can be measured in serum extracts with an untargeted bioassay assessing ex vivo CB1 activity. Application of this principle to a series of SCRA intoxication cases (n = 48) allowed for the determination of activity equivalents, practically entailing a conversion from different SCRA serum concentrations to a JWH-018 equivalent. This allowed for the interpretation of both mono- (n = 34) and poly-SCRA (n = 14) intoxications, based on the intrinsic potential of the present serum levels to exert cannabinoid activity (cf. pharmacological/toxicological properties). A non-distinctive toxidrome was confirmed, showing no relation to CB1 activity. The JWH-018 equivalent was partly related to the poison severity score (PSS) and causality of the clinical intoxication elicited by the SCRA. Altogether, this equivalent concept allows to comparatively and timely interpret (poly-)SCRA intoxications based on CB1 activity.

Prevalence of Drugs of Abuse and Cognitive Enhancer Consumption Monitored in Grab Samples and Composite Wastewater via Orbitrap Mass Spectrometry Analysis.

Wastewater (WW)-based epidemiology is an approach for the objective surveillance of the consumption of (illicit) drugs in populations. The aims of this study were to monitor drugs of abuse, cognitive enhancers, and their metabolites as biomarkers in influent WW. Data obtained from different sampling points and mean daily loads were compared with previously published data. The prevalence of analytes was monitored in WW grab samples collected monthly over 22 months at two sampling points and 24 h composite WW samples collected over 2 weeks at a WW treatment plant in the same city. Quantification was performed using a previously validated and published method based on solid-phase extraction followed by liquid chromatography coupled with high-resolution tandem mass spectrometry. Grab samples allowed for frequent detection of ritalinic acid and sporadic detection of drugs of abuse. The daily mean loads calculated for 24 h WW composite samples were in accordance with data published in an international study. Furthermore, loads of amphetamine and methamphetamine increased compared with those observed in a previously published study from 2014. This study showed frequent quantification of ritalinic acid in the grab samples, while drugs of abuse were commonly quantified in the composite WW samples. Daily mean loads were in accordance with trends reported for Germany.

The LOD paradox: When lower isn't always better in biosensor research and development.

Biosensor research has long focused on achieving the lowest possible Limits of Detection (LOD), driving significant advances in sensitivity and opening up new possibilities in analysis. However, this intense focus on low LODs may not always meet the practical needs or suit the actual uses of these devices. While technological improvements are impressive, they can sometimes overlook important factors such as detection range, ease of use, and market readiness, which are vital for biosensors to be effective in real-world applications. This review advocates for a balanced approach to biosensor development, emphasizing the need to align technological advancements with practical utility. We delve into various applications, including the detection of cancer biomarkers, pathology-related biomarkers, and illicit drugs, illustrating the critical role of LOD within these contexts. By considering clinical needs and broader design aspects like cost-effectiveness, sustainability, and regulatory compliance, we argue that integrating technical progress with practicality will enhance the impact of biosensors. Such an approach ensures that biosensors are not only technically sound but also widely useable and beneficial in real-world applications. Addressing the diverse analytical parameters alongside user expectations and market demands will likely maximize the real-world impact of biosensors.