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Background and Purpose Experimental Approach Key Results Conclusion and Implications Fentanyl analogues have been implicated in many cases of intoxication and death with overdose worldwide. The aim of this study is to investigate the pharmaco‐toxicology of two fentanyl analogues: butyrylfentanyl (BUF) and 4‐fluorobutyrylfentanyl (4F‐BUF).In vitro, we measured agonist opioid receptor efficacy, potency, and selectivity and ability to promote interaction of the μ receptor with G protein and β‐arrestin 2. In vivo, we evaluated thermal antinociception, stimulated motor activity and cardiorespiratory changes in female and male CD‐1 mice injected with BUF or 4F‐BUF (0.1–6 mg·kg−1). Opioid receptor specificity was investigated using naloxone (6 mg·kg−1). We investigated the possible role of stress in increasing cardiorespiratory toxicity using the corticotropin‐releasing factor 1 (CRF1) antagonist antalarmin (10 mg·kg−1).Agonists displayed the following rank of potency at μ receptors: fentanyl > 4F‐BUF > BUF. Fentanyl and BUF behaved as partial agonists for the β‐arrestin 2 pathway, whereas 4F‐BUF did not promote β‐arrestin 2 recruitment. In vivo, we revealed sex differences in motor and cardiorespiratory impairments but not antinociception induced by BUF and 4F‐BUF. Antalarmin alone was effective in blocking respiratory impairment induced by BUF in both sexes but not 4F‐BUF. The combination of naloxone and antalarmin significantly enhanced naloxone reversal of the cardiorespiratory impairments induced by BUF and 4F‐BUF in mice.In this study, we have uncovered a novel mechanism by which synthetic opioids induce respiratory depression, shedding new light on the role of CRF1 receptors in cardiorespiratory impairments by μ agonists. [ABSTRACT FROM AUTHOR]

In recent years, the online sale of kratom (Mitragyna speciosa), a Southeast Asian plant with both medicinal and psychoactive properties, has raised health concerns mainly due to the uncontrolled diffusion of adulterated kratom-related products. This exploratory study provides, for the first time, a snapshot of the availability of kratom products on the darknet which has been further validated by data searches on the surface web. A total of 231 listings of kratom across 23 darknet marketplaces were identified between March 2020 and October 2021. Among these, 40 were found actively sold across five markets by thirteen vendors. Listed items were mainly advertised as "safe" substitutes for medicinal products for the self-management of pain and other health conditions and offered in various forms (e.g., dry leaf powder, pills, capsules). Purchases were made using cryptocurrencies, with some vendors offering Pretty Good Privacy, and were shipped from Europe, Australia, the United States, and the United Kingdom. Goods sold by the same sellers also included illicit drugs and fraud-related products. Our study discovered a previously unknown diffusion of kratom products on the darknet mainly for self-treating a variety of medical conditions, suggesting the need for further research and immediate interventions to safeguard the well-being and health of kratom consumers. [ABSTRACT FROM AUTHOR]

Introduction: Synthetic cannabinoid receptor agonists (SCRAs) are associated with significant toxicity and are increasingly used in electronic vaping devices. We assessed the availability of SCRA vaping products to UK purchasers on the surface web. Methods: An internet snapshot survey was performed between October 2022 and January 2023 on 'google.com' using the search terms "buy c-liquid vape", "buy herbal incense vape liquid", "buy cannabis vape liquid", "buy hashish vape liquid", "buy K2 vape liquid". Results: 62 websites selling 128 SCRA vaping brands were identified. Most were purportedly based in the USA (41 websites, 66%) and most sold other controlled substances. Purchase incentives offered included discreet packaging (38, 61%), discounts for bulk purchase (34, 55%) and tracked delivery (30, 48%). Many websites stated SCRA products were: not for human consumption (41, 66%), for research purposes only (15, 24%), or legal (28, 45%). Websites sold a median (IQR) of 16 (7–25) SCRA vaping brands. Almost all were bottles of vaping liquid (1220/1225, 99.6%). The most common bottle size was 5mL (60%), the median (IQR) total volume of SCRA liquid per sale was 50mL (10–200mL). Median (IQR) price was £3.39/mL (£2.01/mL– £5.29/mL). Price decreased with increasing volume purchased (£6.58/mL for ≤ 5mL, £1.60/mL for > 200mL). Conclusion: SCRA vaping products are easily obtainable online, in both small and bulk quantities. Information provided to purchasers on safety and legality is lacking or misleading. Further studies are needed to confirm the chemistry of these products. Policymakers should consider steps to limit the potential harm caused by the purchase and use of these products. [ABSTRACT FROM AUTHOR]

Accessible Summary: What is known on the subject?: According to recent estimates, 10.4% of adults are patients with substance abuse, which is almost double the global rate.Rural areas are typically marginalized, compounded by a lack of access to mental health care, creating a startling disparity in suffering from drug use issues among rural cohorts. What the paper adds to existing knowledge?: Drawing on data from a descriptive comparative design would provide a distinctive picture related to the similarities and/or differences in relation to craving and how it affects perceived stigma and suicidal risk among patients using old versus novel psychoactive substances. What are the implications for practice?: Substance abuse is a leading public health concern that forces nurses to encompass it into their agendas to tackle this looming problem.Addiction rehabilitation services are frequently run by nurses. They are well‐versed in supporting patients during their journey to recovery and enabling them to adjust to a new lifestyle. Introduction: Substance use disorder is a leading public health concern that currently, nations regulatory agencies are grappled with. The noticeable difference in the chemical structures between old and novel psychoactive substances can result in significant clinical complications among patients with substance abuse. Aim: The study aims to compare substance craving, perceived stigma and suicidal risk among patients addicted to old and novel psychoactive substances (NPS). Method: A descriptive comparative design was adopted on a sample of 105 patients with substance use who completed The Penn Alcohol Craving Scale (PACS), The Perceived Stigma of Addiction Scale (PSAS) and Suicide Probability Scale (SPS). Discussion: Most participants were male, with 89.5% in the old addictive substance group and 93.8% in the new addictive substance group. A statistically significant difference in the NPS groups' perceptions of stigma (23.4 ± 5.3) compared to the old addictive substance group (20.6 ± 4.2), (t = 3.037, p =.003). Implication for Practice: Participants in the new substance group report more suicidal ideation, negative self‐evaluation and hostility than those in the old substance group. Policies and practices should be tailored to the type of drug used and potential risk factors to avoid suicide among patients with substance abuse. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) are everchanging and plague forensic laboratories who must identify an unending variety of emerging substances and evolve current methodologies to detect these substances. Identifying potential regional NPS targets and timely examining trends in seized drug data could help mitigate the burden laboratories face. Over 17 months, NPS seized drug data were processed and categorized from three laboratories located across the United States to determine any NPS regional similarities and prevalent NPS drug categories: the South Carolina Law Enforcement Division (SLED), the Sedgwick County Regional Forensic Science Center (SCRFSC), and the Orange County Crime Laboratory (OCCL). Seized drug materials, including pills, powders, and plant material, were primarily analyzed for NPS via gas chromatography–mass spectrometry and Fourier transform infrared spectroscopy. From June 2022 to October 2023, 1940 NPS seized drug identifications were reported by these laboratories with 63 different NPS reported. Novel synthetic opioids (NSO) were the most prevalent NPS class across all three laboratories (55%), with fluorofentanyl accounting for 74% of NSO identifications. This is unsurprising given the fentanyl epidemic in the United States. Furthermore, these data highlighted varying regional NPS seized drug trends: eutylone, a synthetic cathinone, was one of the most frequently identified NPS in SLED, SCRFSC observed the most diverse set of synthetic cannabinoids, and OCCL observed an increased prevalence in the designer benzodiazepine, bromazolam. NPS scope recommendations are a valuable resource for forensic laboratories; however, most focus on a national perspective. Timely analysis and reporting of NPS seized drug data may help to develop regional NPS scope recommendations laboratories may employ. [ABSTRACT FROM AUTHOR]

A growing number of researchers are trying to provide explanations for continuity and change in drug policy in different contexts. Such research predominantly falls in the pluralist realm of public policy where various actors compete to have their policy proposals accepted. Using a critical framework called Policy Constellations (PC), developed by Stevens and Zampini, this paper attempts to explain reactions of the British Government to Novel Psychoactive Substances (NPS) between 2008 – 2016. Qualitative data comes from in-depth interviews with stakeholders (N = 15), including NGO workers, a former Home Secretary, drugs ministers, governmental advisors, a former senior police officer, former Deputy Drug Coordinator, and a former Advisory Council for the Misuse of Drugs (ACMD) member. Two 'constellations' competed in British NPS policy setting. The PC framework illustrates power imbalances between these competing stakeholders. Abstinence orientated actors (the conservative constellation) enjoyed strategic advantages and media power which allowed them to create a favourable policy setting. These advantages were not enjoyed by the liberal constellation who struggled to access the policy setting and influence policy developments. The prohibitive nature of the policy used to counter NPS can be explained with the domination of actors whose values align with the conservative constellation. [ABSTRACT FROM AUTHOR]

Background: Administering premixed drugs in commodity packets was first reported in Asia in 2015, but there continues to be a dearth of related population-based data. This study aimed at examining (1) the prevalence of drug-packet use in the population and (2) the sociodemographic profiles, particularly gender distribution, of drug-packet users. Methods: Data were derived from a survey of 18,626 Taiwanese civilians, aged 12–64 years, using stratified, multi-stage, random sampling in 2018. Participants anonymously completed a computer-assisted self-interview on tablet computers which covered the use and problematic use of illicit drugs/inhalants, prescription drugs, and other psychoactive substances. Results: Approximately 1.46% of respondents had a lifetime use of illicit drugs, with drugs in commodity packets (0.18%) being ranked the fifth-most commonly used illicit drugs, higher than nitrous oxide (0.14%) and heroin (0.09%). Ten formats of drug packets were endorsed by users. Approximately 81.6% of persons with drug packet use had lifetime use of other illicit drugs. The correlates of the use of drugs in commodity packets were different from those of the exclusive use of other drugs, particularly concerning the lack of gender differences in the former category in the whole sample and the subgroups of various sociodemographic characteristics and other substance use. Conclusion: Drugs in commodity packets have become a common way of administering illicit drugs in the population in Taiwan, and there were no gender differences among users. Our findings have implications for more efficient drug testing and culturally appropriate intervention for drug-packet use.

The previous two decades have been marked by profound societal transformations, including ongoing developments in the illegal drug market and the emergence of numerous novel psychoactive substances. Nevertheless, a comprehensive understanding of the diverse clinical presentations of psychopathological conditions, particularly within the domain of psychotic symptoms, remains deficient. In this clinical overview, our aim is to provide a detailed analysis of the psychotic manifestations induced by various substances. Exogenous psychoses may present with visual hallucinations, delusional perceptions, and paranoid ideation, frequently accompanied by an ego-dystonic experience that deviate from an individual's customary self-identity. Variations in the presentation of symptoms are also influenced by the specific pharmacological pathways with which the substance interacts. Visual hallucinations characterized by vivid colours and associated with positive or negative emotional experiences are most frequently linked to the serotonergic pathway. Paranoid ideation and auditory hallucinations are primarily associated with the dopaminergic pathways. Dissociative responses, often characterized by feelings of derealization and somatopsychic depersonalization, are typically elicited through glutamatergic pathways. Lastly, the endocannabinoid pathways are associated with anxiety-related psychosis-like states, ideas of reference, grandiose delusions, and paranoid delusions.

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G‐PN column containing 2,6‐di‐O‐pentyl‐3‐propionyl‐γ‐cyclodextrin and a Lipodex™ D column containing heptakis‐(2,6‐di‐O‐pentyl‐O‐acetyl)‐β‐cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS‐QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA‐derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G‐PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively. [ABSTRACT FROM AUTHOR]

Background The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted. Methods By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties. Results 2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs. Conclusions This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users. [ABSTRACT FROM AUTHOR]

A confiscated package of street drugs was characterized by the usual mass spectral (MS) and FT–IR analyses. The confiscated powder material was highly crystalline and was found to consist of two very different species, accidentally of sizes convenient for X-ray diffraction. Thus, one each was selected and redundant complete sets of data were collected at 100 K using Cu Kα radiation. The selected crystals contained: (a) 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone hydrochloride hemihydrate or 1-(2-oxo-1,2-diphenylethyl)pyrrolidin-1-ium chloride hemihydrate, C18H20NO+ ·Cl-·0.5H2O, (I), a synthetic cathinone called ‘α-D2PV’, and (b) the sugar myo-inositol, C6H12O6, (II), probably the only instance in which the drug and its diluent have been fully characterized from a single confiscated sample. Moreover, the structural details of both are rather attractive showing: (i) interesting hydrogen bonding observed in pairwise interactions by the drug molecules, mediated by the chloride counter-anions and the waters of crystallization, and (ii) π–π interactions in the case of the phenyl rings of the drug which are of two different types, namely, π–π stacking and edge-to-π. Finally, the inositol crystallizes with Z′ = 2 and the resulting diastereoisomers were examined by overlay techniques [ABSTRACT FROM AUTHOR]

Patients presenting to the ED after using illicit drugs, including novel psychoactive substances, are a unique source of information on substances that are directly causing acute harm in the community. Conventionally, illicit drug intoxications are assessed and managed in EDs based on self‐report and presenting symptoms, with no objective data on the causative agent. The Emerging Drugs Network of Australia (EDNA) is a national toxico‐surveillance system that provides analytic data on these drugs, from sentinel Emergency Departments. It is a collaborative national network of emergency physicians, toxicologists, forensic laboratories and public health authorities. The key benefit of EDNA is the capacity to provide timely laboratory‐confirmed toxicology data on emerging drug‐related threats in the community. This leads to improvements in clinical, forensic laboratory and public health harm reduction responses, reflecting rapid translation of the research. [ABSTRACT FROM AUTHOR]

Over the past decade, new challenges in seized drug analysis have pushed the limits of existing instrumentation and workflows. These challenges include increasing caseloads, complex samples containing previously unidentified substances, and evolving legal requirements. Traditional approaches to seized drug analysis—such as gas chromatography mass spectrometry, color tests, and Fourier transform infrared spectroscopy—can be insufficient for current challenges, motivating the community to explore new instrumentation or data analysis solutions. However, the road to validation, implementation, and adoption of new technologies and solutions can be arduous. In this overview, we discuss the major challenges facing the seized drug community that can be addressed by advances in analytical approaches and highlight some emerging techniques that have been or could be adopted by laboratories in the near‐term. We also discuss specific hurdles limiting the implementation and adoption of new techniques, and approaches to lower these barriers. This article is categorized under:Forensic Chemistry and Trace Evidence > Controlled and Emerging Drug CompoundsForensic Chemistry and Trace Evidence > Emerging Technologies and MethodsForensic Chemistry and Trace Evidence > Presentation and Evaluation of Forensic Science Output [ABSTRACT FROM AUTHOR]

The rise of fentanyl and fentanyl analogs in the drug supply pose serious threats to public health. Much of these compounds enter the United States through shipping routes. Here we provide a method for fentanyl screening and analysis that utilizes pressure‐sensitive adhesive (PSA) lined paper to recover drug residues from parcel‐related surfaces. The paper used is commercially available repositionable notes (also called post‐it or sticky notes). From this paper, mass spectra were obtained by paper spray‐mass spectrometry (PS‐MS), where PSA paper served as both a sampling and analysis substrate. Seven fentanyl‐related compounds were analyzed: fentanyl, 4‐anilino‐N‐phenethylpiperidine (4‐ANPP), N,1‐diphenethyl‐N‐phenylpiperidin‐4‐amine (phenethyl‐4‐ANPP), valerylfentanyl, 4‐fluoroisobutyrylfentanyl (4‐FIBF), carfentanil, and p‐fluorofentanyl. These compounds were recovered by PSA paper and identified by PS‐MS from packaging tape and plastic at 50 ng and from cardboard and shipping labels at 100 ng. The impact of cutting agents on PS‐MS analysis of fentanyl analogs was explored. No trends of analyte suppression were found at high concentrations of the cutting agents caffeine, diphenhydramine, and lidocaine when recovered from surfaces. A cartridge that required no precise cutting of PSA paper prior to sampling or analysis was evaluated for use in PS‐MS for fentanyl screening. Recovery and detection of fentanyl from plastic sheeting was demonstrated with this cut‐free cartridge. The cut‐free cartridge showed somewhat less consistency and lower analyte signal than the standard cartridge, but performance was suitable for potential screening applications. In combining PSA surface sampling with PS‐MS for drug screening, both sampling and detection of fentanyl‐related compounds is simple, rapid, and low‐cost. [ABSTRACT FROM AUTHOR]

Definitive identification of fentanyl analogs based on mass spectral comparison is challenging given the high degree of structural and, hence, spectral similarity. To address this, a statistical method was previously developed in which two electron‐ionization (EI) mass spectra are compared using the unequal variance t‐test. Normalized intensities of corresponding ions are compared, testing the null hypothesis (H0) that the difference in intensity is equal to zero. If H0 is accepted at all m/z values, the two spectra are statistically equivalent at the specified confidence level. If H0 is not accepted at any m/z value, then there is a significant difference in intensity at that m/z value between the two spectra. In this work, the statistical comparison method is applied to distinguish EI spectra of valeryl fentanyl, isovaleryl fentanyl, and pivaloyl fentanyl. Spectra of the three analogs were collected over a 9‐month period and at different concentrations. At the 99.9% confidence level, the spectra of corresponding isomers were statistically associated. Spectra of different isomers were statistically distinct, and ions responsible for discrimination were identified in each comparison. To account for inherent instrument variations, discriminating ions for each pairwise comparison were ranked based on the magnitude of the calculated t‐statistic (tcalc) value. For a given comparison, ions with higher tcalc values are those with the greatest difference in intensity between the two spectra and, therefore, are considered more reliable for discrimination. Using these methods, objective discrimination among the spectra was achieved and ions considered most reliable for discrimination of these isomers were identified. [ABSTRACT FROM AUTHOR]

The standard reference libraries and associated custom software provided by the National Institute of Standards and Technology's Mass Spectrometry Data Center (NIST MSDC) are described with a focus on assisting the seized drug analyst with the identification of fentanyl‐related substances (FRS). These tools are particularly useful when encountering novel substances when no certified sample is available. The MSDC provides three standard reference mass spectral libraries, as well as six software packages for mass spectral analysis, reference library searching, data interpretation, and measurement uncertainty estimation. Each of these libraries and software packages are described with references to the original publications provided. Examples of fentanyl identification by gas chromatography–mass spectrometry (GC–MS) and by direct analysis in real‐time (DART) mass spectrometry are given. A link to online tutorials is provided. [ABSTRACT FROM AUTHOR]

Microorganisms are widespread on the planet being able to adapt, persist, and grow in diverse environments, either rich in nutrient sources or under harsh conditions. The comprehension of the interaction between microorganisms and drugs is relevant for forensic toxicology and forensic chemistry, elucidating potential pathways of microbial metabolism and their implications. Considering the described scenario, this paper aims to provide a comprehensive and critical review of the state of the art of interactions amongst microorganisms and common drugs of abuse. Additionally, other drugs of forensic interest are briefly discussed. This paper outlines the importance of this area of investigation, covering the intersections between forensic microbiology, forensic chemistry, and forensic toxicology applied to drugs of abuse, and it also highlights research potentialities. Key points Microorganisms are widespread on the planet and grow in a myriad of environments. Microorganisms can often be found in matrices of forensic interest. Drugs can be metabolized or produced (e.g. ethanol) by microorganisms. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) are a very diverse group of recreational drugs that mimic effects of classic drugs of abuse and, at least at the beginning, are not usually prohibited. Representative of this group is mephedrone – a cathinone derivative. It is widely used as a recreational drug, particularly among club guests. Mephedrone`s effects are compared to effects of cocaine and MDMA but are more short-lived and include: psychostimulation, enhanced empathy, reduced feeling of tiredness, euphoria, hallucinations. This drug also exerts adverse effects, such as: anxiety, delusions, paranoia, psychosis, increased body temperature, elevated blood pressure, sleep disturbances. According to surveys performed on mephedrone users, it may be addictive. Those findings confirms a growing number of behavioural and molecular studies on animals. Mephedrone acts mainly via increasing monoamine transmission through increasing release of dopamine, serotonin and noradrenaline into synaptic cleft, inhibiting their re-uptake and reducing their metabolism. However, participation of other transmitters, modulators and pathways are investigated, including glutamate and nitric oxide. Favorable routes of administering mephedrone is intranasal and per os. Moreover, most often drug users use it in a binge way, e.g. taking repeated doses of a drug in a short period of time. According to animal studies, this pattern of mephedrone use leaves more neural injuries than taking it regularly, but in smaller doses. Our aim was to present a short, but essential, overview of the current knowledge on mephedrone, focusing on its effects, mechanism of action, animal studies evaluating its influence on the brain structures, toxicity and pharmacokinetics.

Introduction Methods Results Discussion and Conclusions Fielding greater than 100,000 calls annually, telephone helplines are an important point of entry to alcohol and other drug (AOD) support and services in Australia. Methamphetamine and emerging drugs can present a particular challenge for this workforce. We sought to identify training needs for these services, so that appropriate targeted resources can be developed.We distributed an anonymous, online, cross‐sectional survey to helpline staff from New South Wales, Queensland, South Australia, Victoria and Western Australia. Based on the WHO Hennessy‐Hicks training needs analysis tool, participants were asked: to rate on a 7‐point likert scale the importance of a topic to their practice and how well they perform in relation to the topic; open‐ended questions specifying their own self‐perceived training needs; and demographic data.Of 50 participants, 29 completed the full survey (median age 49 [IQR 30–57.5]; median time working in AOD sector 6 years [IQR 1–20]). The results identified a need for: practical community‐informed population relevant information for culturally and linguistically diverse populations and Aboriginal and Torres Strait Islander peoples for calls relating to methamphetamine and emerging drugs of concern; training and resources with a particular focus on families and friends of people who use methamphetamine and emerging drugs; and readily accessible up‐to‐date information on new and emerging drugs and treatment of related disorders.This training needs analysis provides a structured approach to supporting the first‐line AOD counsellors to provide up‐to‐date and accurate information to assist Australians seeking information, support and advice. [ABSTRACT FROM AUTHOR]

Aminoindanes are a class of novel psychoactive substances (NPSs) that have become more prevalent over the past decade. GC–MS is often utilized for identifying seized drugs and is well regarded for its ability to separate mixtures. However, certain aminoindanes have similar mass spectral data and require specific gas chromatographic stationary phases for separation. Derivatization is an alternative method that can be applied to GC–MS to enhance chromatographic results, providing more selective analysis in seized‐drug identification. This study investigates derivatization techniques to provide options for forensic science laboratories in accurately identifying aminoindanes. Three derivatization reagents, N‐methyl‐bis(trifluoroacetamide) (MBTFA), heptafluorobutyric anhydride (HFBA), and ethyl chloroformate (ECF) were evaluated for the analysis of eight aminoindanes by GC–MS using two common gas chromatographic stationary phases, Rxi®‐5Sil MS and Rxi®‐1Sil MS. All three derivatization methods successfully isolated eight aminoindanes, including the isomers 4,5‐methylenedioxy‐2‐aminoindane (4,5‐MDAI), and 5,6‐methylenedioxy‐2‐aminoindane (5,6‐MDAI) that could not be differentiated prior to derivatization. Reduced peak tailing and increased abundance were observed after derivatization for all the compounds, and mass spectra of the derivatives contained individualizing fragment ions that allowed for further characterization of the aminoindanes. This excluded 4,5‐MDAI and 5,6‐MDAI as they shared the same characteristic ions and were only distinguishable by their retention times. All three derivatization techniques used in this study allow for successful characterization of the aminoindanes and give forensic science laboratories flexibility in their analysis approach when they encounter these compounds. [ABSTRACT FROM AUTHOR]

The burden of acute illicit drug use in Australia is largely unknown. Establishing a prospective drug surveillance system in emergency departments using analytical confirmation may facilitate the early identification of emerging drugs. We describe demographic data and acute toxicity patterns, stratified by analytical confirmation of illicit drugs and novel psychoactive substances, to emergency departments in Western Australia. Patients presenting with severe and/or unusual clinical features consistent with recreational drug toxicity were identified across five Western Australian emergency departments participating in the Emerging Drugs Network of Australia between April 2020 and December 2021. Demographic and toxicology patterns in patients with and without analytically confirmed illicit drugs/novel psychoactive substances from blood samples were collected during the emergency department presentation. The cohort included 434 severe and/or unusual toxicology presentations; median age 33 years (first and third quartiles 25–40 years), 268 (61.8%) males. Any substance (illicit, novel psychoactive substance, pharmaceutical) was detected in 405 (93.3%) presentations. Illicit drugs/novel psychoactive substances were detected in 257 (59.2%) presentations, including 73 (28.3%) with more than one confirmed illicit drug/novel psychoactive substance. Frequent illicit drugs identified were metamfetamine (n = 201, 77.9%) and gamma-hydroxybutyrate (n = 30, 11.6%). Forty-eight novel psychoactive substances were detected within 43 (16.7%) presentations. Novel benzodiazepines were most frequently detected (n = 29, 60.4%). Frequent pharmaceuticals detected included diazepam (n = 100, 26.1%) and clonazepam (n = 40, 10.4%). One hundred and fifty-five (35.7%) presentations were discharged home and 56 (12.9%) were admitted to intensive care. Presentations with detected illicit drugs/novel psychoactive substances had a lower median intensive care length of stay compared to presentations without detected illicit drugs/novel psychoactive substances (32.6 h versus 50.8 h respectively, P < 0.001). Integration of clinical and analytic data in patients with severe and/or unusual toxicology presentations via the Emerging Drugs Network of Australia provides insight into illicit drug/novel psychoactive substance use responsible for acute harm across Western Australian emergency departments. [ABSTRACT FROM AUTHOR]

MTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In order to fill this gap, the aim of the present work was to evaluate its genotoxicity on TK6 cells in terms of its ability to induce structural and numerical chromosomal aberrations by means of a cytofluorimetric protocol of the "In Vitro Mammalian Cell Micronucleus (MN) test". To consider the in vitro effects of both the parental compound and the related metabolites, TK6 cells were treated with MTTA in the absence or presence of an exogenous metabolic activation system (S9 mix) for a short-term time (3 h) followed by a recovery period (23 h). No statistically significant increase in the MNi frequency was detected. Specifically, in the presence of S9 mix, only a slight increasing trend was observable at all tested concentrations, whereas, without S9 mix, at 75 µM, almost a doubling of the negative control was reached. For the purposes of comprehensive evaluation, a long-term treatment (26 h) was also included. In this case, a statistically significant enhancement in the MNi frequency was observed at 50 µM. [ABSTRACT FROM AUTHOR]

In this study, we aimed to identify the current trend of novel psychoactive substance (NPS) consumption in Italy and the level of knowledge about NPS in the general population and to explore the presence of risk factors for a lifetime NPS misuse. We conducted an anonymous online survey, administered to a large sample of people of any age living in Italy, asking for their knowledge about NPS as well as their history of drug use. Descriptive statistics were reported, and regression analyses were performed to identify risk factors for lifetime use of NPS. A total of 1097 individuals gave a valid response to the survey. A lifetime use of NPS was reported by 13.5%. Multivariate regression analysis showed that male gender (OR 2.33, 95% CI 1.52–3.55), homosexual sexual orientation (OR 2.52, 95% CI 1.21–5.27), a use of emergency services due to alcohol (OR 3.38, 95% CI 2.23–5.12) and previous contact with mental health services (OR 1.58, 95% CI 1.04–2.41) were risk factors for a lifetime use of NPS (p < 0.05). An improvement of preventive strategies and simplified access to information on NPS, especially tailored to individuals at increased risk of misuse, could slow diffusion of NPS and avert the consequences of substance use. [ABSTRACT FROM AUTHOR]

Rapid drug detection is vital for combating drug abuse and inhibiting transmission, and the emergence of various novel psychoactive substances (NPS) has placed higher demands on field testing. To establish a rapid, nondestructive, and accurate analytical and classification method for testing novel psychoactive substances, shifted‐excitation Raman difference spectroscopy (SERDS) was used to detect 37 NPS including fentanyl, amphetamine, and synthetic cannabinoid under the experimental conditions of laser light source (785 and 785.5 nm). SERDS was also used in conjunction with machine learning to find the best classification prediction model. In this study, the characteristic peaks of 37 NPS analogs were extracted, and the characteristic peaks were attributed to the structures of the substances. We compared the classification effects of Support Vector Machine (SVM), K‐NearestNeighbor (KNN), ensemble classifier, neural network, tree, naive Bayes, and discriminant analysis and provided three hyperparametric optimization methods. Finally, the cross‐validation accuracy of SVM under BOA optimization is 97.3%, which can well distinguish three families of samples. The ability of SERDS to resist strong fluorescence interference makes it a powerful tool for on‐site analysis of NPS. In this study, we have given 37 unreported standard Raman peaks of NPS and three seized samples, which can be used as a reference. Shifted‐excitation differential Raman spectroscopy combined with machine learning can effectively provide solutions for customs, health care, on‐site police, large event security, and trace evidence inspection. [ABSTRACT FROM AUTHOR]

The unprecedented proliferation of novel psychoactive substances (NPS) in the illicit drug market has been a public health concern since their emergence in the 2000s. Their consumption can pose severe health risks as their mechanism of action is poorly understood and their level of toxicity is high mainly due to the diffusion of very potent synthetic cannabinoid receptor agonists and synthetic opioids. This study systemically analyses the evolution of the scientific literature on NPS to gain a better understanding of the areas of major research interests and how they interlink. Findings indicate that the published evidence covers clusters focused on classes of NPS that have received widespread media attention, such as mephedrone and fentanyl, and have largely been concerned with the pharmacological and the toxicological profiles of these substances. This scientometric perspective also provides greater insight into the knowledge gaps within this new and rapidly growing field of study and highlights the need for an interdisciplinary approach in tackling the NPS epidemic.

Over the last year, NPSs have been steadily on the rise in the illicit drug market. Among these, synthetic cathinones seem to become increasingly popular among young adults, mainly because of their ability to replicate the effects of traditional psychostimulant drugs, such as cocaine, MDMA and amphetamines. However, scarce data are available about the in vivo pharmaco-toxicology of these new substances. To this end, this study focused on evaluation of effects induced by repeated administration of mephtetramine (MTTA 0.1–30 mg/kg i.p.) in mice. This atypical cathinone highlighted a sensorial (inhibition of visual and acoustic reflexes) and transient physiological parameter (decrease in breath rate and temperature) change in mice. Regarding motor activity, both a dose-dependent increase (accelerod test) and biphasic effect (drag and mobility time test) have been shown. In addition, blood and urine samples have been analysed to enrich the experimental featuring of the present study with reference to evaluation of potential toxicity related to consumption of MTTA. The latter analysis has particularly revealed important changes in blood cells count and blood and urine physicochemical profile after repeated treatment with this atypical cathinone. Moreover, MTTA induced histological changes in heart, kidney and liver samples, emphasizing its potential toxicity. [ABSTRACT FROM AUTHOR]

Objectives: With an increasingly dynamic global illicit drug market, including the emergence of novel psychoactive substances, many jurisdictions have moved to establish toxicosurveillance systems to enable timely detection of harmful substances in the community. This paper describes the methodology for the Emerging Drugs Network of Australia - Victoria (EDNAV) project, a clinical registry focused on the collection of high-quality clinical and analytical data from ED presentations involving illicit drug intoxications. Drug intelligence collected from the project is utilised by local health authorities with the aim to identify patterns of drug use and emerging drugs of concern. Methods: The project involves 10 public hospital EDs in Victoria, Australia. Patients 16 years and over, presenting to a network ED with a suspected illicit drug-related toxicity and a requirement for venepuncture are eligible for inclusion in the study under a waiver of consent. Clinical and demographic parameters are documented by site-based clinicians and comprehensive toxicological analysis is conducted on patient blood samples via specialised forensic services. All data are then deidentified and compiled in a project specific database. Results: Cases are discussed in weekly multidisciplinary team meetings, with a view to identify potentially harmful substances circulating in the community. High-risk signals are escalated to key stakeholders to produce timely and proportionate public health alerts with a focus on harm minimisation. Conclusions: The EDNAV project represents the first centralised system providing near real-time monitoring of community drug use in Victoria and is fundamental in facilitating evidencebased public health intervention. [ABSTRACT FROM AUTHOR]

Drug forums are considered as the main platform sources that have contributed to the increase in NPS popularity, especially for those not yet known to law enforcement and therefore not yet illegal. An example is the new synthetic stimulant NM2AI, which has a very short history of human use and abuse. Little is known regarding this compound, but some information from internet forums and the scientific literature indicates NM2AI as a structural derivate of MDAI, which is known for its entactogenic activity. Indeed, the purpose of this study is to evaluate, for the first time, the in vivo acute effect induced by the intraperitoneal injection of NM2AI (1–10–30–100 mg/kg) in mice. We demonstrate the sensory (by visual placing and object tests) and physiological (core temperature measurement) function variations, nociceptor (by tail pinch test) and strength (grip test) alterations, and sensorimotor (time on rod and mobility) decrease. Moreover, we verify the mild hallucinogenic effect of NM2AI (by startle/prepulse inhibition test). Lastly, we perform a pharmacokinetic study on mice blood samples, highlighting that the main active metabolite of NM2AI is 2-aminoindane (2AI). Taken together, our data confirm the suspected entactogenic activity of NM2AI; however, these in vivo effects appear atypical and less intense with respect to those induced by the classic stimulants, in surprising analogy with what is reported by networked users. [ABSTRACT FROM AUTHOR]

There is growing concern about the consumption of synthetic cannabinoids (SCs), one of the largest groups of new psychoactive substances, its consequence on human health (general population and workers), and the continuous placing of new SCs on the market. Although drug-induced alterations in neuronal function remain an essential component for theories of drug addiction, accumulating evidence indicates the important role of activated astrocytes, whose essential and pleiotropic role in brain physiology and pathology is well recognized. The study aims to clarify the mechanisms of neurotoxicity induced by one of the most potent SCs, named MAM-2201 (a naphthoyl-indole derivative), by applying a novel three-dimensional (3D) cell culture model, mimicking the physiological and biochemical properties of brain tissues better than traditional two-dimensional in vitro systems. Specifically, human astrocyte spheroids, generated from the D384 astrocyte cell line, were treated with different MAM-2201 concentrations (1–30 µM) and exposure times (24–48 h). MAM-2201 affected, in a concentration- and time-dependent manner, the cell growth and viability, size and morphological structure, E-cadherin and extracellular matrix, CB1-receptors, glial fibrillary acidic protein, and caspase-3/7 activity. The findings demonstrate MAM-2201-induced cytotoxicity to astrocyte spheroids, and support the use of this human 3D cell-based model as species-specific in vitro tool suitable for the evaluation of neurotoxicity induced by other SCs. [ABSTRACT FROM AUTHOR]

Purpose: The emergence of novel psychoactive substances (NPS) has been being a continuous and evolving problem for more than a decade. Every year, dozens of new, previously unknown drugs appear on the illegal market, posing a significant threat to the health and lives of their users. Synthetic cathinones are one of the most numerous and widespread groups among NPS. The purpose of this work was to identify and summarize available data on newly emerging cathinones in very recent years. Methods: Various online databases such as PubMed, Google Scholar, but also databases of government agencies including those involved in early warning systems, were used in search of reports on the identification of newly emerging synthetic cathinones. In addition, threads on various forums created by users of these drugs were searched for reports on the effects of these new substances. Results: We have identified 29 synthetic cathinones that have been detected for the first time from early 2019 to mid-2022. We described their structures, known intoxication symptoms, detected concentrations in biological material in poisoning cases, as well as the countries and dates of their first appearance. Due to the lack of studies on the properties of the novel compounds, we compared data on the pharmacological profiles of the better-known synthetic cathinones with available information on the newly emerged ones. Some of these new agents already posed a threat, as the first cases of poisonings, including fatal ones, have been reported. Conclusions: Most of the newly developed synthetic cathinones can be seen as analogs and replacements for once-popular compounds that have been declining in popularity as a result of legislative efforts. Although it appears that some of the newly emerging cathinones are not widely used, they may become more popular in the future and could become a significant threat to health and life. Therefore, it is important to continue developing early warning systems and identifying new compounds so that their widespread can be prevented. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) have been increasingly reported in the last 15–20 years. We aimed to describe presentations to the emergency department (ED) with acute recreational drug toxicity involving NPS. Data were extracted from the European Drug Emergencies Network (Euro-DEN) Plus database for all presentations to ED (36 EDs in 24 European countries) with acute toxicity between January 2014 and December 2019. Patient demographics, agents involved, and clinical outcomes were described and the subgroup of presentations involving NPS was compared with the rest of the cohort. Out of 43,633 Euro-DEN Plus presentations, 3304 (7.6%) involved at least one NPS. Agents were identified mainly based on self-report or clinical presentation, with analytical confirmation being performed only in 17.9% of NPS presentations. The proportion of NPS presentations varied by centre (0–48.8%). For centres where data were available for all 6 years, NPS-related presentations peaked in 2015 (11.9%). In 2014, 78.4% of NPS agents reported were cathinones, while only 3.4% were synthetic cannabinoids (SCs); conversely, in 2019 only 11.6% of NPS agents reported were cathinones, while 72.2% were SCs. NPS-related presentations involved younger patients (median 30 (23–37) vs. 32 (25–40) years, p < 0.001) and more males (84.8 vs. 75.8%, p < 0.001) compared with the rest of the cohort. Patients presenting to ED after using NPS were more likely to self-discharge (22.8 vs. 15.1%), less likely to be admitted to critical care (3.6 vs. 6.1%) but had a longer length of stay in hospital (median 5.1 (2.7–18.7) vs. 4.7 (2.5–9.2) h, p < 0.001). Death occurred in 0.5% of all presentations involving NPS and in 0.4% of non-NPS presentations. This large multicentre series of NPS presentations to European EDs showed marked geographical variation and changes over time in the proportion of presentations to ED involving NPS, as well as the proportion of NPS subgroups. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) is an umbrella term used to describe a heterogeneous group of compounds that mimic the effects of existing drugs and whose demand and use rapidly emerge, change, or even vanish in the drug market. The novelty of this global phenomenon and its dynamic nature represent major challenges for the scientific community that constantly requires timely evidence-based inputs. Our aim is to review the literature on NPS and compare its temporal evolution according to the topics presented at the International Conference series on NPS over the past decade. Our analysis shows that some new clusters of research recently emerged in comparison to a previous review and that the material presented at the NPS Conferences anticipates the scientific literature by approximately 2.5 years. Such findings not only provide new original insights on the latest NPS trends but also address existing knowledge gaps in the NPS field, while emphasizing the importance of face-to-face thematic events supported by faster publication processes to inform prompt interventions and policy making.

The amphetamine‐type stimulants (ATS) adulteration is currently a common phenomenon that endangers the health of consumers. Among the most common adulterants are new psychoactive substances (NPS), such as synthetic cathinones. This development demands new, low‐cost, and simple detection strategies. In this work, we present, for the first time, the electrochemical detection of two NPSs, the amphetamine 3,4‐methylenedioxymethamphetamine (MDMA) and the synthetic cathinone α‐pyrrolidinopentiophenone (α‐PVP), using an electrochemical biosensor based on cytochrome P450 2D6 (CYP2D6). This biosensor was constructed by electrochemical reduction of the 4‐nitrobenzenediazonium salt on a carbon screen‐printed electrode (C‐SPE), with subsequent reduction of the nitro group into amines, and finally covalent binding with the CYP2D6 enzyme. The biosensor voltammetric response of the molecules studied allowed reaching limits of detection (LOD) of 0.0017 and 0.0022 μg/mL, and limits of quantification (LOQ) of 0.0059 and 0.0076 μg/mL for MDMA and α‐PVP, respectively. [ABSTRACT FROM AUTHOR]

L'objectif de ce travail est de déterminer la fréquence des symptômes psychotiques induits par les psychostimulants, dont les nouveaux produits de synthèse (NPS), leurs caractéristiques cliniques, leur évolution et leurs traitements. Une revue de documents sélectionnés est effectuée suivant les principes de recherche systématique dans le Medline. La recherche retrouve 41 articles portant sur les psychostimulants hors NPS et 9 articles portant sur les NPS. Les symptômes psychotiques induits par les psychostimulants, y compris NPS, sont fréquents, présentent des caractéristiques typiques avec d'importants signes positifs malgré un insight en partie conservé, une possible évolution sur un mode chronique et répondent à des traitements comme les benzodiazépines et les antipsychotiques. Un récapitulatif des implications pratiques est proposé. Les symptômes psychotiques induits par les psychostimulants pourraient constituer un trouble à part ou une vulnérabilité qui devraient faire l'objet d'une prise en charge intégrée portant à la fois sur les consommations et la symptomatologie psychiatrique. Psychostimulants such as cocaine, amphetamines and their derivatives, methamphetamine or novel synthetic drugs such as cathinones are known to cause psychotic symptoms. The objective of this study is to determine the frequency of psychotic symptoms induced by psychostimulants, including novel psychoactive substances (NPS), their clinical characteristics, their evolution, and their treatments. A review of selected documents was carried out following the principles of systematic research in Medline from 02/12/2017 to 02/12/2022. We included articles in French or English dealing with psychotic symptoms, episodes and disorders induced by psychostimulants in humans, and excluded articles dealing with animal models, those not distinguishing between substances other than psychostimulants, and NPS and non-NPS psychostimulants, and articles focusing exclusively on individuals with previously diagnosed schizophrenia. The data was input in a table for non-NPS psychostimulants and another table for NPS psychostimulants. The search found 41 articles on non-NPS psychostimulants and 9 articles on NPS. Psychotic symptoms induced by psychostimulants, including NPS, are frequent in a population of medicalized consumers: 18 to 80% according to studies. Psychotic symptoms show typical features with prominent positive symptoms, especially persecutory delirium, auditory, visual and tactile hallucinations, less negative, and cognitive symptoms. We noted more agitation, even auto-aggressiveness or hetero-aggressiveness. The clinical presentation is frequently accompanied by signs of toxic impregnation, in particular tachycardia, palpitations, hypertension, sweating or mydriasis. The data suggest a possible evolution in a chronic presentation. Psychostimulant-induced psychotic symptoms appear to be improved by treatments such as benzodiazepines for agitation and antipsychotics. The data was less rich regarding NPS but broadly consistent with the findings presented above. A summary of practical implications is provided. The psychotic symptoms induced by psychostimulants present specific, although not exclusive, characteristics. They should be the subject of particular attention, in especially looking for urinary toxins, although certain substances such as cathinones are not detected by current laboratory practices. They may be subject to a specific treatment depending on their severity and duration. In some cases, they could evolve into a chronic presentation and constitute a separate disorder or a vulnerability that should be the subject of integrated care covering both consumptions and psychiatric symptoms. [ABSTRACT FROM AUTHOR]

Synthetic cathinones are a class of novel psychoactive substances, commonly tested in seized materials by forensic chemistry laboratories. These drugs have been found in different types of seized materials including powders, tablets, liquids, herbs, and blotters. A comprehensive review of the literature shows that the analyses of synthetic cathinones have been performed by a diverse repertoire of techniques, from more traditional to emerging methods. Techniques commonly used in the analysis of "traditional" illicit drugs, such as color and microcrystalline tests, chromatography, capillary electrophoresis, mass spectrometry (MS), and infrared (IR), and Raman spectroscopies, have been used for screening and/or confirmatory purposes, depending on the technique and laboratories preference. However, other emerging techniques, such as nuclear magnetic resonance, high‐resolution MS, direct analysis in real‐time MS, gas chromatography with IR detection, and so on, have been drawing the attention of forensic scientists due to the advantages of these techniques in providing important structural data. It is important to consider that each technique presents analytical benefits and limitations, which should be considered when analyzing synthetic cathinones in seized materials. Furthermore, the combination of more than one analytical technique is always recommended, especially when an unknown synthetic cathinone is suspected and/or encountered in the sample. This article is categorized under:Forensic Chemistry and Trace Evidence > Controlled and Emerging Drug CompoundsToxicology > New Psychoactive SubstancesForensic Chemistry and Trace Evidence > Emerging Technologies and Methods [ABSTRACT FROM AUTHOR]

N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals, and acute behavioural effects after subcutaneous administration of 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe; 0.2, 1, and 5 mg/kg) in Wistar rats. Drug concentration peaked 1 h after the administration of 5 mg/kg in both blood serum and brain tissue with a half-life of 1.88 and 2.28 h, respectively. According to Organisation for Economic Co-operation and Development 423 toxicity assay, the drug is classified into category 3 with a lethal dose of 300 mg/kg and an estimated LD50 value of 200 mg/kg. Histological examination of organs collected from rats injected with the lethal dose revealed subtle pathological changes, highly suggestive of acute cardiovascular arrest due to malignant arrhythmia. Altered thermoregulation after 5 mg/kg was demonstrated by reduced body temperature in individually housed rats (p < 0.01). Behavioural effects assessed by the Open Field test and Prepulse Inhibition of Startle Response revealed that the two lower doses (0.2 and 1 mg/kg) caused a reduction in locomotor activity (p < 0.01), increased anxiety (p < 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p < 0.001). In summary, 25CN-NBOMe readily passes the blood-brain barrier and exhibits a moderate level of toxicity and behavioural effect comparable with other NBOMes. [ABSTRACT FROM AUTHOR]

Among novel psychoactive substances, synthetic cannabinoid receptor agonists (SCRA) seem to have the widest diffusion in the population with no limitation to any particular demographic group. Information on drug consumption relies mostly on anonymized surveys and less on clinical or analytical data; notwithstanding, the huge efforts constantly made to enroll subjects to gather epidemiological data. In the present study, we collected 66 oral fluid samples from volunteers in a drug rehabilitation center in 2019 and early 2020. A liquid chromatography–mass spectrometry method previously developed and validated by our Unit was applied to detect SCRA (n = 10) in oral fluid. Results proved the presence of synthetic cannabinoids at a positivity rate of almost 20%, with detection frequency HU211(5/13) > UR144/JWH122 (3/13) > JWH019/JWH081/AM2201 (1/13). Concentrations were in the range < LOQ −0.36 ng/ml. Synthetic cannabinoids consumption had not been declared by any volunteer. This study enabled for the unprecedent detection of synthetic cannabinoids use in the territory of Parma (Italy) in a high‐risk subpopulation. The identified SCRA proved the persistence into the market of the "first‐generation" JWH family into the Italian territory and the marketing of relatively new ones (AM‐2201). Public health consequences represented by NPS consumption are still scarce; therefore, further studies are needed to understand the real diffusion in the population. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances have emerged as drugs of abuse. 2-Fluorodeschloroketamine (2-FDCK) is a ketamine derivative that can be purchased online for as little as $12 per gram. We report the case of a patient with a history of polysubstance use presenting after insufflation of 2-FDCK, with subsequent confirmation of metabolites in the patient's urine. A 28-year-old man presented to the Emergency Department in a dissociated state. He recovered well with supportive care, and described during interview his experience of substance use including the novel psychoactive substance 2-FDCK. A urine sample was sent for analysis and 2-FDCK metabolites were isolated. This case is concerning because 2-FDCK is a relatively new agent that has not yet been reported in the United States. It is easy to obtain over the internet and has significant abuse potential. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) continue to emerge in the marketplace and are often found as substances in traditional illicit drug materials, and users are often unaware of the presence of other drugs. The proper identification and confirmation of the exposure to a drug is made possible when a biological specimen is collected and tested. Sweat is an alternative biological matrix of great interest for clinical, and forensic analysis. One of the reasons is attributed to its expanded drug detection window, enabling a greater monitoring capacity, and provision of information on prospective drug use. However, the concentrations of drugs in sweat samples are often low, which requires highly sensitive and selective methods. Disposable pipette tips extraction (DPX) is a new miniaturized solid phase extraction technique capable of efficiently extracting analytes from biological specimens, providing high recoveries, and requiring minimized solvent use. This study describes the development and optimization of two methods for the extraction of basic and neutral psychoactive substances from sweat samples using GC-MS and Design of Experiments (DoE). The following extraction parameters were optimized by DoE techniques: sample volume, elution solvent volume, washing solvent volume, sample aspiration time, elution solvent aspiration time, and number of cycles performed, including the elution step. It was possible to design a simple extraction protocol that provided optimized recoveries for both basic and neutral compounds. The sum of analyte areas increased at a rate of 54.7% for compounds of basic character and 39.2% for compounds of neutral character. Therefore, our results were satisfactory, demonstrating that DPX can be successfully used for extracting the target drugs from sweat samples., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Novel psychoactive substances (NPS), such as Esketamine (Esket), often contaminate the aquatic ecosystems following human consumption, raising concerns about the residues and potential ecological hazards to non-target organisms. The study used zebrafish as a model organism to investigate the developmental toxicity and ecotoxicological effects of acute Esket exposure. Our findings demonstrate that exposure to Esket significantly affected the early development and angiogenesis of zebrafish embryos/larvae. The mandible length was significantly decreased, and the angles between the pharyngeal arch cartilages were narrowed compared to the control group (all P < 0.05). Additionally, Esket resulted in a decrease of 47.6-89.8 % in the number of neural crest cells (NCC). Transcriptome analysis indicated altered expression of genes associated with cartilage and osteoblast growth. Moreover, Esket significantly inhibited swimming ability in zebrafish larvae and was accompanied by behavioral abnormalities and molecular alterations in the brain. Potential mechanisms underlying Esket-induced behavioral disorders involve neurotransmitter system impairment, abnormal cartilage development and function, aberrant vascular development, as well as perturbations in oxidative stress and apoptosis signaling pathways. Notably, the dysregulation of skeleton development through the bone morphogenetic protein (BMP) signaling pathway is identified as the primary mechanistic behind Esket-induced behavioral disorder. This study enhances our understanding of Esket's ecotoxicology profile and provides a comprehensive assessment of the environmental risks associated with NPS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)