European Monitoring Centre For Drugs And Drug Addiction Research Articles

EMCDDA framework and practical guidance for naming cathinones.

Cathinones are often sold as "legal" alternatives to controlled stimulants such as amphetamine, MDMA and cocaine. Cathinones are the second largest group of new psychoactive substances (NPS), with close to 170 monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Although all cathinones are related to the parent compound cathinone, one of the psychoactive principles in khat, assigning consistent, informative and user-friendly common names to these substances is challenging. Over time different naming approaches have been applied, leading to cathinones being known by several names. This work provides a framework and practical examples for the consistent naming of cathinones which is easy to understand and can be applied by the forensic community, researchers, clinical practitioners, and policy makers. The scope of the issue and rationale for earlier naming approaches are also discussed. The new naming framework has been developed based on established naming approaches and centered around the common "cathinone," and "phenone" motifs/scaffolds. The proposed framework establishes clear rules to derive the EMCDDA framework names for cathinones. Each name is, in turn, composed by a principal name containing a parent letter, derived after the "cathinone" or the "phenone" scaffold. Additional substitutions are prepended to the principal name. The framework also provides for exceptions for several cathinones and structural analogs scheduled under UN and EU legislation.

Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism.

The recreational use of nitrous oxide (N2O), also called laughing gas, has increased significantly in recent years. In 2022, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) recognized it as one of the most prevalent psychoactive substances used in Europe. Chronic nitrous oxide (N2O) exposure can lead to various clinical manifestations. The most frequent symptoms are neurological (sensitive or motor disorders), but there are also other manifestations like psychiatric manifestations or cardiovascular disorders (thrombosis events). N2O also affects various neurotransmitter systems, leading to its anesthetic, analgesic, anxiolytic and antidepressant properties. N2O is very challenging to measure in biological matrices. Thus, in cases of N2O intoxication, indirect biomarkers such as vitamin B12, plasma homocysteine and plasma MMA should be explored for diagnosis and assessment. Others markers, like oxidative stress markers, could be promising but need to be further investigated.

Drug use among non-binary people in Europe: findings from European Web Survey on Drugs

Abstract Traditionally, the survey-based methods used in drug research and drug monitoring at national and European levels tend to be blind to the specific experiences of non-binary people who use drugs. The invisibility of gender-diverse people is related to the use of standard one-step methods in the sex/gender demographic question, specifically the use of binary and mutually exclusive categories (male/ female or M/F). This presentation is based on the quantitative analysis of a sample of 817 non-binary people (non-probabilistic sample) who responded to the European Web Survey on Drugs 2021 (EWSD 2021), promoted by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). In specific, this presentation describes the sociodemographic profile, living conditions, drug use patterns (lifetime prevalence, last year's prevalence, last month's prevalence), and the context of drug use of non-binary people who responded to EWSD. The relationship between the non-binary gender identity and other categorical variables was analysed by using descriptive statistics and the Chi-square test for independence on the software IBM SPSS Statistics. This analysis allowed a preliminary identification of the specific drug use trends and health and social needs of non-binary people who use drugs, which will also be briefly included in this presentation. Moreover, this was the first time EMCDDA used a two-step approach method to collect data regarding sex (M/F) and gender (Man, Woman, Non-binary). In this sense, relevant methodological considerations regarding gender inclusiveness in survey data collection will also be presented, highlighting the relevance of systematically collecting gender-inclusive data to monitor gender-specific drug use patterns and trends and to inform the design of gender-responsive policies and social and health responses to drug problems. Key messages • Non-binary people who use drugs present gender-based specificities in drug use patterns. • It is relevant to systematically collect gender inclusive data to monitor gender-specific drug use patterns and trends.

B-300 Importance of Clinical Chemistry and Metabolism Parameters for the Management of Patient With Chronic Nitrous Oxide Intoxication

Abstract Background Recreational use of nitrous oxide (N2O) has increased exponentially recently and leads to severe neurological disorders. A recent report from European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) showed that the recreational use of N2O is a growing and became a major health issue in Europe. For biological monitoring, serum or urine N2O assays are not routinely performed because they do not allow to ensure a real exposure due to the very short half-life of this gas in the body. Functional disorders of vitamin B12 metabolism, characteristic of N2O intoxication, could be explored by two markers: homocysteine (Hcys) and methylmalonic acid (MMA). We experimented here, management of N2O abused patient thanks to functional markers as Hcys and MMA. Methods We collected clinical and biological data from patients with declared chronic N2O consumption. The patients treated in Lille University Hospital between september 2020 and december 2022 were included in the study. The clinical evaluation included the Peripheral Neuropathy Disability (PND) score which was evaluated by a neurologist. Results Our study included 202 patients with N2O abused, Globally, plasma functional markers concentration are increased in case on consumption (Table). We noticed that clinical sign of patient evaluated by PND score correlated with plasma MMA (P-value < 0.01) but not with plasma hcys (P-value > 0.05). Conclusion The use of functional markers as Hcys and MMA makes it possible to follow the metabolic disturbances of nitrous oxide abused patients and evaluated clinical outcomes. However, in view of the thrombotic risk related to high Hcys and the need to quickly adapt the nutritional treatment, biological and in particular Hcys, current reporting time is not satisfactory using mass spectrometry method. Hence, our medical laboratory aim to improve our method evaluating immunoassay techniques in order to reduce the turnaround time while maintaining analytical reliability.

Geospatiotemporal and Causal Inferential Study of European Epidemiological Patterns of Cannabis- and Substance-Related Congenital Orofacial Anomalies.

Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe. CA data were taken from the EUROCAT database. Drug exposure data were downloaded from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Income was taken from the World Bank's online sources. On the bivariate maps of both orofacial clefts and holoprosencephaly against resin, the Δ9-tetrahydrocannabinol concentration rates of both covariates increased together in France, Bulgaria, and the Netherlands. In the bivariate analysis, the anomalies could be ranked by the minimum E-value (mEV) as congenital glaucoma > congenital cataract > choanal atresia > cleft lip ± cleft palate > holoprosencephaly > orofacial clefts > ear, face, and neck anomalies. When nations with increasing daily use were compared to those without, the former had generally higher rates of FCAs (p = 0.0281). In the inverse probability weighted panel regression, the sequence of anomalies-orofacial clefts, anotia, congenital cataract, and holoprosencephaly-had positive and significant cannabis coefficients of p = 2.65 × 10-5, 1.04 × 10-8, 5.88 × 10-16, and 3.21 × 10-13, respectively. In the geospatial regression, the same series of FCAs had positive and significant regression terms for cannabis of p = 8.86 × 10-9, 0.0011, 3.36 × 10-8, and 0.0015, respectively. Some 25/28 (89.3%) E-value estimates and 14/28 (50%) mEVs were >9 (considered to be in the high range), and 100% of both were >1.25 (understood to be in the causal range). Rising cannabis use is associated with all the FCAs and fulfils the epidemiological criteria for causality. The data indicate particular concerns relating to brain development and exponential genotoxic dose-responses, urging caution with regard to community cannabinoid penetration.

The COVID-19 pandemic and the right to health of people who use drugs

Context: According to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) people who inject drugs (PWID) make up a significant part of the population that needs to be looked after to eliminate infectious diseases such as those caused by HIV and HCV. This situation has been exacerbated by the COVID-19 pandemic. As COVID-19 rapidly spread across the globe, governments implemented various prevention measures which not only caused an increase in problem drug use (PDU) because of their negative impact on mental health and socioeconomic conditions but also prompted a decrease in drug services provided. Therefore, new challenges appeared, such as increased demand for drugs and diversification of clients, and new needs. Nevertheless, in clear contradiction to what was needed, the EMCDDA’s initial reports suggested that there was a decline in European drug services both in providing treatment and harm reduction interventions. COVID-19 increased the need to access drug services, healthcare, and support services creating an increased demand for opioid substitution therapy and other medication. Thus, comprehensive, and sustainable policies are needed to combat the public health threats associated with these challenges and to ensure the continuity of care.
 Policy Options: The challenging circumstances brought by the COVID-19 pandemic require policymakers need to take action to build capacity and resiliency for those facing drug-related health and social problems. These should include the adoption of integrated strategies that combine drug consumption rooms, substance-specific therapies, provision of free needles and naloxone, primary healthcare, and social support.
 Recommendations: The creation of an integrated drug policy framework addressed to European Union member states is necessary to create robust drug services capable of surviving a crisis. This is guided by a relevant policy design and implementation framework, alongside tangible action principles in line with low-threshold service provision.

Zdrowie publiczne w europejskiej polityce zdrowotnej

Public health encompasses a wide range of activities related to almost all aspects of the society’s health. Public health influences the shape of social and health policy of the state, and cooperates with all socio-economic sectors and social organizations. The goal of public health is to reduce morbidity rate, premature deaths and conditions leading to suffering and disability. Public health activities in the European Union are determined by specific regulations which include: the Treaty of Maastricht, the Treaty of Amsterdam and the Treaty of Lisbon. The Directorate-General for Health and Consumer Protection is responsible for the implementation of health policy in the European Union. Other institutions include: Executive Agency for Health and Consumers (EAHC), European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), European Medicines Eval uation Agency (EMEA), European Food Safety Authority (EFSA), European Environment Agency (EEA), European Agency for Safety and Health at Work (EU – OSHA), European Centre for Disease Prevention and Control (ECDC). The European Union plays a significant role in the organization and functioning of health care systems in the Member States. The activities of the European Union determine the directions of cooperation in health services, aimed at the creation of supranational, highly specialized centres focusing on rare medical concerns and problems that require very specific and expensive medical procedures.

EMCDDA framework and practical guidance for naming synthetic cannabinoids.

Synthetic cannabinoids (SCs), often sold as "legal" replacements for cannabis, are the largest group of new psychoactive substances monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Currently, close to 240 structurally heterogeneous SCs are monitored through the European Union (EU) Early Warning System, and attributing consistent, informative, and user-friendly names to SCs has been a challenge in the past. Over time, several naming conventions have been employed with the aim of making SCs more easily recognizable by non-chemists, including regulators. To achieve this, the names assigned need to contain detailed information on the structural features present in the substance. This work provides a theoretical framework and a practical hands-on guideline for consistent naming of SCs, which is easy to understand and can be applied by the forensic community, researchers, clinical practitioners, and policy-makers. The proposed framework builds on the established letter code system for molecular building blocks (core, linker, linked group, and tail) implemented by the EMCDDA in 2013 and has been expanded to incorporate additional structural features through substitution. The scope of the issue of attributing semi-systematic code names is illustrated, and earlier approaches used for naming SCs are discussed. The concepts and rules of the EMCDDA framework are described through a flowchart that provides a basis for naming new SCs, a graphical overview of the chemical diversity of SCs, and a detailed list of the SCs identified in the EU by the Early Warning System of the EMCDDA for reference.

Viral hepatitis micro-elimination: models of care and barriers to implementation in 5 EU/EEA prisons

Abstract Introduction Coverage of essential prevention and control services and adequate monitoring schemes for viral hepatitis are often suboptimal in prison settings. Yet, evidence shows that targeted interventions are feasible and effective in reducing viral hepatitis burden and decreasing virus circulation among people living in prison and the community at large. To promote transferability and improvement of prison health quality in EU/EEA the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) will identify and disseminate models of care for viral hepatitis elimination in prisons. Methods The models of care were gathered using a data collection tool that has been designed for this purpose based on the literature review and agreed with an expert advisory group. Based on the results of the data collection, a survey for healthcare staff working in 5 selected prison institutions in the EU/EEA has been developed. Results The following models of care were collected: HCV micro-elimination in prison; transitional care for HCV treatment or HBV prevention/treatment; HCV or HBV care services tailored to women living in prison; HBV or HAV/HBV vaccination in prison settings. Harm reduction and drug treatment services in the prison are essential at all steps of the prevention and continuum of care. Among barriers identified were: engagement of people living in prison and prison governance structure, availability of infrastructural and human resources, daily prison organisation, inter-sectorial collaboration within prison and between prison and community services, training for prison staff and lack of systematic monitoring. Conclusions Evidence of effective and acceptable interventions in prison to prevent and control viral hepatitis is essential to foster inclusion of prison setting within national elimination programmes. Intra-EU benchmarking may help promote awareness, to allocate adequate resources, monitor of impact and ultimately the achievement of the elimination goal.

Rapid Simultaneous Determination of Three Synthetic Cannabinoids in Urine and Plasma of Rats Using Ultra-High Performance Liquid Chromatography Tandem Mass Spectrometry.

Synthetic cannabinoids, a class of psychoactive compounds, are controlled as new psychoactive substances (NPSs) identified by the early warning system (EWS) of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). At present, several new synthetic cannabinoids have appeared in the illegal drug market, including 4-methylnaphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-122), methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)-L-valinate (5F-AMB), and methyl 2-(1-(4-fluorobenzyl)-1Hindazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA). A convenient, rapid, and highly sensitive analytical method was developed to determine three synthetic cannabinoids in rat plasma and urine. The liquid chromatography tandem mass spectrometry (LC-MS/MS) method was optimized and validated to analyze the three synthetic cannabinoids in rat plasma and urine. The method identified intra-assay precision (1.3–9.0% and 2.8–6.7%), inter-assay precision (3.0–8.6% and 3.9–8.8%), limits of detection (0.003–0.004 ng/mL and 0.00125–0.002 ng/mL) and quantification (0.012–0.016 ng/mL and 0.003–0.005 ng/mL), recovery (95.4–106.8% and 92.0–106.8%) for rat plasma and urine, and the matrix effect (93.4–118.0%) for rat urine, and the correlation coefficients were above 0.99 in the linear range. The established LC-MS/MS method was successfully used to simultaneously detect the JWH-122 and 5F-AMB in rat plasma and JWH-122, 5F-AMB, and AMB-FUBINACA in rat urine. The present study provides methodological support for internal exposure assessment of three synthetic cannabinoids and promotes the quantitative analysis and technical supervision of synthetic cannabinoids.

Drug related harm reduction in the eu and candidate countries - success and gaps


 Background: Evaluation of the state of play of the 2003 Council Recommendation on the prevention and reduction of health-related harms, associated with drug dependence, in the EU and candidate countries and elaboration of proposals for new recommendations.
 Methods: Analysis of epidemiological data available at the European Monitoring Center for Drugs and Drug Addiction (EMCDDA) using statistical modeling, a general literature review on harm reduction measures, four systematic literature reviews (one on peer naloxone pro-grams) and surveys among decision makers in the field of drug policy and among harm reduc-tion providers (“stakeholders”) using online questionnaires and a gap survey among the na-tional focal points of EMCDDA in EU-countries and candidate countries.
 Results: It was possible to decrease the number of HIV-infections among drug users substan-tially in most EU countries and candidate countries during the last decade; unfortunately for the numbers of deaths due to overdoses this effect could not be reached. Stakeholders (harm reduction providers) name improvement of needle and syringe exchange and harm reduction in prison as main priorities in order to reduce drug related infectious diseases. Concerning re-duction of mortality they prioritise peer naloxone programs, drug consumption rooms and first aid training of drug users.
 Conclusions : The increase of coverage of substitution treatment and of the availability of nee-dle exchange programs in most countries can be seen as successes of harm reduction policy although the coverage especially of the latter still needs improvement. Peer naloxone pro-grams and improvement of harm reduction in (and after) prison are two of 13 recommended actions to improve the situation concerning mortality of opioid users. Continuous political strengthening of harm reduction is necessary.

Human metabolism of AP-238. A novel synthetic opioid spreading in the shadow of “fentalogues”

The phenomenon of new psychoactive substances is constantly evolving, with novel synthetic opioids (NSO) representing a particular threat given their sometimes extremely high potencies and their potential to produce respiratory depression. As a consequence of recently implemented legal restrictions on fentanyl analogues, a new “legal” generation of opioids, embodied by the class of cinnamylpiperazines, popped up on the illicit drug market. AP-238 was the latest NSO of this series to be notified to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and is involved in an increasing number of acute intoxications. Adverse effects associated with the abuse of NSO, their continued evolution, increased popularity and high availability constitute a serious concern and pose an imminent hazard to public health. The identification of specific markers of consumption for these NSO is essential for clinical and forensic casework and represents a new challenge for toxicology laboratories. Referring to this, we investigated the in vivo and in vitro metabolism of AP-238. For tentative identification of the main phase-I metabolites, a pooled human liver microsomes (pHLM) assay was used. Incubation was performed for 2 hours at 37 °C in triplicates, including a blank control (no pHLM) and a zero control (no reference standard). Analyses were carried out using liquid chromatography coupled to time-of-flight mass spectrometry (LC-qToF-MS). Full scan and auto MS/MS data were acquired in one run. In a second run, full scan and broadband collision-induced dissociation (bbCID) data were acquired, checking for characteristic fragment ions (e.g., m/z 117.0699) to detect unexpected metabolites. To compare the relative abundance of the metabolites, a multiple reaction monitoring (MRM) method comprising at least two ion transitions of each metabolite, was applied using liquid chromatography coupled to tandem-mass spectrometry (LC-MS/MS). Chromatographic separation was achieved on a Kinetex® C18 column (100 × 2.1 mm, 2.6 μm). Both instruments were operated in positive ion mode. Anticipated phase-I metabolites detected in the pHLM assay were confirmed in three authentic blood samples collected during postmortem examinations and tested positive for AP-238 in the Institute of Forensic Medicine of Freiburg. In total, ten AP-238 phase-I metabolites were identified by means of LC–qToF–MS in the pHLM assay and confirmed five of these by corresponding signals in the human blood samples. They mainly consisted of products of hydroxylation, oxidation, dealkylation, and combinations of these reactions. A dealkylated/monohydroxylated metabolite was detected with the highest abundance in blood. Suggested biomarkers for AP-238 consumption are generated by monohydroxylation combined with dealkylation (most abundant) and by sole hydroxylation at the cinnamyl substituent, with the latter being highly specific. Although this investigation was carried out with blood samples due to the non-availability of urine, it is likely that these metabolites are suitable markers for urine screening as well. The combination of dealkylation with (multiple) hydroxylation(s) was also observed for further minor metabolites. The exact chemical structures of these metabolites remain unclear and would require isolation and structure elucidation e.g. by nuclear magnetic resonance spectroscopy or synthesis of reference material. However, this does not preclude their use as valid biomarkers. Implementing analytical methods for the detection of NPS metabolites is often crucial to document consumption in clinical and forensic toxicology. In vitro methods like the used pHLM assay proved to be suitable tools for prediction of biomarkers for NSO intake, although they have to be confirmed by authentic samples. If urine is not available, blood can be used for this purpose.

Identification of the synthetic cannabinoid-type new psychoactive substance, CH-PIACA, in seized material.

Synthetic cannabinoids (SCs) remain the largest class of new psychoactive substances (NPS), and while the number of NPS that are reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) for the first time each year declines, the number of newly reported SCs still exceeds other NPS classes. This decline can be seen as a result of legislative changes by different jurisdictions which have sometimes transitioned to a more generalized approach when controlling substances by defining common structural scaffolds rather than explicit structures. While the consequences of such legislative changes have been expected over the years, the introduction of so‐called “class‐wide” bans puts further pressure on clandestine laboratories to synthesize compounds which are out of the scope of the legislation, and thus, these compounds are initially harder to detect and/or identify in the absence of analytical data. Recently, a SC with an indole‐3‐acetamide core‐linker scaffold, AD‐18 (i.e., ADB‐FUBIATA or ADB‐FUBIACA), was reported for the first time in China in 2021. Here, an additional cannabinoid with the indole‐3‐acetamide scaffold, N‐cyclohexyl‐2‐(1‐pentyl‐1H‐indol‐3‐yl)acetamide (CH‐PIACA), is reported which was identified for the first time in a seized material in Denmark. Structural characterization was performed using gas chromatography–mass spectrometry (GC–MS), liquid chromatography‐high‐resolution mass spectrometry (LC‐HRMS), and nuclear magnetic resonance (NMR) spectroscopy.

Impact of the COVID-19 pandemic on drug markets, prevention and treatment in Ukraine

This paper aims to highlight some issues, challenges and trends caused by the COVID-19 pandemic in the drug scene and the system of drug prevention in Ukraine. This article is based on the official statistics, available qualitative and quantitative studies conducted by the Institute for Psychiatry, Forensic Psychiatric Examination and Drug Monitoring of the Ministry of Health of Ukraine (Ukrainian National Focal Point), the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and Ukrainian researchers. Of course, some studies are not representative of the general population; however, they give some information on the drug scene in Ukraine during the pandemic. The data used in the article were collected mainly in 2019–2020. Every actor on the drug scene had to adapt to the new reality caused by anti-pandemic measures. Drug sellers proposed “stable work” during lockdown; drug dealers dropped ordered substances closer to the customer’s place. At the same time, OST facilities implemented home-treatment, and many private facilities appeared. OST patients misused methadone and sold it on the illicit market, while drug users started to find substitutes of their main drug and notably increased drug-related deaths.

The future of the drug phenomenon and drug monitoring in Europe until 2030

Abstract We are living in an era of fast and fundamental changes with an uneven impact on geographies and generations. The pace of the social transformations and technology innovations is accelerating and outpacing policies and responses in place. Also, the European drug situation and drug markets are becoming more complex and dynamic, with important implications for the EU drug monitoring system and research. Therefore the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) conducted the first ‘futures exercise' to inform the agency's strategic reflection on how to improve the response of the EU monitoring system in the context of rapid changes in the information environment and new information needs. The EMCDDA piloted the usefulness of the foresight approach for transforming the agency and its monitoring activities into a more sensitive and agile system, which could, in turn, help increase Europe's preparedness for future challenges in health and security areas. The ‘futures exercise' applied the horizon-scanning method to study events, issues, and trends affecting the drug area and went far beyond the drugs or the addiction field and the European region. It analysed global drivers of change that may have in the future implications for the drugs situation, drug monitoring and related responses. The methods applied ranged from literature review, thematic analysis, workshops and expert panels. It had a robust participatory component to enable stakeholders representing different disciplines and countries to contribute to and benefit from the process. Out of 14 Megatrends, five were selected as most significant for the drugs field, and the future EMCDDA work: technological change, climate change and environmental degradation, diversified inequalities, shifts in health challenges and population. Moreover, four categories of emerging changes in the drugs field were identified: shifts in drug policy, the discourse of addictions, drug markets and drug services. Key messages Foresight is a valuable tool for analysis going beyond specific areas of expertise and recognising that a single-issue focus is often insufficient in dealing with emerging threats and opportunities. A participatory approach contributes to building a shared vision of the major drivers of change impacting the drugs field, information needs and future developments in the EU drug monitoring system.

On the relevance of toxicological and hygienic assessment and market regulation of herbal dietary supplements made from Mitragyna speciosa Korth (Rubiaceae family)

Ukraine today does not regulate the sale of products made of Kratom (Mitragyna speciosa Korth. (from the family Rubiaceae) and does not take measures to control the quality and safety of this product, despite its rapid spread throughout the country. Аim of the Work is to summarize the results of scientific research on the toxicity of alternative opioids contained in Mitragyna speciosa and combined products based on them. Material and methods. Reports from the World Health Organization (WHO), the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), the United Nations Office on Drugs and Crime, the results of scientific reviews and individual studies on biochemistry, toxicology, forensic identification of substances contained in products made from Mitragyna speciosa, over the past 10 years (Elsevier, PubMed, ToxNet). Results and Discussion. Recently, kratom has been cultivated on different continents and entered the market under the name "Kратом", in English-language sources - "Kratom". Kratom leaves are dried and sold in the form of green powder, tablets, capsules, extracts and gummies. In Ukraine, kratom is sold under hundreds of commercial names on the Internet as "Kratom", "Kratom product", "Kratom organic tea", "Kratom ethnic tea", "Kratom tea" and others. More than 40 structurally related alkaloids, as well as several flavonoids, terpenoid saponins, polyphenols and various glycosides were found in kratom leaves. The pharmacological and toxic effects of kratom for most of its components have not been studied enough. Like other dietary supplements, kratom products should be standardized for alkaloids, microbial contamination, pesticides, heavy metals, residual solvents, benzo(a)pyrene, aflatoxins, etc., with appropriate labeling requirements. Conclusions. Quality products should enter the Ukrainian market - standardized leaf extract of kratom, or other safe products made on its basis. However, recent studies show that mitraginine contained in kratom has great potential for medical science as a model for developing new approaches in very relevant areas of medicine: to treat pain and get rid of opioid dependence. Key Words: Mitragyna speciosa, alternative opioids, toxicity.

Pharmacological and Toxicological Effects of Phytocannabinoids and Recreational Synthetic Cannabinoids: Increasing Risk of Public Health.

Synthetic Cannabinoids (CBs) are a novel class of psychoactive substances that have rapidly evolved around the world with the addition of diverse structural modifications to existing molecules which produce new structural analogues that can be associated with serious adverse health effects. Synthetic CBs represent the largest class of drugs detected by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) with a total of 207 substances identified from 2008 to October 2020, and 9 compounds being reported for the first time. Synthetic CBs are sprayed on natural harmless herbs with an aim to mimic the euphoric effect of Cannabis. They are sold under different brand names including Black mamba, spice, K2, Bombay Blue, etc. As these synthetic CBs act as full agonists at the CB receptors, they are much more potent than natural Cannabis and have been increasingly associated with acute to chronic intoxications and death. Due to their potential toxicity and abuse, the US government has listed some synthetic CBs under schedule 1 classification. The present review aims to provide a focused overview of the literature concerning the development of synthetic CBs, their abuse, and potential toxicological effects including renal toxicity, respiratory depression, hyperemesis syndrome, cardiovascular effects, and a range of effects on brain function.

Pharmacological and metabolic characterization of the novel synthetic opioid brorphine and its detection in routine casework

After their first emergence in 2009, Novel synthetic opioids (NSO) have become an emerging class of New Psychoactive Substances (NPS) on the market for these new drugs. So far, 67 NSO have been reported to the Early Warning system of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). It is presumed that NSO mainly target the four known opioid receptors, i.e. the μ-opioid (MOR), the δ-opioid (DOR), the κ-opioid (KOR) and nociceptin receptors and that their consumption can result in serious adverse effects such as massive respiratory depression or death. In the present study we investigated the in vivo and in vitro metabolism of brorphine, a NSO that was first identified on the NPS market in August 2019 in the United States, using both a pooled human liver microsome assay and real forensic case samples. For the detection of metabolites LC-HR-MS/MS was used and quantification of brorphine was performed using an LC-MS/MS method. Additionally, we pharmacologically characterized brorphine regarding its activation of the MOR and KOR via G protein recruitment using the [35S]-GTPγS assay. In forensic urine samples, 14 distinct metabolites were identified, whereas in blood only four metabolites could be found. The pooled human liver microsome assay generated six distinct in vitro phase I metabolites. The most prominent in vivo metabolite was formed by N-oxydation, whereas the main in vitro metabolite was formed by hydroxylation. The pharmacological characterization at the MOR and KOR revealed brorphine to be a potent MOR agonist and a weak, partial KOR agonist in the [35S]-GTPγS assay.

Analysis of Google Trends to monitor new psychoactive substance. Is there an added value?

The past decade has seen an increase in the development and availability of a broad category of drugs, known as new psychoactive substances (NPS). NPS are challenging for public health authorities, therefore the two major drug monitoring bodies – the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and the United Nations Office on Drugs and Crime (UNODC) – have implemented the EU Early Warning System (EWS) and Early Warning Advisory (EWA), respectively. While these monitoring systems are informative, it is difficult to keep up with the constant and rapid developmental rate of NPS. The EMCDDA has recognised the need for an alternative and technologically derived early warning system. The aim of this research is to determine whether Google Trends and drug discussion forum data can be used to complement early warning systems for NPS.Forty-eight substances were used in this study and classed into groups based on their chemical structure, following the UNODC classification system. Google Trends data (time range: 2004–2019) and drug forum data (time range: 2003–2018) were extracted for each substance and visual trend profiles were created for class groups as well as individual substances. Analysis was conducted to determine when a substance first appeared on Google Trends and a drug discussion forum as well as their trends over time. This date of first appearance was then compared to the date the substance was first reported to UNODC.Of the three data sources utilised, substances were most likely to appear on Google Trends first. Amongst the different classes of NPS, discernible trends (‘block’, ‘successive’, and ‘generational’ trends) were observed. These trends reflect the evolution of the manufacture of substances or generations of substances that has been observed in the literature. For example, in the synthetic cannabinoids’ category, a generational trend is observed that corresponds to the different generations of synthetic cannabinoids. When comparing Google Trends and Drugs-Forum directly, the order of appearance and duration of presence for substances aligns accurately for most classes.Google Trends showed the emergence, persistence, or transient nature of substances, which could direct the focus of law enforcement, health organisation and laboratory resources towards a limited number of substances. When one considers the reliance of individual information seeking on the Web as well as the prominence of NPS on the Web, it becomes clear that Google Trends and drug discussion forums could be used as a complement to current early warning systems.

Air monitoring for illegal drugs including new psychoactive substances: A review of trends, techniques and thermal degradation products.

The detection of illicit psychotropic substances in both indoor and outdoor air is a challenging analytical discipline, and the data from such investigation may provide intelligence in a variety of fields. Applications of drug monitoring in air include providing data on national and international drug consumption trends, as monitored by organisations such as the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and the United Nations Office on Drugs and Crime (UNODC). Air monitoring enables mapping of illicit drug manufacturing, dealing or consumption in cities and the identification of emergent compounds including the recent proliferation of new psychoactive substances (NPS). The rapid spread of NPS has changed the global drug market with greater diversity and dynamic spread of such compounds over several nations. This review provides an up to date analysis of key thematic areas within this analytical discipline. The process of how illicit psychotropic substances spread from emission sources to the atmosphere is considered alongside the sampling and analytical procedures involved. Applications of the technique applied globally are reviewed with studies ranging from the analysis of individual dwellings through to major international air-monitoring campaigns providing evidence on global drug trends. Finally, we consider thermal breakdown products of illicit psychotropic substances including NPS that are released upon heating, combustion or vaping and related potential for exposure to these compounds in the air.