Legal Highs Research Articles

Exploiting the triple quadrupole mass analyzer for the open detection and tentative identification of synthetic cannabinoid receptor agonists based on common fragmentation pathways

BackgroundThe use of new psychoactive substances (NPS) has emerged as a significant public health concern globally, due to their unknown and unpredictable effects on both physical and mental health. Among them, synthetic cannabinoids receptor agonists (SCRAs) currently stand as the most widely consumed NPS family in Europe. Since the detection of JWH-018 in 2008, the structures of these compounds have evolved to circumvent legislation and/or enhance their effects, consequently increasing the number of reported SCRAs to be monitored. Therefore, new strategies are needed to identify these compounds, whether in seized products or in biological samples. ResultsThis study presents the development of an open method for detecting SCRAs employing a “pseudo-target” screening approach, a strategy previously developed and used in our laboratory for synthetic cathinones identification. The methodology involves monitoring the main product ions and neutral losses derived from 179 SCRAs of the third and fourth generations, based on their fragmentation pathways. This approach allows for the tentative identification of the SCRAs, supported also by the created database. The versatility of the developed methodology is highlighted, extending its utility beyond seizure products or ‘legal highs’, to biological samples. In this sense, it has been successfully applied not only to the detection of SCRAs in research chemicals but also in authentic urine from an anonymous SCRAs consumer, through the identification of a metabolite. SignificanceThis strategy will be particularly useful for the rapid detection of SCRAs in forensic and toxicological laboratories equipped with low-resolution MS/MS instrumentation. This is a valuable tool for the identification and monitoring of SCRAs across various contexts, significantly contributing to public health and forensic security efforts. It is especially beneficial for healthcare providers, enabling them to make informed treatment decisions.

Hemp-based psychoactive use and risk among young adults: Trend theory, policy, and regulation beyond legality

BackgroundHemp-based psychoactives comprise a burgeoning legal substance market with rising trends in use across the U.S. and Canada as well as parts of Europe. Currently, scant empirical research on the use of these Novel Psychoactive Substances (NPS) exists. By examining policy, market conditions, consumer uptake, and related risks, this research extends theory on drug trends by describing the regulatory environments that shape the emergence and popularity of psychoactive hemp-based products among young adults. MethodsRelying on ethnographic fieldwork of hemp-based markets across 3 U.S. state hemp and cannabis policy contexts as well as in-depth interviews with 40 young adult cannabis consumers recruited across 10 U.S. states, we examined how regulatory conditions shape hemp-based psychoactive markets, trends in their use, and associated risks. ResultsYoung adults are motivated to consume hemp-based psychoactives due to the regulatory and market environments that facilitate the production of highly potent products that are inexpensive and easily accessible. States that regulate hemp-based psychoactives as cannabis, do not provide hemp markets with a competitive advantage and as such see minimal uptake. In the absence of hemp specific policies, substantial variations in product potencies, insufficient dosing information, and unscrupulous product packaging practices may increase related risks. ConclusionTrend theory provides insight into the complex relationships that exist between drug policy, markets, and the proliferation of legal highs. Understanding the contextual significance that both market and regulatory conditions have on legal drug production, distribution, and consumption may better inform approaches to reduce the risks commonly associated with novel psychoactive substances like hemp-based psychoactives.

Investigating LSA - a ‘legal high’ analogue to LSD, frequently used in the digital realm with relatively unknown effects

IntroductionPsychedelics are substances consumed for recreational use, the majority of these psychoactive substances are illegal and hard to obtain. Therefore, there is a demand for psychedelics legal and easier to access, these types of drugs are called ‘legal highs’. LSA (lysergic acid amide) is one of these new psychoactive substances, this drug is searched because it is known to have an effect similar to LSD. LSA has negative effects on body functioning not fully understood by the medical field.ObjectivesThis project aims to conduct a systematic review of the scientific health literature on LSA.Methods The following information was included in this review: articles reporting original data on physical effects, neurobiological effects, various bodily symptoms, social and cultural aspects in humans related to LSA, published in English, Portuguese, Spanish, Italian, and French. Studies involving animals, in vitro research, botanical studies, and non-original research were excluded. The following keywords were searched in the PubMed, Google Scholar, and Web of Science databases: (ergine or d-lysergic acid amide or LSA or d-lysergamide or lysergic acid amide). This study followed the PRISMA statement for systematic reviews and PRISMA checklist. The resulting data were tabulated and analyzed according to relevance.ResultsLSA, also known as ergine, is an ergot alkaloid with a chemical formula very similar to LSD. Ergine is found in plants of the Convolvulaceae family and is primarily consumed through chewing the seeds of these plants, soaking them in alcohol, or preparing an extract. The amount of LSA in each seed is inconsistent, making it unpredictable how much will be consumed, and these seeds may contain other harmful compounds. LSA is a partial agonist and antagonist of serotonergic receptors, with a preference for 5-HT1A and 5-HT2, and stimulation of D2 is related to nausea. It can cause symptoms including euphoria, hallucinations, anxiety, nausea, weakness, fatigue, tremors, and elevated blood pressure. In some cases, the use of LSA is associated with the use of other drugs, and there are case reports of LSA-induced PRES (Posterior Reversible Encephalopathy Syndrome), post-use suicides and the need for hospitalization due to psychosis-like states.Studies conducted on the quality of information about LSA on digital platforms indicate misinformation with incorrect data that can be harmful to those who ingest the drug. Additionally, there are studies suggesting that LSA may improve symptoms of cluster headaches.ConclusionsLSA is a legal drug in most countries, with widespread misinformation on the internet and limited control over its use. There are potential serious adverse effects caused by the drug, and it is often associated with other psychoactive substances. Greater knowledge about the drug is needed for diagnosing its use and abuse, as well as for educating the public.Disclosure of InterestNone Declared

Understanding methiopropamine, a new psychoactive substance: an in-depth review on its chemistry, pharmacology and implications to human health.

Methiopropamine or 1-(thiophen-2-yl)-2-methylaminopropane (MPA) is a thiophene ring-based structural analogue of methamphetamine, first synthesized in 1942 but become popular when it started to be available for purchase on websites selling 'legal highs' since 2010. While it is legally controlled in many countries, it remains readily accessible and frequently encountered in recreational settings. The growing prevalence of MPA use results in new therapeutic challenges. Relatively few studies have focused on its pharmacodynamics and pharmacokinetics, making it important to better understand its potential risks and harmful effects in humans in terms of its toxicity. This review provides a comprehensive profiling of MPA toxicological properties, including its chemical properties, analytical methods, prevalence, patterns of use, and legal status. Additionally, it discusses the drug's effects on the central nervous system, its potential for addiction, and its adverse physical and mental health effects. Improving the understanding of safety aspects of MPA and how it imposes health threats for public health will guide the development of therapeutic approach of its intoxication and guide the authorities in deciding its legal status.

Hexahydrocannabinol Pharmacology, Toxicology, and Analysis: The First Evidence for a Recent New Psychoactive Substance.

During the last two years, hexahydrocannabinol (HHC), the hydrogenated derivative of tetrahydrocannabinol has been freely sold by internet websites as a "legal" replacement to THC and cannabis in a range of highly attractive branded and unbranded products, some of which are sold as "legal highs". Potentially, there could be a large demand for HHC products by individuals in Europe and internationally. Studies reporting HHC pharmacology, toxicology and analysis were identified from Pubmed and Scopus databases, and official international organizations' websites were considered. HHC showed the effects of the typical cannabinoid on the central nervous system, with lower potency than Δ9-THC. A few studies highlighted that 9(R)-HHC is more potent than 9(S)-HHC. This molecule showed an affinity for cannabinoid receptor CB1 both in vitro and in vivo, suggesting a possible therapeutic effect in several pathologies. However, the affinity for the CB1 receptor suggests a possible addiction potential, inducing the users to misuse it. Since actual intoxication cases have not yet been reported, the HHC harmful potential was not described, probably due to the lack of effective analytical methods to detect HHC in biological matrices. Conversely, different analytical assays were developed and validated to separate HHC epimers in natural and non-natural sources. Similarly to other NPS, the HHC represents a cheaper alternative to the controlled Δ9-THC. Its monitoring is a crucial challenge for toxicological and forensic purposes. To this concern, it is essential to further investigate HHC to support health providers in the identification of related intoxications.

Metabolism of dipentylone in zebrafish and human liver microsomes determined by liquid chromatography–high resolution mass spectrometry

The consumption of novel psychoactive substances (NPS) is exceedingly prevalent in society, as these substances are sold and distributed as “legal highs.” One novel synthetic cathinone emerging in the market is 1-(1,3-benzodioxol-5-yl)–2-(dimethylamino) pentan-1-one (dipentylone). The goal of this work was to study the in vivo and in vitro metabolism of dipentylone in zebrafish and human liver microsomes (HLMs) by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The zebrafish and HLM samples contained 14 dipentylone metabolites, specifically 12 phase Ⅰ metabolites and 2 phase Ⅱ metabolites. The main metabolic pathways included monohydroxylation (M1 and M2), N-dealkylation (M3), hydroxylation of the aromatic ring and dealkoxylation of M3 (M4), O-dealkylation (M5), N-dealkylation of M5 (M6), reduction of carboxide (M7), monohydroxylation of M5 (M8), dehydrogenation (M9), dealkoxylation (M10), N-dealkylation of M10 (M11), dealkoxylation of M9 (M12), glucuronidation of M5 (M13), and sulfation (M14). The monohydroxylated metabolite (M2) can be recommended as metabolic markers for dipentylone. This study is the first to identify a target compound for monitoring the abuse of dipentylone and to determine the essential chemical structure of the metabolites for further toxicological research.

Forensic Analysis of Synthetic Cathinones on Nanomaterials-Based Platforms: Chemometric-Assisted Voltametric and UPLC-MS/MS Investigation.

Synthetic cathinones (SCs) are a group of new psychoactive substances often referred to as "legal highs" or "bath salts", being characterized by a dynamic change, new compounds continuously emerging on the market. This creates a lack of fast screening tests, making SCs a constant concern for law enforcement agencies. Herein, we present a fast and simple method for the detection of four SCs (alpha-pyrrolidinovalerophenone, N-ethylhexedrone, 4-chloroethcathinone, and 3-chloromethcathinone) based on their electrochemical profiles in a decentralized manner. In this regard, the voltametric characterization of the SCs was performed by cyclic and square wave voltammetry. The elucidation of the SCs redox pathways was successfully achieved using liquid chromatography coupled to (tandem) mass spectrometry. For the rational identification of the ideal experimental conditions, chemometric data processing was employed, considering two critical qualitative and quantitative variables: the type of the electrochemical platform and the pH of the electrolyte. The analytical figures of merit were determined on standard working solutions using the optimized method, which exhibited wide linear ranges and LODs suitable for confiscated sample screening. Finally, the performance of the method was evaluated on real confiscated samples, the resulting validation parameters being similar to those obtained with another portable device (i.e., Raman spectrometer).

Synthetic cannabinoid receptor agonists (Spice): the problem they represent and a chemometric solution

Synthetic cannabinoid receptor agonists (SCRAs) are novel psychoactive substances (NPS) that can bind to and trigger endogenous cannabinoid receptors, initially developed as research agents for studying the endocannabinoid system and later for therapeutic purposes. Significant side effects limited their use as therapeutics, but SCRAs were sold to members of the public in the UK as “legal highs” in the early 2000s. Despite the known adverse effects and implemented legislation changes, SCRAs remain in circulation, particularly amongst vulnerable populations, as the sheer diversity of SCRA chemical structures makes it difficult to detect SCRAs in an adulterated product such as tobacco. To overcome this issue, researchers have looked at multivariate techniques such as Raman and near-infrared spectroscopy in combination with chemometric techniques including principal component analysis and partial least-squares regression to detect the diverse range of SCRAs. This review discusses the problem that SCRAs represent, and then the analytical and chemometric techniques that can/could be brought to bear on said problem.

Incidence of Intoxications in the Emergency Department of Galati Hospital with Examples of Cardiovascular Effects of MDMA Intoxication

MDMA (3,4-methylenedioxymethamphetamine; commonly referred to as "Molly" or "ecstasy") is a synthetic compound, structurally and pharmacologically similar to both amphetamines and mescaline. MDMA differs somewhat from traditional amphetamines in that it is not structurally similar to serotonin. Cocaine is rare and cannabis is consumed less frequently than in Western Europe. Heroin is the drug of choice for the poor in Bucharest, Romania's capital of two million people, and alcoholism is common in villages where more than a third of the population lives in poverty. By far, the most popular drugs are Legal Highs (Romanians call them "ethnobotanics"). All of these drugs have significant effects on cardiovascular function that contribute significantly to adverse events. Most adverse cardiac events occur in young adults and are potentially reversible. Poisoning among patients aged 17 years and over was commonly seen in the Emergency Departments of a large tertiary hospital in the city centre, accounting for 3.2% of all patients. In a third of the poisonings, more than one substance was used. Intoxication with ethnobotanicals was the most frequently observed, followed by use of drugs from the amphetamine group. The majority of patients presenting to the Emergency Department were male. Therefore, this study suggests further research on hazardous alcohol consumption and drug abuse.

Metabolic Evaluation of Synthetic Opioids on the Example of U-47700 with the Use of In Vitro and In Vivo Methods for Forensic Toxicology Application

Legal highs present a great threat to health, especially in groups of people experimenting with psychoactive substances. The lack of available knowledge on the biotransformation of these substances necessitates symptomatic treatment in the event of intoxication, which, unfortunately, may be ineffective. Opioids, including heroin analogues, such as U-47700, constitute a special group of designer drugs. In this study, a multi-directional approach to trace the biotransformation of U-47700 in living organisms was used. For this purpose, the in silico assessment (ADMET Predictor) was used first and then followed by an in vitro study using human liver microsomes and the S9 fraction. The biotransformation was then followed in an animal model (Wistar rats). Tissues such as blood, brain and liver were collected for analysis. The study was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The obtained results were compared to those obtained from the analysis of autopsy materials (cases analysed in the Toxicology Laboratory of the Department of Forensic Medicine, Jagiellonian University Medical College in Krakow).

New Psychoactive Substances Intoxications and Fatalities during the COVID-19 Epidemic.

In January 2020, the World Health Organization (WHO) issued a Public Health Emergency of International Concern, declaring the COVID-19 outbreak a pandemic in March 2020. Stringent measures decreased consumption of some drugs, moving the illicit market to alternative substances, such as New Psychoactive Substances (NPS). A systematic literature search was performed, using scientific databases such as PubMed, Scopus, Web of Science and institutional and government websites, to identify reported intoxications and fatalities from NPS during the COVID-19 pandemic. The search terms were: COVID-19, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, intox*, fatal*, new psychoactive substance, novel psychoactive substance, smart drugs, new psychoactive substance, novel synthetic opioid, synthetic opioid, synthetic cathinone, bath salts, legal highs, nitazene, bath salt, legal high, synthetic cannabinoid, phenethylamine, phencyclidine, piperazine, novel benzodiazepine, benzodiazepine analogue, designer benzodiazepines, tryptamine and psychostimulant. From January 2020 to March 2022, 215 NPS exposures were reported in Europe, UK, Japan and USA. Single NPS class intoxications accounted for 25, while mixed NPS class intoxications represented only 3 cases. A total of 130 NPS single class fatalities and 56 fatalities involving mixed NPS classes were published during the pandemic. Synthetic opioids were the NPS class most abused, followed by synthetic cathinones and synthetic cannabinoids. Notably, designer benzodiazepines were frequently found in combination with fentalogues. Considering the stress to communities and healthcare systems generated by the pandemic, NPS-related information may be underestimated. However, we could not define the exact impacts of COVID-19 on processing of toxicological data, autopsy and death investigations.

Identification of Synthetic Cathinones in Unknown Substances in Sri Lanka

There is a high tendency of ‘legal highs’ entering the local drug market. Most of the countries including Sri Lanka have controlled these drugs, because of their adverse side effects. 4-Methyl methcathinone, (4-MMC, Mephedrone) and 3-Methyl methcathinone (3-MMC, Mataphedrone) are psychoactive substances categorized under the group of synthetic cathinones. These drugs are commonly available in powder forms and crystalline forms and produce effects similar to those of MDMA, amphetamines and cocaine. Three cases containing unknown substances were submitted to the Narcotics Laboratory of the Government Analyst’s Department of Sri Lanka for further examination to find out the presence of narcotic drugs if any. Comprehensive analytical scheme including TLC, UV- Visible spectroscopy, GC-MS and RAMAN spectroscopy was applied for the qualitative analysis. The results obtained from TLC, UV-Visible, GC-MS, and RAMAN spectroscopy, confirmed the presence of Mephedrone (4-MMC) and Metaphedrone (3-MMC) in the unknown substances, and 3-MMC and 4-MMC were identified for the first time in Sri Lanka at the Government Analyst’s Department. Even though, Mephedrone is a controlled substance in Sri Lanka, 3-MMC is still not included as a controlled substance. Therefore, it is high time for Sri Lankan legal authorities to pay more attention in controlling New Psychoactive Substances (NPS).

Old Dog, New Tricks: A Review of Identifying and Addressing Youth Cannabis Vaping in the Pediatric Clinical Setting

Cannabis vaping has emerged as a predominant mode of cannabis use among United States (US) adolescents and young adults (AYA) primarily due to the popularity of modifiable designs of vaping devices coupled with changes in cannabis policies and increased availability of cannabinoid products. New methods for cannabis vaping by e-liquid/oil vaping, dry plant vaping, and cannabis concentrate vaping (ie, dabbing) have had high uptake among American youth with unclear long-term health implications. Issues with contamination, mislabeling, and expansion of the vaped cannabis market to include not only delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD) but also delta-9-THC analogs (eg, delta-8 and delta-10) sold as hemp-derived "legal highs" further complicated this healthcare space. Recent research suggests that cannabis/THC vaping carries distinct and overlapping risks when compared to cannabis smoking and may be associated with greater risk for acute lung injuries, seizures, and acute psychiatric symptoms. Primary care clinicians providing care for AYA are in an ideal position to identify cannabis misuse and intervene early to address cannabis vaping. To improve public health outcomes, a need exists for pediatric clinicians to be educated about different ways/methods that youth are vaping cannabinoid products and associated risks related to cannabinoid vaping. Further, pediatric clinicians need to be trained how to effectively screen for and discuss cannabis vaping with their youth patients. In the current article, we present a clinically focused review of cannabis vaping among young people with 3 main aims to: (1) identify and describe the cannabis vaping products commonly used by American youth; (2) review the health correlates of youth cannabis vaping; and (3) discuss clinical considerations related to identifying and treating youth who vape cannabis.

Rapid Detection of Synthetic Cannabinoid Receptor Agonists Impregnated into Paper by Raman Spectroscopy

Abstract English The last decade has witnessed the emergence of new psychoactive substances that are analogues of classical drugs of abuse in order to escape the regulations surrounding the latter drugs. These drugs were of both herbal and synthetic origin and were advertised initially as ‘legal highs’; thus, they were perceived as safe by users. Hence, upon their emergence, they were not controlled by the Misuse of Drugs Act 1971, which contributed to their popularity and increased sales online and within street markets. In 2016, the Psychoactive Substance Act introduced a blanket ban on all new psychoactive substances except for caffeine, alcohol, and nicotine. This in turn, contributed to the change in the sale of new psychoactive substances products that have been sold as concealed in different matrices, including herbal products, papers, fabrics, and textiles. Concealing drugs in paper has been very popular, especially since the drug product is of lightweight and can be sent via postal services. However, new psychoactive concealed in papers are toxic not only to the users; but also, to the person handling them (i.e. mail employees). One of the classes of new psychoactive substances that have been commonly concealed in papers and that have been linked to toxicity and hospitalization cases is synthetic cannabinoids. Therefore, there is a need to identify new psychoactive substances concealed in papers non-destructively and rapidly to prevent toxicity linked to them. Handheld Raman spectroscopy offers this advantage as it is of lightweight and carries the sample to the matrix. Therefore, this work used handheld Raman spectroscopy for identifying synthetic cannabinoids concealed in papers using Raman spectroscopy combined with machine learning analytics. Synthetic cannabinoid and paper samples were measured non-destructively using a handheld Raman spectrometer equipped with a 1064 nm laser wavelength. Spectral data was exported into Matlab 2020b where machine learning analytics including identification and prediction was. The results showed that Raman spectroscopy could identify specific synthetic cannabinoids in papers that were either deposited on the surface of the paper or diffused inside the paper substrate. When machine learning analytics were applied to the Raman spectra of the papers, quantitative information was obtained regarding the amount of synthetic cannabinoid deposited on the paper surface. In summary, handheld Raman spectroscopy could identify and quantify synthetic cannabinoids on paper rapidly and non-destructively. Future work involves testing other classes of new psychoactive substance and applying deep learning analytics

Psychological and psychiatric characterization of various groups of drugs users

Aim. We aimed to assess the differences among various groups of drugs users, especially in the psychiatric and psychological domains. Materials and Methods. A retrospective study was carried out in collaboration with C.E.T.T.T `St. Stelian` Institute from Bucharest. There were analyzed the medical records of 604 hospitalized patients with heroin or polydrug addiction. Results. Significant differences in diagnosis at submission among groups were outlined (personality and behavior disorders, p-value = .04298, psychotic disorders, p-value = .004274, schizophrenia, p-value = .000141) as well as significant differences among psychiatric parameters: perception (legal highs, opiates), attention (cannabis), consciousness (legal highs), thinking (legal highs), and, instinctive life (legal highs). Conclusions. Personality and behavioral disorders have been particularly linked to opiate use, the psychotic disorder was related to cannabis and legal highs intake, while schizophrenia was related to legal highs intake.

Controlled Delivery of Illegal Drug Parcels in Scotland: Does Policing Practice Align With a Public Health Approach Focused on Drug-Related Harm?

An increase in the flow of drugs into the UK via international postal systems poses challenges for law enforcement. ‘Controlled delivery’ can be used to disrupt supply networks and secure intelligence for prosecution; however, critics argue that law enforcement should instead focus on reducing drug-related harm. In Scotland, national drugs strategy adopts a public health approach but it is unclear whether this extends to policing practice. Therefore, this paper examines whether controlled delivery of drug parcels aligns with a public health policing approach. We find evidence of alignment in terms of potential harm to individual users, particularly in relation to legal highs, but not in terms of drug-related harms within the communities to which parcels were destined. We argue that further investigation is required in order to assess the extent to which political intent and policing practice in Scotland align around the principles of harm reduction and public health.

Trends in Mortality From Novel Psychoactive Substances as "Legal Highs": Gender Differences in Manner of Death and Implications for Risk Differences for Women.

IntroductionThis study aimed to examine drug-related deaths in the UK in which novel psychoactive substances (NPS) are an implicated substance, and to focus on female deaths in comparison with male deaths. While male overdoses dominate epidemiological statistics, there is an increase in female drug-related deaths and a narrowing of the gap between gender mortality rates which is to date unexplained.MethodThis study analyzed data from the National Programme for Substance Abuse Deaths (NPSAD) database that records drug-related deaths in the UK from coronial records. A dataset was constructed using parameters to capture all drug-related cases during the period 2007–2017 when NPS were legal and highly available in the UK, in order to capture deaths recorded among both regular and occasional drug users, and to include all cases recorded during that period regardless of NPS status in order to make comparisons. The final dataset comprised 10,159 cases, with 456 NPS-related deaths. Data for NPS and non-NPS were compared, and comparisons were made between cohorts by gender. The dataset also includes coronial narrative notes which allowed a qualitative analysis of NPS female deaths to add contextual explanation.ResultsThe proportion of male NPS deaths is significantly higher than that for female NPS deaths but does not reflect the generalized difference between male and female drug-related mortality of this period studied. Demographic and outcome data by gender difference were significant for all drug-related deaths, but not for NPS-only deaths, indicating a greater homogeneity among NPS deaths by gender. Older women using NPS were more likely to have methadone or diazepam as another drug implicated and have established histories of drug misuse.ConclusionWhere NPS have been used, differences in drug death profiles are less likely to be accounted for by gender than other demographic or behavioral differences more typically found in opiate deaths. The social and health problems of older women may be key characteristics that differentiate female deaths from male deaths. These findings also support evidence of increasing uptake of NPS among older established drug users that adds further risk to polydrug use.

The Scale of Intoxications with New Psychoactive Substances over the Period 2014-2020-Characteristics of the Trends and Impacts of the COVID-19 Pandemic on the Example of Łódź Province, Poland.

Legal highs are new psychoactive substances (NPSs) which pose a high risk for human health, and the spread of the SARS-CoV-2 pandemic has changed peoples’ behaviours, including the demand for NPS. The aim of the study was to assess both the frequency of intoxication with NPS in Łódź province over the period 2014–2020, and the impact of the COVID-19 pandemic on developing this trend. An analysis was carried out of data on intoxications in Łódź province in the years 2014–2020 reported by hospitals. The medical interventions rate (MI) per 100,000 people in the population was calculated. The frequency of intoxications was compared taking sociodemographic variables into account, and the effect of seasonal influence on intoxications was calculated using the Holt–Winter multiplicative seasonal method. In the period considered, there were 7175 acute NPS poisonings in the Łódź province and 25,495 in Poland. The averaged MI rate between 2014–2020 was 9.45 for Poland and 38.53 for the Łódź province, and the lowest value was found during the COVID pandemic in the year 2020 (respectively, 2.1 vs. 16.94). NPS users were mainly young men of 19–24 years old from a big city. Most cases were registered at weekends and in summer months. The majority of intoxications were caused by unidentified psychoactive substances of legal highs (chi2 = 513.98, p < 0.05). The actual number of NPS-related poisonings in the Łódź province in 2020 was lower than the value extrapolated from trend analysis of data between 2014–2019. NPS use in Poland decreased during the pandemic. It should be noted that a decrease in the number of drug-related incidents can have more than one reason, e.g., preventive programs, increased awareness, or changes in the law. This paper advocates that, in addition to monitoring NPS-related intoxications, there is further investigation into the social, cultural, and behavioural determinants of NPS to facilitate targeted prevention programmes and the development of new medical treatments.

In Vitro Metabolic Study of Four Synthetic Cathinones: 4-MPD, 2-NMC, 4F-PHP and bk-EPDP.

The use of illicit drugs is exceedingly prevalent in society, and several of them can be illegally purchased from the internet. This occurrence is particularly augmented by the rapid emergence of novel psychoactive substances (NPS), which are sold and distributed as “legal highs”. Amongst NPS, the class of synthetic cathinones represents stimulant substances exhibiting similar effects to amphetamine and its derivatives. Despite potentially being less psychoactive than amphetamine, synthetic cathinones are harmful substances for humans, and little or no information is available regarding their pharmacology and toxicology. The present study investigated the in vitro metabolism and metabolites of four recent synthetic cathinones, namely, 1-(4-methylphenyl)-2-(methylamino)-pentanone (4-MPD), 1-(4-methylphenyl)-2-dimethylamino-propanone (2-NMC), 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl-hexanone (4F-PHP) and 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)-1-pentanone (bk-EPDP). Our in vitro metabolism study resulted in 24 identified metabolites, including both phase I and phase II metabolites. All metabolites were detected and identified using liquid chromatography–high-resolution mass spectrometry and may serve as additional markers of abuse of these NPS in toxicological analyses.

Forensic patients’ experiences of Synthetic Cannabinoid Receptor Agonists (SCRAs) within custodial settings

ABSTRACT There has been an enormous growth in New Psychoactive Substances (NPS), sometimes erroneously referred to as ‘legal highs’, over the past 15 years. There are currently at least 800 such compounds, and we lack adequate data on all their effects and harms. Synthetic cannabinoid receptor agonists (SCRAs), often referred to by the generic name ‘spice’, are particularly notable in this regard. There has been a lack of research on forensic patients’ experiences of SCRAs, their consumption, and any adverse impact they might have. This work qualitatively explored the experience of NPS and SCRA use in 19 male patients recruited from three secure forensic services in the South of England. The majority of participants discussed experiences of using SCRAs whilst in prison as opposed to their current forensic hospital admission. Three key themes emerged which describe participants experiences of SCRA use: (i) perpetuating cycle of drug use, mental ill-health, and crime; (ii) environmental injustices and consequences; and (iii) shame and stigma associated with SCRA use. The findings provide insights into the challenges faced by forensic patients as a result of SCRA use, as well as notable opportunities. A common call was for greater psychoeducation on drug harms and treatment opportunities.