Search Results (78)

Since 2019, a growing number of structurally diverse, non-Fentanyl-related novel synthetic opioids (NSOs) have emerged, but little is still known on the toxic profile of several of the molecules belonging to this class. Regarding long-term toxicity, few studies have investigated the genotoxic potential of NSOs, and no genotoxic data at all are available for the subclass of Brorphine-like benzimidazolone opioids. To deepen and broaden our understanding of their toxicological profile, this study was aimed at evaluating the genotoxicity of Brorphine and four of its analogues (Orphine, Fluorphine, Chlorphine and Iodorphine) on human lymphoblastoid TK6 cells employing a flow cytometric protocol of the “In Vitro Mammalian Cell Micronucleus (MN) test”. The results show a statistically significant MNi increase for Fluorphine, Chlorphine and Iodorphine, but not for Brorphine and Orphine, demonstrating for the first three the ability to induce chromosomal damage. Afterwards, Brorphine and Orphine were tested on TK6 cells also in the presence of an exogenous metabolic activation system (S9 mix) to consider the possible genotoxic hazard posed by their metabolites as well. Also, under this experimental condition, no statistically significant increase in the MNi frequency was detected. Full article

Psychoactive substances, including illicit drugs, prescription medications, and novel psychoactive compounds, are frequently analyzed in biological and in non-biological samples. Interpreting results is paramount for ensuring proper medical treatments and judicial decisions. However, false-positive results—where a sample is incorrectly identified as containing a psychoactive substance—remain a persistent issue. In other words, it is important to invest in understanding the meaning of toxicological results. Cross-reactivity in immunoassays, sample contamination, analytical interference with certain endogenous and exogenous substances, inadvertent and accidental exposure due to environmental contamination, second-hand smoke inhalation, or unintentional dermal or mucosal contact with drug residues are some of the major issues to consider. This perspective highlights major sources of artifacts in interpreting amphetamine analytical results in order to provide proper toxicological interpretations. Full article

Over the past decade, more than a thousand new psychoactive substances (NPSs) have emerged worldwide. This rapid proliferation of “designer drugs” poses significant challenges for drug control, forensic analysis, and public health. Artificial intelligence (AI) has increasingly been applied to address these challenges in NPS design and analysis. This review provides a comprehensive overview of AI methodologies—including deep learning, generative models, and quantitative structure–activity relationship (QSAR) modeling—and their applications in the synthesis, prediction, and identification of NPSs. We discuss how AI-driven generative models have been used to design novel psychoactive compounds and predict their pharmacological activity, how QSAR models can forecast potency and toxicological profiles, and how machine learning is enhancing analytical chemistry workflows for NPS identification. Special emphasis is placed on mass spectrometry (MS)-based techniques, where AI algorithms (e.g., for spectral prediction and pattern recognition) are revolutionizing the detection and characterization of unknown NPSs. A dedicated section examines the legal and regulatory implications of AI-generated psychoactive substances in the European Union (EU) and United States (USA), highlighting current policies, potential gaps, and the need for proactive regulatory responses. The review concludes with a discussion of the benefits and limitations of AI in this domain and outlines future directions for research at the intersection of AI, analytical chemistry, and drug policy. Full article

Background: Chemsex is a subtype of sexualized drug use which is increasingly more prevalent amongst gay, bisexual, and other men who have sex with men (MSM). This use of psychoactive substances in sexual contexts poses an emerging public health concern, since it has been associated with an array of health risks, including mental health risks. Objective: As Chemsex appears to be increasing in the UK, this study aimed to explore Chemsex patterns and mental health amongst Chemsex users in the UK. Methods: Chemsex/drug use patterns and the prevalence of coexisting depression and anxiety, based on the Hospital Anxiety and Depression Scale (HADS), were assessed in an MSM sample via an anonymous online survey between December 2023 and February 2024. Results: A total of 141 UK adults participated in the survey (age range: 26–41 years). High overall use of the three common Chemsex-related substances was reported, including γ-hydroxybutyrate/γ-butyrolactone (GHB/GBL) (77.3%), synthetic cathinones (64.5%), and methamphetamine (47.5%). Injecting (“slamming”) was less prevalent (17.0%), although this practice was the most common amongst weekly Chemsex users (54.2%). Based on provided HADS responses, a high incidence of anxiety (49.9%) was reported among the study population, with the highest (abnormal) anxiety scores observed among weekly Chemsex users (44.4%). The incidence of depression was lower overall (27.0%), whilst the highest (abnormal) scores were also observed in weekly Chemsex users (61.5%). Conclusions: As relevant UK data remain limited, this study offers novel insight into Chemsex patterns and mental health challenges among MSM in the UK, suggesting unmet needs for targeted interventions on mental health issues among this population. Further large-scale and prospective studies are necessary to explore the nuanced interplay between the frequency of Chemsex use and its impact on mental health. Full article

Introduction: Novel psychoactive substances (NPSs) are substances not controlled by the United Nations’ 1961 Narcotic Drugs and 1971 Psychotropic Substances convention, which pose a threat to public health. The use of NPSs is growing among recreational drug users. NPSs mimic the effects of the existing illegal drugs; they are used as substitutes for the traditional drugs of use. NPSs are commonly marketed as safe substances. NPS abuse is especially risky among vulnerable individuals, such as children and adolescents. The Aim: This study aims to analyze the knowledge and attitudes of primary and high school students regarding NPSs, determining the frequency and patterns of NPS use, and examine motivational factors for their consumption. Methodology: The questionnaire was employed to primary and secondary school students of the city of Novi Sad in November 2024. The data were analyzed using the methods of descriptive and inferential statistics in the statistical software package JASP 0.18.1.0. Results: A total of 1095 participants took part in the survey (53.6% males and 46.4% females). The age range of participants was 11–18 years (mean age 14.637 years). The majority of pupils lived in the city (70.5%). The most numerous students were students with the highest overall grade. The proportion of students who were familiar with NPSs was 38.3%, while 61.7% of them were not aware of their existence. Living in cities correlated positively with the NPS knowledge. The NPS risk awareness was notably low. The proportion of students who tried one or more novel drugs was 1.918%. Conclusions: The abuse of novel psychoactive substances is a growing concern, particularly among young individuals, requiring increased awareness and education on their risks. Educational systems should provide accurate information to prevent false beliefs, while policymakers must legally regulate new drugs. A coordinated approach is crucial for effective prevention, involving education, media, and support from different organizations. Future studies should focus on the impact of education on attitudes towards NPSs. Full article

Background: Numerous individuals suffer from attentional issues, such as ADHD. While medication is considered the first-line treatment, it is unavailable to some. As a result, certain individuals are choosing to self-medicate with novel stimulants, a phenomenon that remains poorly understood. We aimed to investigate which NPSs are being used to self-medicate ADHD, evaluate their perceived effectiveness, and explore the experiences and motivations of those self-medicating. Methods: Data from respondents (n = 225) (mean age [SD] = 29.5 ± 9.6; male = 83%; female = 12%; non-binary = 5%) were collected via an online survey, with nine participants (mean age = 31.4; male = 5; female = 1; non-binary = 3) undertaking further semi-structured interviews and the data being investigated using a framework analysis. Results: The most-used NPSs were 4F-MPH and 2-FMA. Some individuals perceived self-medication to be more effective than conventional treatment (p < 0.001). A framework analysis identified the following themes surrounding novel stimulant self-medication: (1) the use of NPS stimulants as a stopgap between treatments; (2) poor access to ADHD treatment; (3) a lack of openness and confidence in psychiatrists and healthcare providers. Conclusion: Novel stimulants are being used when access to ADHD treatment is poor. Interventions should aim to reduce long treatment wait times and issues surrounding geographical access. Careful consideration should be given before denying stimulant medication to individuals with co-occurring substance use and psychiatric comorbidity. Individuals desire a more patient-centred ADHD treatment with broader pharmacotherapies. Full article

New psychoactive substances (NPSs) emerged in the 2000s as legal alternatives to illicit drugs and quickly became a huge public health threat due to their easy accessibility online, limited information, and misleading labels. Synthetic cannabinoids and synthetic cathinones are the most reported groups of NPSs. Despite NPSs being widely studied, due to their structural diversity and the constant emergence of novel compounds with unknown properties, the development of new techniques is required to clarify their mode of action and evaluate their toxicological effects. Metabolomics has been a useful tool to evaluate the metabolic effects of several xenobiotics. Herein, a systematic review was performed, following PRISMA guidelines, regarding metabolomic studies on synthetic cathinones and synthetic cannabinoids to evaluate their effects in cellular metabolism. In the studies, in vivo models were the most employed (86%) and the analysis mostly followed untargeted approaches (75%) using LC-MS techniques (67%). Both groups of NPSs seem to primarily interfere with energy metabolism-related pathways. Even though this type of study is still limited, metabolomics holds great promise as a tool to clarify mechanisms of actions, identify biomarkers of exposure, and explain the toxicological effects of NPSs. Full article

Substance-induced psychosis (SIP) is an increasingly prevalent and complex condition that presents significant diagnostic and therapeutic challenges. With the rising use of novel psychoactive substances (NPSs) and potent traditional compounds like cannabis and cocaine, particularly among adolescents and young adults, understanding the mechanisms and clinical manifestations of SIP has become more critical. This review examines the psychopathological characteristics of SIP, focusing on the differentiation between substance-induced and primary psychotic disorders. Two key concepts are explored: Gaëtan de Clérambault’s “mental automatism”, which describes involuntary thoughts and sensations experienced as alien to the self, and the “twilight state” of consciousness, characterized by an altered perception of space, time, and social interaction. These phenomena are essential in understanding how substance use triggers psychotic processes and how SIP differs from endogenous psychosis. This review also highlights the clinical and phenomenological distinctions between acute and chronic psychotic episodes, emphasizing the potential transition from SIP to persistent psychosis, especially in cases of frequent and potent substance use. It discusses the diagnostic and therapeutic importance of recognizing specific psychopathological markers such as alterations in temporality, spatiality, and intersubjectivity. Understanding these features enhances the clinician’s ability to accurately differentiate SIP from primary psychotic disorders, which is often complicated by the widespread use of substances that may not be easily detectable in standard tests. This review concludes by advocating for a clinical–phenomenological approach to empathically engage with patients and provide a solid diagnostic framework for improved treatment strategies, particularly for those at risk of transitioning to chronic psychosis. Full article

Background: Piperazines, synthetic compounds known for their stimulant and hallucinogenic effects, have gained prominence among novel psychoactive substances (NPS) and are frequently associated with adverse psychiatric outcomes, including psychosis. Methods: A systematic review of the literature available up to 23 May 2024 was conducted, using the PubMed, Scopus, and Web of Science databases, in addition to the related gray literature, utilizing the following search strategy: “piperazines” AND (“psychosis” OR “hallucination” OR “delusion” OR “schizophrenia” OR “delusional” OR “schizoaffective”) NOT review NOT animal. Data collection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research methods were registered with PROSPERO (CRD42024549204). Results: Out of a total of 4547 articles identified, 4 met the inclusion criteria. We observed an important relationship between piperazine abuse and the onset of acute psychotic episodes, marked by symptoms such as paranoia, auditory, and visual hallucinations. Conclusion: The complex polyreceptor action mechanism of piperazines may explain these psychopathological effects, similar to those observed with other NPS. Although studies confirm a link between piperazine use and psychosis, data on long-term outcomes are limited. Recovery is common following cessation and treatment. Further research into the effects of piperazine abuse and the development of specific treatment protocols for substance-induced psychosis is necessary. Full article

Background: The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have become a fast-growing subgroup of these new psychoactive substances (NPSs), and their overdose may potentially turn fatal, especially when combined with other central nervous system depressants. In 2021, flubrotizolam, a potent thieno-triazolo designer benzodiazepine, emerged on the illicit market, available online as a “research chemical”. The identification of markers of consumption for this designer benzodiazepine is essential in analytical toxicology, especially in clinical and forensic cases. Methods: We therefore aimed to identify biomarkers of flubrotizolam uptake in ten-donor-pooled human hepatocytes, applying liquid chromatography high-resolution mass spectrometry and software-aided data mining supported by in silico prediction tools. Results: Prediction studies resulted in 10 and 13 first- and second-generation metabolites, respectively, mainly transformed through hydroxylation and sulfation, methylation, and glucuronidation reactions. We identified six metabolites after 3 h human hepatocyte incubation: two hydroxylated metabolites (α- and 6-hydroxy-flubrotizolam), two 6-hydroxy-glucuronides, a reduced-hydroxy-N-glucuronide, and an N-glucuronide. Conclusions: We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam. Full article

The widespread use of novel psychoactive substances (NPSs)—defined as new narcotic or psychotropic agents not classified under the Single Convention on Narcotic Drugs of 1961 or the Convention on Psychotropic Substances of 1971—poses a significant challenge to contemporary mental health paradigms due to their impact on psychiatric disorders. This study revisits and expands upon the theory of mental automatism as proposed by Gaëtan Gatian de Clérambault, aiming to elucidate the psychopathological mechanisms underlying substance-induced psychoses (SIP) and their distinction from non-induced psychoses (schizophrenia and related disorders). Through a phenomenological and clinical investigation, we explore the relevance of mental automatism in the development of toxic psychoses, drawing upon the historical and contemporary literature. This research highlights the psychopathological distinctions between induced and non-induced psychoses and the transition mechanisms from acute to chronic psychosis states. De Clérambault’s theory, supplemented by Janet, Jackson, and Bonhoeffer’s contributions, provides a foundational framework for understanding the genesis of SIP. Our findings suggest that NPS consumption, particularly among adolescents and psychiatric patients, significantly correlates with increased risks of SIP, marked by a transition to chronicity influenced by biological lesions triggered by substance use. Furthermore, we propose a comprehensive framework for SIP, integrating mental automatism, psychopathological distinctions, and transition mechanisms. This framework aims to refine diagnostic criteria and therapeutic approaches, addressing gaps in clinical practice and research. The study underscores the need for a nuanced understanding of SIP, advocating for a paradigm shift in psychiatric assessment and treatment approaches to better address the complexities of substance-induced mental health disorders. Full article

This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing advanced toxicology in silico tools, it was possible to predict crucial aspects of the toxicological profile of 4-CMC, including acute toxicity (LD₅₀), genotoxicity, cardiotoxicity, and its potential for endocrine disruption. The obtained results indicate significant acute toxicity with species-specific variability, moderate genotoxic potential suggesting the risk of DNA damage, and a notable cardiotoxicity risk associated with hERG channel inhibition. Endocrine disruption assessment revealed a low probability of 4-CMC interacting with estrogen receptor alpha (ER-α), suggesting minimal estrogenic activity. These insights, derived from in silico studies, are critical in advancing the understanding of 4-CMC properties in forensic and clinical toxicology. These initial toxicological findings provide a foundation for future research and aid in the formulation of risk assessment and management strategies in the context of the use and abuse of NPSs. Full article

Novel psychoactive substances (NPSs) are compounds plotted to modify the chemical structures of prohibited substances, offering alternatives for consumption and evading legislation. The prompt emergence of these substances presents challenges in health concerns and forensic assessment because of the lack of analytical standards. A viable alternative for establishing these standards involves leveraging in silico methods to acquire spectroscopic data. This study assesses the efficacy of utilizing infrared spectroscopy (IRS) data derived from density functional theory (DFT) for analyzing NPSs. Various functionals were employed to generate infrared spectra for five distinct NPS categories including the following: amphetamines, benzodiazepines, synthetic cannabinoids, cathinones, and fentanyls. PRISMA software was conceived to rationalize data management. Unsupervised learning techniques, including Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE), were utilized to refine the assessment process. Our findings reveal no significant disparities among the different functionals used to generate infrared spectra data. Additionally, the application of unsupervised learning demonstrated adequate segregation of NPSs within their respective groups. In conclusion, integrating theoretical data and dimension reduction techniques proves to be a powerful strategy for evaluating the spectroscopic characteristics of NPSs. This underscores the potential of this combined methodology as a diagnostic tool for distinguishing IR spectra across various NPS groups, facilitating the evaluation of newly unknown compounds. Full article

Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses. This comprehensive review presents the intricate pharmacological profiles of phytocannabinoids while exploring the diverse impacts these substances have on biological systems. From the more than one hundred cannabinoids which were identified in the Cannabis plant so far, cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the most extensively studied phytocannabinoids. CBD is a non-psychoactive compound, which exhibits potential anti-inflammatory, neuroprotective, and anxiolytic properties, making it a promising candidate for a wide array of medical conditions. THC, known for its psychoactive effects, possesses analgesic and antiemetic properties, contributing to its therapeutic potential. In addition to THC and CBD, a wide range of additional phytocannabinoids have shown intriguing pharmacological effects, including cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN). The endocannabinoid system, made up of the enzymes involved in the production and breakdown of endocannabinoids, cannabinoid receptors (CB1 and CB2), and endogenous ligands (endocannabinoids), is essential for preserving homeostasis in several physiological processes. Beyond their effects on the endocannabinoid system, phytocannabinoids are studied for their ability to modify ion channels, neurotransmitter receptors, and anti-oxidative pathways. The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine. This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids. Full article

Alcohol acts as a central nervous system depressant and falls under the category of psychoactive drugs. It has the potential to impair vital bodily functions, including cognitive alertness, muscle coordination, and induce fatigue. Taking the wheel after consuming alcohol can lead to delayed responses in emergency situations and increases the likelihood of collisions with obstacles or suddenly appearing objects. Statistically, drivers under the influence of alcohol are seven times more likely to cause accidents compared to sober individuals. Various techniques and methods for alcohol measurement have been developed. The widely used breathalyzer, which requires direct contact with the mouth, raises concerns about hygiene. Methods like chromatography require skilled examiners, while semiconductor sensors exhibit instability in sensitivity over measurement time and has a short lifespan, posing structural challenges. Non-dispersive infrared analyzers face structural limitations, and in-vehicle air detection methods are susceptible to external influences, necessitating periodic calibration. Despite existing research and technologies, there remain several limitations, including sensitivity to external factors such as temperature, humidity, hygiene consideration, and the requirement for periodic calibration. Hence, there is a demand for a novel technology that can address these shortcomings. This study delved into the near-infrared wavelength range to investigate optimal wavelengths for non-invasively measuring blood alcohol concentration. Furthermore, we conducted an analysis of the optical characteristics of biological substances, integrated these data into a mathematical model, and demonstrated that alcohol concentration can be accurately sensed using the first-order modeling equation at the optimal wavelength. The goal is to minimize user infection and hygiene issues through a non-destructive and non-invasive method, while applying a compact spectrometer sensor suitable for button-type ignition devices in vehicles. Anticipated applications of this study encompass diverse industrial sectors, including the development of non-invasive ignition button-based alcohol prevention systems, surgeon’s alcohol consumption status in the operating room, screening heavy equipment operators for alcohol use, and detecting alcohol use in close proximity to hazardous machinery within factories. Full article