Search Results (110)

Narcotics trafficking is a fundamental part of organized crime, posing significant and evolving challenges for forensic investigations. Addressing these challenges requires rapid, precise, and scientifically validated analytical methods for reliable identification of illicit substances. Over the past five years, forensic drug testing has advanced considerably, improving detection of traditional drugs—such as tetrahydrocannabinol, cocaine, heroin, amphetamine-type stimulants, and lysergic acid diethylamide—as well as emerging new psychoactive substances (NPS), including synthetic cannabinoids (e.g., 5F-MDMB-PICA), cathinones (e.g., α-PVP), potent opioids (e.g., carfentanil), designer psychedelics (e.g., 25I-NBOMe), benzodiazepines (e.g., flualprazolam), and dissociatives (e.g., 3-HO-PCP). Current technologies include colorimetric assays, ambient ionization mass spectrometry, and chromatographic methods coupled with various detectors, all enhancing accuracy and precision. Vibrational spectroscopy techniques, like Raman and Fourier transform infrared spectroscopy, have become essential for non-destructive identification. Additionally, new sensors with disposable electrodes and miniaturized transducers allow ultrasensitive on-site detection of drugs and metabolites. Advanced chemometric algorithms extract maximum information from complex data, enabling faster and more reliable identifications. An important emerging trend is the adoption of green analytical methods—including direct analysis, solvent-free extraction, miniaturized instruments, and eco-friendly chromatographic processes—that reduce environmental impact without sacrificing performance. This review provides a comprehensive overview of innovations over the last five years in forensic drug analysis based on the ScienceDirect database and highlights technological trends shaping the future of forensic toxicology. Full article

Background/Objectives: The emergence of cathinone-based psychostimulants necessitates ongoing research and analysis of the characteristics and properties of novel derivatives. The metabolic fate of five novel cathinone-derived substances (ASProp, MASProp, MASPent, PySProp, and PySPent) containing a selenophene moiety was investigated in vitro and in vivo. Methods: All compounds were incubated individually with pooled human liver S9 fraction. A monooxygenase activity screening investigating the metabolic contribution of eleven recombinant phase I isoenzymes was conducted. Rat urine after oral administration was prepared by urine precipitation. Liquid chromatography–high-resolution tandem mass spectrometry was used for the analysis of all samples. Reversed-phase liquid chromatography (RPLC) and zwitterionic hydrophilic interaction liquid chromatography (HILIC) were used to evaluate and compare the metabolites’ chromatographic resolution. Results: Phase I reactions of ASProp, MASProp, MASPent, PySProp, and PySPent included N-dealkylation, hydroxylation, reduction, and combinations thereof. The monooxygenase activity screening revealed the contribution of various isozymes. Phase II reactions detected in vivo included N-acetylation and glucuronidation. Both chromatographic columns complemented each other. Conclusions: All substances revealed metabolic reactions comparable to those observed for other synthetic cathinones. Contributions from isozymes to their metabolism minimized the risk of drug–drug interactions. The identified metabolites should be considered as targets in human biosamples, especially in urine screening procedures. RPLC and HILIC can both be recommended for this purpose. Full article

New psychoactive substances (NPSs) are emerging narcotics or psychotropics that pose a public health risk. The most commonly reported NPSs are synthetic cannabinoids and synthetic cathinones. Synthetic cannabinoids mimic the effects of Δ9-tetrahydrocannabinol (Δ9-THC), often with greater potency, while synthetic cathinones act as stimulants, frequently serving as cheaper alternatives to amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. While some synthetic cannabinoids exhibit chirality depending on their synthesis precursors, synthetic cathinones are intrinsically chiral. Biotargets can recognize and differentiate between enantiomers, leading to distinct biological responses (enantioselectivity). Understanding these differences is crucial; therefore, the development of enantioresolution methods to assess the biological and toxicological effects of enantiomer is necessary. This work systematically compiles enantioselectivity studies and enantioresolution methods of synthetic cannabinoids and synthetic cathinones, following PRISMA guidelines. The main aim of this review is to explore the impact of chirality on these NPSs, improving our understanding of their toxicological behavior and evaluating advances in analytical techniques for their enantioseparation. Key examples from both groups are presented. This review highlights the importance of continuing research in this field, as demonstrated by the differing properties of synthetic cannabinoid and synthetic cathinone enantiomers, which are closely linked to variations in biological and toxicological outcomes. Full article

Glioblastoma multiforme is a highly aggressive intrinsic brain tumor with a very poor survival rate. The main treatment for cancer is surgery combined with postoperative radiotherapy and temozolomide chemotherapy. Since the outcomes of treatment are unsatisfactory, the search for more effective drugs is crucial. Our previous study indicated that mephedrone, a synthetic cathinone, reduced neuron and astrocyte viability and oligodendrocyte proliferation. The aim of the present study was to investigate the effect of mephedrone on selected human glioblastoma (LN-18, LN-229, T98G) and human anaplastic astrocytoma (MOGGCCM) cell lines. The effects of mephedrone on cell viability and proliferation, DNA synthesis, cell cycle progression and the type of cell death were studied. Our results showed that mephedrone possesses potential anticancer activity. The viability and proliferation of all four human glioblastoma and human anaplastic astrocytoma cell lines used were decreased in a concentration-dependent manner. Studies conducted on LN-18 and T98G cells confirmed the significant antiproliferative properties of mephedrone, which reduced DNA synthesis and affected cell cycle progression. Microscopic evaluation supported the antiproliferative effect of the tested compounds. Moreover, substantial cytoplasmic vacuolization in the LN-18 cell line was revealed. This finding may indicate the potential of mephedrone in anticancer therapy. Full article

In this study, two isomeric cathinone derivatives, N-butyl-norbutylone and N-ethylhexylone, seized on the illicit drug market in Poland, were described and characterized by various instrumental analytical methods. The compounds were characterized by electrospray ionization mass spectrometry, high-resolution mass spectrometry, gas chromatography–mass spectrometry, and nuclear magnetic resonance spectroscopy. The two investigated compounds were confirmed as 1-(2H-1,3-benzodioxol-5-yl)-2-(butylamino)butan-1-one and 1-(2H-1,3-benzodioxol-5-yl)-2-(ethylamino)hexane-1-one, both of which were cathinone derivatives available on the new psychoactive substances (NPS) market. The obtained analytical data should be useful for forensic and toxicological purposes for quick and reliable compound identification. Full article

Background: Synthetic cathinones (SCs) are the second most representative class of New Psychoactive Substances, with more than 100 analogues identified in the illicit drug market up to 2024. According to the United Nations Office on Drugs and Crimes, N-ethylhexedrone (NEH) and N-ethyl-nor-pentedrone (NEP) were identified among the most frequently seized SCs worldwide. However, still, little is known with regard to their pharmacological effects in humans. Methods: For the first time, we conducted a naturalistic, prospective observational study in 16 participants (7 women and 9 men) with a previous history of psychostimulant recreational use. They intranasally self-administered a single dose of NEP (n = 8, 20–40 mg) or NEH (n = 8, 20–40 mg). The physiological effects (systolic and diastolic blood pressure, heart rate, and temperature) and subjective effects (visual analogue scales, Addiction Research Center Inventory questionnaire and Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire) were assessed up to 4 h after the self-administration at different time points (0, 20 and 40 min and 1, 1.5, 2, 3 and 4 h). Results: Despite several differences, both NEP and NEH produced significant effects within 20 min, with a return to baseline 3–4 h after self-administration. In general, NEP showed a faster onset and a more rapid disappearance of subjective effects than NEH. Moreover, intranasal self-administration of NEH and NEP in experienced recreational drug users, within a non-controlled setting, induces a constellation of psychostimulant-like effects. Conclusion: NEH and NEP showed similar pharmacological properties after insufflation, with typical effects of SCs Full article

Background: “Chemsex” involves the intake of a range of drugs (e.g., synthetic cathinones, gamma-hydroxybutyric acid/gamma-butyrolactone (GHB/GBL), ketamine, methamphetamine, “poppers”, type V phosphodiesterase (PDE) inhibitors, MDMA/ecstasy, cocaine, cannabis, and occasionally a few other molecules as well, to enhance and prolong sexual experiences. This paper aims to provide an overview of the clinical pharmacology of the vast range of drugs that are being used for chemsex with a focus on both the medical and psychopathological disturbances that they can produce. Methods: A narrative literature review was conducted using Pubmed, Scopus, and Web of Science databases. A total of 273 papers published up to January 2025 were screened; articles were selected based on relevance to chemsex/sexualized used behaviour and related substances. Both human and preclinical studies were considered. Results: The use of stimulants is likely related to the need to increase as much as possible both sexual arousal and performance but also to increase social interactions. Furthermore, the empathogenic/entactogenic activities of some MDMA-like “love drugs” facilitate the occurrence of “feeling closer/more intimate” emotional sensations, and GHB/GBL may provide the user with a subjective sensation of disinhibition, hence facilitating condomless meetings with a higher number of random partners. Conversely, ketamine may be used to both enjoy its psychotropic dissociative characteristics and facilitate the potentially painful receptive anal intercourse and/or fisting experiences. Most typically, these drugs are consumed in combination, with polydrug exposure possibly facilitating the occurrence of serotonergic syndrome, seizures, drug–drug pharmacokinetics’ interaction, and sympathomimetic overstimulation. Following these polydrug exposures, a range of psychopathological conditions have at times been reported. These issues may lead to misuse of opiates/opioids, gabapentinoids, and/or antipsychotics. Conclusions: Further actions should aim at reducing the stigma that prevents individuals from accessing necessary healthcare and support services. A multidisciplinary approach that combines medical, psychological, and social support remains key to managing the complex challenges posed by chemsex-related drug use. Full article

Cathinones, a class of synthetic new psychoactive substances (NPSs), continue to emerge and pose public threats. Government control efforts often lead to the emergence of new isomers, which have adverse repercussions on NPSs identification and risk prediction. This work reports on the synthesis and structural characterization of twenty chloro-cathinones, including different isomers, to create analytical data to facilitate their identification in forensic and clinical contexts. Additionally, the potential of these cathinones to cause neuronal damage was evaluated. In vitro cytotoxicity was assessed using a differentiated human neuroblastoma cell line (SH-SY5Y) as a dopaminergic neuronal model. The tested cathinones showed LC₅₀ values from 0.6 to 2.5 mM, with 4-CBC being the most cytotoxic. The most toxic cathinones increase reactive oxygen species levels and/or cause mitochondrial membrane potential depolarization. Furthermore, this study explored, for the first time, the effect of cathinones on the cholinergic system through acetylcholinesterase (AChE) inhibition. All tested cathinones inhibited AChE with IC₅₀ values between 0.1 and 2 mM. Molecular docking analysis revealed that the most inhibitory cathinones interacted with the CASs and PASs in AChE’s active gorge. These findings provide valuable insights into the effects of cathinones, highlighting potential health risks and structural features that may influence their toxicity towards the cholinergic system and neuronal damage. 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

Drug abuse presents a significant global health challenge as the illicit drug market progresses from classic drugs to a growing prevalence of New Psychoactive Substances (NPS), particularly synthetic cathinones, which, although illegal, are often falsely marketed as safe and legal alternatives. The rapid increase in the use of these drugs complicates the assessment of their safety and effects on human health. However, they pose unique toxicological concerns that remain largely uncharacterized. This study investigated the toxic effects of three synthetic cathinones, namely, methylone, pentedrone, and 4-methylethcathinone (4-MEC), using the model organism C. elegans. We assessed the impact of these substances on animal survival, development, reproductive behavior, and longevity. Our results showed that short-term exposure (24 h) to concentrations of 5.0 mM or higher significantly reduced animal survival rates, while prolonged exposure (72 h) led to more pronounced toxicity, significantly reducing survival rates at concentrations as low as 1.0 mM. Moreover, sublethal concentrations resulted in developmental arrest. Additionally, pentedrone impaired reproductive capacity, while 4-MEC significantly shortened C. elegans lifespan. These findings highlight the urgent need for further investigation into the implications of synthetic cathinone use on human health through in vivo models as their prevalence in the illicit drug market continues to rise. Full article

Khat, derived from the Catha edulis plant, is widely consumed in East Africa and the Arabian Peninsula, where it holds significant socio-cultural importance. This review examines the multifaceted effects of khat, particularly focusing on its cardiovascular implications. Khat’s active constituents, notably cathinone and cathine, exhibit stimulant and psychoactive properties akin to amphetamines, leading to heightened alertness and euphoria. However, chronic consumption is associated with adverse effects, including cardiovascular diseases such as hypertension, myocardial infarction, and cardiomyopathy. The review highlights the pharmacokinetics of khat, with cathinone being rapidly absorbed and leading to sympathomimetic effects. Studies indicate a correlation between chronic khat use and increased risks of hypertension, acute coronary syndromes, and cardiomyopathy. These cardiovascular conditions are exacerbated by prolonged hemodynamic stress, catecholamine release, and oxidative stress induced by khat’s active compounds. Additionally, khat’s impact extends beyond the cardiovascular system, affecting neurological, reproductive, and gastrointestinal health. Despite its legality in certain regions, khat is classified as a controlled substance in many countries, emphasizing the need for global awareness of its health risks. This review calls for longitudinal studies to elucidate the pathophysiological mechanisms of khat-induced cardiomyopathy and to identify potential biomarkers for its early detection. Furthermore, it advocates for culturally sensitive public health initiatives and clinical guidelines to mitigate the adverse health effects of khat consumption, especially among immigrant populations in developed nations. Recognizing and addressing khat’s cardiovascular implications is crucial for improving patient outcomes and guiding effective clinical practice. Full article

Background: Synthetic cathinones and cannabinoids have emerged as significant public health concerns, particularly in pediatric populations. Marketed under deceptive names such as “bath salts” and “K2/Spice”, these substances pose unique challenges due to their accessibility, potency, and unpredictable effects. This narrative review synthesizes evidence on the toxicological effects of synthetic cathinones and cannabinoids in pediatric patients, emphasizing clinical presentations, management challenges, and public health implications. Methods: A structured narrative review was conducted using PubMed and Scopus databases to identify peer-reviewed studies published between January 2010 and September 2024. The selected articles focus on neuropsychiatric, systemic, and management outcomes associated with these substances in individuals aged 0–18 years. Results: Five studies demonstrate that synthetic cathinones frequently cause seizures, sympathomimetic toxidrome (tachycardia, hypertension), and neuropsychiatric effects like paranoia and catatonia. Seven studies show synthetic cannabinoids induce psychosis, respiratory depression requiring ventilation in 12% of cases, and cardiovascular complications like myocardial ischemia. One study highlighted severe outcomes in pediatric accidental exposures, emphasizing the unpredictable and life-threatening effects of these substances, often exacerbated by co-ingestion with alcohol or THC. Conclusions: Pediatric exposure to synthetic cathinones and cannabinoids results in severe and unpredictable toxicological effects, necessitating tailored clinical management strategies and enhanced diagnostic capabilities. Public health measures, including stringent regulatory controls, targeted education initiatives, and robust surveillance systems, are critical to mitigating these risks. A multidisciplinary approach is essential to safeguard vulnerable pediatric populations from the escalating dangers posed by synthetic drugs, and future research must address the long-term impacts and mechanisms of toxicity. 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

Cathinone and its synthetic derivatives belong to organic compounds with narcotic properties. Their structural diversity and massive illegal use create the need to develop new analytical methods for their identification in different matrices. NMR spectroscopy is one of the most versatile methods for identifying the structure of organic substances. However, its use could sometimes be very difficult and time-consuming due to the complexity of NMR spectra, as well as the technical limitations of measurements. In such cases, molecular modeling serves as a good supporting technique for interpreting ambiguous spectral data. Theoretical prediction of NMR spectra includes calculation of nuclear magnetic shieldings and sometimes also indirect spin–spin coupling constants (SSCC). The quality of theoretical prediction is strongly dependent on the choice of the theory level. In the current study, cathinone and its 12 fluorinated derivatives were selected for gauge-including atomic orbital (GIAO) NMR calculations using Hartree–Fock (HF) and 28 density functionals combined with 6-311++G** basis set to find the optimal level of theory for ¹H, ¹³C, and ¹⁹F chemical shifts modeling. All calculations were performed in the gas phase, and solutions were modeled with a polarized-continuum model (PCM) and solvation model based on density (SMD). The results were critically compared with available experimental data. Full article

The emergence of new psychoactive substances (NPS) in the global drug market since the 2000s has posed major challenges for regulators and law enforcement agencies. Among these, synthetic cathinones have gained prominence due to their stimulant effects on the central nervous system, leading to widespread recreational use. These compounds, often marketed as alternatives to illicit stimulants such as amphetamines and cocaine, have been linked to numerous cases of intoxication, addiction and death. The structural diversity and enantiomeric forms of synthetic cathinones further complicate their detection and regulation and pose challenges to forensic toxicology. In addition to their psychoactive and toxicological effects, new research suggests that cathinones may have antimicrobial properties. Compounds derived from Catha edulis (khat), including cathinone, have shown antimicrobial activity against multidrug-resistant bacteria such as Staphylococcus aureus and Escherichia coli, highlighting their potential role in the fight against antibiotic resistance. This article provides an overview of the chemistry, pharmacokinetics, pharmacodynamics, toxicological effects and potential antimicrobial applications of synthetic cathinones. The potential therapeutic use of cathinone-derived compounds to combat antimicrobial resistance represents an exciting new frontier in drug development, although further research is needed to balance these benefits with the psychoactive risks. Full article