Search Results (33)

Synthetic cathinones are cathinone analogues that humans have artificially created. The first compounds appeared on the European market in 2005. They belong to a class of drugs called stimulants, classified as new psychoactive substances. Synthetic cathinones are very popular; people use these drugs because they are cheaper “substitutes” for other stimulants. They produce psychostimulant and hallucinogenic effects similar to cocaine, amphetamine, and MDMA, among others. Despite their presence on the market for several years, the precise toxicological impacts of these compounds on the human body remain unknown. Studies were conducted on the effects of selected cathinones (mephedrone, clephedrone) on blood cells: erythrocytes and platelets. The effect of cathinones was determined by measuring the surface density of biological membranes using microelectrophoresis. The continued popularity of these compounds, coupled with limited knowledge of their precise effects on the human body, makes the problem significant and requires ongoing research. Based on the results obtained for mephedrone and clephedrone, it can be concluded that at the tested concentrations (170 ng/mL and 2700 ng/mL), they alter the surface charge density of the biological membranes of red blood cells and platelets. Full article

In recent years, the issue of drivers under the influence of medications and psychoactive substances as a cause of road accidents has gained increasing importance. This study aimed to assess the prevalence and blood concentration ranges of alcohol and psychoactive substances among drivers in northeastern Poland between 2013 and 2024. To determine the prevalence of medications and psychoactive substances in drivers’ blood, data were collected from 266 blood samples obtained from drivers (251 men and 15 women). Among these, 79 drivers died immediately, 61 drivers survived the accident, and 126 drivers were stopped for roadside checks. The presence of the studied substances was confirmed using gas chromatography combined with mass spectrometry detection (GC-MS) and liquid chromatography combined with mass spectrometry detection (LC-MS). Blood alcohol content was measured using headspace gas chromatography with a flame ionisation detector (HS-GC-FID). Psychoactive substances were detected in 152 of the 266 samples. Drivers testing positive for medications and psychoactive substances were most frequently stopped during roadside controls—67.46%. Among the total positive cases, psychoactive substances used alone or in combination included THC—46.3% (range 0.2–20 ng/mL), alcohol—26.8% (range 0.1–4.1‰), amphetamines—20.7% (range 15–2997 ng/mL), opiates—4.3% (morphine 66.0 ng/mL; methadone 174.0 ng/mL; ranges: tramadol 15.0–600.0 ng/mL; fentanyl 45.0–100.0 ng/mL), benzodiazepines—9.8% (ranges: diazepam 55.0–480.0 ng/mL; midazolam 17.0–1200.0 ng/mL; clonazepam 21.0–36.0 ng/mL), stimulants—6.10% (ranges: amphetamine 15.0–2997.0 ng/mL; cocaine 4.0–30.0 ng/mL; benzoylecgonine 38.0–602.0 ng/mL; PMMA 45.0–360.0 ng/mL; MDMA 20.0–75.0 ng/mL; mephedrone 37.5 ng/mL; alfa-PVP 120 ng/mL), psychotropic drugs—3.1% (carbamazepine 8.0–2100.0 ng/mL; zolpidem 233.0 ng/mL; citalopram 320.0 ng/mL; opipramol 220 ng/mL). The most commonly used substance among car and motorcycle drivers was THC (37.7% of car drivers and 60% of motorcyclists). Among operators of other types of vehicles, alcohol was the most frequently detected substance, present in 35% of cases. The majority of drivers (81.1%) were under the influence of a single substance. Among the drivers, 7.3% consumed alcohol in combination with at least one other substance, and 11.6% used two or more substances excluding alcohol. Among the psychoactive substances most frequently used alone or in combination with others, THC was predominant. Roadside testing, based on effects similar to alcohol intoxication, was mainly conducted on male drivers. Full article

New psychoactive substances (NPSs) have emerged as a significant global public health challenge due to their ability to mimic traditional drugs. Among these, mephedrone has gained attention because of its widespread use and associated toxicities. This review provides a comprehensive analysis of the structure, pharmacokinetic properties, and metabolic pathways of mephedrone, highlighting its phase I and phase II metabolites as potential biomarkers for detection and forensic applications. A comprehensive literature search was performed without date restrictions. The search employed key terms such as “mephedrone metabolites”, “pharmacokinetics of mephedrone”, “phase I metabolites of mephedrone”, and “phase II metabolites of mephedrone”. Additionally, the reference lists of selected studies were screened to ensure a thorough review of the literature. Mephedrone is a chiral compound existing in two enantiomeric forms, exhibiting different affinities for monoamine transporters and distinct pharmacological profiles. In vivo animal studies indicate rapid absorption, significant tissue distribution, and the formation of multiple phase I metabolites (e.g., normephedrone, dihydromephedrone, 4-carboxymephedrone) that influence its neurochemical effects. Phase II metabolism involves conjugation reactions leading to metabolites such as N-succinyl-normephedrone and N-glutaryl-normephedrone, further complicating its metabolic profile. These findings underscore the importance of elucidating mephedrone’s metabolic pathways to improve detection methods, enhance our understanding of its toxicological risks, and inform future therapeutic strategies. 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

Background/Objectives: This study evaluates the applicability of a comprehensive two-dimensional gas chromatography−flame ionisation detection (GC×GC−FID) approach for the simultaneous determination of 12 underivatised psychoactive drugs, including new psychoactive substances, that comprised of amphetamine, methamphetamine, mephedrone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, α-pyrrolidinovalerophenone, n-ethylpentylone (ephylone), norketamine, ketamine, 3,4-methylenedioxypyrovalerone, methadone, and cocaine. Methods: Separation was effected using a non-polar first dimension (¹D) and a polar second dimension (²D) column, demonstrating an improved separation of drug compounds compared to a polar/non-polar column configuration. Interference-free baseline separation of all psychoactive compounds in a urine matrix was achieved within 8 min. The GC×GC−FID method was validated according to the guidelines defined by Standard Practices for Method Validation in Forensic Toxicology. Results: The calibration curves for the 12 psychoactive drugs were well correlated (r² > 0.99) within the concentration ranges of 50–1500 ng mL⁻¹. Detection limits of 10–20 ng mL⁻¹ were obtained, and good repeatability and reproducibility (CV < 11.4%) were attained for retention times and peak areas. Method recoveries for the small-scale solvent extraction procedure ranged from 96.9 to 114.5%, and bias was between −3.1% and 14.5%. Conclusions: The validated approach was successfully applied for the determination of these illicit compounds in spiked urine samples of different concentrations, highlighting its potential for rapid forensic drug screening. Full article

The present study examined three hallucinogenic amphetamine derivatives, namely, 2,5-dimethoxy-4-iodoamphetamine (DOI) as well as 2,5-dimethoxy-4-methylamphetamine (DOM) and 4-methylmethcathinone (mephedrone). The objective of this study was to test the hypothesis that DOI, DOM, and mephedrone would increase the contractile force in isolated human atrial preparations in a manner similar to amphetamine. To this end, we measured contractile force under isometric conditions in electrically stimulated (1 Hz) human atrial preparations obtained during open surgery. DOI and DOM alone or in the presence of isoprenaline reduced the contractile force concentration-dependently in human atrial preparations. These negative inotropic effects of DOM and DOI were not attenuated by 10 µM atropine. However, mephedrone increased the contractile force in human atrial preparations in a concentration- and time-dependent manner. Furthermore, these effects were attenuated by the subsequent addition of 10 µM propranolol or pretreatment with 10 µM cocaine in the organ bath. Therefore, it can be concluded that amphetamine derivatives may exert opposing effects on cardiac contractile force. The precise mechanism by which DOI and DOM exert their negative inotropic effects remains unknown at present. The cardiac effects of mephedrone are probably due to the release of cardiac noradrenaline. Full article

Background: In recent years, in Europe, there has been a growing concern about the use of sexualized drugs among men who have sex with men (MSM), due to its possible link to an increase in sexually transmitted infections. The aim of this review is to study the prevalence of chemsex, and the sexualized drug used in Europe, describing both different consumption patterns and other sexual behaviors considered risky and their possible relationship with positivity in diagnoses of sexually transmitted infections, including human immunodeficiency virus. Methods: We conducted a literature review in the main scientific databases (PubMed, Embase, Scopus, Cochrane Library, Web of Science), filtering for articles published between January 2018 and April 2023 that collect information on sexualized drug use and sexual practices conducted in European countries among men who have sex with men, including whether these behaviors can lead to diagnoses of sexually transmitted infections. Results: The definition of drugs included in chemsex is not clearly defined and shows heterogeneity between study publications; the three drugs presented in all manuscripts are mephedrone, GHB/GBL, and crystal methamphetamine. The prevalence of chemsex in Europe is 16% [11–21%] among MSM. The most frequent risky sexual behavior associated with chemsex practice was unprotected sex with a high number of partners. The log risk ratio of STIs was 0.86 (95% CI: 0.49 to 1.23). Conclusions: Adherence to definitions, stringent research methodologies, and focused interventions are needed to tackle the intricate relationship between substance use, sexual behavior, and the risk of HIV/STI transmission in MSM. Full article

The characteristic alkaloid component of the leaves of the catnip shrub (Catha edulis) is cathinone, and its synthetic analogs form a major group of recreational drugs. Cathinone derivatives are chiral compounds. In the literature, several chiral methods using cyclodextrins (CDs) have been achieved so far for diverse sets of analogs; however, a comprehensive investigation of the stability of their CD complexes has not been performed yet. To characterize the enantioselective complex formation, a systematic experimental design was developed in which a total number of 40 neutral, positively, and negatively charged CD derivatives were screened by affinity capillary electrophoresis and compared according to their cavity size, substituent type, and location. The functional groups responsible for the favorable interactions were identified in the case of para-substituted cathinone analog mephedrone, flephedrone, and 4-methylethcathinone (4-MEC) and in the case of 3,4-methylendioxy derivative butylone and methylenedioxypyrovalerone (MDPV). The succinylated-β-CD and subetadex exhibited the highest complex stabilities among the studied drugs. The complex stoichiometry was determined using the Job’s plot method, and the complex structures were further studied using ROESY NMR measurements. The results of our enantioselective complex formation study can facilitate chiral method development and may lead to evaluate potential CD-based antidotes for cathinone analogs. Full article

The increasing number of new psychoactive substances (NPS) entering the illicit drug market, especially synthetic cathinones, as well as the risk of cardiovascular complications, is intensifying the need to quickly assess their cardiotoxic potential. The present study aims to evaluate the cardiovascular toxicity and lethality induced by first-generation synthetic cathinones (mephedrone, methylone, and MDPV) and more classical psychostimulants (cocaine and MDMA) in zebrafish embryos using a new approach methodology (NAM). Zebrafish embryos at 4 dpf were exposed to the test drugs for 24 h to identify drug lethality. Drug-induced effects on ventricular and atrial heart rate after 2 h exposure were evaluated, and video recordings were properly analyzed. All illicit drugs displayed similar 24 h LC₅₀ values. Our results indicate that all drugs are able to induce bradycardia, arrhythmia, and atrial-ventricular block (AV block), signs of QT interval prolongation. However, only MDPV induced a different rhythmicity change depending on the chamber and was the most potent bradycardia and AV block-inducing drug compared to the other tested compounds. In summary, our results strongly suggest that the NAM presented in this study can be used for screening NPS for their cardiotoxic effect and especially for their ability to prolong the QT intervals. Full article

Mephedrone is a psychoactive drug that increases dopamine, serotonin and noradrenaline levels in the central nervous system via interaction with transporters or monoamines. The aim of the presented study was to assess the role of the GABA-ergic system in the expression of mephedrone-induced reward. For this purpose, we conducted (a) a behavioral evaluation of the impact of baclofen (a GABA_B receptors agonist) and GS39783 (a positive allosteric modulator of GABA_B receptors) on the expression of mephedrone-induced conditioned place preference (CPP) in rats, (b) an ex vivo chromatographic determination of the GABA level in the hippocampi of rats subchronically treated with mephedrone and (c) an in vivo evaluation of GABA hippocampal concentration in rats subchronically administered with mephedrone using magnetic resonance spectroscopy (MRS). The results show that GS39783 (but not baclofen) blocked the expression of CPP induced by (20 mg/kg of) mephedrone. The behavioral effect was consistent with chromatographic analysis, which showed that mephedrone (5 and 20 mg/kg) led to a decrease in GABA hippocampal concentration. Altogether, the presented study provides a new insight into the involvement of the GABA-ergic system in the rewarding effects of mephedrone, implying that those effects are at least partially mediated through GABA_B receptors, which suggests their potential role as new targets for the pharmacological management of mephedrone use disorder. Full article

Sexualized drug use (SDU) has been identified as a health risk factor among gay, bisexual, and other men who have sex with men (GBMSM). This study aimed to analyze the associations between SDU frequency and a broad set of substances, motives, consequences, and self-perceptions. Sampling was conducted through an online survey. The final sample consisted of 185 GBMSM aged between 18 and 78 years old (mean age = 38.38, SD = 11.52) who engaged in SDU. We analyzed the frequency of SDU in terms of practicing it “once,” “moderately” (“once a month or less” or “a few times a month”), or “frequently” (from “once a week” to “daily”) during the previous 18 months. A questionnaire was administered through which sociodemographic variables, substances, reasons, consequences, and self-perceptions of SDU practice were analyzed. Participants who did so frequently were significantly more likely to use mephedrone, methamphetamine, and GHB/GBL than those who performed SDU less often (large effect sizes). In addition, habitual SDU was associated with motivations to achieve pleasurable emotions and sensations and manage negative feelings. Health implications, such as blackout moments, were also significantly related to frequent SDUs. Finally, those who practiced frequent SDU perceived it as a severe problem and wanted to control it. These data indicate the importance of raising awareness of chemsex as a public health problem among GBMSM. Specific identification, education, and prevention programs need to be strengthened to reduce the incidence of the most undesirable implications of SDU among GBMSM. Full article

Chemsex is described as the use of certain drugs—commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone—before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical harm, such as sexually transmittable infections (STIs), and are more likely to experience mental health symptoms. To further assess this, we reviewed the recent literature to evaluate whether the psychological impact of chemsex behavior includes suicidal ideation and suicidal attempts. Pubmed/MEDLINE was searched for articles reporting suicidal ideation and behavior among chemsex users with the terms “chemsex”, “sexualized drug use”, “suicide”, and “mental health”. Twelve articles (three case reports and nine cross-sectional studies) were included in the final narrative review. Overall, we retrieved mixed results regarding the relationship between chemsex practice and suicidality outcomes. Considering the inhomogeneous nature of the studies, the findings indicate that suicidality could be an issue of concern among MSM in general but among chemsex users in particular. Possible risk factors for suicidality among chemsex participants may include adversities experienced due to one’s sexual orientation and an increased risk for HIV and other STI infections and the resulting negative impact on mental well-being. These aspects warrant further investigations. Full article

Treatment of Post-Traumatic Stress Disorder (PTSD) is complicated by the presence of drug use disorder comorbidity. Here, we examine whether conditioned fear (PTSD model) modifies the rewarding effect of mephedrone and if repeated mephedrone injections have impact on trauma-related behaviors (fear sensitization, extinction, and recall of the fear reaction). We also analyzed whether these trauma-induced changes were associated with exacerbation in metalloproteinase-9 (MMP-9) and the GluN2A and GluN2B subunits of N-methyl-D-aspartate (NMDA) glutamate receptor expression in such brain structures as the hippocampus and basolateral amygdala. Male adolescent rats underwent trauma exposure (1.5 mA footshock), followed 7 days later by a conditioned place preference training with mephedrone. Next, the post-conditioning test was performed. Fear sensitization, conditioned fear, anxiety-like behavior, extinction acquisition and relapse were then assessed to evaluate behavioral changes. MMP-9, GluN2A and GluN2B were subsequently measured. Trauma-exposed rats subjected to mephedrone treatment acquired a strong place preference and exhibited impairment in fear extinction and reinstatement. Mephedrone had no effect on trauma-induced MMP-9 level in the basolateral amygdala, but decreased it in the hippocampus. GluN2B expression was decreased in the hippocampus, but increased in the basolateral amygdala of mephedrone-treated stressed rats. These data suggest that the modification of the hippocampus and basolateral amygdala due to mephedrone use can induce fear memory impairment and drug seeking behavior in adolescent male rats. Full article

Background: The main objective was to examine sexual assertiveness and sexual satisfaction in people who have sex under the influence of alcohol and drugs, considering the type of substance consumed, the frequency of consumption, gender, and sexual orientation. Methods: The sample consisted of 274 adults who had sexual relationships consuming substances. A questionnaire composed of sociodemographic, sexual history and substance use items, the Sexual Assertiveness Scale and the Global Measure of Sexual Satisfaction were administered. Results: Gender differences were found in sexual assertiveness and in the frequency of substance use. Women reported greater sexual assertiveness and greater alcohol consumption. Men reported greater consumption of different types of substances. Furthermore, bisexual participants showed greater assertiveness and STI prevention. Homosexual participants reported a higher frequency of the consumption of poppers, mephedrone, and GBL/GHB. Sexual assertiveness was associated with sexual satisfaction. Greater consumption of some types of substances was related to sexual assertiveness, STI prevention, and sexual satisfaction. Conclusions: The association found between sexual assertiveness and sexual satisfaction in a specific context of substance use in sexual relationships corroborates the important role that these psychosexual variables have in sexual health, in view of the frequency and type of drug consumed, gender, and sexual orientation. Full article

Predictors of mortality in illicit drug users involving Novel Psychoactive Substances (NPS) and multiple substances have not been elucidated. We aimed to define predictors of mortality in the NPS endemic era’s illicit drug users to strengthen patient care in emergency treatment. This was a retrospective study. LC-MS/MS-confirmed positive illicit drug users who visited the emergency departments (ED) of six medical systems were enrolled. Demographic information, physical examinations, and laboratory data were abstracted for mortality analysis. There were 16 fatalities in 355 enrolled patients. The most frequently used illicit drugs were amphetamines, followed by opioids, cathinones, and ketamine. The most frequently detected cathinones among the 16 synthetic cathinones were eutylone, followed by mephedrone. The combined use of cathinones and ketamine was most commonly observed in our results. Univariate analysis revealed that the mortality patients were older, with deep coma, faster heart rate and respiratory rate, lower blood pressures and O₂ room air saturation, more seizures, abnormal breath sounds, and had urine incontinence compared to the survivor patients. The mortality patients also had acute kidney injury, higher potassium, blood sugar, liver function test, and lactate level. The results of multiple logistic regression demonstrated that SBP < 90 mmHg, dyspnea, blood sugar > 140 mg/dl, and HCO₃ < 20.6 mmHg were independent predictors of in-hospital mortality. Regardless of the pattern of the use of illicit drugs, the predictors allow for risk stratification and determining the optimal treatment. Full article