Nunzia La Maida

Prenatal alcohol exposure (PAE) is a major public health concern, yet maternal self-reporting remains unreliable. Meconium accumulates alcohol metabolites during the second half of gestation, and ethyl glucuronide (EtG) is considered a stable and specific biomarker of late-pregnancy alcohol exposure. Diapers containing meconium may serve as a noninvasive method for collecting anonymous biological samples, which could help reduce participation bias in studies of this sensitive subject. This pilot study assessed the feasibility of anonymously collecting meconium-containing diapers for subsequent quantitative EtG analysis after extended periods of frozen storage and international transport, and examined intra-pair consistency in samples from the same newborn. Mothers collected their newborns’ diapers, which were then divided into two aliquots (A and B) by a study assistant and stored at −80 °C until analysis. Out of 178 samples collected from 105 infants, 137 samples were analyzable. Eleven samples exceeded the limit of quantification (10 ng/g), while two samples (one pair) surpassed the 30 ng/g cutoff, indicating significant PAE. EtG concentrations showed high intra-pair agreement, supporting the robustness of the biomarker and analytical method. Anonymous diaper-based meconium collection is feasible but operationally demanding. Although the low participation rate and methodological factors, including sample loss, precluded true prevalence estimation, making it exploratory, the detection of quantifiable EtG in 8% of analyzable samples suggests that PAE remains an issue.

In 2024, 3-Chloromethcathinone (3-CMC) accounted for over 63% of all New Psychoactive Substances seized in Europe, yet its human pharmacology remains poorl

Synthetic cathinones represent the second most frequently reported group of new psychoactive substances identified annually, according to the United Nations. It remains unknown whether specific derivatives differ in the onset of effects related to absorption kinetics. Clephedrone (4-chloromethcathinone, 4-CMC) has been among the most frequently seized cathinones in recent years; however, available data on its pharmacology and abuse potential remain scarce. A non-controlled, prospective, observational study was conducted involving eight healthy volunteers (six women) who self-administered a single oral dose of clephedrone (100 or 150 mg). Study variables were assessed at baseline and over a 5-h period following administration, including vital signs and subjective effects. Oral fluid concentrations of clephedrone and cortisol were determined. For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects. Results indicated that both clephedrone and methylone produced stimulant-like subjective effects. However, clephedrone exhibited a delayed onset and peak of effects compared with methylone, indicating a clinically relevant pharmacokinetic difference. Both substances were detected in oral fluid, with peak concentrations occurring later following clephedrone administration, consistent with its delayed pharmacodynamic profile.

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

Synthetic cathinones (SCs) were confirmed as the second most prevalent class of New Psychoactive Substances (NPS) in 2024, underscoring their widespread availability and use. Notably, the SCs seizure and related intoxication cases increased within the European Union, involving mostly 3-chloromethcathinone, 3-methylmethcathinone, 2-methylmethcathinone, and N-ethylnorpentedrone. Italy has observed a distinct trend, with methylendioxy pyrrolidinohexanophenone (MDPHP) emerging as a significant concern. This technical note aims to provide a comparative analysis of the most recent data concerning the emergence and the spread of MDPHP in Italy. Data from the National Early Warning System on Drugs indicate that the total amount of seized MDPHP increased from 2021 to 2024. In 2023, MDPHP-related intoxication cases peaked at 47, considering either alone or in combination with other drugs, followed by a slight decrease in 2024. In Italy, MDPHP seems to dominate the Italian black market of SCs and with two fatalities reported. This increased demand for MDPHP raises health concerns, indicating the necessity to enhance drug-related harm reduction services and improve a multidisciplinary network that provides data for understanding the complex phenomenon of NPS.

Nitazenes represent a new synthetic opioids sub-class belonging to new psychoactive substances (NPSs). Their high pharmacological potency has led to numerous intoxications and fatalities, even at minimum doses. The aim of this study was to assess the stability of four nitazenes (etazene, flunitazene, isotonitazene and protonitazene) in dried blood spot (DBS) samples at different storage temperatures (room temperature and 4 °C) and determine the optimal storage conditions. Moreover, we developed and validated a new and fast liquid chromatography–high-resolution mass spectrometry method by the optimization of chromatographic conditions with the use of a different chromatographic column and mobile phases. Two concentrations, 1 and 5 ng/mL, were chosen based on the available data on nitazenes-related intoxications and their stability was evaluated at days 0 (control), 1, 7 and 30. The results showed that all analytes at 1 ng/mL were not detectable after 30 days at room temperature; a similar pattern was observed for 1 ng/mL etazene and isotonitazene samples when stored at 4 °C, whereas flunitazene and protonitazene decreased to a mean of 66% and 69% initial concentrations, respectively, at day 30. Differently, all analytes at 5 ng/mL were quantified above 44% and 41% initial concentrations at room temperature and 4 °C, respectively, showing a higher stability. The study of nitazenes stability in DBSs represents an important tool to determine the optimal sample storage conditions, such as temperature and time between sample collection and analysis. In contrast to another study, our study showed distinct stability behaviors for every investigated analyte, which also depended on the concentration. Therefore, it is difficult to define an optimal storage condition acceptable for all nitazenes. Room temperature proved to be the best medium- and long-term storage conditions for the highest concentrations, but the stability of low levels of flunitazene and protonitazene improved at 4 °C.

Nitazenes represent a New Synthetic Opioids sub-class, belonging to the New Psychoactive Substances (NPS). Their high pharmacological potency has led to numerous intoxications and fatalities, even at minimum doses. The aim of this study was to assess the stability of four nitazenes (etazene, flunitazene, isotonitazene and protonitazene) in dried blood spot (DBS) samples at different storage temperatures (room temperature and 4°C), using a newly developed and validated liquid chromatography-high resolution mass spectrometry method. Two concentrations, 1 and 5 ng/mL were chosen based on the available data on nitazene-related intoxications and stability was evaluated at day 0 (control), 1, 7 and 30. Results showed that all analytes at 1 ng/mL were not detectable after 30 days at room temperature; a similar pattern was observed for 1 ng/mL etazene and isotonitazene samples when stored at 4°C, whereas flunitazene and protonitazene decreased to a mean of 66% and 69% initial concentration, respectively, at day 30. Differently, all analytes at 5 ng/mL were quantified above 44% and 41% initial concentration at room temperature and 4°C, respectively, showing a higher stability. The study of nitazenes stability in DBS represents an important tool to determine the optimal samples storage conditions, such as temperature and time between sample collection and analysis.

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae.

Prenatal exposure to alcohol can cause Fetal Alcohol Spectrum Disorders (FASDs) after birth, encompassing a spectrum of physical, cognitive, and behavioral abnormalities. FASD represents a severe non-genetic disability avoidable through alcohol abstinence during pregnancy and when planning it. Clinical severity depends on alcohol impact, symptomatology, and resulting disabilities. FASD is a permanent disability with no recognized specific medical care. Conversely, secondary FASD-related disabilities can be symptomatically treated. This integrative review aims to provide information about the novel pharmacological treatments of FASD-associated comorbidities by selecting the last ten years of studies carried out on animals and humans. PRISMA guidelines were followed to search human/animal model studies of pharmacological interventions on FASD comorbidities, using different databases (PubMed, Cochrane, etc.). From 1348 articles, 44 met the criteria after full-text analysis. Firstly, all the reported studies point out that early diagnosis and tailored interventions are the principal tools to reduce FASD-related secondary disabilities, due to the fact that there is currently no approved pharmacological treatment for the tissue damage which produces FASD. Despite limitations in study designs and small sample sizes, these review results highlight how the treatment strategies of children with FASD have changed. In the past, studies focused on treating symptoms, but in the last years, researchers have turned their attention to the prevention targeting central nervous system embryogenesis. Novel treatments like choline and natural antioxidants and nutritional supplements are the most investigated treatments in humans with promising results. More follow-up studies need to be performed, to confirm and generalize reported efficacy to a wide sample size.