Advances in the study of pharmacotherapy for addiction to naturally-derived psychoactive substances.

Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs); alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors; and psychostimulants that interact with monoamine transporters.

A Novel Nontargeted Screening Strategy for New Psychoactive Substances: A Case Study of Synthetic Cannabinoids Based on Electron-Activated Dissociation High-Resolution Mass Spectrometry and Intelligent Elucidation.

Nontargeted screening of new psychoactive substances (NPSs) has always been a challenging task, typically involving data acquisition, the extraction of suspicious peaks, and mass spectrometry elucidation in the screening process. The ongoing advancement of instrument acquisition technology and data analysis methods has resulted in an increasing amount of sample data requiring manual elucidation, significantly reducing the efficiency of forensic identification work and leading to issues such as missed detections and false positives. This study proposed a novel nontargeted screening strategy that is capable of automatically elucidating the NPS classes and chemical structures of unknown designer drugs.

Multi-omics Analysis Reveals miR-7220-5p Alleviates NO Addictive Behaviors via NR2B/ERK/CREB Signaling.

Nitrous oxide use disorder (NUD) has recently received increasing social concern for its sharp rise among young people. However, the underlying mechanisms of NUD remain largely unexplored, which obstructs treatment strategy development and may exacerbate the epidemic of NO abuse. Thus, specifying the essential mechanisms and targets in NUD are desperately needed.

Assessment of Abuse Potential of Three Indazole-Carboxamide Synthetic Cannabinoids 5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA.

5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA are three potent indazole-carboxamide synthetic cannabinoids (SCs) that have been widely abused in recent years. However, the pharmacological research on these compounds remains limited, especially in vivo research data. The purpose of the present study was to investigate the pharmacological effects of 5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA in mice, comparing their in vivo effects with those caused by Δ-tetrahydrocannabinol (Δ-THC), the main psychoactive substance in cannabis.

In vivo and in vitro protective effect of lutein against inflammatory response in lipopolysaccharide-induced broilers.

Lutein, a naturally occurring xanthophyll carotenoid abundant in leafy green vegetables, is known for its antioxidative and anti-inflammatory effects. This research assessed how lutein modulates intestinal inflammation triggered by lipopolysaccharide (LPS) exposure in vivo and in vitro. In vivo trials involved 240 male yellow-feathered broilers (1-day-old) divided into four groups: control (basal diet), lutein-supplemented (40 mg/kg), LPS-challenged (1 mg/kg), and lutein+LPS.

Age-specific effects of synthetic cannabinoids on cognitive function and hippocampal gene expression in mice: insights from behavioral and molecular correlates.

The increasing use of Synthetic cannabinoids (SCs) in adolescents and young adults poses significant medical and psychiatric risks, and previous reports have been dominated by single-age animal studies. Here, we first investigated the effects of a single exposure of the fourth-generation synthetic cannabinoid 4F-ABUTINACA on cognitive behaviors in adolescent (PND 28-35 days) and adult (PND 49-56 days) male mice in an animal model, followed by an age-specific systematic study by conducting a whole-gene transcriptomics study of hippocampal tissue in the brain. Behavioral results showed that 4F-ABUTINACA impaired recognition memory, fear memory extraction, and spatial navigation memory in adolescent mice, as well as spatial navigation memory in adult mice.

Effects of three tryptamines: alpha-methyltryptamine, 5-methoxy-alpha-methyltryptamine, and 5-methoxy- N , N -diisopropyltryptamine on acute toxicity, locomotor activity, and hallucinogenic behavior in mice.

Alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), and 5-methoxy- N , N -diisopropyltryptamine (5-MeO-DiPT) are synthetic tryptamines with hallucinogenic-like properties that are widely abused worldwide. There, however, has been a paucity of research and a lack of available data on their pharmacological properties. The objective of this study was to investigate the safety of AMT and 5-MeO-DiPT and to compare the effects of AMT, 5-MeO-AMT, and 5-MeO-DiPT under identical conditions in terms of locomotor performance and hallucinogenic-like behavior, and the role of 5-hydroxytryptamine-2A receptor antagonists (M100907) on hallucinogenic-like behavior.

Investigating peroxide-induced Asp epimerization in peroxiredoxin 2 using enzymatic hydrolysis and LC-MS/MS.

Stereoinversion of amino acids from the -form to the -form alters protein structure and, possibly, biological activity. This modification causes no change in protein m/z and is often overlooked during protein analysis. Aspartic acid epimerization (AAE) occurs faster than other amino acids and is known to be accelerated by free radicals and peroxides.

High-throughput screening of 311 new psychoactive substances and metabolites in wastewater by direct injection UPLC-MS/MS.

The rapid global spread of new psychoactive substances (NPS) in recent years has become an issue in many countries. One emerging technology that can provide early warnings and assessments of drug situations is the monitoring of NPS in wastewater. In this study, we developed and optimized a high-throughput qualitative screening method based on direct injection that enabled the simultaneous detection of 311 NPS and metabolites (87 synthetic cannabinoids, 43 synthetic cathinones, 71 phenylethylamines, 10 tryptamines, 40 phencyclidines, 9 benzodiazepines, 38 fentanyls, and 13 piperazines) in wastewater.

Detection of Retinoic Acid in Cosmetics Using Reactive Paper Spray Ionization Mass Spectrometry.

Chromatography-mass spectrometry typically requires a time-consuming and costly pretreatment to detect illegal additives in cosmetics. Retinoic acid is classified as a prohibited additive in cosmetics by the European Union and China. Therefore, a rapid and convenient method is needed for its detection.

Surface Plasmon Resonance (SPR) for the Binding Kinetics Analysis of Synthetic Cannabinoids: Advancing CB1 Receptor Interaction Studies.

Synthetic cannabinoids (SCs), a class of widely abused new psychoactive substances, are characterized by their structural diversity and rapid evolution. Structure-affinity relationships are crucial for predicting pharmacological effects and potential toxicity. Traditional methods for affinity testing are often complex and less applicable to newly modified compounds.

Occurrence and removal of pharmaceuticals in hospital wastewater and the contribution to wastewater treatment plants.

The pervasive presence of drugs in aquatic environments has emerged as a pressing global issue, with hospital wastewater (HWW) recognized as a significant pollution source. This study evaluates the occurrence, removal efficiency, and environmental risks of 21 common pharmaceuticals or their metabolites in HWW. The 21 compounds included opioids, methylxanthines, β-blockers, non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines, β-adrenoceptor agonists, phenylethylamines, benzodiazepines, organic amine compounds, neuraminidase inhibitors, and amide local anesthetics.

A systematic study of changes in monoamine neurotransmitters in the rat brain following acute administration of alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT).

Alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT) are three synthetic tryptamines with hallucinogenic properties that are widely abused worldwide. The hallucinogenic effects of tryptamines are primarily related to activation of the 5-HT receptor, and among the many subtypes of 5-HT receptors, the 5-HT receptor is the key receptor for hallucinogenic effects. In the present study, the monoamine neurotransmitters DA and its metabolites 3,4-Dihydroxyphenylacetic Acid (DOPAC) and homovanillic acid (HVA), 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were systematically investigated in the prefrontal cortex (PFC), nucleus accumbent (NAc), dorsolateral striatum (DLS) and hippocampus (HIP) using a validated HPLC-ECD analytical method after administration of the three tryptamines at different doses.

Assessment of abuse potential of furanylfentanyl and tetrahydrofuranylfentanyl.

Rational: Furanylfentanyl and tetrahydrofuranylfentanyl (THF-F) have been emerging in numerous intoxication and overdose cases in recent years. However, there remains a data deficiency regarding the abuse potential of these novel fentanyl analogs.

Objectives: This study was designed to systematically assess the abuse potential of furanylfentanyl and THF-F.

Simultaneous enrichment and ultra-high sensitivity detection of multi-structural synthetic cannabinoids in large-volume wastewater.

Nowadays, the abuse of synthetic cannabinoids has aroused the world's great attention. However, the determination of synthetic cannabinoids in wastewater faces the bottleneck of complex species and very low content. Therefore, this work integrated GO-FeO with an ionic liquid (ILs-GO-FeO) to create a mixed hemimicelles magnetic solid-phase extraction (MHMSPE) system for the detection of synthetic cannabinoids (SCs) in wastewater samples using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

Pharmaco-toxicological effects of the synthetic cannabinoids 4F-ABUTINACA, SDB-005, and JWH-018 in mice. In vitro and in vivo studies.

Background: Synthetic cannabinoids (SCs) are currently one of the most severely abused new psychoactive substances in the world. However, there remains a notable lack of pharmacological data on the newly emerged synthetic cannabinoids. In the present study, the in vitro and in vivo pharmacological effects of the fourth-generation synthetic cannabinoids 4F-ABUTINACA and SDB-005 are determined and compared to those of the first-generation synthetic cannabinoid JWH-018.

Effects of Dietary Nano-Composite of Copper and Carbon on Antioxidant Capacity, Immunity, and Cecal Microbiota of Weaned Ira White Rabbits.

This experiment investigated the effects of dietary supplementation with nano-composites of copper and carbon (NCCC) on antioxidants, immune functions, and the cecum microbiota of weaned Ira white rabbits. A total of 240 weaned 35-day-old Ira white rabbits were randomly allocated to five dietary treatments ( = 6 per treatment, each replicate consisted of eight rabbits) that included the control group (CON) with a basal diet, the SAL group with 60 mg/kg salinomycin (SAL) in addition to the basal diet, and the NCCC I, II, III groups, which were supplemented with 50, 100, and 200 mg/kg NCCC, respectively, in addition to the basal diet. The test lasted for 28 d.

STNGS: a deep scaffold learning-driven generation and screening framework for discovering potential novel psychoactive substances.

The supervision of novel psychoactive substances (NPSs) is a global problem, and the regulation of NPSs was heavily relied on identifying structural matches in established NPSs databases. However, violators could circumvent legal oversight by altering the side chain structure of recognized NPSs and the existing methods cannot overcome the inaccuracy and lag of supervision. In this study, we propose a scaffold and transformer-based NPS generation and Screening (STNGS) framework to systematically identify and evaluate potential NPSs.

Direct injection UPLC-MS/MS method for analysing 77 compounds including human biomarkers, illicit drugs, new psychoactive substances and metabolites in wastewater.

Wastewater analysis technology has emerged as a promising tool for monitoring illicit drug consumption. However, the current reliance on the solid-phase extraction (SPE) pre-treatment method presents significant challenges for widespread adoption and high-throughput monitoring, as it consumes a large amount of time and labor as well as requires specialized instruments. This study has developed a direct injection (DI) technique for UPLC-MS/MS, enabling the detection of 77 compounds encompassing metabolites of human biomarkers, illicit drugs, and new psychoactive substances.

Improved entropy-CRITIC population model based on temporal and spatial variability: Construction and application in wastewater epidemiology.

Numerous factors contribute to the uncertainty inherent in conducting wastewater-based epidemiology (WBE), with shifting populations exerting a significant influence. However, traditional single- and multi-parameter population models suffer from certain limitations. This study employs an evaluation model framework to construct a model (EC model) based on data characteristics.

Multi-Omics and Physiological Analysis Reveal Crosstalk Between Aphid Resistance and Nitrogen Fertilization in Wheat.

The availability of nitrogen (N) can dramatically influence crops resistance to herbivorous insects. However, the interaction between N fertilization and crop resistance to insects is not well understood. In this study, the effects of N fertilization on the grain aphid (Sitobion miscanthi) were investigated using three wheat (Triticum aestivum) cultivars with different aphid resistances.

CBMAFF-Net: An Intelligent NMR-Based Nontargeted Screening Method for New Psychoactive Substances.

With the proliferation and rapid evolution of new psychoactive substances (NPSs), traditional database-based search methods face increasing challenges in identifying NPS seizures with complex compositions, thereby complicating their regulation and early warning. To address this issue, CBMAFF-Net (CNN BiLSTM Multistep Attentional Feature Fusion Network) is proposed as an intelligent screening method to rapidly classify unknown confiscated substances using C nuclear magnetic resonance (NMR) and H NMR data. Initially, we utilize the synergy of a convolutional neural network (CNN) and bidirectional long short-term memory network (BiLSTM) to extract the global and local features of the NMR data.