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.

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.

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.

Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study.

The pharmacokinetic (PK) profile of remimazolam, a ultra-short-acting benzodiazepine, has been investigated for procedural sedation and anesthesia, but its pharmacokinetics, pharmacodynamics, and optimal dosing for ICU sedation are still unclear. This prospective, single-center, double-blind randomized controlled trial studied ICU adults on mechanical ventilation for over 24 h. Participants were divided into three groups, each receiving a 0.

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.

Determination of seven precursor substances of 1-phenyl-2-propanone in atmospheric particulate matter by LC-MS/MS: A novel strategy for monitoring illicit drug synthesis and assessing potential health risks.

In the process of illicit drug production and manufacture, some of the precursors might escape into the air and adhere to the surface of airborne particulate matter. The detection of precursor substances in atmospheric particulate matter in the vicinity of suspected drug manufacturing facilities can assist in the deduction of drug synthesis pathways and the reduction of illicit drug preparation at the source. In recent years, there has been a notable transition in methamphetamine synthesis from the ephedrine/pseudoephedrine-based route to the 1-phenyl-2-propanone (P2P)-based route, underscoring the growing significance of P2P and its precursor chemicals in the surveillance and control of illicit drug manufacturing.

Potential drug exposure risk assessment of analysts in analytical laboratories through fingernail, hair, and atmospheric environment analyses.

Analysts in drug testing laboratories are frequently exposed to drugs as part of their daily work activities. Certain drug components can vaporise and adhere to atmospheric particles. Therefore, the presence of drugs in laboratory settings can affect the health and well-being of the laboratory personnel.

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.

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.

Assessment of pharmacological effects and abuse potential of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 in mice.

Rationale: The newly emerging synthetic cannabinoids (SCs) 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 have been observed to produce effects by activating cannabinoid type 1 (CB1) receptors. Nevertheless, the pharmacological effects and potential for abuse of these three substances remain to be studied. These substances have yet to be regulated in many countries.

Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.

Rationale: Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored.

Feature-Based Molecular Network-Assisted Cannabinoid and Flavonoid Profiling of Leaves and Their Antioxidant Properties.

() leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of leaves from various regions.

Preparation of amphiphilic poly(divinylbenzene--vinylpyrrolidone)-functionalized polydopamine magnetic nanoadsorbents for enrichment of synthetic cannabinoids in wastewater.

Concerns have been raised about synthetic cannabinoids (SCs), which are among the most often trafficked and used illegal substances. An analytical method that holds promise for determining illicit drug use in the general population is wastewater-based epidemiology (WBE). Unfortunately, the concentration of SCs in wastewater is often extremely low on account of their hydrophobic nature, thus presenting a significant obstacle to the accurate detection and quantification of SCs using WBE.