Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies.
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ABSTRACT:
SUBMITTER: Costa G
PROVIDER: S-EPMC6990793 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The emergence of new psychoactive substances has earned a great deal of attention, and several reports of acute poisoning and deaths have been issued involving, for instance, synthetic opiates. In recent years, there have been profound alterations in the legislation concerning consumption, marketing, and synthesis of these compounds; rapid alert systems have also been subject to changes, and new substances and new markets, mainly through the internet, have appeared. Their effects and how they originate in consumers are still mostly unknown, primarily in what concerns chronic toxicity. This review intends to provide a detailed description of these substances from the point of view of consumption, toxicokinetics, and health consequences, including case reports on intoxications in order to help researchers and public health agents working daily in this area.
| S-EPMC9028227 | biostudies-literature
Project description:Fourteen substances from the class of drugs sometimes known as "legal highs" were screened against a battery of human receptors in binding assays, and their potencies as inhibitors of monoamine uptake determined in functional in vitro assays. Thirteen of the test substances acted as inhibitors of monoamine uptake at submicromolar concentrations, including 9 potent inhibitors of the dopamine transporter (DAT), 12 potent inhibitors of the norepinephrine transporter (NET) and 4 potent inhibitors of the serotonin transporter (SERT). Seven compounds acted as submicromolar inhibitors of both DAT and NET, and three substances 1-(benzofuran-5-yl)propan-2-amine (5-APB), 1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride ("naphyrone") and 1-naphthalen-1-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride ("1-naphyrone") were submicromolar inhibitors of all three monoamine transporters. There was a lack of correlation between results of functional uptake experiments and in vitro binding assays for the monoamine transporters. There was also no correlation between the human behavioral effects of the substances and the results of bindings assays for a range of receptor targets, although 1-(benzofuran-5-yl)propan-2-amine (5-APB), 1-(benzofuran-6-yl)propan-2-amine hydrochloride (6-APB) and 5-iodo-2,3-dihydro-1H-inden-2-amine hydrochloride (5-iodo-aminoindane) exhibited <100 nM affinities for 5HT(2B) and ?(2C) receptors. Functional assays revealed that 5-APB and 6-APB were potent full agonists at 5HT(2B) receptors.
| S-EPMC3582025 | biostudies-literature
Project description:Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4'-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.
| S-EPMC8268582 | biostudies-literature
Project description:Identification of new psychoactive substances (NPS) in biological and non-biological samples represents a hard challenge for forensic toxicologists. Their great chemical variety and the speed with which new NPS are synthesised and spread make stringent the need of advanced tools for their detection based on multidisciplinary approaches. For this reason, in August 2016, the "Unit of Research and Innovation in Forensic Toxicology and Neuroscience of Addiction" (U.R.I.To.N.) was founded by the Forensic Toxicology Division of the University of Florence. In this Research Unit, various professionals (i.e. forensic toxicologists, chemists, physicians) collaborate to study all the aspects of drugs of abuse, especially NPS. Herein, we describe the multidisciplinary approach comprising liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), gas chromatography hyphenated to mass spectrometry (GC-MS) and solution nuclear magnetic resonance analysis that allowed the identification of three NPS such as 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethan-1-one (bk-2C-B), and 3-(2-aminopropyl)indole (α-methyltryptamine) in seized materials.
| S-EPMC6445230 | biostudies-literature
Project description:OBJECTIVES:Non-illicit alternatives to controlled drugs, known as novel psychoactive substances (NPS), have recently risen to prominence. They are readily available, with uncertain pharmacology and no widely available assay. Given that psychiatric patients are at risk of comorbid substance abuse, we hypothesised that NPS use would be present in the psychiatric population, and sought to determine its prevalence and investigate the characteristics of those who use these drugs with a retrospective review of discharge letters. SETTING:General adult inpatient wards of a psychiatric hospital in a Scottish city. PARTICIPANTS:All adult inpatients (18-65) discharged from general psychiatric wards between 1 July 2014 and 31 December 2014. Of the 483 admissions identified, 46 were admissions for maintenance electroconvulsive therapy (ECT) and were excluded. Of the remaining 437 admissions, 49 discharge letters were unobtainable, leaving 388 admissions to analyse. PRIMARY OUTCOME MEASURE:The mention, or lack thereof, of NPS use in discharge letters was our planned primary outcome measure and was also the primary outcome measure we used in our analysis. RESULTS:NPS use was identified in 22.2% of admissions, contributing to psychiatric symptoms in 59.3%. In comparison to non-users, NPS users were younger (p<0.01), male and more likely to have a forensic history ((p<0.001) for both). The diagnosis of drug-induced psychosis was significantly more likely in NPS users (p<0.001, OR 18.7, 95% CI 8.1 to 43.0) and the diagnosis of depression was significantly less likely (p<0.005, OR 0.133, CI 0.031 to 0.558). Use of cannabis was significantly more likely in NPS users (p<0.001, OR 4.2, CI 2.5 to 7.1), as was substitute opiate prescribing (p<0.001, OR 3.7, CI 1.8 to 7.4). CONCLUSIONS:NPS use was prevalent among young, male psychiatric inpatients, in particular those with drug-induced psychosis and often occurred alongside illicit drug use.
| S-EPMC4874170 | biostudies-literature
Project description:Background and Objectives: Over the past twenty years a large number of new psychoactive substances (NPS) have entered and modified the recreational drug scene. Their intake has been associated with health-related risks, especially so for vulnerable populations such as people with severe mental illness, who might be at higher risk of suicidality or self-injurious behavior. This paper aims at providing an overview of NPS abuse and the effects on mental health and suicidality issues, by performing a literature review of the current related knowledge, thereby identifying those substances that, more than others, are linked to suicidal behaviors. Materials and Methods: A comprehensive and updated overview of the literature regarding suicidality and NPS categories has been undertaken. An electronic search was performed, including all papers published up to March 2021, using the following keywords "NPS" OR "new psychoactive substances" OR "novel psychoactive substances" OR "synthetic cannabinoids" OR "phenethylamines" OR "synthetic cathinones" OR "tryptamines" OR "piperazines" OR "new synthetic opioids" OR "designer benzodiazepines" AND ("suicide" OR "suicidality") NOT review NOT animal on the PubMed, Cochrane Library, and Web of Science online databases. Results: Suicidality and self-injurious behavior appear to be frequently associated with some NPS such as cathinones, synthetic cannabinoids, and new synthetic opioids. The results are organized according to the substances recorded. Conclusion: The growing use of NPS has become a significant clinical issue, causing increasing concern and challenges for clinicians working in both mental health and emergency departments. Thus, considering the associations between NPS and suicidality or self-injurious behaviors, areas where suicide-prevention efforts and strategies might be focused are the early detection, monitoring, and restriction of NPS.
| S-EPMC8226910 | biostudies-literature
Project description:Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.
| S-EPMC4463694 | biostudies-literature
Project description:ObjectiveAttention disorder and substance use disorder are linked to driving impairment and increased road crash involvement. This study explores attention deficits in a population of drivers found driving under the influence (DUI) of psychoactive substances.MethodsA case-control study was conducted comparing subjects with a previous DUI episode (cases) to subjects who were negative for DUI offenses (controls). Personal, socio-demographic, and DUI data were collected for both groups. All subjects were administered the Continuous Performance Test-third edition (CPT-3), which measures dimensions of attention, including inattentiveness, impulsivity, sustained attention, and vigilance. Possible associations with a previous DUI episode, the use of illicit substances or excessive alcohol use, and road crash involvement were analyzed statistically.ResultsOverall, the study included 147 subjects (100 cases, 47 controls). The parameter distributions of detectability, probability of ADHD, and inattentiveness indicated statistical differences between the two groups. No attention deficits predicted substance use disorder or excessive alcohol consumption. Inattentiveness was an independent risk factor for previous road collision involvement.ConclusionsThe results suggest that alterations exist in some attention dimensions in a population of DUI subjects who were users of alcohol or other psychoactive substances and involved in road traffic crashes. The CPT-3 had successfully distinguished between the two study groups, and after validation, it could be useful in the process of reinstating a driver's license. Future research should expand the study sample to better understand the relevance of the proposed methodological approach in terms of prevention, rehabilitation, and the monitoring of subjects evaluated for driving eligibility requirements.
| S-EPMC10825441 | biostudies-literature
Project description:Intracranial aneurysms (IAs) are a significant public health concern because they have the potential to cause deva-stating consequences, including death and disability. Despite advances in diagnostic and treatment modalities, the outcomes for patients with aneurysmal subarachnoid haemorrhage (aSAH) remain poor, with high rates of rebleeding, vasospasm, and cerebral ischaemia. IAs are a significant risk factor for aSAH, and it is estimated that up to 3% of the general population have IAs. Recent studies using novel imaging modalities have shown that the prevalence of IAs may be much higher, with 6.6% of adults aged 40-84 years having intradural saccular IAs ≥ 2 mm. The risk of rupture for IAs is difficult to predict, and the decision to treat them invasively is based on a balance between the estimated rupture risk and the procedural risks of the treatment. However, the mortality and morbidity rates among patients treated for IAs can be as high as 5%. There is a need for clear guidelines on the treatment of IAs, and this review aims to provide an update on recent findings in this area. To achieve this goal, the authors identified and summarized recent, high-impact studies on IAs. The review focuses on the diagnostic and treatment options for IAs, as well as the risks associated with these interventions. The authors also provide an overview of the natural history of IAs and discuss the challenges and uncertainties in managing these patients.
| S-EPMC10867953 | biostudies-literature
Project description:The market for illicit drugs has been reshaped by the emergence of more than 1100 new psychoactive substances (NPS) over the past decade, posing a major challenge to the forensic and toxicological laboratories tasked with detecting and identifying them. Tandem mass spectrometry (MS/MS) is the primary method used to screen for NPS within seized materials or biological samples. The most contemporary workflows necessitate labor-intensive and expensive MS/MS reference standards, which may not be available for recently emerged NPS on the illicit market. Here, we present NPS-MS, a deep learning method capable of accurately predicting the MS/MS spectra of known and hypothesized NPS from their chemical structures alone. NPS-MS is trained by transfer learning from a generic MS/MS prediction model on a large data set of MS/MS spectra. We show that this approach enables a more accurate identification of NPS from experimentally acquired MS/MS spectra than any existing method. We demonstrate the application of NPS-MS to identify a novel derivative of phencyclidine (PCP) within an unknown powder seized in Denmark without the use of any reference standards. We anticipate that NPS-MS will allow forensic laboratories to identify more rapidly both known and newly emerging NPS. NPS-MS is available as a web server at https://nps-ms.ca/, which provides MS/MS spectra prediction capabilities for given NPS compounds. Additionally, it offers MS/MS spectra identification against a vast database comprising approximately 8.7 million predicted NPS compounds from DarkNPS and 24.5 million predicted ESI-QToF-MS/MS spectra for these compounds.
| S-EPMC10733899 | biostudies-literature