Cannabinoid receptor agonists

大麻素受体激动剂
  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    大麻是全球最常见的休闲药物,合成大麻素受体激动剂是目前最大的新型精神活性物质。这项研究的目的是比较孤立的急性大麻毒性与孤立的急性合成大麻素受体激动剂毒性的临床特征和结果,在2013年至2020年之间向欧洲急诊科进行的一系列介绍中。
    自我报告的药物暴露,临床,和结果数据来自欧洲药物紧急情况网络Plus,该网络是一个监测网络,记录向24个欧洲国家的36个中心提供的药物相关急诊科报告数据.在所有分析中,大麻暴露被认为是对照。为了比较单独的大麻和单独的合成大麻素受体激动剂组,使用卡方检验的单变量分析用于分类变量,而非参数Mann-WhitneyU检验用于连续变量。统计学显著性定义为P值<0.05。
    在2013-2020年之间,有54,314个与药物相关的陈述,其中2,657个是单独的大麻暴露和503个单独的合成大麻素受体激动剂暴露。合成大麻素受体激动剂的表现具有统计学上明显较高的嗜睡率,昏迷,激动,报告时的癫痫发作和心动过缓。大麻介绍明显更有可能出现心悸,胸痛,高血压,心动过速,焦虑,呕吐和头痛。
    涉及单独的合成大麻素受体激动剂暴露的急诊科报告更有可能具有神经精神特征,并被送进精神科病房,单独接触大麻更有可能具有心血管特征。先前的研究表明,与大麻相比,合成大麻素受体激动剂的急性毒性存在差异,但很少有单独暴露的比较数据。目前的文献中,单独的合成大麻素受体激动剂和单独的大麻暴露之间的直接比较有限,只有两个以前的毒药中心系列和两个临床系列。虽然这项研究是有限的自我报告被用来确定药物(S)参与演示文稿,以前的研究表明,在急性药物毒性的急诊科报告中,自我报告是可靠的.
    这项研究直接比较了与单独使用大麻或合成大麻素受体激动剂有关的急性药物毒性的介绍。它支持先前的发现,与大麻相比,合成大麻素受体激动剂的神经精神毒性增加,并提供了有关单独使用大麻的心血管毒性的进一步数据。
    UNASSIGNED: Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020.
    UNASSIGNED: Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a P value of <0.05.
    UNASSIGNED: Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache.
    UNASSIGNED: Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity.
    UNASSIGNED: This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use.
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  • 文章类型: Journal Article
    物质成瘾(SA)是自杀念头和行为(STB)的危险因素,尽管尚不清楚哪些SA与自杀意念的风险增加可靠相关,规划,和尝试。当前的研究旨在使用全国药物使用和健康调查(NSDUH)的数据来实现这一目标,该数据涉及2008年至2020年的年份。提取的信息包括社会人口统计和上下文信息,11个SA(例如,尼古丁,酒精,大麻,可卡因,止痛药,海洛因,吸入剂,致幻剂,镇静剂,兴奋剂,和镇静剂),还有STB.分析显示,酒精的SAs,止痛药,大麻,和可卡因是STB稳定可靠的预测因子(例如,自杀意念,规划,并尝试),而可卡因不是自杀企图的稳定预测因子。选定的SAs模型显示出比仅社会人口统计学和背景因素以及未选定的SAs更高的预测准确性。此外,选定的SA显示出与完整模型相当的预测准确性。此外,SA对酒精的预测显示出非常有效的STB,与所有其他十个SA一起具有相当的预测准确性。总之,SAs到止痛药,酒精,大麻,和可卡因可以被认为是并发STB的重要危险因素。
    Substance addiction (SA) is a risk factor of suicidal thoughts and behaviors (STB), although it is still unclear which SAs are reliably associated with increased risk for suicidal ideation, planning, and attempt. The current study aimed to meet this goal using data from the National Survey on Drug Use and Health (NSDUH) referring to years from 2008 to 2020. The information extracted included sociodemographic and contextual information, eleven SAs (e.g., nicotine, alcohol, marijuana, cocaine, pain relievers, heroin, inhalants, hallucinogens, sedatives, stimulants, and tranquillizers), and STB. The analysis revealed that SAs for alcohol, pain relievers, marijuana, and cocaine were stable and reliable predictors for STB (e.g., suicidal ideation, planning, and attempt), while cocaine was not a stable predictor for suicide attempt. The selected SAs model showed a greater predictive accuracy than only sociodemographic and contextual factors as well as not selected SAs. Moreover, selected SAs showed comparable predictive accuracy to the full model. Furthermore, SA to alcohol showed to be an extremely effective predictor of STB, having a comparable predictive accuracy to all the other ten SAs together. In conclusion, SAs to pain relievers, alcohol, marijuana, and cocaine can be considered as important risk factors for concurrent STB.
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  • 文章类型: Case Reports
    新精神活性物质(NPS)的管理,特别是合成大麻素受体激动剂(SCRAs),通过电子烟,监狱内的环境已经广为宣传。这项研究概述了2022年5月至2023年7月从苏格兰监狱缉获的五个电子烟盒样本,其中合成代谢-雄激素类固醇(AASs)在气相色谱-质谱(GC-MS)分析后鉴定了甲甾烷酮和oxandrolone。这些电子烟样品占所有含有电子烟弹的样品的2.9%(n=170)和在同一时期内发现的含有AAS的所有样品的9.4%(n=53)。AAS与其他药物联合检测,包括可卡因,Δ9-四氢大麻酚(Δ9-THC),SCRAs和尼古丁。这代表了一种新的AAS给药途径。
    The administration of new psychoactive substances (NPS), in particular synthetic cannabinoid receptor agonists (SCRAs), via e-cigarettes, within prison settings has been well publicized. This study provides an overview of five e-cigarette case samples seized from Scottish prisons between May 2022 and July 2023 where the anabolic-androgenic steroids (AASs) mestanolone and oxandrolone were identified following gas chromatography-mass spectrometry (GC-MS) analysis. These e-cigarette samples represented 2.9% of all samples containing e-cigarette cartridges (n = 170) and 9.4% of all samples found to contain AASs (n = 53) seized during the same time period. The AASs were detected in combination with other drugs, including cocaine, Δ9-tetrahydrocannabinol (Δ9-THC), SCRAs and nicotine. This represents a new and novel route of administration for AASs.
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  • 文章类型: Journal Article
    背景:处方药用大麻(MC)是澳大利亚越来越常见的治疗疼痛的处方,焦虑,和睡眠障碍。规定的MC产品通常含有各种剂量水平和形式的四氢大麻酚(THC)和/或大麻二酚(CBD)。目前尚不清楚THC和CBD产品是否被具有不同特征和不同条件的患者使用。
    目的:检查消费者使用含有THC和CBD的处方MC产品的体验,以更好地了解它们在澳大利亚的使用情况。
    方法:我们利用从个人的在线匿名横断面调查(CAMS-20调查)收集的数据,由澳大利亚居民出于治疗原因使用大麻组成。我们关注接受处方MC产品的一组参与者(N=546)。我们利用线性,logistic,和多项回归模型,根据处方产品的大麻素概况分析对调查问题的答复。
    结果:从统计学上讲,以THC为主的MC产品的参与者更可能更年轻,男性,与使用CBD主导产品的参与者相比,他们更喜欢吸入给药途径,女性,和优选的口服给药途径。疼痛和心理健康是所有类型处方MC的最常见原因,但是,尽管轻度至重度嗜睡的风险明显更高,但THC比CBD更有可能治疗,口干和眼睛刺激。消费者报告处方MC的有效性非常积极,特别是对于含有THC的产品。与仅含CBD的产品相比,使用阿片类药物和抗精神病药的消费者在统计学上更有可能服用含THC的产品,尽管减值风险更大。
    结论:这项在澳大利亚范围内的研究发现,消费者报告的含THC和CBD产品的处方体验存在明显差异。这些产品的当前处方并不总是与相关的临床指导一致。对处方者进行大麻素产品的教育对于确保最佳的处方实践和防止可避免的药物副作用和相互作用至关重要。
    BACKGROUND: Prescribed medicinal cannabis (MC) is an increasingly common prescription in Australia for treating pain, anxiety, and sleep disorders. Prescribed MC products generally contain tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in a variety of dose levels and forms. It is unclear whether THC and CBD products are used by patients with different characteristics and for different conditions.
    OBJECTIVE: To examine consumer experiences of using THC- and CBD-containing prescribed MC products to better understand how they are being used within the Australian context.
    METHODS: We utilised data collected from an online anonymous cross-sectional survey of individuals (CAMS-20 survey), consisting of Australian residents using cannabis for therapeutic reasons. We focused on a subgroup of participants (N = 546) receiving prescribed MC products. We utilised linear, logistic, and multinomial regression modelling to analyse responses to survey questions based on the cannabinoid profile of the prescribed product.
    RESULTS: Participants prescribed THC-dominant MC products were statistically more likely to be younger, male, and to prefer inhaled routes of administration than participants using CBD-dominant products who were older, female, and preferred oral routes of administration. Pain and mental health were the most common reasons for all types of prescribed MC, but were more likely to be treated with THC than CBD despite the significantly higher risk of mild to severe drowsiness, dry mouth and eye irritation. Consumer reported effectiveness of prescribed MC was very positive, particularly for THC-containing products. Consumers on opioids and antipsychotics were statistically more likely to be prescribed THC-containing products than products containing CBD only, despite the greater risk of impairment.
    CONCLUSIONS: This Australia-wide study found clear differences in consumer-reported experiences of prescribed THC- and CBD-containing products. Current prescriptions of these products do not always align with relevant clinical guidance. Educating prescribers around cannabinoid products is essential to ensure optimal prescribing practices and to prevent avoidable drug side effects and interactions.
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  • 文章类型: Journal Article
    物质使用,尤其是青少年,是一个重大的公共卫生问题,对身体和心理发展有着深远的影响。这项研究旨在评估青少年有关多种药物使用的可用信息的数量和来源。在塔拉戈纳进行了一项横断面调查,涉及平均年龄为16.44岁的青少年。这项研究评估了使用的物质的数量(酒精,香烟,和大麻)在过去的一个月里,以及与物质使用相关的信息来源。受监控的源(例如,学校,父母,和大众媒体)和不受监控的来源(例如,同行,兄弟姐妹,互联网)是杰出的。此外,考虑了四个个体和四个环境控制变量。多项logistic回归分析显示,纳入与青少年物质使用信息及其来源相关的变量可以增强解释模型,超越控制变量。关于物质使用的信息程度并不能显著解释消费模式,但是信息来源的数量,监控和不监控,did.未监测的来源与多药物使用增加有关。相反,更多地依赖受监督的信息来源与减少单一物质和多种药物的使用有关.这种保护作用随着所用物质数量的增加而增加。总之,从监测来源获得的信息对物质消费起到威慑作用,与研究结果一致,这表明青少年更高的健康素养会阻止药物使用。相反,这项研究表明,来自更非正式来源的信息可能会鼓励更多的多药物使用,与报告一致表明,对药物使用后果有更全面了解的青少年倾向于从事更重的药物使用。
    Substance use, especially among adolescents, is a significant public health concern, with profound implications for physical and psychological development. This study aimed to evaluate the quantity and sources of information available to adolescents regarding polydrug use. A cross-sectional survey was conducted in Tarragona involving adolescents with an average age of 16.44 years. This study assessed the number of substances used (alcohol, cigarettes, and cannabis) in the past month, along with information sources related to substance use. Monitored sources (e.g., schools, parents, and mass media) and unmonitored sources (e.g., peers, siblings, internet) were distinguished. In addition, four individual and four environmental control variables were considered. Multinomial logistic regression analysis revealed that incorporating variables related to adolescents\' substance use information and its sources enhanced the explanatory model, surpassing control variables. The degree of information about substance use did not significantly explain consumption patterns, but the number of information sources, both monitored and unmonitored, did. The unmonitored sources were associated with increased polydrug use. Conversely, greater reliance on supervised sources for information was linked to reduced single-substance and polydrug use. This protective effect increased with an increase in the number of substances used. In conclusion, information obtained from monitored sources acts as a deterrent to substance consumption, consistent with findings suggesting that greater health literacy among adolescents discourages substance use. Conversely, this study suggests that information from more informal sources may encourage heavier polydrug use, aligning with reports indicating that adolescents with a more comprehensive understanding of substance use consequences tend to engage in heavier drug use.
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  • 文章类型: Journal Article
    目标:2019年冠状病毒病(COVID-19)对意外儿科中毒的影响尚不清楚。我们检查了COVID-19大流行之前和期间急诊科(ED)就诊和中毒住院的变化。我们比较了大麻与非大麻中毒事件的变化,考虑到最近2018年10月大麻合法化和2020年1月大麻食品合法化。
    方法:对安大略省0-9岁儿童的人口水平ED就诊和中毒住院的变化进行了时间序列(ITS)分析,加拿大(每年有140万儿童),在两个时间段内:大流行前(2010年1月至2020年3月)和大流行(2020年4月至2021年12月)。
    结果:总体而言,有28,292例急诊就诊和2641例意外中毒住院。大流行期间,每100,000人年的ED就诊中毒事件减少了14.6%(40.15比34.29期间),住院期间增加35.9%(3.48前与4.73during).ED访视立即下降(发病率比率[IRR],0.76;95%CI,0.70-0.82)在大流行开始时,随后逐步回归基线(季度变化,内部收益率1.04,95CI1.03-1.06),而住院率立即增加(IRR1.34;95%CI,1.08-1.66),且无逐渐变化.中毒的唯一增加是大麻,其ED就诊次数增加了10.7倍(每100,000人年0.45至4.83),住院次数增加了12.1倍(每100,000人年0.16至1.91)。不包括大麻,中毒住院治疗总体上没有增加.
    结论:COVID-19大流行与任何类型的无意儿科中毒的增加无关,除了大麻中毒。大麻中毒的增加可以解释为2020年1月加拿大非医用大麻食品合法化。
    The impact of coronavirus disease 2019 (COVID-19) on unintentional pediatric poisonings is unclear. We examined changes in emergency department (ED) visits and hospitalizations for poisonings before and during the COVID-19 pandemic. We compared changes in cannabis vs non-cannabis poisoning events given the recent legalization of cannabis in October 2018 and cannabis edibles in January 2020.
    Interrupted time-series (ITS) analyses of changes in population-level ED visits and hospitalizations for poisonings in children aged 0-9 years in Ontario, Canada (annual population of 1.4 million children), over two time periods: pre-pandemic (January 2010-March 2020) and pandemic (April 2020-December 2021).
    Overall, there were 28,292 ED visits and 2641 hospitalizations for unintentional poisonings. During the pandemic, poisonings per 100,000 person-years decreased by 14.6% for ED visits (40.15 pre- vs. 34.29 during) and increased by 35.9% for hospitalizations (3.48 pre- vs. 4.73 during). ED visits dropped immediately (Incidence Rate Ratio [IRR], 0.76; 95% CI, 0.70-0.82) at the onset of the pandemic, followed by a gradual return to baseline (quarterly change, IRR 1.04, 95%CI 1.03-1.06), while hospitalizations had an immediate increase (IRR 1.34; 95% CI, 1.08-1.66) and no gradual change. The only increase in poisonings was for cannabis which had a 10.7-fold for ED visits (0.45 to 4.83 per 100,000 person-years) and a 12.1-fold increase for hospitalizations (0.16 to 1.91 per 100,000 person-years). Excluding cannabis, there was no overall increase in poisoning hospitalizations.
    The COVID-19 pandemic was not associated with increases in any type of unintentional pediatric poisonings, with the exception of cannabis poisonings. Increased cannabis poisonings may be explained by the legalization of non-medical cannabis edibles in Canada in January 2020.
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  • 文章类型: Journal Article
    背景:先前的研究强调了大麻使用与糖尿病及其并发症之间的关联;然而,因果关系仍然模棱两可。
    方法:单变量孟德尔随机化(MR),多变量MR,调解先生,和连锁不平衡评分(LDSC)分析,以评估大麻使用与12种糖尿病表型之间的因果关系。来自全基因组关联研究的终生大麻使用(N=184,765)和大麻使用障碍(CUD)(N=374,287)的汇总统计数据。使用的主要方法是逆方差加权(IVW)。一系列的灵敏度分析确保了结果的鲁棒性。
    结果:LDSC分析显示CUD和T2DM之间存在显著的遗传相关性,以及终生使用大麻和四种糖尿病表型之间(P<0.05)。通过错误发现率(FDR)校正后,主要IVW分析表明,遗传预测的CUD与糖尿病性低血糖(OR=1.11,95%CI1.04-1.20,P=0.003,PFDR=0.04)和增生性糖尿病性视网膜病变(PDR)(OR=1.12,95%CI1.04-1.19,P=4.89×10-4,PFDR=0.01)的风险呈正相关.此外,提示证据表明CUD与糖尿病肾病的风险增加,1型糖尿病(T1DM),糖尿病视网膜病变,T1DM与糖尿病酮症酸中毒相关(P<0.05,PFDR>0.05)。终生使用大麻与糖尿病表型之间未检测到因果关系(P>0.05和PFDR>0.05)。多变量和中介MR分析显示,糖化血红蛋白A1c部分介导了CUD对PDR和糖尿病性低血糖的因果关系。
    结论:这项MR研究表明,CUD可能在几种糖尿病疾病表型中具有因果关系。
    BACKGROUND: Previous studies have highlighted the association between cannabis use and diabetes and its complications; however, the causality remains ambiguous.
    METHODS: Univariate Mendelian randomization (MR), multivariate MR, mediation MR, and linkage disequilibrium score (LDSC) analysis to assess the causal relationship between cannabis use and 12 diabetic phenotypes. Summary statistics for lifetime cannabis use (N = 184,765) and cannabis use disorder (CUD) (N = 374,287) from genome-wide association studies. The primary method used was inverse-variance-weighted (IVW). A range of sensitivity analyses ensured the robustness of the results.
    RESULTS: LDSC analysis revealed a significant genetic correlation between CUD and T2DM, as well as between lifetime cannabis use and four diabetic phenotypes (P < 0.05). After correction by false discovery rate (FDR), the primary IVW analysis indicates that the genetically predicted CUD is positively associated with the risk of diabetic hypoglycemia (OR = 1.11, 95% CI 1.04-1.20, P = 0.003, PFDR = 0.04) and proliferative diabetic retinopathy (PDR) (OR = 1.12, 95% CI 1.04-1.19, P = 4.89×10-4, PFDR =0.01). Additionally, suggestive evidence links CUD with increased risks of diabetic nephropathy, type 1 diabetes mellitus (T1DM), diabetic retinopathy, and T1DM associated with diabetic ketoacidosis (P < 0.05 & PFDR > 0.05). No causal relationship was detected between lifetime cannabis use and diabetic phenotypes (P > 0.05 & PFDR > 0.05). Multivariable and mediation MR analyses revealed that glycated hemoglobin A1c partially mediates the causal effect of CUD on PDR and diabetic hypoglycemia.
    CONCLUSIONS: This MR study suggests that CUD may have a causal role in several diabetic disease phenotypes.
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  • 文章类型: Observational Study
    背景:大麻消费与驾驶障碍和撞车风险增加有关,危害道路安全。毒理学分析在检测最近的精神活性物质消费中起着基本作用。这项研究的目的是检查受影响驾驶(DUI)罪犯的血液样本中大麻素的浓度,以调查延迟样本收集是否会影响罪犯的毒理学评估。
    方法:使用匿名的毒理学数据进行了一项观察性回顾性研究,这些数据涉及2017年1月1日至2021年12月31日在帕多瓦大学医院法律医学和毒理学系存档的涉及道路交通事故(RTA)或被警察逮捕的大麻相关DUI罪犯。意大利。
    结果:在总共318个驾驶员的样本中,143份血液样本的四氢大麻酚(THC)和代谢物11-羟基-Δ9-四氢大麻酚(11-OH-THC)和11-nor-Δ9-四氢大麻酚-9-羧酸(THC-COOH)呈阳性,173份血样THC-COOH阳性,THC阴性。在第一组中,THC和THC-COOH的平均浓度分别为4.05ng/mL和28.29ng/mL,分别。在THC阴性病例中,THC-COOH的平均浓度为7.3ng/mL.事件和样品收集之间经过的时间从15分钟到7小时不等(平均2小时29分钟)。消耗大麻素后经过的平均估计时间为3小时7分钟(模型I)和2小时36分钟(模型II)。
    结论:本研究讨论了大麻影响下驾驶员毒理学评估的主要困难。与RTA和样本收集之间的时间有关的问题,介绍了各国现行的法律和法律限制。
    BACKGROUND: Cannabis consumption is associated with driving impairment and increased crash risk, endangering road safety. Toxicological analyses play a fundamental role in detecting a recent consumption of psychoactive substances. The aim of this study was to examine the concentration of cannabinoids in blood samples of driving-under-the-influence (DUI) offenders in order to investigate whether delayed sample collection affects the toxicological assessment of the offenders.
    METHODS: An observational retrospective study was performed using anonymized toxicological data referring to cannabis-related DUI offenders involved in road traffic accidents (RTA) or apprehended by the police from 1 January 2017-31 December 2021 archived at Legal Medicine and Toxicology Department of the University Hospital of Padova, Italy.
    RESULTS: In a total sample of 318 drivers, 143 blood samples tested positive for tetrahydrocannabinol (THC) and metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), and 173 blood samples were positive for THC-COOH with THC negative. In the first group, the mean concentrations of THC and THC-COOH were 4.05 ng/mL and 28.29 ng/mL, respectively. In THC-negative cases, the mean THC-COOH concentration was 7.3 ng/mL. The time elapsed between the event and sample collection varied from 15 min to 7 h (mean 2 h 29 min). The average estimated time elapsed after consumption of cannabinoids was 3 h 7 min (Model I) and 2 h 36 min (Model II).
    CONCLUSIONS: The present research discussed the main difficulties in the toxicological evaluation of drivers under the influence of Cannabis. Issues related to the time between RTA and sample collection, the laws and legal limits in force in various Countries were presented.
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  • 文章类型: Journal Article
    据报道,医用大麻(相对于大麻衍生物)具有镇痛药,免疫调节,和抗炎特性。最近在关节炎动物模型中的研究表明,大麻素,一组由大麻产生的化合物,可能减轻关节损伤。然而,大麻副产物是否可以抑制骨关节炎(OA)相关的软骨降解以前没有报道.在这项研究中,从健康的关节软骨中分离人软骨细胞,在体外扩展,并在软骨形成培养基中进行颗粒培养以形成软骨组织。我们首先通过用合成大麻素激动剂处理软骨细胞来源的组织来检查大麻副产物对正常软骨的影响,Win-55,212-2(Win),在0.01至10µM的不同浓度下。治疗后,使用糖胺聚糖(GAG)分析和实时PCR评估组织表型.接下来,用白细胞介素-1β(IL-1β)预处理软骨组织以产生发炎的表型,然后用Win培养以评估其治疗潜力。结果表明,在浓度低于1µM时,Win治疗没有显著损害软骨细胞生长或软骨形成能力,但在高水平(>10µM),它显著抑制细胞增殖。有趣的是,在IL-1β预处理条件下,Win能够部分保留软骨基质并减少白细胞介素6的产生,尽管保护作用温和。一起来看,我们的结果表明,Win对软骨细胞的可变效应以浓度依赖性方式发生。大麻素衍生物是否可以用于治疗软骨降解或可以改变OA的其他结构变化值得进一步研究。
    Medical marijuana (versus Marijuana derivatives) has been reported to possess analgesic, immunomodulatory, and anti-inflammatory properties. Recent studies in animal models of arthritis showed that cannabinoids, a group of compounds produced from marijuana, may attenuate joint damage. However, whether marijuana byproducts can suppress osteoarthritis (OA)-associated cartilage degradation has not been previously reported. In this study, human chondrocytes were isolated from healthy articular cartilage, expanded in vitro, and subjected to pellet culture in a chondrogenic medium to form cartilage tissues. We first examined the influence of marijuana byproducts on normal cartilage by treating chondrocyte-derived tissues with a synthetic cannabinoid agonist, Win-55,212-2 (Win), at different concentrations ranging from 0.01 to 10 µM. After treatment, the tissue phenotype was assessed using glycosaminoglycan (GAG) assay and real-time PCR. Next, cartilage tissues were pre-treated with interleukin-1β (IL-1β) to generate an inflamed phenotype and then cultured with Win to assess its therapeutic potential. The results showed that at concentrations lower than 1 µM, Win treatment did not significantly impair chondrocyte growth or cartilage formation capacity, but at a high level (>10 µM), it remarkably suppressed cell proliferation. Interestingly, under the condition of IL-1β pre-treatment, Win was able to partially preserve the cartilage matrix and decrease the production of interleukin-6, although the protective effect was mild. Taken together, our results indicated that the variable effects of Win on chondrocytes occur in a concentration-dependent manner. Whether cannabinoid derivatives can be used to treat cartilage degradation or can alter other structural changes in OA deserve further investigation.
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