Cannabinoid receptor agonists

大麻素受体激动剂
  • 文章类型: Journal Article
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    背景:在过去的二十年中,由于监管变化和对该物质的潜在治疗作用的兴趣,大麻的使用有所增加,然而,该物质的许多方面及其对健康的影响仍存在争议或不清楚。
    方法:2020年11月,美国区域麻醉和疼痛医学学会责成大麻工作组制定围手术期使用大麻的指南。围手术期使用大麻和大麻素指南委员会负责使用改良的德尔菲方法起草对九个关键问题的答复,其总体目标是制作一份文件,重点是使用大麻素对手术患者进行安全管理。共识建议要求≥75%同意。
    结果:选择了9个问题,就第三轮投票达成100%共识。主题包括围手术期筛查,推迟择期手术,围手术期同时使用阿片类药物和大麻,对产妇的影响,术中调整麻醉和镇痛药,术后监测,大麻使用障碍,和术后担忧。使用大麻素的手术患者围手术期不良结局的潜在风险增加。
    结论:成功创建了大麻和大麻素的围手术期处理的具体临床建议。
    The past two decades have seen an increase in cannabis use due to both regulatory changes and an interest in potential therapeutic effects of the substance, yet many aspects of the substance and their health implications remain controversial or unclear.
    In November 2020, the American Society of Regional Anesthesia and Pain Medicine charged the Cannabis Working Group to develop guidelines for the perioperative use of cannabis. The Perioperative Use of Cannabis and Cannabinoids Guidelines Committee was charged with drafting responses to the nine key questions using a modified Delphi method with the overall goal of producing a document focused on the safe management of surgical patients using cannabinoids. A consensus recommendation required ≥75% agreement.
    Nine questions were selected, with 100% consensus achieved on third-round voting. Topics addressed included perioperative screening, postponement of elective surgery, concomitant use of opioid and cannabis perioperatively, implications for parturients, adjustment in anesthetic and analgesics intraoperatively, postoperative monitoring, cannabis use disorder, and postoperative concerns. Surgical patients using cannabinoids are at potential increased risk for negative perioperative outcomes.
    Specific clinical recommendations for perioperative management of cannabis and cannabinoids were successfully created.
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    简介-关于大麻素消费的监管框架的活力已将其对认知和精神运动技能的影响置于科学辩论的中心。考虑到对公共安全的潜在影响,特别关注的是驾驶技能的损害,开放需要专门规范大麻素作用下的驾驶。药代动力学-天然大麻素和代谢物在生物液体中的低浓度下显示出长阳性,特别是在长期消费的情况下。大麻素的定性阳性本身并不能证明存在有害影响,这需要存在的活性物质在相关浓度。驾驶技能损害-多项研究强调了基于四氢大麻酚(THC)浓度的驾驶技能改变,主要影响自动化,而接受认知控制的技能被保留到更高的剂量。与其他物质有关的证据,慢性消费和其他大麻素,另一方面,仍然承受着高度的不确定性。法规政策-在大麻素影响下的驾驶法规中可以采用不同的模型:在定性阳性的情况下可以应用制裁,大麻素浓度高于定义的阈值,或存在已证明的认知改变状态。结论-目前可以认为定量THC截止值在3.5和5ng/ml之间的“本身限制”是最平衡的选择。最后,进行的分析可以找出科学和立法领域的陷阱,以改善安全政策。
    BACKGROUND: The dynamism in the regulatory frameworks concerning the consumption of cannabinoids has placed their effects on cognitive and psychomotor skills at the center of the scientific debate. In consideration of the potential repercussions on public safety, particular attention has been focused on the impairment of driving skills, opening up the need to specifically regulate driving under the effects of cannabinoids.
    RESULTS: Both native cannabinoids and metabolites show a long positivity at low concentrations in the biological fluids, especially in the case of chronic consumption. Qualitative positivity to cannabinoids does not itself prove the presence of detrimental effects, which require the presence of active substances at relevant concentrations. Driving Skill Impairment: Multiple studies highlight a tetrahydrocannabinol (THC) concentration- based alteration of driving skills mainly affecting automatisms, whereas skills subjected to cognitive control are preserved up to higher dosages. The evidence relating to associations with other substances, chronic consumption and other cannabinoids, on the other hand, is still burdened by a high degree of uncertainty. Regulation Policies: Different models can be adopted in the regulation of driving under the effects of cannabinoids: sanctions can be applied in case of qualitative positivity, cannabinoids concentration above a defined threshold, or in presence of a demonstrated state of cognitive alteration.
    CONCLUSIONS: \"Per se limit\" with a quantitative THC cut-off between 3.5 and 5 ng/ml can currently be considered the most balanced choice. Finally, the analysis carried out allowed to identify pitfalls in both scientific and legislative fields for the improvement of safety policies.
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    视觉模拟量表广泛用于测量主观反应。Norris\'16视觉模拟量表(N_VAS)测量警觉性和情绪的主观感觉。到目前为止,不同的科学家将N_VAS的项目聚集成不同的方式,而Bond和Lader的方式是临床研究中最常用的方式。然而,人们担心这种聚类在不同受试者样本和不同药物类别上的稳定性。这项研究的目的是测试Bond和Lader的聚类在受试者样本和药物作用方面是否稳定。测试了N_VAS的替代聚类。来自3种药物的研究数据:大麻素受体激动剂(δ-9-四氢大麻酚[THC]),毒蕈碱拮抗剂(东pol碱),和苯二氮卓类药物(咪达唑仑和劳拉西泮),2005年至2012年收集的数据用于本分析。采用探索性因子分析(EFA)对Bond和Lader的聚类算法进行检验。进行一致性聚类以测试样本和不同药物类型的聚类结果的稳定性。使用三簇假设进行稳定性分析,然后是其他替代假设。共识矩阵(CM)的热图和密度图显示了三簇假设的不稳定性,并暗示了3种药物类别的不稳定性。还测试了二簇和四簇假设。CM和密度图的热图表明,两个集群的假设是更好的。总之,根据所使用的数据,二组假设可证明样本和3种药物类型的结果稳定.
    UNASSIGNED: Visual analogue scales are widely used to measure subjective responses. Norris\' 16 visual analogue scales (N_VAS) measure subjective feelings of alertness and mood. Up to now, different scientists have clustered items of N_VAS into different ways and Bond and Lader\'s way has been the most frequently used in clinical research. However, there are concerns about the stability of this clustering over different subject samples and different drug classes. The aim of this study was to test whether Bond and Lader\'s clustering was stable in terms of subject samples and drug effects. Alternative clustering of N_VAS was tested.Data from studies with 3 types of drugs: cannabinoid receptor agonist (delta-9-tetrahydrocannabinol [THC]), muscarinic antagonist (scopolamine), and benzodiazepines (midazolam and lorazepam), collected between 2005 and 2012, were used for this analysis. Exploratory factor analysis (EFA) was used to test the clustering algorithm of Bond and Lader. Consensus clustering was performed to test the stability of clustering results over samples and over different drug types. Stability analysis was performed using a three-cluster assumption, and then on other alternative assumptions.Heat maps of the consensus matrix (CM) and density plots showed instability of the three-cluster hypothesis and suggested instability over the 3 drug classes. Two- and four-cluster hypothesis were also tested. Heat maps of the CM and density plots suggested that the two-cluster assumption was superior.In summary, the two-cluster assumption leads to a provably stable outcome over samples and the 3 drug types based on the data used.
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