Advances in the clinical management and laboratory detection of synthetic cannabinoid receptor agonists (SCRAs).

合成大麻素受体激动剂（SCRA）的临床管理和实验室检测进展。

• 批准号: 2444683
• 金额: --
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2444683
• 关键词: Advances; clinical; management; laboratory; detection

SCRAs are a diverse and rapidly changing group of compounds with a broad pharmacology. With 190 different SCRAs currently being monitored, they now represent the largest group of substances monitored by the EU Early Warning System (EMCDDA, 2019). Due to their high binding affinity at CB1 receptors, SCRAs carry a substantial risk of adverse effects including mental (psychotic symptoms, anxiety) and physical (seizures, death) health outcomes. In 2018, Public Health England reported that SCRAs were the most prevalent novel psychoactive substance requiring specialist addiction treatment in secure settings, increasing by 35% in the past two years (Public Health England, 2018). However, the clinical presentation of SCRA disorders are not currently well understood and there are no evidence-based guidelines for their clinical management. Additionally, the rapidly evolving nature of different SCRA compounds is obfuscating the screening and detection of these substances in seized and biological materials required for forensic and clinical purposes. Therefore, in a series of interdisciplinary studies, this PhD will seek to address these challenges in the clinical management and laboratory detection of SCRAs. In the first study, I will aim to characterise the profile of SCRA withdrawal using data collected from clients presenting at the 'Spice Clinic' at the Bristol Drugs Project. Then, combing previously collected clinical trial data (obtained from Dr. Freeman), I will also test for symptom specificity by comparing symptomology with natural cannabis withdrawal. In the next study, I will evaluate the potential of a novel pharmacological detoxification procedure - which uses benzodiazepines (Librium) and antiemetics (Cyclizine) - to improve SCRA clinical management. Using pilot data collected from the Bristol Drugs Project, I will evaluate its acceptability and feasibility and compare substance use outcomes with a control group after 4 weeks. In the third study, I will explore how novel analytical techniques may improve the detection of SCRAs from biological and street material. After receiving training in quantitative Nuclear Magnetic Resonance (q-NMR) spectroscopy and a novel, cutting-edge method of Fluorescence Spectral Fingerprints (FSFs), I will apply these methods to analyse samples of SCRAs and saliva collectedfrom clients in studies 1 and 2. Finally, combining data from studies 1-3, I will examine whether a) changes in salivary measures of SCRAs can be used as a marker of abstinence during detoxification and b) the profile of SCRA compounds detected in drug and saliva samples predict the clinical profile of withdrawal and dependence.

scas是一种多样且变化迅速的化合物，具有广泛的药理作用。目前有190种不同的scra受到监测，它们现在是欧盟预警系统（EMCDDA, 2019）监测的最大物质组。由于它们与CB1受体的高结合亲和力，scra具有很大的不良影响风险，包括精神（精神病症状、焦虑）和身体（癫痫发作、死亡）健康结果。2018年，英国公共卫生部报告称，scra是最普遍的新型精神活性物质，需要在安全环境中进行专业成瘾治疗，在过去两年中增加了35%（英国公共卫生部，2018年）。然而，SCRA疾病的临床表现目前尚不清楚，也没有基于证据的临床管理指南。此外，不同SCRA化合物的快速演变性质使法医和临床所需的缉获物和生物材料中这些物质的筛选和检测变得模糊。因此，在一系列跨学科的研究中，该博士将寻求解决scra临床管理和实验室检测中的这些挑战。在第一项研究中，我将利用从布里斯托尔药物项目“香料诊所”的客户那里收集的数据来描述SCRA戒断的特征。然后，结合之前收集的临床试验数据（来自Dr. Freeman），我还将通过比较症状与天然大麻戒断来测试症状特异性。在下一项研究中，我将评估一种新型药物解毒程序的潜力，该程序使用苯二氮卓类药物（利布宁）和止吐剂（环clizine）来改善SCRA的临床管理。使用从布里斯托尔药物项目收集的试点数据，我将评估其可接受性和可行性，并在4周后将药物使用结果与对照组进行比较。在第三项研究中，我将探索新的分析技术如何改善从生物和街道材料中检测scra。在接受定量核磁共振（q-NMR）波谱学和荧光光谱指纹（fsf）的新颖前沿方法的培训后，我将应用这些方法分析研究1和2中从客户收集的scas和唾液样本。最后，结合研究1-3的数据，我将检验a)唾液中SCRA含量的变化是否可以作为戒毒期间戒断的标志，b)在药物和唾液样本中检测到的SCRA化合物的特征能否预测戒断和依赖的临床特征。