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

SCRA是一组变化迅速的化合物，具有广泛的药理作用。目前正在监测190种不同的SCRA，它们现在是欧盟预警系统监测的最大一组物质(EMCDDA，2019年)。由于其与CB1受体的高度结合，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、死亡)健康后果。2018年，英国公共卫生组织报告说，SCRA是最普遍的新型精神活性物质，需要在安全的环境中进行专门的成瘾治疗，在过去两年中增加了35%(英国公共卫生组织，2018年)。然而，SCRA疾病的临床表现目前还不是很清楚，也没有循证的临床治疗指南。此外，不同SCRA化合物的快速演变性质使法医和临床所需的查获和生物材料中这些物质的筛选和检测变得模糊。因此，在一系列跨学科研究中，本博士将寻求解决SCRA临床管理和实验室检测方面的这些挑战。在第一项研究中，我的目标是利用从布里斯托尔药物项目的“香料诊所”展示的客户收集的数据来描述SCRA停药的特征。然后，结合之前收集的临床试验数据(从弗里曼博士那里获得)，我还将通过将症状学与自然大麻戒断进行比较来测试症状特异性。在下一项研究中，我将评估一种新的药物戒毒方法--使用苯二氮卓类药物(Librium)和止吐药物(Cyclzine)--改善SCRA临床治疗的可能性。使用从布里斯托尔药物项目收集的试点数据，我将在4周后评估其可接受性和可行性，并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进从生物和街道材料中检测SCRA。在接受了定量核磁共振(Q-核磁共振)波谱和一种新的尖端荧光光谱指纹(FSFs)方法的培训后，我将应用这些方法分析研究1和研究2中从客户那里收集的SCRA和唾液样本。最后，结合研究1-3的数据，我将检查a)唾液中SCRA含量的变化是否可以作为戒断的标志，以及b)在药物和唾液样本中检测到的SCRA化合物的特征可以预测戒断和依赖的临床特征。

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.