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

SCRA是一组具有广泛药理学的多样化且快速变化的化合物。目前正在监测190种不同的SCRA，它们现在是欧盟早期预警系统（EMCDDA，2019）监测的最大物质组。由于它们对CB1受体的高结合亲和力，SCRA具有很大的不良反应风险，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）。然而，SCRA疾病的临床表现目前还没有得到很好的理解，也没有基于证据的临床管理指南。此外，不同的SCRA化合物的性质迅速变化，使法医和临床所需的缉获材料和生物材料中这些物质的筛选和检测变得模糊不清。因此，在一系列跨学科研究中，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，我将使用从布里斯托药物项目的"香料诊所"中收集的数据来描述SCRA戒断的概况。然后，结合以前收集的临床试验数据（从Freeman博士那里获得），我还将通过比较生理学与天然大麻戒断来测试症状特异性。在下一项研究中，我将评估一种新的药理学解毒程序的潜力-使用苯二氮卓类药物（利多卡因）和止吐药（环丙嗪）-以改善SCRA的临床管理。使用从布里斯托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周后将物质使用结果与对照组进行比较。在第三项研究中，我将探索新型分析技术如何改善生物和街道材料中SCRA的检测。在接受定量核磁共振（q-NMR）光谱学和荧光光谱指纹（FSF）的新的尖端方法的培训后，我将应用这些方法分析研究1和2中从客户收集的SCRA和唾液样本。最后，结合研究1 - 3的数据，我将研究a）SCRA唾液测量的变化是否可以用作戒毒期间戒断的标志物，以及B）药物和唾液样本中检测到的SCRA化合物的特征是否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.