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

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 collected
from 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.