Comprehensive Drug Surveillance by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry: Insights into Medicinal Cannabis Metabolism..

药用大麻对加拿大人来说具有重大的科学和公共利益，有望带来重大的社会经济效益。然而，仍然缺乏科学研究来指导循证大麻疗法的发展，以治疗慢性疼痛等使人衰弱的健康状况。大麻植物是一种多药物质，含有500多种化学成分，包括100种不同的大麻素，其协同生物活性仍然知之甚少。到目前为止，加拿大卫生部的指导方针侧重于对两种大麻素（THC，CDB）的效力进行分析测试，这并没有从根本上解决患者如何代谢大麻素的问题。事实上，剂量方案和治疗反应在患者之间变化很大，导致次优反应，具有来自生活方式的潜在不良影响（例如，烟草）和合并用药（例如，阿片类药物）。我们的提案旨在解决这一重大的知识差距，该项目是基于麦克马斯特大学和PureSinse研究人员之间的合作研究项目，PureSinse是一家持牌生产商，致力于开发针对个体患者的创新药用大麻产品。我们的研究将招募正在接受慢性疼痛，焦虑和/或失眠治疗的首次和返回患者。我们的提案将对在临床访视期间从患者收集的三周内的配对尿液样本进行全面的药物监测，这些患者已被处方干燥植物（烟熏/雾化）或油提取物（摄入）。重要的是，我们的数据工作流程将包括尿液中的非靶向代谢物分析，以发现新型大麻素代谢物和其他未通过常规测试筛选的相关药物暴露。这种方法不仅可以确认患者的依从性，还可以揭示吸入或摄入大麻产品的患者之间的大麻素代谢差异，包括其他处方药物的潜在不良反应。我们令人兴奋的试点研究将为医疗保健提供者提供客观而准确的筛选工具，指导最佳药用大麻处方，以改善患者的治疗效果。

Medicinal cannabis is of great scientific and public interest to Canadians that promises major socioeconomic benefits. However, there remains a lack of scientific studies that can guide the development of evidence-based cannabis therapeutics for treatment of debilitating health conditions, such as chronic pain. The cannabis plant is a polypharmaceutical substance containing more than 500 chemical constituents, including 100 different cannabinoids whose synergistic biological activities remain poorly understood. To date, guidelines from Health Canada focus on analytical testing for potency of only two cannabinoids (THC, CDB) that do not fundamentally address how patients metabolize cannabinoids. Indeed, dosage regimes and treatment responses vary widely between patients resulting in sub-optimal responses with potential adverse effects from lifestyle (e.g., tobacco) and concurrent medications (e.g., opioids). Our proposal aims to address this major knowledge gap based on a collaborative research project between researchers at McMaster University and PureSinse, a licensed producer with interests in developing innovative medicinal cannabis products tailored to individual patients. Our study will recruit both first-time and returning patients who are being treated for chronic pain, anxiety and/or insomnia. Our proposal will perform comprehensive drug surveillance on paired urine samples collected from patients over a three week period during clinical visits who have been prescribed either dried plants (smoked/vaped) or oil extracts (ingested). Importantly, our data workflow will include non-targeted metabolite profiling in urine for the discovery of novel cannabinoid metabolites and other relevant drug exposures not screened by conventional tests. This approach will not only confirm patient adherence but also reveal differential cannabinoid metabolism between patients from inhaled or ingested cannabis products, including potential adverse effects with other prescribed drugs. Our exciting pilot study will provide healthcare providers an objective yet accurate screening tool that guides optimal medicinal cannabis prescriptions for improved treatment outcomes in patients.