Methodology for controlled administration of smoked synthetic cannabinoids JWH-018 and JWH-073.
Methodology for controlled administration of smoked synthetic cannabinoids JWH-018 and JWH-073.
复制标题
熏制合成大麻素 JWH-018 和 JWH-073 的控制给药方法。
DOI：
10.1016/j.neuropharm.2017.11.020
复制
发表时间：
2018
影响因子：
4.7
通讯作者：
Liu,Fei
中科院分区：
文献类型：
--
作者：
Cooper,ZivaD;Poklis,JustinL;Liu,Fei
合成大麻素（SC）是一个重大的公共卫生问题，因为它们的广泛使用和严重影响与中毒。然而，有一个控制的人类研究调查这些化合物的行为和生理作用和药代动力学的不足。设计一种可靠的方法来管理一致的，浓度依赖性的合成大麻素是这些化合物的对照研究的一个组成部分。此外，为了能够在给药后建立其药代动力学，优化方法以评估血浆中的母体化合物和代谢物至关重要。为了开发一种可靠的方法来施用可抽吸的浓度依赖性SC，用掺入SC产品JWH-018和JWH-073中发现的浓度增加的第一代大麻素的植物物质制备香烟。在制备后1-6个月，使用超高效液相色谱-串联质谱法（UPLC-MS/MS）评估香烟，以确定化合物随时间的稳定性和整个香烟的浓度一致性。还确定了检测人血浆中代谢物的最佳条件，作为储存温度（−4 °C至−80 °C）和时间（24 h - 1个月）的函数。分析证实，用于开发SC香烟的方法在预期浓度的25%范围内产生一致的浓度依赖性产品。加标血浆中的JWH-018、JWH-073和代谢产物在时间和温度条件下稳定;浓度在目标值的±20%范围内。这些研究提供了技术和方法来进行第一代SC的剂量依赖性效应的控制调查，以开始了解与使用相关的风险。本文是题为“设计师药物和法律的高”的特刊的一部分。
Synthetic cannabinoids (SCs) are a significant public health concern given their widespread use and severe effects associated with intoxication. However, there is a paucity of controlled human studies investigating the behavioral and physiological effects and pharmacokinetics of these compounds. Designing a reliable method to administer consistent, concentration-dependent synthetic cannabinoids is an integral component of controlled study of these compounds. Further, optimizing methods to assess the parent compounds and metabolites in plasma is critical in order to be able to establish their pharmacokinetics after administration. To develop a reliable method to administer smokable, concentration-dependent SCs, cigarettes were prepared with plant matter adulterated with increasing concentrations of the first generation cannabinoids found in SC products, JWH-018 and JWH-073. Cigarettes were assessed 1–6 months after preparation using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine compound stability over time and concentration consistency throughout the cigarettes. Optimal conditions to detect metabolites in human plasma as a function of storage temperature (−4 °C to −80 °C) and time (24 h - 1 month) were also determined. Analyses verified that the method utilized to develop SC cigarettes yielded consistent, concentration-dependent products within 25% of the expected concentrations. JWH-018, JWH-073 and metabolites in spiked plasma were stable under the time and temperature conditions; concentrations were within ±20% of target values. These studies provide techniques and methods to conduct controlled investigations of the dose-dependent effects of first generation SCs to begin understanding risks associated with use.This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’