Center for Advanced Research and Development in Experimental Medicine (CEMEX), "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.
Department of Rheumatology and Physiotherapy, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universității Street, 700115 Iasi, Romania.
Medicina (Kaunas). 2020 Jan 9;56(1):24. doi: 10.3390/medicina56010024.
Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography-mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.
大麻自公元前 2900 年就被用于止痛。20 世纪，合成大麻素开始出现，从而为提高疗效开辟了道路。对新型合成大麻素的研究仍在继续，因此，本综述的目的是为这一有前途的药物类别提供一个全面的研究和开发工具。本文介绍了用于评估细胞毒性、致突变性或发育影响的体外方法，随后介绍了大麻研究中使用的主要体内疼痛模型以及不同给药方式（全身、鞘内和吸入）的结果。还讨论了用于评估副作用和长期使用的动物模型。在本综述的第二部分，介绍了合成大麻素生物分布的药代动力学和药效动力学研究，以及从啮齿动物到人生物体液中合成大麻素的液相色谱-质谱鉴定。最后但同样重要的是，讨论了提高合成大麻素的溶解度和物理化学稳定性的不同策略，及其对疼痛管理的潜在影响。总之，合成大麻素是疼痛医学中最有前途的药物类别之一，临床前研究应侧重于确定新的和改进的替代方案，以获得更好的临床和临床前结果。
