Jones Jermaine D, Varshneya Neil B, Hudzik Thomas J, Huhn Andrew S
Division on Substance Use Disorders, Department of Psychiatry, New York State Psychiatric Institute, and Columbia University Irving Medical Center, 1051 Riverside Drive, New York, NY 10032, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, 410 N 12th St, Richmond, VA 23298, USA.
Curr Addict Rep. 2021 Mar;8(1):109-121. doi: 10.1007/s40429-020-00353-5. Epub 2021 Jan 12.
Pharmacotherapies are the most effective means of reducing the harms associated with opioid use disorder (OUD). Translational research seeking to develop novel medications to treat OUD has been challenging due to the complex etiology of addiction. Preclinical outcome measures are often behavioral, and it is difficult, if not impossible, to fully mirror the various emotional and cognitive processes that motivate opioid use in humans. The goal of the current narrative review was to summarize the translational progression of three potential medications for OUD, which had varying levels of success.
Memantine, lorcaserin, and lofexidine all showed promise in preclinical studies; however, only lofexidine was able to consistently replicate these findings in human subjects, and receive FDA approval. It was the authors' objective to use this review to identify areas of needed improvement in translational research for OUD.
Preclinical studies vary significantly in their ability to forecast effectiveness in clinical trials. Among the various preclinical models, suppression of opioid self-administration appears to have the best predictive validity. As they model a mostly physiological phenomenon, preclinical assessments of opioid withdrawal also appear to have high predictive validity. In our review of the literature, the authors noted numerous examples of clinical trials that were underpowered, lack precision, and proper outcomes. Better-validated preclinical targets and improved design of proof-of-concept human studies should allow investigators to more efficiently develop and test medications for OUD.
药物治疗是减少与阿片类物质使用障碍（OUD）相关危害的最有效手段。由于成瘾的病因复杂，致力于开发治疗OUD新药物的转化研究一直具有挑战性。临床前的结果测量通常是行为学方面的，而且即使不是不可能，也很难完全反映驱动人类使用阿片类物质的各种情感和认知过程。本叙述性综述的目的是总结三种治疗OUD的潜在药物的转化进展情况，这三种药物取得了不同程度的成功。
美金刚、洛卡塞林和洛非西定在临床前研究中均显示出前景；然而，只有洛非西定能够在人类受试者中持续重复这些发现，并获得美国食品药品监督管理局（FDA）的批准。作者的目标是利用本综述确定OUD转化研究中需要改进的领域。
临床前研究在预测临床试验有效性方面的能力差异很大。在各种临床前模型中，抑制阿片类物质自我给药似乎具有最佳的预测效度。由于它们模拟的大多是生理现象，阿片类物质戒断的临床前评估似乎也具有较高的预测效度。在我们对文献的综述中，作者注意到许多临床试验存在样本量不足、缺乏精确性和合适结局指标的例子。经过更好验证的临床前靶点和改进的概念验证人体研究设计应能使研究人员更有效地开发和测试治疗OUD的药物。
