Gipson Cassandra D, Fallin-Bennett Amanda, Khokhar Jibran Y, Knackstedt Lori, Stoops William W, Vickers-Smith Rachel, Cottler Linda
Department of Pharmacology and Nutritional Sciences, College of Medicine.
College of Nursing, University of Kentucky, Lexington, Kentucky.
Curr Opin Psychiatry. 2025 Jul 1;38(4):282-286. doi: 10.1097/YCO.0000000000001010. Epub 2025 Apr 23.
Preclinical (nonhuman) research on neurobehavioral underpinnings of addiction often focuses on one addictive drug studied in isolation, however, this does not reflect real-world substance use patterns of polysubstance use (PSU). Here we make a case against purity, incorporating patterns of clinically relevant PSU into preclinical models. We argue that the meaningful inclusion of people with living experience as integral collaborators in translational addiction models is critical to advance the identification of novel efficacious therapeutics to reduce the harms associated with PSU.
Substance use disorders are complex as clinically defined and diagnosed. Further, PSU is highly prevalent and individuals may use multiple substances within the illicit drug supply which continually evolves and is tracked via surveillance efforts (e.g., the National Drug Early Warning System). Preclinical models often model monosubstance use patterns which do not reflect real world drug use and omits expertise from people who use drugs in driving preclinical addiction science.
Here, we argue a case against purity in the development, design, and implementation of preclinical translational studies of addictive drugs, a need for inclusion of individuals with living experience, and highlight the need for additional research on PSU across the translational spectrum.
成瘾神经行为基础的临床前(非人类)研究通常聚焦于单独研究一种成瘾药物,然而,这并不能反映多物质使用(PSU)的现实世界物质使用模式。在此,我们提出反对纯粹性的观点,将临床相关的PSU模式纳入临床前模型。我们认为,让有实际生活经验的人作为不可或缺的合作者切实参与到转化成瘾模型中,对于推进新型有效疗法的识别以减少与PSU相关的危害至关重要。
物质使用障碍在临床定义和诊断上很复杂。此外,PSU非常普遍,个体可能在不断演变且通过监测工作(如国家毒品早期预警系统)追踪的非法毒品供应范围内使用多种物质。临床前模型通常模拟单物质使用模式,这无法反映现实世界的药物使用情况,并且在推动临床前成瘾科学发展方面遗漏了吸毒者的专业知识。
在此,我们对成瘾药物临床前转化研究的开发、设计和实施中存在的纯粹性提出反对意见,强调需要纳入有实际生活经验的个体,并突出在整个转化领域对PSU进行更多研究的必要性。