A substantive volume of research on autism spectrum disorder (ASD) has emerged in recent years adding to our understanding of the etiopathological process. Preclinical models in mice and rats have been highly instrumental in modeling and dissecting the contributions of a multitude of known genetic and environmental risk factors. However, the translation of preclinical data into suitable drug targets must overcome three critical hurdles: (i) ASD comprises a highly heterogeneous group of conditions that can markedly differ in terms of their clinical presentation and symptoms, (ii) the plethora of genetic and environmental risk factors suggests a complex, non-unitary, etiopathology, and (iii) the lack of consensus over the myriad of preclinical models, with respect to both construct validity and face validity. Against this backdrop, this Chapter traces how the endocannabinoid system (ECS) has emerged as a promising target for intervention with predictive validity. Recent supportive preclinical evidence is summarized, especially studies in mice demonstrating the emergence of ASD-like behaviors following diverse genetic or pharmacological manipulations targeting the ECS. The critical relevance of ECS to the complex pathogenesis of ASD is underscored by its multiple roles in modulating neuronal functions and shaping brain development. Finally, we argue that important lessons have been learned from the novel mouse models of ASD, which not only stimulate game-changing innovative treatments but also foster a consensual framework to integrate the diverse approaches applied in the search of novel treatments for ASD.

近年来，对自闭症谱系障碍（ASD）的研究已有大量研究，这加深了我们对病因病理过程的理解。小鼠和大鼠的临床前模型在建模和剖析众多已知的遗传和环境危险因素方面发挥了重要作用。然而，将临床前数据转化为合适的药物靶标必须克服三个关键的障碍：（i）ASD包括一组高度异质的疾病，其临床表现和症状可能明显不同；（ii）过多的遗传和环境因素危险因素表明其病因复杂，不统一，并且（iii）在众多临床前模型方面，就结构效度和面部效度而言缺乏共识。在这种背景下，本章追溯了内源性大麻素系统（ECS）如何成为具有预测效度的有希望的干预目标。总结了最近的支持性临床前证据，尤其是在小鼠中进行的研究，这些研究表明在针对ECS进行了多种遗传或药理操作后，出现了ASD样行为。ECS与ASD复杂发病机制的关键相关性在于其在调节神经元功能和塑造大脑发育中的多种作用。最后，我们认为，从ASD的新型小鼠模型中学到了重要的教训，这不仅刺激了改变游戏规则的创新疗法，而且还建立了一个共识框架，以整合用于寻找ASD新颖疗法的多种方法。