The cannabinoid type-1 (CB1) receptor, a G-protein-coupled receptor, is an attractive target for drug discovery due to its involvement in many physiological processes. Historically, drug discovery efforts targeting the CB1 receptor have focused on the development of orthosteric ligands that interact with the active site to which endogenous cannabinoids bind. Research performed over the last several decades has revealed substantial difficulties in translating CB1 orthosteric ligands into druggable candidates. The difficulty is mainly due to the adverse effects associated with orthosteric CB1 ligands. Recent discoveries of allosteric CB1 modulators provide tremendous opportunities to develop CB1 ligands with novel mechanisms of action; these ligands may potentially improve the pharmacological effects and enhance drug safety in treating the disorders by regulating the functions of the CB1 receptor. In this paper, we review and summarize the complex pharmacological profiles of each class of CB1 allosteric modulators, the development of new classes of CB1 allosteric modulators and the results from in vivo assessments of their therapeutic value.

中文翻译：

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靶向大麻素 CB1 受体的变构调节剂的转化潜力。

大麻素 1 型 (CB1) 受体是一种 G 蛋白偶联受体，由于其参与许多生理过程，因此是药物发现的一个有吸引力的目标。从历史上看，针对 CB1 受体的药物发现工作集中在开发与内源性大麻素结合的活性位点相互作用的正构配体。过去几十年进行的研究揭示了将 CB1 正构配体转化为可药用候选物的巨大困难。困难主要是由于与正构CB1配体相关的不利影响。变构 CB1 调节剂的最新发现为开发具有新作用机制的 CB1 配体提供了巨大的机会；这些配体可能通过调节 CB1 受体的功能来改善治疗疾病的药理作用并提高药物安全性。在本文中，我们回顾和总结了每类 CB1 别构调节剂的复杂药理学特征、新类别 CB1 别构调节剂的开发及其治疗价值的体内评估结果。