There has been an expanding public interest towards the notion that modulation of the sophisticated endocannabinoid system can lead to various therapeutic benefits that are yet to be fully explored. In recent years, the drug discovery paradigm in this field has been largely based on the development of selective CB₂ receptor agonists, avoiding the unwanted CB₁ receptor-mediated psychoactive side effects. Mechanistically, target engagement studies are crucial for confirming the ligand–receptor interaction and the subsequent biological cascades that lead to the observed therapeutic effects. Concurrently, imaging techniques for visualisation of cannabinoid receptors are increasingly reported in the literature. Small molecule imaging tools ranging from phytocannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) to the endocannabinoids as well as the purely synthetic cannabimimetics, have been explored to date with varying degrees of success. This Review will cover currently known photoactivatable, electrophilic, and fluorescent ligands for both the CB₁ and CB₂ receptors. Structural insights from techniques such as ligand-assisted protein structure (LAPS) and the discovery of novel allosteric modulators are significant additions for better understanding of the endocannabinoid system. There has also been a plethora of fluorescent conjugates that have been assessed for their binding to cannabinoid receptors as well as their potential for cellular imaging. More recently, bifunctional probes containing either fluorophores or electrophilic tags are becoming more prevalent in the literature. Collectively, these molecular tools are invaluable in demonstrating target engagement within the human endocannabinoid system.

对复杂的内源性大麻素系统的调节可以导致尚未充分探索的各种治疗益处的观点越来越受到公众的关注。近年来，该领域的药物发现范式主要基于选择性 CB ₂受体激动剂的开发，避免了不需要的 CB ₁受体介导的精神活性副作用。从机制上讲，靶标参与研究对于确认配体-受体相互作用以及导致观察到的治疗效果的后续生物级联反应至关重要。同时，越来越多的文献报道了大麻素受体可视化的成像技术。迄今为止，已经探索了从植物大麻素（如四氢大麻酚（THC）和大麻二酚（CBD））到内源性大麻素以及纯合成大麻素的小分子成像工具，并取得了不同程度的成功。本综述将涵盖目前已知的 CB ₁和 CB _{2 的可}光活化、亲电子和荧光配体受体。来自配体辅助蛋白质结构 (LAPS) 等技术的结构洞察和新型变构调节剂的发现是更好地了解内源性大麻素系统的重要补充。还有大量的荧光偶联物已被评估为它们与大麻素受体的结合以及它们的细胞成像潜力。最近，包含荧光团或亲电子标签的双功能探针在文献中变得越来越普遍。总的来说，这些分子工具在证明人类内源性大麻素系统中的目标参与方面非常宝贵。