Core Viewpoint - The research published in Nature reveals the crystal structures of human cannabinoid receptor CB 1 bound to two agonists, providing insights into the activation mechanism of the receptor and its implications for drug design [3][9]. Group 1: Research Findings - The study identifies two agonists, Δ9-tetrahydrocannabinol (AM11542) and hexahydrocannabinol (AM841), that bind to the human cannabinoid receptor CB 1 [9]. - Significant conformational changes were observed in the CB 1 receptor when bound to these agonists, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G protein-binding region [10]. - The research highlights the importance of specific residues, Phe200 and Trp356, in the receptor activation process, suggesting they act as critical switches [10]. Group 2: Context and Background - CB 1 is the most abundantly expressed GPCR in the central nervous system, playing a role in regulating various physiological processes such as mood, appetite, and pain perception [3]. - The study builds on previous work that faced data integrity issues, leading to a retraction and subsequent re-publication after independent verification of the main conclusions [6].