Key pharmacophoric elements for the (aminoalkyl)indole (AAI) CB1 cannabinoid receptor agonists are the aminoalkyl moiety, the lipophilic aroyl group, and the heterocyclic indole ring. In the present study, the docking space allowed for (R)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)methanone (WIN55212-2; 1) within the CB1 receptor was extensively explored by a docking approach that combines Monte Carlo (MC) and molecular dynamics (MD) simulations. The goals were to understand the key binding interactions of AAIs within the CB1 receptor and to examine the role of the ligand in inducing a receptor conformational change. From the findings of extensive SAR studies on the cannabinoid compounds and correlation between AAI binding affinity data and calculated binding energies, we proposed two alternative binding conformations, aroyl-up1 and aroyl-up2. These denote the directionality of the ligand naphthyl ring within the receptor upward with respect to the extracellular side. A comprehensive structural analysis of 1 demonstrated that the aroyl ring moiety could be important as the steric trigger for inducing CB1 receptor conformational change. Thus, it appears that aromatic-aromatic interactions are important not only for the binding of 1 but also for inducing receptor conformational change. It is possible that differences in the nature of the ligand binding could contribute to ligand-specific conformational changes in the receptor.