The CB1 allosteric modulator, ORG27569 (ORG), is an inverse agonist of the G-protein signaling pathway and agonist of the beta-arrestin-1 pathway (Ahn et.al JBC 2013). The intracellular conformational change associated with arrestin-biased signaling is outward movement of the intracellular TMH7/HX8 elbow region away from TMH2 (Rahmeh et.al PNAS 2012). We report here a 1.4μs molecular dynamics study of ORG interacting with CB1R via the lipid bilayer that revealed productive binding: ORG entered CB1 via the TMH6/7 interface, interacting with Y6.57 and F7.35. Subsequently, direct interactions between EC3 loop and ORG induced an outward movement of the TMH7/HX8 elbow region creating an opening between TMH2/7 that permitted docking beta-arrestin-1 with CB1. The active human beta-arrestin-1 structure used for docking was derived from the phosphorylated V2R C-terminal peptide activated rat beta-arrestin-1 crystal structure (Shukla et.al. Nature 2013) via peptide removal and mutation to the human sequence. CB1 residues, T460/S462/S464/T465/T467/S468, in the distal C-terminus, important for beta-arrestin association (Daigle et.al. J Neurochem 2008), were phosphorylated and placed to interact with beta-arrestin-1 N-domain positively charged residues, including critical lysines K10/K11 (Ostermaier et.al. PNAS 2014). The arrestin finger loop residues 66-70(EDLDV) were modelled as helical, based on photoactivated rhodopsin and visual-arrestin peptide NMR studies (Feuerstein et.al. Biochemistry 2009). Two orientations of beta-arrestin-1 relative to CB1 were modelled to have the N-domain underneath the TMH7/HX8 region based on a recent visual-arrestin-1 fingerloop crystallized in Opsin (Szczepek et.al. Nature Comm 2014), or underneath the TMH5/6 IC3 loop based on a beta-arrestin-1 K77C/beta-2 adrenergic receptor TMH5 K5.78C crosslinking study (Shukla et.al. Nature 2014). MD simulations, in AMBER14 with the CHARMM36 forcefield, addressing stability of the two CB1/beta-arrestin-1 complexes in fully hydrated POPC bilayers will be presented. [Support: RO1 DA003934, KO5 DA021358 (PHR)]