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Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB 1 receptor (CB 1 R) distal C-terminal-associated protein that alters CB 1 R interactions with G-proteins. We tested the hypothesis that CRIP1a is capable of also altering CB 1 R interactions with β-arrestin proteins that interact with the CB 1 R at the C-terminus. Coimmunoprecipitation studies indicated that CB 1 R associates in complexes with either CRIP1a or β-arrestin, but CRIP1a and β-arrestin fail to coimmunoprecipitate with each other. This suggests a competition for CRIP1a and β-arrestin binding to the CB 1 R, which we hypothesized could attenuate the action of β-arrestin to mediate CB 1 R internalization. We determined that agonist-mediated reduction of the density of cell surface endogenously expressed CB 1 Rs was clathrin and dynamin dependent and could be modeled as agonist-induced aggregation of transiently expressed GFP-CB 1 R. CRIP1a overexpression attenuated CP55940-mediated GFP-CB 1 R as well as endogenous β-arrestin redistribution to punctae, and conversely, CRIP1a knockdown augmented β-arrestin redistribution to punctae. Peptides mimicking the CB 1 R C-terminus could bind to both CRIP1a in cell extracts as well as purified recombinant CRIP1a. Affinity pull-down studies revealed that phosphorylation at threonine-468 of a CB 1 R distal C-terminus 14-mer peptide reduced CB 1 R-CRIP1a association. Coimmunoprecipitation of CB 1 R protein complexes demonstrated that central or distal C-terminal peptides competed for the CB 1 R association with CRIP1a, but that a phosphorylated central C-terminal peptide competed for association with β-arrestin 1, and phosphorylated central or distal C-terminal peptides competed for association with β-arrestin 2. Thus, CRIP1a can compete with β-arrestins for interaction with C-terminal CB 1 R domains that could affect agonist-driven, β-arrestin-mediated internalization of the CB 1 R., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)