Options to reduce cocaine addiction could be the use of brain-penetrant-interfering peptides that disrupt the A2AR-D2R-Sigma1R complex or brain-penetrant heterobivalent drugs with D2R agonist and A2AR antagonist pharmacophores to reduce the D2R brake in the A2AR-D2R-Sigma1R complexes (Borroto-Escuela et al. 2018b). This evidence concerns the gene SIGMAR1 and cocaine dependence.