Allosteric protein modulation gains an increasing attention in drug design. Its application as a mechanism of action could bring forth safer and more effective medicines. Targeting opioid receptors with allosteric modulators can result in better treatment of pain, depression, respiratory and immune disorders. In this work we use recent reports on negative modulators of μ opioid receptor as a starting point for identification of allosteric sites and mechanisms of opioid receptor modulation using homology modeling, docking and molecular dynamics studies. Allosteric binding site description is presented. Results suggest a shared binding region for lipophilic allosteric ligands, reveal possible differences in modulation mechanism between cannabinoids and salvinorin A and show ambiguous properties of the latter. Also, they emphasize the importance of native-like environment in molecular dynamics simulations, and uncover relationships between modulator and orthosteric ligand binding and receptor behavior. Relationships between ligands, transmission switch and hydrophobic lock are analyzed.