Opioid Regulation of Social Homeostasis: Connecting Loneliness to Addiction

Loneliness heightens the risk of substance use disorder, and a desire to escape this negative feeling motivates drug use. Opioid drugs in particular are believed to target neurobiological circuits involved in social bonding, increasing vulnerability to opioid addiction when social connectedness is lacking. In this narrative review, we consider how current understanding of μ opioid modulation of reward and threat processing across domains sheds light on the mechanisms that link loneliness and substance use. We discuss evidence for state- and context-dependent μ opioid modulation of social affect and behaviors, which appears to promote prioritization of high-value reward options also in the context of threat. Tying this literature to the model of social homeostasis, we argue for a role of μ opioids in regulating social homeostasis across species. Finally, we explore how disruption of social homeostasis in chronic opioid use contributes to continued drug use. We highlight how increasing patients' psychosocial resources and opportunities for social bonding can improve recovery from drug addiction. Throughout, we consider the translational robustness and generalizability of the nonhuman animal evidence in light of existing human research.