Opioids and social bonding: Effect of naltrexone on feelings of social connection and ventral striatum activity to close others.

Abstract

Close social bonds are critical to immediate and long-term well-being. However, the neurochemical mechanisms by which we remain connected to our closest loved ones are not well understood. Opioids have long been theorized to contribute to social bonding via their actions on the brain. But feelings of social connection toward one’s own close others and direct comparisons of ventral striatum (VS) activity in response to close others and strangers, a neural correlate of social bonding, have not been explored. Therefore, the current clinical trial examined whether opioids causally affect neural and experiential signatures of social bonding. Eighty participants were administered naltrexone (n = 40), an opioid antagonist that blocks natural opioid processing, or placebo (n = 40) before completing a functional MRI scan where they viewed images of their close others and individuals they had not seen before (i.e., strangers). Feelings of social connection to the close others and physical symptoms commonly experienced when taking naltrexone were also collected. In support of hypotheses, naltrexone (vs. placebo) reduced feelings of social connection toward the close others (e.g., family, friends, romantic partners). Furthermore, naltrexone (vs. placebo) reduced left VS activity in response to images of the same close others, but did not alter left VS activity to strangers. Finally, the positive correlation between feelings of connection and VS activity to close others present in the placebo condition was erased by naltrexone. Effects remained after adjusting for physical symptoms. Together, results lend support to theories suggesting that opioids contribute to social bonding, especially with our closest loved ones.

The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies

“…Increased negative facial reactions after opioid blockade were also reported during viewing of smiling faces [84], consistent with a role for MOR signalling in automatic behavioural responses (mimicry) that support social bonding [66]. Moreover, opioid antagonism has been reported to reduce ratings of the feeling of being connected to other people [56,57]. The magnitude of the shift in feelings of connectedness is modest, comparable to effect sizes of acute opioid drug effects on other high-value rewards.…”

The role of mu-opioids for reward and threat processing in humans: Bridging the gap from preclinical to clinical opioid drug studies

“…Increased negative facial reactions after opioid blockade were also reported during viewing of smiling faces (Meier et al, 2016), consistent with a role for MOR signalling in automatic behavioural responses (mimicry) that support social bonding (Lakin et al, 2003). Moreover, opioid antagonism has been reported to reduce ratings of the feeling of being connected to other people (Inagaki et al, 2016;Inagaki et al, 2020). The magnitude of the shift in feelings of connectedness is modest, comparable to effect sizes of acute opioid drug effects on other high-value rewards.…”

Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial

“…First, assuming that having and maintaining social connections is vital to human functioning, the opioid theory of social attachment suggests that endogenous opioids are released during these experiences of social bonding, which then underlie the pleasant feelings of social bonding to positively reinforce the formation of such bonds. Based on this theory, studies have shown that naltrexone reduces feelings of social connection, especially to one’s closest others [ 21 , 22 ]. Reduced positive associations with significant others, especially the deceased, may make bereavement feel less lonely and isolated while diminishing the reward derived from reminiscing about the deceased.…”