Understanding how opioids affect the experiential and neural signatures of feelings of social connection with close others

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Project Summary The proposed project is a new submission by a New and Early Stage Investigator for an R01 (PAR-19-384). Social connection with close others is a fundamental human need. Feeling connected to others reliably and robustly predicts health and wellbeing whereas feeling disconnected or isolated from others negatively impacts health. Less well understood, however, are the processes by which subjective feelings of social connection are maintained over time. Consistent with long-standing animal models dating back to the 1970’s, recent experimental work in humans has shown that opioids contribute to social connection with close friends, romantic partners, and family. Specifically, naltrexone, a common medication prescribed to assist in the recovery from addiction that blocks the action of naturally occurring opioids, unfortunately leads to a reduction in feelings of social connection toward close others in an otherwise healthy sample. These findings raise the possibility that the medication used to treat addiction may introduce an unintended barrier to one of the most effective contributors to long-term maintenance: close social relationships. Indeed, close social relationships and the feelings of ‘social connection’ within such relationships are major contributors to relapse prevention and one of the most valued tools for enhancing the effectiveness of medication-assisted treatment. Based on these findings, there has been a growing interest in whether opioid pathways contribute to feelings of social connection with close others in a causal manner and how these effects might occur. However, it remains surprising that the social psychological consequences of opioids and their contribution to social connection have not been more fully explored in humans. Therefore, the primary objective of this project is to conduct a novel experimental manipulation in humans to clarify the causal role of opioids in (1) daily, naturalistic feelings of social connection outside of the laboratory, (2) the neural signatures of feelings of social connection, and (3) feelings of social connection in response to personalized experiences with friends and family using standardized laboratory tasks. For these purposes, we propose targeting a sample of 210 young, healthy adults on a multi-method randomized placebo-controlled clinical trial. Additional exploratory aims will examine whether naltrexone induced changes in daily feelings of social connection predict variation in neural responding to social tasks, and whether naltrexone differently affects feelings of social connection in women and men. The proposal will link pharmacological mechanisms with neuroimaging parameters of brain function and affective social experience both outside of the laboratory and in the laboratory setting. We therefore anticipate that this study will contribute to new fundamental knowledge of the neurobiological pathways underlying the maintenance of social connection with implications for the treatment of opioid addiction.