Opioid overdose mortality is among the leading causes of death among adults (Centers for Disease Control and Prevention, 2023). Efforts to reduce mortality include increased access and availability of evidence-based approaches, such as medications for OUD (MOUD (Department of Health and Human Services, 2019; Dowell et al., 2016; Gellad et al., 2017). Additional efforts are essential in reducing opioid-related morbidity and mortality, such as identifying and addressing novel therapeutic targets (Volkow, 2020). Loneliness and social isolation are ideal potential candidates for intervention among individuals with OUD.

The US Surgeon General has expressed an urgency to address loneliness and social isolation because of its devastating effects (Office of the Surgeon General, 2023). Research has echoed this need to address loneliness worldwide, given its relatively high prevalence at the population level and its links to morbidity and mortality (Rico-Uribe et al., 2018, Surkalim et al., 2022). Loneliness is a cognitive-affective construct reflective of one’s perception of social isolation (Cacioppo et al., 2015). While loneliness and objective social isolation are associated and there may be overlap, they are different. Specifically, individuals may have social interactions with others yet have the perception that they are socially isolated because they feel as though they have no close connections (Hawkley and Cacioppo, 2010).

Among individuals with OUD, loneliness has been identified as a motivator of use and driver of craving, and is associated with key precipitants of a return to use (e.g., pain, sleep disturbance) (Li et al., 2017, Li et al., 2017). Cross-sectional analyses have also reported that loneliness is associated with non-suicidal self-injury and lower quality of life (Yang et al., 2017, Zhong et al., 2018), while recent longitudinal studies found that it was associated with both substance use and substance use severity (Bonar et al., 2022, Gutkind et al., 2022). Among individuals receiving medications for opioid use disorder (MOUD), higher loneliness scores predicted positive urine drug screens at the 6-month follow-up (McDonagh et al., 2020).

Despite the detrimental effects of both loneliness and OUD, there are no randomized clinical trials explicitly focused on addressing both loneliness among individuals with OUD. A meta-analysis of randomized clinical trials on interventions to address loneliness more broadly, suggest that cognitive-behavioral interventions reduce loneliness to a greater extent relative to other approaches such as social skills training and increasing opportunities for social interactions (Masi et al., 2011). Cognitive-behavioral approaches target identifying and changing maladaptive thoughts related to social situations and interpersonal relationships and behavioral activation focused on increasing social engagement among other strategies (Kall et al., 2020b).

Given the promise of cognitive-behavioral interventions to address loneliness, application of cognitive-behavioral skills to address loneliness as an antecedent and consequence of opioid use among individuals with OUD reporting elevated loneliness are needed. The purpose of the current randomized controlled trial was to assess feasibility, acceptability, and preliminary effects of Cognitive-Behavioral Therapy for Perceived Social Isolation (CBT-PSI) compared to a health education control.