PROJECT SUMMARY / ABSTRACT This Phase I project is a pilot randomized clinical trial designed to show commercial potential for a novel virtual reality intervention in preparation for Phase II development. We propose testing our adjunctive intervention for efficacy on reducing opioid use and increasing abstinence in early recovering opioid use disorder (OUD) persons, with concomitant increases in self-reported and behavioral focus on future outcomes. Impaired future orientation is a hallmark of OUD and other addictions. With recovery attempts usually failing within 6 months of treatment, there is considerable room for improved efficacy. Converging evidence, including our preliminary data, indicates that increasing visualization of the future should improve recovery outcomes. Our pilot testing of the intervention was promising, with n=14 out of N=18 participants remaining abstinent 30 days later; importantly, 10 of the 14 abstainers showed a positive response to the intervention, i.e., 100% of responders remained abstinent—suggesting an efficacy marker. The VR intervention increased future self-identification and delay-of-reward in people recovering from substance use disorder and engaged brain networks governing prospection. Further, the VR effect on delay-of-reward correlated with introspective-executive brain connectivity. Extending prior work on episodic future thinking, we employed a personalized, immersive virtual experience that integrates personal details and maximizes sensory engagement. Our intervention increases connectedness with one’s future through a realistic interaction with Future Selves in diverging futures resulting from different choices. Importantly, we integrate self-discrepancy theory, focusing on the stark contrast between these futures to heighten impact, and we promote engagement by maximizing the novelty and emotional salience of the experience. Participants in early recovery enter a realistic virtual world, are introduced to a time travel narrative, and interact with two digitally age-progressed Future Selves; one after 15 years of ongoing opioid abuse, and the other after 15 years of recovery. Future Selves speak to the participant about their recovery rewards, or losses from returning to habitual drug use, and personal struggles during the journey. Strong emphasis is placed on agency, optimism, and decision-making. After iterative development and tests of feasibility and safety, the paradigm yielded a promising efficacy signal, behavioral change, and brain target engagement. The current proposal will validate this paradigm in an expanded and more homogenous OUD sample to show efficacy and behavioral mechanisms using the same VR paradigm. Aim 1 will test for efficacy on opioid use outcomes (days of use and abstinence) with longitudinal assessments at 30 days. Aim 2 will determine mechanisms by testing for changes in future self-identification, future orientation, and behavioral delay discounting. Successful validation i...