PROJECT SUMMARY / ABSTRACT We propose a novel virtual reality intervention to test for efficacy on reducing stimulant use and increasing abstinence, with concomitant increases in future self-identification, future time perspective, and delay-of- reward, in early recovering stimulant use disorder (StUD) persons. Impaired future orientation and delay-of- reward appear to be behavioral endophenotypes for substance use disorders. With recovery attempts usually failing within 6 months of treatment, there is considerable room for improved efficacy. Converging evidence indicates that a hallmark of StUD is impaired visualizing and planning for the future, which corresponds to greater devaluation of delayed rewards. Our preliminary tests of the intervention were 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, suggesting an efficacy marker. The intervention increases future self-identification and delay-of-reward in people recovering from substance use disorder, and engages 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 precision medicine approach in designing a personalized immersive virtual experience that integrates personal details and maximizes sensory engagement. Our intervention increases connectedness with one’s future by immersing subjects in a realistic portrayal of interacting with their Future Selves in divergent futures. Importantly, we integrate self-discrepancy theory, focusing on the gap between “what is” and “what could be” to heighten motivation, and we promote engagement by maximizing the novelty and emotional salience of the experience. Early-recovering StUD persons 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 stimulant abuse, and the other after 15 years of recovery. Both 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 sample to show efficacy and behavioral mechanisms using the same VR paradigm. Aim 1 will test for efficacy on stimulant and drug use outcomes (amount, frequency, type, relapse, and abstinence) with longitudinal assessments at 1 and 6 months. Aim 2 will determine mechanisms by testing for changes in future self-identification, future time perspective, and behavioral delay discounting. The long- term goal of the project is to validate a potent adjunctive intervention with long-term recovery benefits that is readily implemented during post-treatment aftercare or in a treatment setting.

PROJECT NARRATIVE The long-term goal of this project is to test a virtual reality experience designed to reduce drug use and increase abstinence, and increase identification with the future self, future time perspective, and delayed reward choice in persons recovering from stimulant use disorder. Through increasing future orientation and delay-of-reward behavior with a precision medicine personalized experience, the intervention is designed to increase beneficial decision-making and positive future outcomes. The results of this study will provide vital information on the effectiveness and behavioral mechanisms of this adjunctive intervention intended to facilitate recovery outcomes.