Virtual Reality Facilitation of Recovery from Opioid Use Disorder

PROGRAM PLAN Executive Summary of Predicate STTR Phase I Grant and Team The goals of our predicate STTR Phase I (R41 DA055405) are to demonstrate (i) intervention efficacy, (ii) effectiveness in the target population, (iii) practicable delivery, (iv) validation of remote deployment in a multi- site collaboration, and to produce (v) critical non-directive user feedback. These goals emerge from the two proposed specific aims that target key outcomes in early recovery from opioid use disorder participants recruited from addiction treatment centers. Demonstrating in-sample effectiveness in the recovery-related outcomes from Aims 1 and 2 will indicate completion of Phase I and preparation to transition to Phase II. Converging evidence suggests that psychological disconnection with the future is a central underlying mechanism in substance use disorder (SUD). Interventions that successfully increase valuation of the future (i.e., delayed outcomes) present episodic, autobiographical, future-oriented, vivid, and content-specific stimuli. We developed an immersive virtual reality (VR) intervention that is personalized and hyper-realistic to increase connection with one’s personal future. This emotionally charged narrative interaction with future selves, (i) after 15 years of substance misuse, and (ii) after 15 years of sustained recovery elicited high rates of abstinence, increased preference for delayed rewards, increased future-self identification, and decreased craving. STTR Phase I Specific Aims: Aim 1: Determine the efficacy of VR future self-experiences on opioid use. The VR Test group, relative to VR Control, will show (1a) a lower number of opioid use days; (1b) longer abstinence periods during follow-up; and (1c) significantly increased opioid abstinence rates. Aim 2: Determine the behavioral effects of VR future self-experiences. The VR Test experience, compared to baseline and VR Controls, will (2a) increase future self-identification; (2b) increase future orientation; (2c) increase preference for delayed rewards in a laboratory delay discounting task; and that (2d) the VR Test group will exceed the VR Control group in the behavioral effects (H2a-c) at the 30-day follow-up. STTR Phase I randomized controlled trial (NCT05908097) Progress and Preliminary Results: We modified the paradigm to work on currently available VR equipment, i.e., the Meta Quest 3 (a state-of-the- art standalone headset), as the original paradigm was designed for the wired Samsung Odyssey headset. We initiated a multi-site collaboration with an out of state partner, Serenity Lane in Oregon. To-date, we scheduled n=153 in-person interviews and n=54 study days with participants in early SUD recovery. We collected study day data from n=37 (n=17 VR Test and n=20 VR Controls), 18 female and 19 male, with a mean age of 41.8 ±9.8 years. Preliminary data suggest gains in abstinence and other key metrics for sustained recovery. In parallel, our team has devoted considerable effort in business development, including conference presentations, meeting with treatment industry stakeholders, customer surveys, and regulatory consulting. We overcame several significant challenges during the ongoing Phase I trial. Realistic voice cloning required testing many hardware and software solutions (including a purpose-built audio recording booth). We eventually discovered a hardware/software combination well-matched to the python-based AI model (TortoiseTTS). Participant recruiting was another major hurdle. Numerous in-person recruiting efforts and locally posted physical flyers fell short of recruiting goals. We overcame this problem with a dual solution: contracting an online recruiting service, and a participant referral voucher system (IRB-approved). The multi-site collaboration further expanded our reach for data collection and increased our parallel throughput. The team comprises Isaiah Branam, Brandon Oberlin, and Andrew Nelson. Mr. Branam’s robust entrepreneurial experience makes him ideal for business strategy and development. Dr. Oberlin provides the scientific expertise and testing capacity for the project, and Mr. Nelson’s ongoing industry experience as CEO of Half Full Nelson, LLC and seven-year collaboration on the project, provide the unique insight and skill set to continue achieving our aims. While we believe our clear vision will lead us successfully to market, we are eager to amend that or go back to the drawing board, as needed, based on what we learn at I-Corps. Similarly, all team members are committed to the time requirements of the program.