Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) for Opioid Use Disorder

PROJECT SUMMARYEvon Medics LLC proposes to evaluate and optimize the portable, home-based product, Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT), as an alternative strategy for relapse prevention in patients with Opioid Use (OUD) and other substance use disorders (SUD). Opioid and other forms of drug addiction can be defined as a failure to control drug-seeking behavior, and reflect an exaggerated drive to consume drugs, and/or an inability to engage in outcome-guided behaviors involving non-drug rewards such as food, health, social status and money. In contrast to overlearned drug-related associations, non-drug outcomes are often less well established and need to be inferred or mentally simulated. The orbitofrontal cortex (OFC) plays important role in regulation of addiction through provision of an associative structure (i.e. cognitive map) for these mental simulations. Additionally, the OFC plays critical role in emotion regulation through enhanced cognitive reappraisal of negative affective cues; and negative affect is a strong predictor of substance relapse. People with OUD have reduced OFC volume and function, and heroin and cocaine dose-dependently diminish OFC neuronal functions, thereby fueling recurrent drug use.The CBOT is a programmed, portable, safe, user-friendly device for conjoined chemosensory stimulation of OFC neural activity with stimulation parameters that overcome OFC desensitization, and for administration of olfactory cognitive tasks that synergistically engage the OFC with high fidelity sufficient to induce lasting changes in OFC functions. Phase I research and development met or exceeded stated technical milestones: CBOT intervention led to increased performance in outcome-guided behavior tasks, increased retention of OUD patients in treatment and reduced relapse rate during 12 weeks follow-up. Compared to sham treatment, CBOT-treated OUD patients also experienced less severe opioid withdrawal and cravings, and less sleep disruptions and negative affect rating, independent of severity and duration of drug use. Evon Medics is seeking SBIR Phase II funding to demonstrate its utility for home application by non- treatment seeking and treatment-seeking OUD populations, to engage in long-term, successful opioid recovery. This proposal will enable additional product refinement to allow broad implementation and commercialization of the device that increases long-term OUD treatment retention and abstinence and increases engagement in recovery through acute reduction of withdrawal severity and negative affect. At the same time, Evon Medics is engaging strategic partnerships that will be used to drive development through manufacturing, regulatory filings, sales, and distribution. Evon Medics scientists, engineers and commercial experts are mission-driven and highly motivated to make an impact on mental and social health worldwide. Key technical objectives of this Phase II project are to: (1) establish the effectiveness of CBOT for improved retention and relapse prevention in a large sample of OUD subjects; (2) establish its effectiveness for acute reduction of withdrawal severity and negative affect early in recovery; and (3) configure and optimize a commercial-ready CBOT version for improved efficacy, user-friendliness and acceptability. These objectives will lead to an optimized CBOT product that overcomes the drawbacks of traditional olfactory therapy and other noninvasive neuromodulation approaches in the treatment of drug addictions and prevention of relapses. Upon completion of Phase II, we will be poised to expand the research to Phase III efficacy study, or an implementation study of effectiveness in the real-world setting through commercial partnerships developed over the course of this project. To the best of our knowledge, this will be the first evaluation of a home-based, scalable, computerized, chemosensory-based brain stimulation with potential broad impact for both treatment- seeking and non-treatment seeking OUD populations.NARRATIVE Opioid Use Disorders (OUD) cause significant burden to individuals, families and the society. Our product – Computerized Chemosensory-Based Orbitofrontal Cortex Training (CBOT) – is a cost-saving, home-based, user-friendly brain stimulation system that significantly increased 6-month retention of OUDs in treatment in Phase I SBIR, through targeted modulation of orbitofrontal cortex function to enhance behavior that involves non-drug outcomes in OUD patients; and also, acutely reduced opioid withdrawal severity and negative affect during induction into opioid maintenance therapy. This proposal will establish its effectiveness in a large clinical trial, and enable final product optimization to a commercial grade home-based neuromodulatory device for treatment of a broad category of OUD subjects at different stages of OUD care continuum.