Combined tDCS and cognitive training as an adjunctive treatment in opioid use disorder - Project Summary / Abstract Despite widespread use of buprenorphine to treat opioid use disorder (OUD), 50% of patients return to use within months. Non-invasive prefrontal stimulation is a highly promising buprenorphine augmentation strategy to enhance prefrontal plasticity to boost executive functioning (EF) needed for recovery. We reported that a neuromodulation intervention combining prefrontal stimulation and EF training delivered to individuals with alcohol use disorder increased prefrontal-incentive salience network connectivity and resulted in a significant reduction in relapse rates. This intervention has not yet been tested as a buprenorphine augmentation strategy for OUD. This proposal investigates the added benefit of the intervention in individuals under buprenorphine maintenance treatment for OUD (bOUD) to determine whether this intervention can: (i) induce circuit-based target engagement, (ii) enhance EF, and (iii) improve treatment outcomes. UG3 phase, open-label, within- subjects. Deliver 10 days of active transcranial direct current stimulation (tDCS) to individuals with bOUD concurrent with cognitive training. Brain imaging data and EF performance will be collected at pre-, mid- and post-intervention. UG3 aims to determine if there is a dose-dependent tDCS effect by contrasting change from baseline after 5 vs after 10 tDCS sessions in the following metrics: (SA1) circuit-based target engagement of a prefrontal-incentive salience network associated with abstinence and (SA2) EF improvement, i.e. working memory, cognitive flexibility, inhibitory control, decision making. SA3 will involve a pre-submission meeting with the FDA and NIH to review and obtain feedback on: regulatory process, UH3 design and study endpoints. UH3 phase, randomized-controlled trial, between-subjects. With FDA feedback and UG3-determined dose, a between-subjects, triple-blind, randomized-controlled clinical trial will assign 120 individuals with bOUD to either active tDCS or sham concurrent with cognitive training. We will collect brain imaging and EF changes at pre- and post- intervention, treatment outcome measures at 1-, 3- and 6-month follow-up timepoints. UH3 aims to contrast active tDCS vs sham groups on (SA4) clinical efficacy and durability of active tDCS on treatment outcome (craving, opioid use) over the 6-month follow-up period. To examine intermediate factors playing a key role in the intervention’s mechanism of action, we will (SA5) determine the relationship between changes in target engagement, EF and treatment outcomes. The UH3 is positioned to be in Phase 2 of the FDA Regulatory Pathway, to design either a Phase 2 or 3 Clinical Trial to support a Premarket Approval application. Impact: We propose the first study to examine the added benefit of a non-invasive prefrontal neuromodulation intervention designed as a highly promising buprenorphine augmentation strategy to dually target executive functioning deficits and excessive craving in individuals with bOUD. Success in these aims would provide crucial information about this combined intervention, setting the stage for clinical translation of a low-cost, scalable, neuroscience-based treatment for OUD.
