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.

Grant Number: 1UG3DA061615-01A1
NIH Institute/Center: NIH
Principal Investigator: Y. Jazmin Camchong