Autonomous Digital CBT Intervention for Opioid Use Disorder in Individuals with Co-Occurring Internalizing Disorders

Project Summary
The prevailing neuroscientific characterization of addiction is that of evolving neuro-behavioral responses to
chronic drug use that are initially motivated by increasing pleasure (impulsive drug use) that over time causes
neuro-adaptations such that drug use is increasingly motivated by relief from negative affect (compulsive use).
The compulsive stage of addiction can be seen as a “vicious cycle” since the short-term relief from negative
affect through drug use ultimately exacerbates negative affect through neuroadaptations to chronic use. Our
early work demonstrated that the vicious cycle was a primary factor in maintaining comorbidity between alcohol
use disorder (AUD) and internalizing disorders (anxiety and depression). This provided the ground work for the
development and validation of a cognitive-behavioral therapy program for AUD comorbidity that directly
targeted the vicious cycle of addiction (VC-CBT). Further, we developed a fully autonomous and easily scaled
digital platform to deliver VC-CBT that has proved to be as effective as the therapist-delivered version. The
intervention is premised on educating individuals about the reversibility of the vicious cycle, and training them
to use proven coping skills to manage negative affect without drugs can significantly aid them in achieving
desired treatment goals. In this project, we leverage the trans-addiction status of the neuroscientific
underpinnings of the VC-CBT intervention and its flexibility as a digital therapeutic to develop and test a digital
treatment for comorbidity in opioid use disorder (OUD). Relative to other drugs of abuse, the progression from
initial impulsive use to negatively reinforced compulsive use is known to be truncated and nearly universal
among those who routinely use opioids, and those with co-occurring internalizing disorders are especially
susceptible. This, along with the relatively high lethality of OUD, makes it an ideal near-term target for this
trans-addiction therapy. To achieve this, we propose to test the clinical efficacy of digitally-delivered VC-CBT
for OUD-INTD comorbidity in a UG3/UH3 program consisting of two phases. The overarching aim of Phase 1
is the modification and pilot testing of the established digitally-delivered negative affect VC-CBT for application
in OUD. The overarching aim of Phase 2 is to conduct a scientifically rigorous clinical trial of the modified VC-
CBT for OUD. The impact of this work would be to provide a scalable and inexpensive means of improving the
otherwise poor OUD treatment outcomes among those with co-occurring anxiety or depression. Moreover, the
project would support the viability of trans-addiction interventions that target processes common to multiple
addiction types.

Grant Number: 5UG3DA059414-02
NIH Institute/Center: NIH
Principal Investigator: JUSTIN ANKER