Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD

PROJECT SUMMARY/ABSTRACT
Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated
with significant morbidity, mortality, and health care expenditures. Military Veterans are at increased risk for co-
occurring AUD and PTSD, with prevalence rates 2-4 times higher than the general population. Our group
developed an integrated intervention entitled Concurrent Treatment of PTSD and Substance Use Disorders
using Prolonged Exposure (COPE). COPE incorporates empirically validated cognitive-behavioral techniques
for AUD with Prolonged Exposure (PE) therapy for PTSD. Several randomized controlled trials among Veterans
and civilians demonstrate efficacy of COPE in significantly reducing AUD and PTSD symptoms. Despite the
positive findings, there remains substantial room for improving treatment outcomes and enhancing retention.
Accumulating data suggest that the neuropeptide oxytocin (OT) is a promising candidate to enhance
psychosocial interventions for co-occurring AUD and PTSD, as OT targets neurobiological and behavioral
dysregulation common to both disorders. Preclinical and clinical studies demonstrate the ability of OT to
ameliorate a variety of alcohol-related behaviors (e.g., craving, withdrawal symptoms, tolerance, ethanol self-
administration), enhance fear extinction, and promote prosocial behaviors associated with successful
psychosocial treatment outcomes (e.g., trust, social cognition). In a randomized controlled pilot study, our group
found that OT administration prior to weekly PE therapy sessions was safe, well-tolerated, and resulted in
accelerated reduction in PTSD symptoms as compared to placebo. Although the empirical and theoretical
support for augmenting psychosocial interventions such as COPE with OT is robust, no studies to date have
examined this combined approach. The primary objective of the proposed Stage II study is to examine the
efficacy of OT as compared to placebo in reducing (1) alcohol use, and (2) PTSD symptoms among Veterans
receiving COPE therapy. To accomplish this, we will employ a manualized, evidence-based, cognitive-behavioral
intervention (COPE); a randomized, double-blind, placebo-controlled study design; standardized, repeated
dependent measures of clinical outcomes at multiple time points; and we will leverage close collaboration with
well-established VA clinics prepared to efficiently translate positive findings into practice. In addition, to evaluate
purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI)
at pre- and post-treatment and examine AUD biomarkers. The proposed study directly addresses the mission of
the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in that it aims to identify pharmacologic
treatments to address co-occurring AUD and PTSD simultaneously. The findings from this study will provide new
information and mechanistic insights to directly inform clinical practice and accelerate the research in this highly
understudied area.

Grant Number: 5R01AA028811-05
NIH Institute/Center: NIH
Principal Investigator: Sudie Back