High rates of substance use disorders in Veterans compared to the general population are heavily influenced by psychosocial factors ? such as difficulty reintegrating into civilian life due to avoidance of vital support systems ? leading to disproportionately elevated unmet addiction treatment needs. Those using both cocaine and heroin have mortality rates 14.3 times higher than the general population. 30-60% of patients receiving methadone maintenance therapy (MMT) for opioid use disorder actively use cocaine. There are currently no approved psychopharmacological treatments for cocaine use disorder, and drop-out rates from MMT programs and vital psychosocial treatments are as high as 80% for cocaine users. What?s more, cocaine use, compared to other drugs, is particularly driven by social stress, and cocaine is associated with hyperreactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Preclinical and pilot clinical findings suggest that administration of oxytocin, a mammalian neuropeptide, may have a multitude of direct anti-addiction effects, improve engagement in psychosocial treatments, and attenuate hyperreactivity of the HPA axis in patients with cocaine use disorder. This is a double-blinded, placebo-controlled, clinical trial of fifty Veterans with active cocaine use disorder, also receiving MMT in an opioid treatment program, randomized to receive either oxytocin 40 IU or placebo intranasally twice daily for six weeks. The primary outcome measure will be oxytocin?s effectiveness at reducing cocaine use as measured by quantitative levels of the cocaine metabolite, benzoylecgonine, in weekly urine samples. Potential mechanisms of treatment response will be evaluated by measuring oxytocin?s effectiveness at a) improving therapeutic alliance with treatment providers (Working Alliance Inventory, client and therapist forms) and attendance in existing clinic-run treatment components and b) attenuating social stress-reactivity by measuring self- reported cocaine craving, psychophysiological stress measures, and salivary cortisol in response to a Trier Social Stress Test. In sum, discrepancies between Veterans and civilians in addiction prevalence, severity, and successful intervention are largely driven by higher rates of social avoidance and posttraumatic stress symptoms among Veterans. This study will uniquely combine psychopharmacological and evidence-based psychosocial interventions targeted at reducing cocaine use, improving treatment engagement, and preventing stress-related cocaine use among Veterans with co- occurring cocaine and opioid use disorders receiving MMT.

Public Health Relevance

Substance use disorder prevalence (SUD) in Veteran populations is estimated to be almost seven times higher compared to civilians. 25% of Veterans 18- to 25-years-old returning from Iraq or Afghanistan in the past ten years met full criteria for a SUD diagnosis when presenting to care for the first time, and only 11% of them had their addiction treatment needs met. These discrepancies in addiction prevalence, severity, and intervention between Veterans and civilians are known to be heavily influenced by psychosocial factors, such as low adherence to available treatment programs, mental health stigma within military culture, and general problems with reintegration into civilian life. Avoidance behavior is highly prevalent among Veterans and increases the risk for both posttraumatic stress symptoms and SUDs. An integrative intervention that would address addiction-related neural processes, engagement in vital psychosocial treatments, and improve stress regulation would greatly benefit Veterans with SUDs.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
Project #
Application #
Study Section
Neurobiology A (NURA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Portland VA Medical Center
United States
Zip Code
Stauffer, Christopher S; Woolley, Joshua D (2014) Can we bottle psychosocial treatments for addiction? The role of oxytocin. J Clin Psychiatry 75:1028-9