Stimulant Oxytocin Study

High rates of substance use disorders (SUDs) 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. Although the gold standard for treatment for most
SUDs involves pharmacological interventions, there are currently no effective pharmacological
interventions approved by the Federal Drug Administration for stimulant users, who have the
most difficulty adhering to treatment programs and the most susceptibility to stress-induced
relapse of any SUD. Administering oxytocin, a mammalian neuropeptide, intranasally to healthy
controls facilitates the stress-buffering properties of social support. Oxytocin may also
have an independent role in mitigating the symptoms of SUDs. For example, in animal models of
addiction, oxytocin administration directly reduces tolerance, withdrawal effects,
self-administration, and stress-induced reinstatement of drug seeking for a range of
addictive substances. A more integrated understanding of oxytocin's distinct effects on the
behavior and psychology of 1) addiction, 2) sociality, and 3) stress reactivity could be the
key to defining oxytocin's role in SUD treatment. This study proposes to translate promising
preclinical and early proof-of-concept clinical results related to the anti-addiction,
pro-social, and stress-tempering properties of oxytocin administration in Veterans with
moderate-severe cocaine use disorders enrolled in a opioid replacement therapy (ORT) program
for cooccurring opioid use disorder (OUD) at the San Francisco VA Medical Center (SFVAMC).
The investigators' primary outcome is Aim 1) reduction in cocaine use, as measured by
quantitative urine levels of cocaine and amphetamine metabolites. Secondarily, the
investigators will focus on Aim 2) improving psychosocial treatment engagement (social
support) and Aim 3) mitigating social stress-related relapse, targeting two important
barriers to cocaine use disorder recovery likely to respond to oxytocin administration.

Inclusion Criteria:

1. At least 18 years old

2. Enrolled as a patient at the SFVAMC Opioid Treatment Program

3. Stable dose of opioid replacement therapy for at least 2 consecutive weeks

4. Veteran

5. One documented urine toxicology screen positive for cocaine in the past 12 months.

Exclusion Criteria:

1. Severe neuropsychological disorder

2. Suicidal or homicidal ideation within the past 90 days or a suicide attempt in the
past 6 months

3. Hemodialysis, unless participant can produce urine samples weekly

4. Sensitivity to potassium sorbate

5. Positive urine pregnancy test or women of childbearing age not practicing effective
means of non-hormonal birth control

6. Chronic nasal obstruction, discharge, or bleeding