Oxytocin Suppresses Substance Use Disorders Associated With Chronic Stress
Condition: Alcohol Use Disorders
MeSH terms: Substance-Related Disorders; Alcoholism
Intervention: Oxytocin; Placebo
Intervention description: One 40 IU dose of intranasal oxytocin will be self-administered (5 puffs in each nostril) by participants.; Each participant will self-administer a 40 IU dose of intranasal saline.
Intervention MeSH terms: Oxytocin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Enrollment: 73.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Alcohol; Oxytocin; Stress reactivity

Summary:

      In comparison to the general population, military personnel and veterans are at increased
      risk of developing both substance use disorders (SUDs) and post-traumatic stress disorder
      (PTSD). Despite promising developments in the past decade, the treatment of patients with
      SUDs and comorbid PTSD is woefully inadequate (Back, 2010; Back et al., 2014; Brady et al.,
      2007; McCauley et al., 2012). One of the adverse effects of abused drugs is their long-term
      negative impact on social behavior that is thought to involve oxytocin (OT) dysregulation
      (McGregor et al., 2008). In preclinical and clinical experiments, local, intra-nasal, or
      systemic OT administration decreases activation of the amygdala in response to visual
      fearful/threatening stimuli (Kirsch et al., 2005), ameliorates the effects of stressful
      events, and decreases drug-taking and seeking behavior (McGregor et al., 2008; Baskerville
      and Douglas, 2010; Carson et al., 2010a; Bowen et al., 2011; Cox et al 2013). However, little
      attention has been focused on whether OT decreases SUD vulnerability after exposure to
      traumatic stress in preclinical or clinical studies. This clinical project will determine
      whether intra-nasally administered OT will decrease craving (Aim 1) to use alcohol and
      decrease stress reactivity (Aim 2) following exposure to laboratory-induced stress (Trier
      Social Stress Task) among veterans with a dual diagnosis of alcohol use disorder and PTSD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female; any race or ethnicity; age 21-65 years.

          -  Female subjects will be required to complete the laboratory testing during the early
             to mid-follicular phase of their menstrual cycle (days 1-7 following the onset of
             menses).

          -  Veteran of the US military; any service branch.

          -  Able to provide informed consent and function at an intellectual level sufficient to
             allow accurate completion of the assessment instruments.

          -  Subjects must be able to comprehend English.

          -  Meet DSM-5 criteria for a current alcohol use disorder (assessed via the Mini
             International Neuropsychiatric Interview; MINI). Note that we will use the currently
             available diagnostic measure (MINI for DSM-IV) and will make appropriate modifications
             to update for compatibility with DSM-5.

          -  Meet DSM-5 criteria for current PTSD (assessed via the Clinician Administered PTSD
             Scale; CAPS). Note that we will use the currently available assessment instrument
             (CAPS for DSM-IV), and will make appropriate modifications to update for compatibility
             with DSM-5.

          -  A CAPS score of 50 or greater.

          -  Subjects will be required to have at least 5 days of abstinence from alcohol or other
             substances (except caffeine or nicotine) prior to completing the laboratory testing,
             as verified by multiple methods including self-report, breathalyzer tests, and urine
             drug screen tests.

          -  Subjects may also meet criteria for a mood disorder (except bipolar affective
             disorder, see Exclusion Criteria) or anxiety disorders (e.g., agoraphobia, social
             phobia, generalized anxiety disorder). The inclusion of subjects with affective and
             anxiety disorders is essential because of the marked frequency of the co-existence of
             mood and other anxiety disorders among patients with PTSD and alcohol use disorders.

          -  Subjects taking psychotropic medications will be required to be maintained on a stable
             dose for at least eight weeks before study initiation. This is because initiation or
             change of psychotropic medications during the course of the trial may interfere with
             interpretation of results.

          -  Must consent to random assignment to oxytocin or placebo.

        Exclusion Criteria:

          -  Subjects meeting DSM-5 criteria for a history of or current psychotic or bipolar
             affective disorders, or with current suicidal or homicidal ideation and intent. Those
             subjects will be referred clinically.

          -  Subjects who would present a serious suicide risk or who are likely to require
             hospitalization during the course of the study. Those subjects will be referred
             clinically.

          -  Subjects on maintenance anxiolytic, antidepressant, or mood stabilizing medications,
             which have been initiated during the past 8 weeks.

          -  Subjects with a history of a major medical illness (e.g., endocrine, cardiovascular,
             central nervous system disorders, peripheral neuropathy, or pulmonary disease) or
             other acute or unstable medical condition that might interfere with safe conduct of
             the study or accurate interpretation of the results.

          -  Subjects meeting DSM-5 criteria for another substance use disorder, except caffeine or
             nicotine, within the past 12 months.

          -  Subjects experiencing withdrawal symptoms, as evidence by a score of 10 or above on
             the Clinical Institute Withdrawal Assessment of Alcohol (CIWA)

          -  Females who are unable or unwilling to be scheduled for lab testing during the early
             to mid-follicular phase of their menstrual cycle.

          -  Pregnant women will be excluded from the proposed study.