Please select the eligibility criteria that correspond to the clinical trial below.
Title: Oxytocin Suppresses Substance Use Disorders Associated With Chronic Stress
Brief 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.


Options:
A: Key Inclusion Criteria:

* Veteran or civilian adult outpatients 18-55 years of age, with primary PTSD as defined by Diagnostic and Statistical manual of Mental Disorders-IV (DSM-IV) for at least 6 months
* Must be in general good health-confirmed by medical history, physical examination, and screening laboratory results
* Negative urine drug screen for drugs of abuse
* Negative urine pregnancy test for females of childbearing potential
* Sexually active participants are required to use a medically acceptable form of birth control

Key Exclusion Criteria

* Clinically unstable medical disease; progressive CNS disorder/disease; history of seizures (except childhood febrile seizure); moderate or severe traumatic brain injury (TBI)
* Females who are pregnant or currently breast feeding
* Current or past psychotic disorder, bipolar Type I disorder, or dementia
* Participants with recent drug abuse or dependency (excluding nicotine and caffeine)
* Participants unwilling to comply with the required alcohol prohibition during the trial
* Current suicidal or homicidal ideation necessitating intervention, and those with a history of suicide attempt in the past 10 years
* Participants with pending litigation related to the traumatic event
* Participants who are unwilling to withhold grapefruit or grapefruit juice for the duration of the study
* Participants receiving psychotherapy without a stable paradigm for at least 3 months
* Non-English speaking participants.
B: Inclusion Criteria:

* Men or women, 18-65 years of age;
* Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;
* Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD
* Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);
* Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;
* Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop).

Exclusion criteria:

* Women who plan to become pregnant, are pregnant or are breast-feeding
* Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury;
* Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
* Renal impairment, as reflected by a BUN \>20 mg/dL, and/or creatinin clearance of \>1.3 mg/dL;
* Thyroid impairment, as reflected by TSH\> 4.2 mU/L Patients with uncorrected hypothyroidism or hyperthyroidism;
* Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;
* Use of evidence-based individual psychotherapy (such as prolonged exposure) during the study;
* History of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome; History of one or more seizures without a clear and resolved etiology;
* History of (hypo)mania;
* Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;
* Drug or alcohol abuse or dependence within the preceding 3 months
* Previous recreational use of ketamine or PCP;
* Current diagnosis of bulimia nervosa or anorexia nervosa;
* Diagnosis of schizotypal or antisocial personality disorder
* Patients judged clinically to be at serious and imminent suicidal or homicidal risk.
* A blood pressure of one reading over 160/90 or two separate readings over 140/90 at screen or baseline visits
* Patients who report current treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to randomization
C: Inclusion Criteria:

* Being between the ages of 18-65
* Having gone through a potentially traumatic event.

Exclusion Criteria:

* Not suffering from chronic PTSD
* Systolic blood pressure \<100 mm Hg;
* Heart rate below 55 beats per minute;
* Having a medical condition that contraindicates the administration of propranolol, e.g., history of congestive heart failure, heart block, insulin-requiring diabetes, chronic bronchitis, emphysema, or asthma. With regard to asthma, because many persons who say they have had an asthma attack, especially as a child, may only have had hay fever, another allergy, or another non-asthmatic episode, a blanket exclusion criterion may be overly restrictive. Therefore, asthma attacks will only be exclusionary if they a.) occurred within the past 10 years, b.) occurred at any time in life if induced by a β-blocker, or c.) are currently being treated, regardless of the date of last occurrence. Cardiological consultation will be obtained as necessary;
* Previous adverse reaction to, or non-compliance with, a β-blocker;
* Current use of a medication that may involve potentially dangerous interactions with propranolol, including, other β-blockers, antiarrhythmics, calcium channel blockers, and potent P450 2D6 inhibitors, e.g., fluoxetine, paroxetine, miconazole, sulconazole, metoclopramide, quinidine, ticlopidine, and ritonavir. Because the protocol does not require to take large doses of propranolol on a daily basis, the decision to exclude participants will be taken by the physician on a case-by-case basis;
* Pregnancy or breast feeding. Although propranolol can be used during pregnancy we will advise women not to participate in they are or become pregnant. Women breastfeeding will also be advised not to participate because propranolol has been found in human milk. That the quantity absorbed by the breast feeding infant is inferior to 1% of the therapeutic dose (Vidal, 2008).
* Contraindicating psychiatric condition, including current psychotic, bipolar, melancholic, or substance dependence or abuse disorder; suicidality;
* Initiation of, or change in, psychotropic medication within the previous 2 months. For participants receiving stable doses of pharmacotherapy, they and their providers will be asked not to change the regimen except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis with regard to retaining the participant or terminating participation;
* Current participation in any psychotherapy (other than strictly supportive). Participants will be asked not to initiate psychotherapy during the course of the proposed study except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis with regard to retaining the participant or terminating participation;
* Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation;
* Understanding neither French nor English.
D: 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.

Answer: D