Please select the eligibility criteria that correspond to the clinical trial below.
Title: Glial Regulators for Treating Comorbid Posttraumatic Stress and Substance Abuse Disorders
Brief Summary: Examine the effects of N-acetylcysteine on PTSD symptoms, craving and substance use in veterans with PTSD and comorbid substance use disorders.


Options:
A: 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.
B: Inclusion Criteria:

* 18-65 year old
* U.S. military Veteran, Reservist, or National Guard member
* DSM-IV diagnostic criteria for current (past 6 months) SUD and PTSD or subthreshold PTSD (i.e., met criteria for cluster B (re-experiencing) and either cluster C (avoidance) or D (hyperarousal), as well as duration of one month and clinically significant impairment)
* Score of \> 21 on the Mini-Mental State Exam (MMSE).

Exclusion Criteria:

* Unstable medical conditions
* Bipolar or psychotic disorders
* Seizures or asthma
* Prior treatment with NAC
* Suicidality
* Enrolled in ongoing PTSD treatment (pharmacotherapy or psychosocial)
* Females: could not be pregnant or lactating
C: Inclusion Criteria:

* Participants must satisfy DSM-IV diagnostic criteria for chronic PTSD
* Evidence of PTSD disease base upon one or more of the following:
* Mild or greater depression on the Beck Depression Inventory -II (BDI-II, score\> 12).
* May have other symptom co-morbid with PTSD (e.g., anxiety or somatic pain)
* Ability to comprehend and satisfactorily comply with protocol required and signed written informed consent prior to entering study procedure
* May be in psychotherapy if initiated at least three months prior to the screening visit. Subject must not discontinue or otherwise alter therapy during the study.
* Subject may not have taken any psychopharmacological medications within 7 days prior to Baseline visit.
* Negative urine pregnancy test at screening visit and for the duration of the study for women of childbearing potential.

Exclusion Criteria:

* Patients with a concurrent DSM-IV Axis I diagnosis in any of the following categories:

  1. Delirium, Dementia, Amnestic and other Cognitive disorders
  2. Lifetime Schizophrenia and other Psychotic Disorders
  3. lifetime Bipolar I Disorder
  4. Bipolar-II Disorder with an episode of hypomania within the last year
  5. Alcohol or Substance Dependence or Abuse (excluding nicotine) in one month prior to the Screening Visit
  6. Any other concurrent Axis I Disorder (including Major Depressive Disorder) must be secondary to the primary diagnosis of PTSD.
* Decisional incapacity (dementia)
* Use of centrally acting medications that potentially have an effect on biological expression
* Chronic pain levels requiring use of any opiate medications
* Known exposure to chemicals of physical traumas that cause neuropsychiatric sequelae
* Past chronic PTSD
* History of 2 or more treatment failures on SSRIs given primarily for the treatment of PTSD, in adequate does at the Investigator's opinion, for at least 8 weeks
* History of intolerance or hypersensitivity to SSRI's
* History of seizures
* Significant risk of committing suicide, or are homicidal or violent and in the Investigator's opinion in significant imminent risk of hurting others
* Treated with depot-neuroleptic within 3 months or MAO inhibitors within 30 day prior to Baseline visit
* Received ECT within 3 months prior to Screening visit
* Pregnant or nursing, women of childbearing potential who are sexually active and do not use adequate contraception, or who are judged to be unreliable in their use of contraception
* Positive urine drug screen, unless proven to be prescribed for a short-term course of treatment. Drug screen must be repeated at least 7 days after the last dose of prescription medication containing narcotics
* A medical condition, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial
* Requiring concomitant treatment with any psychotropic drug (except zolpidem for sleep)
* Plans to initiate or terminate any form of psychotherapy or behavior therapy during the study
* Receiving disability payments (\> 50 % service connections or total Social Security) or who are involved in litigation for PTSD or other psychiatric illnesses.
* Unable to speak, read, and understand English or are judged by the investigator to be unable or unlikely to follow the study protocol and complete all scheduled visits
D: Inclusion Criteria:

* Age \>18 years.
* Exposure to one or more life-threatening war zone trauma events per the Combat
* Exposure Scale \[78\] and documented by Department of Defense (DD) Form 214, Combat Action Ribbon (Marines), Combat Infantry Badge (Army), or other clear evidence of war zone trauma exposure.
* Eligible for VA health care.
* Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnosis of PTSD derived from the CAPS.
* CAPS total score \>50.
* CAPS Recurrent Distressing Dreams item score \>5 (of maximum score of 8).
* Capable of giving informed consent.
* Stable dose of non-exclusionary (see below) medications for at least 4 weeks prior to randomization.
* Psychotherapeutic treatment stable for at least 4 weeks prior to randomization.
* Good general medical health (see Medical Exclusion Criteria below).
* Female participants must agree to use a reliable form of birth control during the study.

Exclusion Criteria:

Medical:

* Acute or unstable chronic medical illness, including unstable angina, recent myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension (systolic \<110) or orthostatic hypotension (systolic drop \> 20 millimeters of mercury after two minutes standing or any drop accompanied by dizziness); chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy.
* Untreated sleep apnea, diagnosed by a sleep study, is exclusionary. Treated sleep apnea (e.g., Continuous Positive Airway Pressure, surgery) will not be exclusionary.
* Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist.
* Wounds requiring surgery, embedded shrapnel, and recent surgical amputation do not comprise an exclusion if the individual is otherwise medically eligible.
* Women of childbearing potential with positive pregnancy test or refusal to use effective birth control method, or who are breastfeeding will be excluded.

Psychiatric/Behavioral:

* Meets DSM-IV criteria for current schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS), delirium, or any DSM-IV cognitive disorder.
* Exclusion for psychotic disorder is not to be confused with combat trauma-induced reexperiencing symptoms (transient dissociative states or flashbacks), which will not be exclusionary.
* Substance dependence disorder within 3 months or any current substance dependence (stable methadone maintenance will not be exclusionary).
* Current cocaine or stimulant abuse.
* Severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others.
* Nonsuicidal depression comorbid with PTSD will not be exclusionary (see below).

Medications/Therapies:

* Current use of prazosin or other alpha-1 antagonist.
* Previous adequate trial of prazosin for PTSD.
* Subjects on trazodone will undergo a 2-week washout period before baseline assessment. (Combining prazosin and trazodone may increase risk of priapism).
* Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) will be not be permitted during the study dose titration period because of increased risk of hypotension in combination with alpha-1 blockers. Following achieving stable dose of study drug, sildenafil, tadalafil, and vardenafil will be permitted at 1/2 the usual starting dose.
* Stimulants or alternative medications with stimulant properties (e.g., ephedra).
* Recent exposure therapy and/or Eye Movement Desensitization and Reprogramming (EMDR). These therapies must have been completed \> 4 weeks before randomization.
* Other psychotropic medications and/or maintenance psychotherapy at a stable dose for at least 4 weeks will not be exclusionary.

Answer: B