Prazosin and Cerebrospinal Fluid (CSF) Biomarkers in Mild Traumatic Brain Injury (mTBI)

Inclusion Criteria: * Age 21 years of age or older * Ability to complete psychometric and other clinical assessments in English * No clinically significant laboratory abnormalities at screen * Platelet count \>100,000/mm2 within two weeks of lumbar puncture (LP) * Body mass index (BMI) between 18 and 36 inclusive (BMIs outside this range affect CSF biomarker measurements and/or make LPs for CSF collection difficult to perform). * Women of childbearing potential must agree to abstain from sexual relations that could result in pregnancy or use an effective method of birth control acceptable to both participant and the study clinician during the study. Men are not required to use contraception during the study * Meeting criteria for at least one of the following: 1\. History of mild or moderate TBI: * Exposure to at least one blast or experiencing at least one collision of the head associated with acute symptoms that meet VA/DoD criteria for mild or moderate TBI (loss of consciousness, if present, \<24 hours; posttraumatic amnesia, if present, \<1 week; Glasgow Coma Scale (if available) 9-15) -\>6 months since last TBI. 2. Documented diagnosis of PTSD related to combat trauma (from any conflict) Exclusion Criteria: Medical * History of severe TBI (Glasgow Coma Scale (if available) \<9, loss of consciousness \>24 hours, posttraumatic amnesia \>1 week) * 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 \> 20mmHg after two minutes standing or any drop accompanied by dizziness), autoimmune disorders; insulin-dependent diabetes * Chronic renal or hepatic failure, acute pancreatitis, Meniere's disease, benign positional vertigo, narcolepsy, or diagnosed untreated sleep apnea (sleep apnea currently being treated is not exclusionary). * Contraindications to LP (e.g., spinal cord injury; deformity, severe disease or infection in the region of the lumbosacral spine; bleeding tendency, clotting abnormalities, use of anticoagulant medications, or platelet count \<100,000/mm2); trauma or infection in the 4 weeks before LP * Current pregnancy or lactation. Women of childbearing potential must agree to abstain from sexual relations that could result in pregnancy or use an effective method of birth control acceptable to both participant and the study clinician during the study. Men are not required to use contraception during the study. Psychiatric/Behavioral * Meets DSM(IV or 5, depending on what evaluative method was used in this subject) criteria for current schizophrenia, schizoaffective disorder, other specified or unspecified psychotic disorder, delirium, or any DSM cognitive disorder * Current substance use disorder (except caffeine-related disorders, tobacco-related disorders, or cannabis intoxication) other than in remission for at least 3 months. The use of cannabis other than that meeting criteria for cannabis use disorder is not exclusionary. Use of cannabis will be documented. * Current use of any stimulant, including prescribed stimulant medications * Current use (within the past 1 month, ongoing, or expected during the study period) of any drugs that are illegal under Washington state law. * 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 participant or others. Medications/Therapies * Current use of prazosin or other alpha-1 antagonist or trazodone, or use of such agent within the 3 month period prior to when the baseline 2 visit would be scheduled (a 3-month washout is required due to the potential effects it may have on the biomarker measurements). * Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist * Use of exclusionary medications in the 4 weeks prior to screening: selected CNS-acting medications; antipsychotics, anti-Parkinson's disease medications and CNS stimulants; Coumadin or other medications affecting coagulation and/or inflammation (low-dose aspirin and use of NSAIDs for pain will not be exclusionary); potent immune-modulating medications, such as hydrocortisone or methotrexate; anti-HIV medications. * Use of avanafil (Stendra), 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, but will be allowed at 1/2 the usual starting dose following dose titration * Current use of stimulants or nitrates, or of alternative medications or supplements with stimulant properties (e.g., ephedra) or vasodilatory properties (e.g., nitrate containing supplements) * Recent evidence based trauma- or sleep-focused psychotherapy, such as Prolonged Exposure therapy (PE), Cognitive Processing Therapy (CPT), Eye Movement Desensitization and Reprogramming (EMDR), Cognitive Behavioral Therapy for Insomnia (CBTi) or Image Rehearsal and Rescripting therapy for nightmares. These therapies must have been completed \> 4 weeks before first baseline assessment visit (study visit 2). Other * Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist * Receiving another medication in another interventional study