Intervention: Prasterone
Trial phase: Phase 2
ATC code: A14AA07 | G03EA03 | G03XX01
SMILES: [H][C@]1(O)CC[C@@]2(C)C(=CC[C@]3([H])[C@]2([H])CC[C@]2(C)C(=O)CC[C@@]32[H])C1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 2
Group description: Subjects will receive a one-time oral dose of DHEA prior to initial brain imaging followed by sustained administration of DHEA for 6 weeks.

DHEA: Subjects will be randomized to receive a one-time oral dose of DHEA (400mg) or PBO and sustained administration of the study drug for 6 weeks. There will be a 2 week placebo lead-in period [all participants], followed by subjects continuing in the randomization block of DHEA or placebo for 6 weeks following acute administration).
Eligibility criteria:
Inclusion Criteria:

OEF/OIF/OND era Veterans
PTSD diagnosis (CAPS-5 score 33).

Negative pregnancy test if female.

Sexually active subjects are required to use a medically acceptable form of birth control if they are of childbearing potential and could become pregnant during the study.
A medically acceptable form of birth control includes non-hormonal intrauterine devices, surgical sterilization, or double barrier methods (e.g., diaphragm with contraceptive jelly, condom with contraceptive foam, cervical caps with contraceptive jelly).
Sexual abstinence with agreement to continue abstinence or to use a medically acceptable method of contraception should sexual activity occur is permissible.
Female participants must have had a normal mammogram within the last year (if older than 40)
Female participants must have had a normal pelvic exam within the last year
No change in medications less than 4 weeks before baseline assessment
No anticipated need to alter medications for PTSD for the 6-week study duration (as determined by study physician's review of records and/or discussion with prescribing physician).
Ability to fully participate in the informed consent process

Exclusion Criteria:

Unstable medical or neurological illness, including seizures, renal impairment or CVA and inability to participate in neuroimaging (fMRI).
Use of oral contraceptives or other hormonal supplements, as it is unclear if DHEA metabolism to other neurosteroids such as estradiol may potentially impact contraceptive efficacy.
Significant suicidal or homicidal ideation.
Current DSM-5 diagnosis of bipolar disorder, schizophrenia, or other psychotic disorder (including major depression with psychotic features), or cognitive disorder due to a general medical condition.
Female patients who are pregnant or breast-feeding.
Known allergy to study medication.
History of moderate or severe TBI.
Substance dependence within past three months, per DSM-5 criteria (excluding caffeine and nicotine).
Abnormal prostate specific antigen (PSA; >2.5ng/ml in males age 49 or less; >4ng/ml in males age 50 or greater) or history of prostate cancer, breast cancer, or uterine cancer.
A family history of prostate, breast or endometrial cancer in a first-degree relative.
Presence of any factors/conditions, medical or non-medical, that may interfere with conduction of study assessments in the judgment of the study team.
Serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions or behaviors that would compromise participation and/or likely to lead to worsening of symptoms during the course of the study in the opinion of study physician and research team.
Are non-ambulatory or require the use of crutches or a walker.
Taking Narcotic medications or benzodiazepines for any reason.