Clinical Research Directory

Inclusion Criteria: * At study outset: DSM-5 diagnosis of PTSD with CAPS-5 Total Score \>=30. Following protocol amendment effective 4/13/2023: criterion modified to require diagnosis of PTSD using the CAPS-5 definition, defined by the following: at least one Criterion B symptom, at least one Criterion C symptom, at least 2 Criterion D symptoms and at least 2 Criterion E symptoms. This thus replaced the firm cutoff of CAPS-5 Total Score \>=30. * Females will be required to use a medically and study approved contraceptive or otherwise not be of child-bearing potential * Birth control methods must be non-hormonal * No anticipated need to alter psychiatric medications for duration of study involvement * Ability to participate fully in the informed consent process Exclusion Criteria: * History of allergy to pregnenolone * Medical disorders that may preclude safe administration of pregnenolone or exacerbate PTSD symptoms * Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern * Prior suicide attempt history or suicidal ideation that does not require clinical intervention or represent an imminent concern is permitted * Serious unstable medical illness, such as: * history of cerebrovascular accident * prostate, uterine, or breast cancer * others (at the discretion of the PI and medical oversight team) * Medical conditions not well controlled will be excluded, at the discretion of the PI and Medical Team * Standard pharmacological interventions for PTSD will not be exclusionary, including, but not limited to: * antidepressant medications such as SSRIs, SNRIs, tricyclics, bupropion, mirtazapine, venlafaxine, and nefazodone * mood stabilizers such as carbamazepine, divalproex, lamotrigine, topiramate * atypical antipsychotics, and other agents including prazosin * However, there may be no changes in psychotropic medications for PTSD 4 weeks prior to study randomization * Benzodiazepine use * Current diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than mild TBI (assessed at screening) * Initiation or change in psychotherapy within 3 months of randomization, i.e. psychotherapy must be stable for 3 months prior to study start * Participants on hormonal therapies such as finasteride or hormonal birth control * Female participants who are pregnant or breast-feeding * As indicated by the DSM-5, moderate or severe Substance Use Disorders (excluding caffeine and tobacco) within 1 month of study entry * Mild Alcohol Use Disorder is not exclusionary, at the judgment of the PI and her medical team