Development of Pregnenolone as a Treatment for Depression

In this study, 26 adult women meeting criteria for Major Depressive Disorder (MDD) as defined in DSM 5, will be randomized to a double‐blind, placebo‐controlled, crossover phase I clinical trial of pregnenolone (i.e. each participant receives 500 mg/d, 800 mg/d pregnenolone and placebo in random order). The study will consist of three 7‐day treatment exposures to each pregnenolone dose with a 14‐day washout between each exposure. Baseline evaluation will include medical and psychiatric history, psychiatric interview, standard laboratory analyses (i.e., blood draw, ECG), and a brief cognitive battery. Neuroimaging will be collected after each study drug or placebo administration. Study drug tolerability and participant safety will be assessed throughout the study (6 in‐clinic visits + a safety visit) using structured clinical interviews, self‐report questionnaires, and standard laboratory analyses.