Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids.
Marx CE, Lee J, Subramaniam M, Rapisarda A, Bautista DC, Chan E, Kilts JD, Buchanan RW, Wai EP, Verma S, Sim K, Hariram J, Jacob R, Keefe RS, Chong SA. Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. Psychophamacology (Berlin), 2014, 231(17): 3647-3662.