A Rationale for Allopregnanolone Treatment of Alcohol Use Disorders: Basic and Clinical Studies

For many years, research from around the world has suggested that the neuroactive steroid (3 alpha,5 alpha)-3-hydroxypregnan-20-one (allopregnanolone or 3 alpha,5 alpha-THP) may have therapeutic potential for treatment of various symptoms of alcohol use disorders (AUDs). In this critical review, we systematically address all the evidence that supports such a suggestion, delineate the etiologies of AUDs that are addressed by treatment with allopregnanolone or its precursor pregnenolone, and the rationale for treatment of various components of the disease based on basic science and clinical evidence. This review presents a theoretical framework for understanding how endogenous steroids that regulate the effects of stress, alcohol, and the innate immune system could play a key role in both the prevention and the treatment of AUDs. We further discuss cautions and limitations of allopregnanolone or pregnenolone therapy with suggestions regarding the management of risk and the potential for helping millions who suffer from AUDs.