A Rationale for Allopregnanolone Treatment of Alcohol Use Disorders: Basic and Clinical Studies. (17th December 2019)

• Record Type: Journal Article
• Authors: Morrow, A. Leslie; Boero, Giorgia; Porcu, Patrizia
• Is Part Of: Alcoholism. Volume 44:Number 2(2020)
• Page Start: 320
• Page End: 339
• Publication Date: 2019-12-17
• Subjects: Allopregnanolone -- Neuroactive Steroid -- GABA Inhibition -- Corticotropin‐Releasing Factor Signaling -- Neuroimmune Signaling; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.14253
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : For many years, research from around the world has suggested that the neuroactive steroid (3α, 5α)‐3‐hydroxypregnan‐20‐one (allopregnanolone or 3α, 5α‐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. Abstract : Theoretical framework of the CNS dysregulation caused by alcohol addiction and the restoration of homeostasis by the neuroactive steroid allopregnanolone. Alcohol addiction decreases GABAergic signaling while increasing CRF and proinflammatory neuroimmune signaling in the brain. Allopregnanolone (and possibly its precursors) may restore homeostasis by simultaneously increasing GABAA receptor‐mediated inhibition, and decreasing CRF and deleterious neuroimmune signaling, all of which contribute to the etiology of AUDs. Our review details the evidence for this hypothesis.