CNS Drugs

, Volume 32, Issue 5, pp 421–435 | Cite as

Role of Exogenous Progesterone in the Treatment of Men and Women with Substance Use Disorders: A Narrative Review

  • MacKenzie R. Peltier
  • Mehmet Sofuoglu
Review Article


Substance use disorders (SUDs) remain problematic as many individuals are untreated or do not benefit from the currently available interventions. Thus, there is an urgent need to develop novel pharmacological interventions to treat SUDs. Evidence suggests that the female sex hormone, progesterone, attenuates the craving for and the euphoric effects of drugs of abuse. Research to date has demonstrated that progesterone may modulate responses to drugs of abuse and may have utility as a novel treatment for SUDs. A literature search was conducted to identify and examine studies that administered exogenous progesterone. Sixteen publications were identified, exploring the utility of exogenous progesterone or its metabolite, allopregnanolone, among a range of substances, including amphetamines (one study), benzodiazepines (one study), cocaine (nine studies), and tobacco/nicotine (five studies). Results indicated that exogenous progesterone and, its metabolite allopregnanolone, demonstrated preliminary efficacy as a treatment for substance use in both men and women. Notably, progesterone appears to target negative affect and augment cognitive functioning, especially among female substance users. Additional research is needed to explore the potential use of exogenous progesterone and allopregnanolone in the treatment of SUDs, including that associated with alcohol and opioids, but considering the current promising findings, exogenous progesterone and allopregnanolone may have utility as novel pharmacological treatments for SUDs.


Compliance with Ethical Standards


Article preparation was supported by the Veterans Affairs New England Mental Illness Research, Education and Clinical Center, as well as a National Institute of Drug Abuse Training Grant T32-DA007238.

Conflict of interest

MacKenzie Peltier and Mehmet Sofuoglu have no conflicts of interest directly relevant to the content of this article.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PsychiatryYale School of MedicineNew HavenUSA
  2. 2.VA Connecticut Healthcare SystemWest HavenUSA

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