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However, levels of NAS in addicted individuals have not been systematically examined. Here, we evaluated a panel of NAS in men and women with cocaine use disorder (CUD) who participated in a clinical laboratory study of progesterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty six CUD individuals were enrolled in a randomized placebo\u2010controlled laboratory study to evaluate progesterone effects on levels of various NAS. On day 5 of a 7\u2010day inpatient treatment regimen of 400\u2009mg\/day progesterone (15M\/8F) or placebo (14M\/9F), plasma levels of NAS known to be downstream of progesterone (allopregnanolone, pregnanolone), and NAS not in the progesterone synthesis pathway (androstanediol, testosterone, dehydroepiandrosterone [DHEA] and the NAS precursor, pregnenolone) were analyzed using highly sensitive gas chromatography\/mass spectrometry (GC\/MS). The relationship between each of the NAS and chronicity of cocaine use was also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Progesterone versus placebo significantly increased the GABAergic NAS allopregnanolone and pregnanolone in both CUD men and women. Levels of pregnenolone, testosterone, its GABAergic metabolite androstanediol, and the non\u2010GABAergic DHEA were unaffected by progesterone treatment, and testosterone and androstanediol levels were significantly higher in men than women. Importantly, lower pregnenolone and androstanediol levels were associated with greater years of cocaine use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Scientific Significance<\/jats:title><jats:p>GABAergic NAS that are upstream from the progesterone synthesis pathway appear susceptible to chronic effects of cocaine use. (Am J Addict 2019;28:16\u201321).<\/jats:p><\/jats:sec>","DOI":"10.1111\/ajad.12828","type":"journal-article","created":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T15:18:43Z","timestamp":1544541523000},"page":"16-21","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Neuroactive steroid levels and cocaine use chronicity in men and women with cocaine use disorder receiving progesterone or placebo"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6752-2223","authenticated-orcid":false,"given":"Verica","family":"Milivojevic","sequence":"first","affiliation":[{"name":"The Yale Stress Center, Department of Psychiatry Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Covault","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry University of Connecticut School of Medicine Farmington Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo A.","family":"Angarita","sequence":"additional","affiliation":[{"name":"Connecticut Mental Health Center, Department of Psychiatry Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Siedlarz","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry University of Connecticut School of Medicine Farmington Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajita","family":"Sinha","sequence":"additional","affiliation":[{"name":"The Yale Stress Center, Department of Psychiatry Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,11]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15\u20134927 NSDUH Series H\u201050). 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Structured Clinical Interview for the DSM\u2010IV Axis I Disorders Patient Edition (SCID\u2010I\/P Version 20 4\/97 Revision). 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