Neuroactive Steroid Levels and Cocaine Use Chronicity in Men and Women with Cocaine Use Disorder Receiving Progesterone or Placebo

Overview

Journal Am J Addict

Specialty Psychiatry

Date 2018 Dec 12

PMID 30537098

Citations 7

Authors

Verica Milivojevic

Jonathan Covault

Gustavo A Angarita

Kristen Siedlarz

Rajita Sinha

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Neuroactive steroids (NAS) may play a role in addiction, with observed increases in response to acute stress and drug use, but decreases with chronic substance use, suggesting that NAS neuroadaptations may occur with chronic substance use. 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.

Methods: Forty six CUD individuals were enrolled in a randomized placebo-controlled laboratory study to evaluate progesterone effects on levels of various NAS. On day 5 of a 7-day inpatient treatment regimen of 400 mg/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.

Results: 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-GABAergic 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.

Scientific Significance: GABAergic NAS that are upstream from the progesterone synthesis pathway appear susceptible to chronic effects of cocaine use. (Am J Addict 2019;28:16-21).

Citing Articles

Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.

Balan I, Boero G, Chery S, McFarland M, Lopez A, Morrow A Life (Basel). 2024; 14(5).

PMID: 38792602 PMC: 11122352. DOI: 10.3390/life14050582.

Acute, but not repeated, cocaine exposure alters allopregnanolone levels in the midbrain of male and female rats.

McFarland M, Machado M, Sansbury G, Musselman K, Boero G, OBuckley T Psychopharmacology (Berl). 2024; 241(5):1011-1025.

PMID: 38282126 PMC: 11180476. DOI: 10.1007/s00213-024-06534-8.

Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.

Milivojevic V, Sullivan L, Tiber J, Fogelman N, Simpson C, Hermes G Psychopharmacology (Berl). 2022; 240(1):101-114.

PMID: 36445398 PMC: 10630889. DOI: 10.1007/s00213-022-06278-3.

Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder.

Milivojevic V, Charron L, Fogelman N, Hermes G, Sinha R Biomolecules. 2022; 12(11).

PMID: 36358943 PMC: 9687893. DOI: 10.3390/biom12111593.

Neurosteroids (allopregnanolone) and alcohol use disorder: From mechanisms to potential pharmacotherapy.

Gatta E, Camussi D, Auta J, Guidotti A, Pandey S Pharmacol Ther. 2022; 240:108299.

PMID: 36323379 PMC: 9810076. DOI: 10.1016/j.pharmthera.2022.108299.

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