# The role of neuroactive steroids in stress, drug craving and drug use in cocaine use disorders

> **NIH NIH K01** · YALE UNIVERSITY · 2022 · $182,596

## Abstract

Project Summary/Abstract
 The research and training described in this Mentored Research Scientist Development (K01) Award
application will provide the candidate with the skills necessary to become an independent investigator in the
development of novel treatment targets in addictions. A multidisciplinary training and mentoring program is
proposed at the Yale University School of Medicine that will help assist in the transition to independent
research by providing structured mentoring, supervision and didactic techniques to address the following
training goals: a) treatment development and clinical outcomes in addictions, b) advanced training in drug
development pharmacology, and c) data analytical techniques relevant to experimental
psychopharmacological studies with repeated time-points and longitudinal multilevel drug use outcomes.
 In order to achieve these career training goals, an innovative research proposal has been designed to
use pregnenolone (PREG) as a mechanistic probe to increase levels of the potent GABA potentiating
neuroactive steroid allopregnanolone (ALLO) and examine (a) its effects on provoked stress and drug-cue
induced craving, and physiological, cognitive, emotional responses to stress and drug cue craving states, b)
the safety and pharmacokinetic (PK) / pharmacodynamic (PD) profile of various doses of PREG and its
conversion profile to downstream neuroactive steroids, and (c) explore its effects on daily cocaine craving,
mood symptoms and cocaine use outcomes for 8 weeks; and also explore gender differences in each of these
aims. The knowledge obtained from this MRSDA project would inform us on the role of PREG and ALLO in
emotional, physiological and neuroendocrine arousal in response to stress and drug-cue exposure which are
important predictors of relapse; its safety and PK/PD, and its metabolism into downstream neuroactive steroids
which have not been previously tested in CUD; its effects on individual cocaine craving and drug use in
ecologically valid environments of cocaine users; and gender differences that may exist in these outcomes. All
of these are novel and never before addressed questions in cocaine addiction.
 The hands-on design and execution of the proposed research, combined with the structured mentoring,
supervision and didactic training, will allow the candidate to meet much needed training goals, and generate
preliminary data on pregnenolone and other neurosteroid analogs as novel and potential treatment targets in
cocaine addiction for the design and submission of an R01 proposal in Year 04 of MRSDA training. Hence, this
MRSDA will be a crucial stepping stone in the candidate's progression toward scientific independence.

## Key facts

- **NIH application ID:** 10337189
- **Project number:** 5K01DA046561-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** VERICA MILIVOJEVIC
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,596
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337189

## Citation

> US National Institutes of Health, RePORTER application 10337189, The role of neuroactive steroids in stress, drug craving and drug use in cocaine use disorders (5K01DA046561-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10337189. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*