Pregnenolone Treatment for Alcohol Use Disorder and Major Depressive Disorder

NCT07734701 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STU20261165R01AA033156
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate whether pregnenolone is an effective treatment for adults with Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD). Participants will be randomly assigned to receive either pregnenolone or placebo for 12 weeks in a double-blind study. Researchers will assess alcohol consumption, alcohol craving, depressive symptoms, and anxiety symptoms throughout treatment. The study will also use magnetic resonance imaging (MRI) to examine how pregnenolone affects brain circuits involved in addiction and mood regulation. The goal is to determine whether pregnenolone can improve both alcohol-related and mood-related outcomes and to identify the neural mechanisms associated with treatment response.

Conditions

Alcohol Use Disorder (AUD); Major Depressive Disorder (MDD)

Keywords

Pregnenolone; Alcohol Use Disorder; Major Depressive Disorder; Neurosteroids; fMRI; Anxiety; Substance Use Disorders

Outcome Measures

Primary Outcomes (1)

• Alcohol Consumption

  Change in alcohol consumption from baseline to Week 12. The timeline follow-back (TLFB) is a semi-structured interview method assessing recent drinking in which participants retrospectively estimate daily quantity of alcohol consumption during specified time periods. The TLFB will be used to assess alcohol use including drinks/drinking day and drinks/day (7-day average).

  Baseline to Week 12

Secondary Outcomes (4)

• Alcohol Craving

  Baseline to Week 12

• Depressive Symptom Severity

  Baseline to Week 12

• Anxiety Symptom Severity

  Baseline to Week 12

• Amygdala-Prefrontal Functional Connectivity

  Baseline and Week 12

Study Arms (2)

Pregnenolone

EXPERIMENTAL

Participants will receive pregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks.

Drug: Pregnenolone

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo capsules administered twice daily for 12 weeks.

Drug: Placebo

Interventions

Pregnenolone DRUG

Pregnenolone 500 mg/day administered as 250 mg twice daily for 12 weeks.

Pregnenolone

Placebo DRUG

Matching placebo capsules administered twice daily for 12 weeks.

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 21 to 55 years.
• Meets DSM-5 criteria for Alcohol Use Disorder (AUD).
• Meets DSM-5 criteria for Major Depressive Disorder (MDD).
• Able to provide informed consent.
• Willing and able to comply with study procedures and assessments

You may not qualify if:

• Current diagnosis of bipolar disorder, schizophrenia spectrum disorder, or other psychotic disorder.
• Current substance use disorder requiring immediate treatment other than alcohol or nicotine.
• Significant unstable medical or neurologic illness that would interfere with participation or study assessments.
• Contraindications to magnetic resonance imaging (MRI).
• Current pregnancy or breastfeeding.
• Current use of medications or treatments that would interfere with study participation or interpretation of results.
• Significant suicide risk requiring a higher level of care.
• Any condition that, in the investigator's judgment, would make participation unsafe or compromise study integrity.

Sponsors & Collaborators

• Duke University: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• Sherwood Brown, MD, PhD: lead
• The University of Texas at Dallas: collaborator

Study Sites (2)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas at Dallas

Richardson, Texas, 75080, United States

Location

Related Publications (2)

• Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014 Nov;39(12):2867-73. doi: 10.1038/npp.2014.138. Epub 2014 Jun 11.

  PMID: 24917198 BACKGROUND

• Mason BL, Van Enkevort E, Filbey F, Marx CE, Park J, Nakamura A, Sunderajan P, Brown ES. Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis Use Disorders. J Clin Psychopharmacol. 2017 Dec;37(6):684-688. doi: 10.1097/JCP.0000000000000793.

  PMID: 29045302 BACKGROUND

MeSH Terms

Conditions

Alcoholism; Depressive Disorder, Major; Anxiety Disorders; Substance-Related Disorders

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Depressive Disorder; Mood Disorders

Intervention Hierarchy (Ancestors)

Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Central Study Contacts

E. Sherwood Brown

CONTACT

214-645-6950; SHERWOOD.BROWN@UTSouthwestern.edu

Francesca Filbey

CONTACT

972-883-2313; francesca.filbey@utdallas.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a randomized, double-blind, placebo-controlled trial. Participants, investigators, and care providers will remain blinded to treatment assignment throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomized in a parallel-group design to receive either pregnenolone 500 mg/day or matching placebo for 12 weeks.

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 29, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031
• Last Updated: July 29, 2026

Record last verified: 2026-07

Locations

US (2)