Pregnenolone for Cannabis Use Disorder and Depression

(PREG-CUD-MDD Trial)

Not yet recruiting at 1 trial location
ES
FF
Overseen ByFrancesca Filbey
Age: 18 - 65
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: University of Texas Southwestern Medical Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This is UG3 phase of a multi-site, milestone-driven UG3/UH3 research program evaluating pregnenolone for individuals with co-occurring cannabis use disorder (CUD) and major depressive disorder (MDD). Pregnenolone is a neurosteroid that modulates cannabinoid receptor signaling and may reduce cannabis-related effects while also improving mood-related symptoms.

The primary objective of the UG3 phase is to establish feasibility and generate preliminary data to support a subsequent UH3 randomized clinical trial. Key preparatory activities include obtaining regulatory approvals (including FDA Investigational New Drug \[IND\] protocol amendment and Institutional Review Board approvals), harmonizing study procedures across participating sites, and implementing data management and monitoring systems.

The UG3 phase includes two main components. First, a pharmacokinetic study willcharacterize pregnenolone pharmacokinetics in adults with CUD and MDD, including measures such as half-life and clearance. Second, a pilot clinical study will evaluate the feasibility, safety, and tolerability of pregnenolone administered orally over approximately 12 weeks. Feasibility outcomes include recruitment rates, retention, and adherence to study procedures, while safety and tolerability will be assessed through adverse event monitoring and discontinuation rates.

Participants will be adults aged 18 to 50 years with diagnoses of cannabis use disorder and major depressive disorder, who report frequent cannabis use and express interest in reducing their use. Clinical assessments of cannabis use, mood symptoms, and related behavioral outcomes will be collected.

The UG3 phase will be used to refine study procedures, inform dosing strategies, and establish benchmarks necessary for progression to the UH3 phase. The subsequent UH3 phase will involve a multi-site, randomized, double-blind, placebo-controlled trial evaluating the efficacy of pregnenolone in reducing cannabis use and improving depressive symptoms in this population.

Who Is on the Research Team?

ES

E. Sherwood Brown

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 50 who have both major depression and cannabis use disorder. Participants must use cannabis frequently and want to cut down their use.

Inclusion Criteria

Cannabis use on at least 4 days per week in the past 4 weeks
I am between 18 and 50 years old.
Diagnosis of cannabis use disorder according to DSM-5 criteria
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Exclusion Criteria

Current diagnosis of other substance use disorders (except nicotine)
Current or past diagnosis of psychotic disorders, bipolar disorder, or severe psychiatric conditions
Significant or unstable medical conditions that would interfere with study participation
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What Are the Treatments Tested in This Trial?

Interventions

  • Pregnenolone

Trial Overview

The study is testing pregnenolone, a neurosteroid taken by mouth, to see if it can help people with both depression and heavy cannabis use. The first phase checks how the body processes the drug and whether it's safe over about 12 weeks.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Group I: Pregnenolone 500mg/dExperimental Treatment1 Intervention
Group II: Pregnenolone 300mg/dExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials
1,102
Recruited
1,077,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials
2,658
Recruited
3,409,000+

The University of Texas at Dallas

Collaborator

Trials
71
Recruited
108,000+