Cannabis Use Disorder, Major Depressive Disorder (MDD)
Conditions
Keywords
Pregnenolone, Cannabis Use, Depression, Neurosteroid, Pharmacokinetics, Feasibility Study
Brief summary
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.
Detailed description
This study represents the UG3 phase of a multi-site, milestone-driven UG3/UH3 research program evaluating pregnenolone as a novel pharmacotherapy 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 will be conducted to characterize 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 DSM-5 diagnoses of cannabis use disorder and major depressive disorder, who report frequent cannabis use and express interest in reducing their use. Standardized clinical assessments of cannabis use, mood symptoms, and related behavioral outcomes will be collected. Data obtained during 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.
Interventions
DRUGPregnenolone
Pregnenolone is a neurosteroid administered orally. It is being studied for its pharmacokinetics, safety, tolerability, and feasibility in adults with cannabis use disorder and major depressive disorder.
Sponsors
University of Texas Southwestern Medical Center
National Institute on Drug Abuse (NIDA)
The University of Texas at Dallas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study in which participants, care providers, investigators, and outcomes assessors are masked to treatment assignment.
Intervention model description
Participants will be assigned to different intervention conditions in parallel groups to evaluate pharmacokinetics, feasibility, safety, and tolerability of pregnenolone in adults with cannabis use disorder and major depressive disorder.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 18 to 50 years * Diagnosis of cannabis use disorder according to DSM-5 criteria * Diagnosis of major depressive disorder according to DSM-5 criteria * Cannabis use on at least 4 days per week in the past 4 weeks * Positive urine screen for tetrahydrocannabinol (THC) * Willingness to reduce cannabis use * Medication-free or on a stable dose of antidepressant medication * Able to provide informed consent
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 * Pregnant or breastfeeding * Active suicidal or homicidal ideation requiring immediate intervention * Use of medications that may interfere with study drug or outcomes, unless stable * Allergy or sensitivity to pregnenolone or related compounds * History of hormone-sensitive cancer or tumor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Days of Cannabis Use | 12 weeks | The Timeline Follow Back (TLFB) interview will be used to assess cannabis use. The percent days of cannabis use will be the primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptom Severity | 12 Weeks | The Montgomery-Asberg Depression Rating Scale (MADRS) is a widely used 10-item observer-rated measure of depressive symptomatology designed for use in clinical trials. |
| Marijuana Craving | 12 Weeks | The Marijuana Craving Questionnaire (MCQ) will be used to assess marijuana craving at each study visit. The MCQ was adapted from a valid tobacco craving questionnaire and has proven to be useful in previous marijuana (MJ) studies. This measure will be used to determine subjective craving. |
Countries
United States
Contacts
CONTACTE. Sherwood Brown
CONTACTFrancesca Filbey
PRINCIPAL_INVESTIGATORE. Sherwood Brown
University of Texas Southwestern Medical Center
Outcome results
None listed