Cannabis Use DisorderPhase 1/2PREG-CUD-MDDNCT07685964
Pregnenolone for Cannabis Use Disorder and Depression
A Phase 1/2 study testing Pregnenolone in people with Cannabis Use Disorder and Major Depressive Disorder (MDD), run by University of Texas Southwestern Medical Center at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Cannabis Use Disorder, Major Depressive Disorder (MDD)
- What is being tested?
- Pregnenolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2026to Aug 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
UT Southwestern Medical Center
Dallas, Texas, 75390
E. Sherwood Brown, 214-645-6950, SHERWOOD.BROWN@UTSouthwestern.edu
Reagan Volzer, Reagan.Volzer@UTSouthwestern.edu
University of Texas at Dallas
Richardson, Texas, 75080
Francesca Filbey, 972-883-2313, francesca.filbey@utdallas.edu
Aishwarya Veerkumar, 972-742-5842, aishwarya.veerkumar@utdallas.edu
About this study
Official title: Advancing Pregnenolone as a Novel Therapy for Co-Occurring Cannabis Use Disorder and Depression
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.
Read more
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.
Read the 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.
- Being tested
- Pregnenolone
- Keywords
- Pregnenolone, Cannabis Use, Depression, Neurosteroid, Pharmacokinetics, Feasibility Study
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregnenoloneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Pregnenolone 300mg/d | Experimental | Participants receive pregnenolone 300mg/d administered orally for approximately 12 weeks. The study will evaluate pharmacokinetics, safety, tolerability, and feasibility in adults with cannabis use disorder and major depressive disorder. Receives: Drug: Pregnenolone |
| Pregnenolone 500mg/d | Experimental | Participants receive pregnenolone 500mg/d administered orally for approximately 12 weeks. The study will evaluate pharmacokinetics, safety, tolerability, and feasibility in adults with cannabis use disorder and major depressive disorder. Receives: Drug: Pregnenolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Days of Cannabis Use
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.
Measured: 12 weeks
Secondary outcomes (2)
Depressive Symptom Severity
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.
Measured: 12 Weeks
Marijuana Craving
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.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2026
- Study startSep 2026 (estimated)
- Primary completionAug 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cannabis Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), The University of Texas at Dallas
- Responsible party
- Principal investigator, Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center
- Investigators
- E. Sherwood Brown, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07685964
- Sponsor's protocol ID
- STU20260979
- Other IDs
- 1UG3DA066242-01
- Acronym
- PREG-CUD-MDD
- Status last verified
- Jun 2026
- First submitted
- 29 Jun 2026
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mason BJ, Mustafa A, Filbey FM, Brown ES. Novel pharmacotherapeutic interventions for cannabis use disorders. Current Addiction Reports. 2016.
Osuji IJ, Vera-Bolanos E, Carmody TJ, Brown ES. Pregnenolone for cognition and mood in dual diagnosis patients. Psychiatry Res. 2010 Jul 30;178(2):309-12. doi: 10.1016/j.psychres.2009.09.006. Epub 2010 May 21.
PubMed 20493557Brown 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.
PubMed 24917198
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Advancing Pregnenolone as a Novel Therapy for Co-Occurring Cannabis Use Disorder and Depression
- ClinicalTrials.gov ID
- NCT07685964
- Acronym / sponsor ID
- PREG-CUD-MDD / STU20260979
- Keywords
- Pregnenolone, Cannabis Use, Depression, Neurosteroid, Pharmacokinetics, Feasibility Study
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), The University of Texas at Dallas
- Study start
- Sep 2026 (estimated)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 6 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Pregnenolone 300mg/d | Experimental | Drug: PregnenoloneParticipants receive pregnenolone 300mg/d administered orally for approximately 12 weeks. The study will evaluate pharmacokinetics, safety, tolerability, and feasibility in adults with cannabis use disorder and major depressive disorder. |
| Pregnenolone 500mg/d | Experimental | Drug: PregnenoloneParticipants receive pregnenolone 500mg/d administered orally for approximately 12 weeks. The study will evaluate pharmacokinetics, safety, tolerability, and feasibility in adults with cannabis use disorder and major depressive disorder. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PregnenolonePregnenolone 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. | Drug | Pregnenolone 300mg/d, Pregnenolone 500mg/d |
Primary outcome
Percent Days of Cannabis Use
Time frame: 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.
2 secondary outcomes
Depressive Symptom Severity
Time frame: 12 Weeks
Marijuana Craving
Time frame: 12 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- BackgroundMason BJ, Mustafa A, Filbey FM, Brown ES. Novel pharmacotherapeutic interventions for cannabis use disorders. Current Addiction Reports. 2016.
- Background: PubMed 20493557Osuji IJ, Vera-Bolanos E, Carmody TJ, Brown ES. Pregnenolone for cognition and mood in dual diagnosis patients. Psychiatry Res. 2010 Jul 30;178(2):309-12. doi: 10.1016/j.psychres.2009.09.006. Epub 2010 May 21.
- Background: PubMed 24917198Brown 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
E. Sherwood Brown principal investigator
University of Texas Southwestern Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pregnenolone in people with Cannabis Use Disorder and Major Depressive Disorder (MDD), run by University of Texas Southwestern Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact E. Sherwood Brown (214-645-6950, SHERWOOD.BROWN@UTSouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Days of Cannabis Use (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07685964, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.