Pregnenolone for Cannabis Use Disorder and Depression

Официальное название

Advancing Pregnenolone as a Novel Therapy for Co-Occurring Cannabis Use Disorder and Depression

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Pregnenolone
  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.

Первичные конечные точки

• Percent Days of Cannabis Use [Срок оценки: 12 weeks]

Вторичные конечные точки (2)

• Depressive Symptom Severity [Срок оценки: 12 Weeks]
• Marijuana Craving [Срок оценки: 12 Weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• UT Southwestern Medical Center — Dallas
• University of Texas at Dallas — Richardson

Публикации

• 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. PMID 20493557
• 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

Идентификаторы

NCT: NCT07685964 · STU20260979 · 1UG3DA066242-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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