Federal Cooperative Agreement Summary

The University of Texas Southwestern Medical Center received a $825,374 Cooperative Agreement from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) awarded on May 15, 2026, with completion targeted for April 30, 2028. The primary deliverable is research advancing pregnenolone as a novel pharmacotherapeutic intervention for individuals with co-occurring cannabis use disorder (CUD) and depression. The research initiative will examine how pregnenolone, a neurosteroid that acts as a negative allosteric modulator of the cannabinoid CB1 receptor, can simultaneously reduce cannabis use while alleviating depressive symptoms by leveraging the endocannabinoid system's dual involvement in both mood regulation and cannabis reinforcement. This work directly addresses a significant clinical gap, as no FDA-approved pharmacotherapies currently exist for CUD, particularly for patients with comorbid depression—a population exhibiting more severe clinical profiles, earlier symptom onset, greater functional impairment, and poorer treatment outcomes.

The research builds upon preliminary human studies demonstrating pregnenolone's capacity to attenuate cannabis effects in the brain and prior clinical work showing pregnenolone's efficacy in reducing both substance use and depressive symptoms in individuals with bipolar disorder and alcohol use disorder. The cooperative agreement mechanism reflects NIDA's collaborative support for translational research converting preclinical findings into clinically applicable interventions addressing substance use, addiction, and related health outcomes.