How gene changes tied to cannabis use and depression affect the brain
Official title: Functional convergence following disruption of diverse genes associated with cannabis use and major depression
Funded at Yale University · NIH-11179270 · Data updated 2026-11-12
This project looks for molecular changes in brain tissue from people with cannabis use disorder or major depression to link cannabis exposure with biological changes that may raise depression risk.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Yale University NIH-funded |
| Lab location | 1 site (New Haven, United States) |
| Project start | September 1, 2024 |
| Project end | July 31, 2029 |
| Funding year | 2025 |
| Award (this year) | $441,000 |
| NIH project number | 5DP1DA060811-02 |
| Project ID | NIH-11179270 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal participants are people with a history of cannabis use disorder or major depressive disorder, and individuals willing to participate in tissue donation programs tied to the study.
✕Less likely to help
People without a history of cannabis use or depression and those seeking immediate clinical care are unlikely to gain direct benefit from this basic and discovery-focused research.
What this research studies
The team will analyze single-cell genomic and chromatin data from postmortem brain tissue of 120 donors, including people with cannabis use disorder, people with major depression, and neurotypical controls. They will focus on the dorsolateral prefrontal cortex and the ventral striatum to measure gene activity and DNA packaging in specific cell types. The researchers will connect those findings to genetic risk signals from large studies and prioritize genomic regions and genes that may drive vulnerability. Prioritized genes will be tested in human iPSC-derived brain organoids using large-scale genetic perturbations to see how disrupting them changes brain development and stress responses.
Why it matters
Potential benefit: If successful, this work could reveal biological targets and pathways that explain how cannabis use raises the risk of depression, guiding future prevention or treatment strategies.
How similar studies have gone: Prior postmortem genomic studies and iPSC organoid experiments have shed light on psychiatric disorders, but combining single-cell postmortem genomics with GWAS-linked reverse genetics for cannabis-related depression is relatively new.
Where this research is happening
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Yale University
New Haven, United States Active
Researchers
- Principal investigator: Girgenti, Matthew J — Yale University
- Study coordinator: Girgenti, Matthew J
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.