Award
National Institute on Drug Abuse 5R01DA059874-02
Cannabinoid inhibition of CNS inflammasome activation via modulation of the gut-brain axis
Recipient
University of Nebraska Medical Center, Omaha, NE, United States
Award Amount
$879,451.00
Ceiling
$879,451.00
Awarded
February 20, 2026
Identifier
5R01DA059874-02
This NIH grant funds research on how cannabinoids may reduce inflammasome activation and inflammation in the CNS and gut caused by cocaine and HIV, potentially slowing disease progression through epigenetic mechanisms.
Description
The primary objective of this proposal is to investigate Cocaine/HIV/SIV induced changes in inflammasome activation and their epigenetic regulation in the intestine and brain and its modulation by long-term, low-dose cannabinoids and combination antiretroviral therapy. The NLRP3 inflammasome is a multiprotein complex that elicits an innate immune response to infection and cell stress through activation of caspase-1 and processing of pro-IL-1β and pro-IL-18 to their bioactive forms. Cocaine induces expression of inflammasomes and their associated genes in chronic HIV/SIV infection leading to persistent CNS and gastrointestinal inflammation, contributing to microbial translocation, immune activation, and disease progression. The study hypothesizes that supplementing Δ9-THC along with cART may reduce inflammasome activation, dysbiosis, restore immune function, and slow disease progression by modulating DNA methylation and gene expression.