$11.6 million NIDA grant supports the study of cannabis effects on HIV-infected brains

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Weill Cornell Medicine has been awarded a five-year, $11.6 million grant from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health to study the effects cannabis, including marijuana and compounds derived from it, may have on the brains of those living with HIV.

We know that the virus may cause changes within the brain, but it's not clear yet how the use of cannabis might interact with the infection."

Dr. Lishomwa Ndhlovu, principal investigator, professor of immunology in medicine in the Division of Infectious Diseases at Weill Cornell Medicine

Cannabis may exacerbate HIV's effects on the brain, or it may protect against them, researchers don't know yet, he said. "This support from NIDA will allow us to collect the data we need to explore this relationship."

The project is the newest component of NIDA's SCORCH program, which seeks to investigate how substances that can lead to addiction may modify the effects of HIV in the brain, at the level of individual cells. Dr. Ndhlovu; Dr. Michael Corley, an assistant professor of immunology in medicine in the Division of Infectious Diseases; and Dr. Dionna Whitney Williams, an assistant professor of molecular and comparative pathobiology at Johns Hopkins University School Medicine, are leading the cannabis research, which is the second SCORCH project based at Weill Cornell Medicine. An earlier project, begun in 2021, is mapping the effects of chronic opioid exposure in the brain.

Advancements in treatment have turned HIV into a chronic condition. Although those with the virus can now live longer lifespans, HIV may still cause damage, including to the brain. Up to half of those living with HIV may experience declines in cognitive function, particularly in working memory and attention.

Studies have found that people living with HIV frequently use cannabis, recreationally or to treat symptoms related to HIV. As a potentially addictive substance, it too alters the brain, and people with HIV may be at risk for cannabis use disorder.

Cannabis may also offer benefits for those living with HIV. It has an anti-inflammatory effect that researchers speculate could tamp down the chronic, harmful inflammation caused by the virus. Researchers think this inflammation contributes to the long-term health problems, including cognitive deficits, that people living with HIV may experience.

"Findings from our lab and others demonstrate that inflammation can influence cognition in people living with HIV, and we're aiming to understand whether cannabis can mitigate those effects and how it does this on a molecular level," said Dr. Williams.

To examine the interaction between cannabis and HIV, the research team will focus on several brain regions, including the hippocampus, where new neurons form, in a process critical to learning and memory. Using brain tissue samples collected from human patients after death and from non-human animal models, they intend to look at gene activity and the mechanisms controlling it within individual cells.

"It's unclear how different types of brain cells react to cannabis in the context of HIV," Dr. Corley said. "New single-cell technologies will allow us to map these changes at a resolution high enough to examine the effects on specific cell types."

The information this project generates could, over the long-term, aid efforts to better prevent and treat HIV-related cognitive deficits and cannabis use disorder, according to the researchers.

Dr. Robert O'Brien, assistant professor of immunology in medicine, and Dr. Howard Fine, founding director of the Brain Tumor Center at NewYork-Presbyterian Weill Cornell Medical Center and associate director for translational research at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, are also investigators on this project.

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