Cannabis May Have a Beneficial Effect on HIV-Associated Blood-Brain Barrier Injury

By Marilynn Larkin

April 30, 2020

NEW YORK (Reuters Health) - For people living with HIV, cannabis use may have a beneficial impact on HIV-associated blood-brain barrier (BBB) injury, a small study suggests.

"HIV infection leads to (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy and is associated with adverse clinical outcomes," note Dr. Ronald Ellis of the University of California, San Diego and colleagues. "In preclinical models, cannabis restores BBB integrity."

"Since BBB disruption may permit entry of toxins into the brain, cannabis may help protect against consequent CNS injury," Dr. Ellis told Reuters Health by email.

The team studied people with HIV (PWH) and HIV-negative individuals who had used cannabis recently. They assessed two biomarkers of BBB permeability: the cerebrospinal fluid (CSF)-to-serum albumin ratio (CSAR), and CSF levels of soluble urokinase plasminogen activator receptor (suPAR), a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB.

As reported in Clinical Infectious Diseases, 45 PWH and 30 HIV-negative individuals (mean age, 41) were included in the study; 17% of participants in the PWH group were women versus none in the control group.

Among PWH, higher CSF suPAR levels correlated with higher CSAR values. PWH had higher (more abnormal) BBB index values than HIV-negative individuals (0.361 vs. -0.501).

HIV serostatus interacted with cannabis use frequency - i.e., more frequent use of cannabis was associated with lower BBB index values in PWH but not in those who were HIV-negative. Further, worse BBB index values were associated with higher neurofilament light in CSF.

Dr. Ellis said, "We are currently conducting studies aimed at determining effecting doses, and whether potential benefits are attributable to THC or cannabidiol."

"It is possible that HIV-positive individuals without BBB breakdown would not benefit from cannabis," he added. "We need to determine the long-term effects of exogenous cannabinoids on the endocannabinoid system and whether long-term use might have deleterious rather than beneficial effects."

Dr. Robert Powers, of the Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, Connecticut, commented in an email to Reuters Health, "HIV infection can lead to some degree of blood-brain barrier dysfunction, with the potential for a deleterious effect on the patient."

"Using a complex statistical evaluation of brain biomolecules, the researchers demonstrated, among a relatively small group of HIV-positive and HIV-(negative) individuals, that marijuana use frequency was apparently associated with a somewhat improved measure of blood-brain barrier function," he said.

"These results, while slight and perhaps somewhat tenuous, are at least suggestive that cannabis use may be associated in some users, with lessened impact of HIV infection on the blood brain barrier," he concluded.

SOURCE: Clinical Infectious Diseases, online April 16, 2020.