Background: HIV infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity.

Methods: We studied people with HIV (PWH) and HIV- individuals who had used cannabis recently. We 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. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay.

Results: Participants were 45 PWH and 30 HIV- individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r=0.47; p<0.001). PWH had higher (more abnormal) BBB index values than HIV- individuals (mean +/- SD 0.361 +/-1.20 versus -0.501 +/- 1.11; p=0.0214). HIV serostatus interacted with cannabis use frequency such that more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV-. Worse BBB Index values was associated with higher NFL in CSF (r=0.380, p=0.0169).

Conclusions: Cannabis may have a beneficial impact on HIV-associated BBB injury. Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity.