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BENEFICIAL EFFECTS OF CANNABIS ON BLOOD-BRAIN BARRIER AND INFLAMMATION IN HIV
Ronald J. Ellis1, Jennifer Iudicello2, Erin Morgan1, Brook Henry1, Rachel Schrier2, Mariana Cherner2, Martin Hoenigl2, Scott L. Letendre2
1University of California San Diego, La Jolla, CA, USA,2University of California San Diego, San Diego, CA, USA
HIV infection is associated with increased permeability of the blood-brain barrier (BBB), which may permit increased entry of toxins with consequent CNS injury. Cannabis, which is commonly used among people living with HIV (PLWH); has anti-inflammatory effects; and stabilizes the BBB in animal models. One potential mechanism of increased BBB permeability is upregulation of the urokinase plasminogen activator (uPA), a matrix-degrading proteolytic enzyme, and its receptor, uPAR, disrupting the basal lamina around cerebral capillaries. This study sought to determine the effects of recent cannabis use on cerebrospinal fluid (CSF) concentrations of uPAR, CSF-to-serum albumin ratio (CSAR, an indicator of BBB permeability), and neuroinflammation among PLWH.
Participants were 45 recent (i.e., within the past month) cannabis users with (HIV+) or without HIV (HIV-) who were comparable in age (mean age=39.3) and sex (93.3% male). CSF levels of soluble uPAR, soluble CD14 (sCD14) and CXCL-10 were measured by immunoassay. Albumin was measured in CSF by nephelometry and in serum by a clinical assay. Data were analyzed using standard statistical methods, including regression and t-tests.
A statistically significant interaction (p=0.025) was present between HIV and cannabis use frequency (total days over the past month): more frequent use of cannabis was associated with lower concentrations of uPAR in CSF in the HIV+ group (p=0.043) but not in the HIV- group. The CSAR showed similar but non-statistically significant effects. Within the HIV+ group, higher CSF uPAR levels correlated with higher CSAR values (rho=0.47; p<0.001), and more inflammation [higher concentrations of CXCL-10 (p=0.003) and sCD14 (p<0.0001)].
These preliminary findings suggest that cannabis may have a beneficial impact on HIV-associated BBB injury and neuroinflammation. Given the role of the BBB in HIV-associated CNS injury, these results support the potential therapeutic role of cannabis among PLWH, and may have important treatment implications for antiretroviral therapy effectiveness and toxicity.