BACKGROUND: Human immunodeficiency virus (HIV) infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity. METHODS: We studied persons with HIV (PWH) and HIV-negative (HIV-) individuals who had used cannabis recently. We assessed 2 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 < .001). PWH had higher (more abnormal) BBB index values than HIV- individuals (mean ± SD, 0.361 ± 1.20 vs -0.501 ± 1.11; P = .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- individuals. Worse BBB index values were associated with higher NFL in CSF (r = 0.380, P = .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.
BACKGROUND: Human immunodeficiency virus (HIV) infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity. METHODS: We studied persons with HIV (PWH) and HIV-negative (HIV-) individuals who had used cannabis recently. We assessed 2 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 < .001). PWH had higher (more abnormal) BBB index values than HIV- individuals (mean ± SD, 0.361 ± 1.20 vs -0.501 ± 1.11; P = .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- individuals. Worse BBB index values were associated with higher NFL in CSF (r = 0.380, P = .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.
Authors: R Constantinescu; B Holmberg; L Rosengren; O Corneliusson; B Johnels; H Zetterberg Journal: Acta Neurol Scand Date: 2010-10-29 Impact factor: 3.209
Authors: Ana María Martín-Moreno; David Reigada; Belén G Ramírez; R Mechoulam; Nadia Innamorato; Antonio Cuadrado; María L de Ceballos Journal: Mol Pharmacol Date: 2011-02-24 Impact factor: 4.436
Authors: Oscar A Marcos-Contreras; Sara Martinez de Lizarrondo; Isabelle Bardou; Cyrille Orset; Mathilde Pruvost; Antoine Anfray; Yvann Frigout; Yannick Hommet; Laurent Lebouvier; Joan Montaner; Denis Vivien; Maxime Gauberti Journal: Blood Date: 2016-08-16 Impact factor: 22.113
Authors: Elen V Fagherazzi; Vanessa A Garcia; Natasha Maurmann; Thielly Bervanger; Luis H Halmenschlager; Stefano B Busato; Jaime E Hallak; Antônio W Zuardi; José A Crippa; Nadja Schröder Journal: Psychopharmacology (Berl) Date: 2011-08-26 Impact factor: 4.530
Authors: Magnus Gisslén; Richard W Price; Ulf Andreasson; Niklas Norgren; Staffan Nilsson; Lars Hagberg; Dietmar Fuchs; Serena Spudich; Kaj Blennow; Henrik Zetterberg Journal: EBioMedicine Date: 2015-11-22 Impact factor: 8.143
Authors: L J H Rasmussen; A Knudsen; T L Katzenstein; J Gerstoft; N Obel; N R Jørgensen; G Kronborg; T Benfield; A Kjaer; J Eugen-Olsen; A-M Lebech Journal: HIV Med Date: 2015-09-14 Impact factor: 3.180
Authors: Rowan Saloner; Jerel Adam Fields; Maria Cecilia Garibaldi Marcondes; Jennifer E Iudicello; Sofie von Känel; Mariana Cherner; Scott L Letendre; Marcus Kaul; Igor Grant Journal: J Neuroimmune Pharmacol Date: 2020-09-15 Impact factor: 4.147
Authors: C Wei-Ming Watson; Laura M Campbell; Ni Sun-Suslow; Suzi Hong; Anya Umlauf; Ronald J Ellis; Jennifer E Iudicello; Scott Letendre; Thomas D Marcotte; Robert K Heaton; Erin E Morgan; Igor Grant Journal: J Int Neuropsychol Soc Date: 2021-07 Impact factor: 3.114