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Effect of Cannabis Use on Brain Metabolites in People with HIV Using Whole-Brain Magnetic Resonance Spectroscopic Imaging

Teddy Salan, PhD
University of Miami

Co-Authors: Fernando M Moradel Cano1, Sulaiman A Sheriff1, Dario N Ayala1, Ranya Marrakchi El Fellah1, Eva Widerstrom-Noga1, Suresh Pallikkuth1, Denise C Vidot1, Allan E Rodriguez1, Robert L Cook2, Varan Govind1
1University of Miami, 2University of Florida

Background: Cannabis use among people with HIV (PWH) is higher than the general population, with studies reporting 77% of lifetime cannabis use in PWH, compared to 44.5% generally. While both HIV and cannabis are known to alter metabolites in the brain, little is known about their additive effect. 

Objective: The goal of this study is to investigate neurometabolite alterations due to cannabis and HIV infection at the whole-brain level, using our unique Magnetic Resonance Spectroscopic Imaging (MRSI) technique. Measured brain metabolites include N-acetyl aspartate (NAA; neuronal viability marker), creatine (Cre; cellular energy marker), choline (Cho; membrane turnover marker), glutamate+glutamine (Glx; neurotransmitters) and myo-inositol (m-Ins; inflammation marker).

Methods: MRI data were collected on a 3T scanner from 54 subjects, following a 2×2 design: 16 PWH using cannabis (PWH+C; 38±7.5 y.o.), 7 PWH not using cannabis (PWH; 39±4.2 y.o.), 17 people without HIV (PWoH) using cannabis (PWoH+C; 37.4±7.8 y.o.), and 14 PWoH not using cannabis (PWoH; 30.4±8.8 y.o.) as healthy controls. The protocol included whole-brain short-TE MRSI (TE/TR: 17.6/1551 ms; 17 minutes) and T1-MRI. MRSI data were processed using MIDAS software to estimate neurometabolite concentrations at 47 brain anatomical regions-of-interest (ROI) from the AAL47 atlas, using appropriate data quality criteria. At each ROI, we performed non-parametric two-way ANOVA to find the effect of HIV and cannabis on metabolite levels (significance at p<0.05 in this preliminary analysis).

Results: We found significant independent effects of cannabis and HIV, with significant interaction effect, on NAA in key brain regions (precentral lobe, p<0.001; frontal lobe, p=0.004; superior motor cortex, p=0.016; cingulate gyrus, p=0.007). Among PWoH, NAA was lower in PWoH+C compared to PWoH; among cannabis non-users, NAA was lower in PWH than PWoH. Similar findings were observed for Glx (precentral lobe, p=0.005; frontal lobe, p=0.006; superior motor cortex, p=0.02), Cho (precentral lobe, p=0.016), and Cr (precentral lobe, p=0.016; frontal lobe, p=0.003). We found significantly higher m-Ins for PWoH+C compared to PWoH (rolandic operculum, p=0.002; insula, p =0.002), with no significant interactions.

Conclusions: Significant interactions between HIV and cannabis on NAA, Glx, Cho, and Cr, with lower concentrations for PWoH+C vs. PWoH and PWH vs. PWoH, showed that cannabis and HIV both accentuates neurometabolite alterations, neuronal dysfunction, and neurotransmitters disruption. However, neuroinflammation (m-Ins) was only found to be higher in PWoH+C vs. PWoH. Future analyses will examine the effect of relevant co-variates such as BMI, sex, frequency/duration and mode of cannabis administration, and cannabinoid metabolites in blood.