Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users

Background: Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes. Methods: Proton magnetic resonance spectroscopy (H-1-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects. Results: A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p =.0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R-2 =.66, p =.004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids. Conclusions: Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease.