Aim: Prescription opioids are psychoactive substances that can elicit many neuropsychological effects. There are no studies that directly demonstrate the effects of prescription opioid addiction (POA) on the human brain. This study aimed to quantify γ-aminobutyric acid (GABA) and glutamate (Glu) levels in the prefrontal cortex (PFC) of POA patients using proton magnetic resonance spectroscopy ( 1 H-MRS), and to explore their association with impulsive behavior and cognitive impairment.Methods: Thirty-five patients with a definitive clinical diagnosis of codeine-containing cough syrup dependence and 35 matched healthy controls underwent neuropsychological assessments, namely the Barratt Impulsiveness Scale (BIS-11) and the Montreal Cognitive Assessment Scale (MoCA). Point-resolved spectroscopy was performed to detect GABA and glutamate within the medial PFC, and the corresponding levels were estimated using jMRUI and corrected for fraction of cerebrospinal fluid in the 1 H-MRS voxel. The difference in metabolite levels between groups and the correlation between metabolite levels and psychometric scores in patients were analyzed statistically.Results: The peak level predominantly consisting of GABA with a relatively small influence of other chemicals (GABA+) was lower and that of glutamate was higher in the PFC of POA patients than in healthy controls. GABA+ levels correlated negatively with BIS-11 scores but correlated positively with MoCA scores. In contrast, glutamate levels showed a positive correlation with BIS-11 scores but no significant correlation with MoCA scores. Conclusion:The quantitative in vivo measurement of GABA and glutamate levels in the PFC by 1 H-MRS could be a reliable way to evaluate impulsivity and cognitive function of POA.

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