Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use

This study investigated whether group-I metabotropic glutamate receptor subtype 5 (mGlu5) availability is altered in individuals with methamphetamine use disorder (MUD) during early abstinence (mean of 42 days). Researchers used positron emission tomography (PET) with the [18F]FPEB radiotracer to compare mGlu5 volume of distribution (VT) in the brains of 14 abstinent MUD participants and 14 matched controls. Additionally, they assessed the relationship between mGlu5 availability and performance on cognitive tasks covering verbal learning, spatial working memory, and inhibitory control, while also examining the impact of cigarette smoking on these receptor levels.

The researchers found no significant differences in global or regional mGlu5 availability between the MUD and control groups, suggesting that any initial receptor downregulation may recover during short-term abstinence. However, cigarette smoking was identified as a significant factor, with smokers across both groups exhibiting lower global mGlu5 availability compared to nonsmokers. In terms of cognition, while MUD participants significantly underperformed on spatial working memory, mGlu5 availability in the dorsolateral prefrontal cortex and superior frontal gyrus showed a positive correlation with verbal learning performance across all participants, regardless of group.

The results suggest that while mGlu5 expression does not remain chronically downregulated in MUD patients who have achieved short-term abstinence, this receptor system remains a relevant neurobiological target for cognitive function. Because cognitive impairment is a major barrier to successful MUD recovery, the link between dorsolateral prefrontal cortex mGlu5 levels and verbal memory highlights the potential for future pharmacological interventions aimed at improving cognitive outcomes in this population.