Widespread reductions in cortical thickness following ketamine abuse.

Chronic, non-medical use of ketamine is associated with widespread thinning of the brain's outer layer, the cortex. Compared with healthy controls, 95 people with ketamine use disorder showed reduced cortical thickness in many regions, most extensively in the frontal and parietal lobes, including the dorsolateral prefrontal cortex and precuneus. No areas of increased thickness were observed. Greater estimated lifetime ketamine consumption correlated with thinner cortex in the right inferior parietal and right rostral middle frontal regions. These findings highlight potential long-term structural brain changes from non-medical ketamine use and serve as a reference for its antidepressant use.

Study at a glance

Abstract

Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.