Insular Cortical Thinning and Altered Structural Connectivity in Chronic Cannabis Users: A High-Resolution Morphometry and Diffusion Tractography Study

Abstract

Background: Available evidence concerning the influence of sustained cannabis use on insular structure remains inconsistent, and comparatively little is known about whether localized cortical alterations coexist with changes in insular white-matter connections. This research investigated the shape of the insula and the structural connectivity centered on the insula in individuals who are chronic cannabis users (CCU). Methods: A group of twenty-six men, consisting of 13 regular cannabis users and 13 non-users, participated in structural and diffusion MRI scans at 3 Tesla. The YBA-696 parcellation was used to estimate insular thickness and volume at parcel and hemispheric levels, while FreeSurfer provided subcortical volumetric measures. We mapped insular pathways using probabilistic iFOD2 tractography in MRTrix3 and described them by fractional anisotropy, axial diffusivity, mean diffusivity, and radial diffusivity. The data were analyzed using general linear models that incorporated a comprehensive set of relevant covariates, with the Benjamini-Hochberg procedure subsequently applied to control the family-wise error rate by controlling the false discovery rate. Results: Compared with controls, cannabis users exhibited thinner cortices in both insulae, with eight individual parcels remaining significant after false-discovery-rate correction. Insular volume was similar across groups. Additionally, cannabis users showed reduced total gray-matter volume and smaller brainstem, right thalamus, left cerebellar cortex, left amygdala, and right orbitofrontal gyrus volumes. Connectivity analyses demonstrated lower mean diffusivity in the left insula-amygdala pathway, additional parcel-specific abnormalities within this system, and lower fractional anisotropy in connections linking the right insula to the hippocampus and precentral gyrus, and the left insula to occipital regions. Conclusion: Rather than inducing generalized atrophy of the insula, long-term cannabis exposure was associated with focal cortical thinning in this region and selective microstructural changes confined primarily to limbic and cortical pathways. These findings implicate networks involved in salience, affective processing, and sensorimotor integration. Because the study was cross-sectional, larger longitudinal investigations are needed to establish the direction and clinical relevance of these associations. Copyright © 2026 The Author(s); This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-By-NC: https://creativecommons.org/licenses/by-nc/4.0/legalcode.en), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.