Cannabis-related hippocampal volumetric abnormalities specific to subregions in dependent users

Rationale: Cannabis use is associated with neuroanatomical alterations in the hippocampus. While the hippocampus is composed of multiple subregions, their differential vulnerability to cannabis dependence remains unknown. Objectives: The objective of the study is to investigate gray matter alteration in each of the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields CA1–4, and dentate gyrus (DG)) as associated with cannabis use and dependence. Methods: A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and 39 dependent (CB-dep) cannabis users were recruited. We investigated group differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep users. We further explored the association between CB use variables (age of onset of regular use, monthly use, lifetime use) and hippocampal subregions in CB-nondep and CB-dep users separately. Results: The CA1, CA2/3, CA4/DG, as well as total hippocampal gray matter were reduced in volume in CB-dep but not in CB-nondep users, relative to HC. The right CA2/3 and CA4/DG volumes were also negatively associated with lifetime cannabis use in CB-dep users. Conclusions: Our results suggest a regionally and dependence-specific influence of cannabis use on the hippocampus. Hippocampal alteration in cannabis users was specific to the CA and DG regions and confined to dependent users.