Only cannabis-dependent users, not regular users, showed smaller hippocampi in a large multi-site study

Cannabis users as a whole (n=140) did not differ from controls (n=121) in hippocampal volume or shape. However, dependent users (n=70) had significantly smaller right and left hippocampi compared to both controls (n=106) and non-dependent users (n=50), regardless of cannabis dosage. Shape analysis revealed localized deflations in the superior-medial body of the hippocampus.

Multi-site study aggregating MRI data from four research sites. Three comparison levels: users vs controls; dependent vs non-dependent vs controls; matched subsample controlling for onset age and dosage. Volumetric and vertex-level shape analysis.

This study resolves a longstanding debate by showing that hippocampal changes are specific to dependence, not cannabis use per se. The finding held after controlling for dose, suggesting dependence involves neurobiological changes beyond the direct pharmacological effects of cannabis.

The distinction between cannabis use and cannabis dependence may be the key variable that reconciles conflicting findings in the neuroimaging literature. Studies that lump all users together may miss dependence-specific effects or falsely attribute them to cannabis use in general.

Cross-sectional design cannot determine if smaller hippocampi preceded or followed dependence. Multi-site aggregation introduces variability. Cannabis dependence diagnosis varied across sites. Other substance use and mental health comorbidities may contribute.