Shared Predisposition in the Association Between Cannabis Use and Subcortical Brain Structure

Area of Science:

• Neuroimaging
• Genetics
• Addiction Research

Background:

• Prior studies suggest cannabis use alters brain structure.
• Siblings discordant for cannabis use allow disentangling causal effects from shared familial/genetic factors.

Purpose of the Study:

• To investigate the association between cannabis use and brain structure differences.
• To examine discordant sibling pairs to differentiate causal vs. predispositional factors.

Main Methods:

• Cross-sectional study of 483 participants (Human Connectome Project).
• Assessed lifetime cannabis use and brain volumes (whole-brain, hippocampus, amygdala, ventral striatum, orbitofrontal cortex).
• Utilized linear regressions and linear mixed models in sibling pairs (concordant and discordant for use).

Main Results:

• Cannabis exposure associated with smaller left amygdala and right ventral striatum volumes.
• Amygdala volume differences linked to shared genetic factors (ρg = -0.43).
• No significant brain volume differences found between discordant siblings; however, both showed reduced amygdala volumes compared to unexposed pairs.

Conclusions:

• Amygdala volume differences in cannabis users are largely attributable to shared genetic or environmental predispositional factors.
• Little evidence supports a direct causal influence of cannabis use on amygdala volume.
• Potential causal effects on other brain regions or with severe use warrant further investigation.