Association Between Cannabis Use and Brain Structures: A Mendelian Randomization Study

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Observational studies suggest cannabis use alters brain structures.
• Confounding factors in previous studies limit causal inference.
• Mendelian randomization (MR) offers a robust approach to investigate causality.

Purpose of the Study:

• To investigate the potential causal association between cannabis use and brain structure.
• To analyze effects on both cortical and subcortical brain regions.
• To differentiate between lifetime cannabis use (LCU) and cannabis use disorder (CUD).

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analysis.
• Employed genome-wide association studies (GWAS) data for LCU, CUD, and brain structures (cortical surface area/thickness, subcortical volumes).
• Applied inverse-variance weighted (IVW), MR-Egger, and weighted median methods, with heterogeneity and pleiotropy tests.

Main Results:

• Lifetime cannabis use (LCU) showed no causal link with global cortical surface area or thickness.
• LCU was associated with decreased thickness in fusiform and lateral occipital cortex, and increased thickness in the postcentral cortex.
• LCU was linked to increased brainstem volume, but these findings lacked statistical significance after multiple comparison corrections. Cannabis use disorder (CUD) showed no causal associations.

Conclusions:

• Current evidence is insufficient to establish a causal relationship between cannabis use and brain structure alterations.
• Further research with larger datasets and advanced methodologies may be needed.
• The study highlights the complexity of investigating cannabis's neurological effects.