Cannabis use leaves a distinct DNA methylation signature in people with first-episode psychosis

Current cannabis use was associated with differential methylation at a site in the CAVIN1 gene, independent of tobacco effects. High-potency cannabis (THC >= 10%) was associated with a site in the MCU gene. Pathway analysis identified epigenetic variation near genes linked to immune and mitochondrial function. An interaction analysis suggested that first-episode psychosis status may moderate how cannabis affects DNA methylation.

Two independent cohorts totaling 682 participants (188 current cannabis users, 494 never users) with first-episode psychosis and controls. DNA methylation profiles were generated from blood samples using Illumina arrays. Meta-analysis across cohorts identified significant sites, controlled for tobacco-related methylation signatures.

Epigenetic changes represent a molecular mechanism through which cannabis exposure could have lasting biological effects. Identifying cannabis-specific methylation changes, separate from tobacco, and finding that psychosis status may modify these effects adds mechanistic insight to the cannabis-psychosis relationship.

The finding that immune and mitochondrial pathways are epigenetically affected by cannabis aligns with known cannabinoid biology. The interaction between cannabis use and psychosis status on methylation patterns raises the possibility that people who develop psychosis may process cannabis exposure differently at the molecular level.

Cross-sectional design cannot determine whether methylation changes preceded or followed cannabis use or psychosis onset. Blood-based methylation may not reflect brain tissue changes. The modest sample of 188 users limits power to detect smaller effects. Only current use was assessed, not lifetime exposure patterns.