Ponto, Nicole2025-08-222025-08-222025-08-21https://hdl.handle.net/10222/85378This thesis investigated whether cannabis use and psychotic-like experiences jointly affect adolescent white matter development. It introduced the first adolescent-specific white matter atlas, found no significant group or interaction effects, but highlighted sex differences and the importance of continuous cannabis measures, providing a methodological foundation for future research.Adolescence is a sensitive period of white matter development, during which cannabis use and psychotic-like experiences (PLEs) each increase risk for later psychotic disorders. This thesis examined whether cannabis use and PLEs have interactive effects on adolescent white matter microstructure and neuroinflammation. A total of 123 adolescents (aged 15–16; 36 cannabis users, 87 non-users) completed structured interviews and MRI scans. To address methodological limitations, I first developed and validated the first adolescent population-specific white matter atlas (n = 54 screened healthy adolescents). Using this atlas, I then compared white matter metrics across cannabis users, PLE+ individuals, and controls. No significant group differences or cannabis × PLE interactions were observed. Exploratory analyses highlighted sex differences and associations with continuous cannabis use. These findings provide a novel foundation for adolescent diffusion MRI and suggest that larger samples and dimensional measures are required to clarify neurodevelopmental risk pathways to psychosis.enCannabis UseNeuroimagingPsychotic-Like Experiences