A transient mitochondrial switch underlies long lasting effects of adolescent cannabis

Christina Ioannidou, Irene Manzanares-Sierra, Daniel Jimenez-Blasco, Darío García-Rodriguez, Israel Manjarrés-Raza, Francisca Julio-Kalajzić, Antonio C. Pagano Zottola, Martina Di Bartolomeo, Guillaume Ferreira, Juan P. Bolaños, Giovanni Marsicano, Arnau Busquets-Garcia
Neuropsychopharmacology. 2026-08-27; :
DOI: 10.1038/s41386-026-02539-3

Abstract
Adolescent cannabis use produces lasting and sex-specific effects into adulthood, although poorly explained mechanistically. This study links these cannabis-induced effects to sex-dependent changes in phosphorylation of mitochondrial Complex I subunit NDUFS4 during adolescence, identifying mitochondrial pathways as causal mechanisms and potential therapeutic targets to reduce their long-term consequences.