A study has uncovered a possible explanation for the long-term psychological effects of cannabis use during adolescence. Scientists from the Neurocentre Magendie in Bordeaux, working with researchers in Barcelona, found that exposure to cannabis during adolescence in mice caused a chemical change to a mitochondrial protein known as NDUFS4. This change reduced mitochondrial activity and led to behavioral changes in adulthood, especially in male mice. The research, led by Giovanni Marsicano, an Inserm researcher at the Neurocentre Magendie, suggests that this chemical modification—called dephosphorylation—plays a role in the long-term negative effects of cannabis use during adolescence. The researchers found that when they blocked this dephosphorylation in adolescent mice exposed to tetrahydrocannabinol (THC), the active ingredient in cannabis, the behavioral symptoms did not appear in adulthood. This suggests that the chemical change in NDUFS4 is a key factor in the lasting effects of cannabis on the brain. However, this modification was not observed in adult mice, indicating that the biological process is temporary but leads to long-term consequences. Interestingly, the study found that female mice were not affected by the behavioral changes observed in males. The reason for this gender difference remains unclear and is an area for further research. The findings could have important implications for preventive medicine, as mitochondrial function is a growing area of scientific interest. The researchers have also developed a molecular tool that increases mitochondrial activity by about 10%, which can partially counteract the effects of cannabis on mitochondria. This study adds to the understanding of how substances like cannabis can influence brain development and behavior over time. It highlights the importance of studying the long-term effects of drug use during critical developmental periods, such as adolescence, and opens the door for potential interventions aimed at mitigating these effects.